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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation V158M

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 26 clinical trials

Clinical Trials


1 The Use of an Open Label Placebo to Treat Cancer Related Fatigue in Cancer Survivors

The purpose of this randomized-controlled, crossover pilot trial is to evaluate the feasibility, acceptability and effects of a non-deceptive (open-label) administration of placebo pills for treating cancer related fatigue (CRF). If significant effects are found, the investigators will later determine if the presence of a COMT Val18Met genotype variant predicts placebo responses.

NCT02522988
Conditions
  1. Fatigue
Interventions
  1. Behavioral: Open-label placebo intervention
MeSH:Fatigue
HPO:Fatigue

Test for the presence of a COMT Val158Met/Val or Val/Val variant gene. --- Val158Met ---

Investigators will collect and store saliva samples so, should significant OLPI effects be obtained, we can evaluate whether a potential biomarker (COMT Val158Met variant) associates with placebo responsiveness.. Inclusion Criteria: - Clinical diagnosis of Stage II - IV cancer; - Completed primary treatment 6months to 10 years; - Report ≥4 (moderate fatigue) on a 0-10 fatigue severity rating scale; - Agree not to change any medications or treatments during the study; - Willingness to make 4 clinical site visits over the course of the 49-day study. --- Val158Met ---

Primary Outcomes

Description: Unit of measure: number of enrollees / number of eligible participants as a measure of feasibility.

Measure: Enrollment Rate

Time: End of Study (7 weeks)

Description: Unit of measure: number of accrued participants / recruitment goal (80); odds ration of expected time-to-first participant/ actual time-to-first patient enrollment.

Measure: Accrual Rate as a Measure of Feasibility

Time: End of Study (7 weeks)

Description: Unit of measure: number of placebos taken / number prescribed (84)

Measure: Adherence Rate as a Measure of Feasibility

Time: End of Study (7 weeks)

Description: Unit of measure: number eligible for enrollment / number screened

Measure: Eligibility as a measure of Feasibility

Time: End of Study (7 weeks)

Description: Unit of measure: number retained in study / number enrolled (goal = 75% of enrolled

Measure: Retention as a measure of Acceptability

Time: End of Study (7 weeks)

Secondary Outcomes

Description: Units of measure: units on a scale using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) instrument. 30-questions measure the global, somatic, affective, behavioral and cognitive manifestations of fatigue. Scale for items = 0 (not at all) - 4 (extremely)

Measure: Measure of fatigue manifestation

Time: Baseline, 3 weeks, 4 weeks and 7 weeks

Description: Unit of measure: units on a scale using the Medical Outcomes Study 36-Item Short Form (MOS-36) instrument. The 36-item instrument measures the impact of fatigue on vitality, physical functioning, emotional functioning, social functioning and mental health. Scale for items = 1 (limited a lot) - 3 (Not limited at all)

Measure: Measurement of impact of fatigue on quality of life

Time: Baseline, 3 weeks, 4 weeks and 7 weeks

Description: Unit of measure: units on a scale using the FACT-Fatigue instrument; scale for impact is 0 = not at all; 10 = very much.

Measure: Measurement of the impact of fatigue on physical function

Time: Baseline, 3 weeks, 4 weeks and 7 weeks

Description: Units of measure: units on a scale using the Fatigue Symptom Inventory (FSI) instrument. Scale = 0 (no fatigue / no interference) to 10 (extreme fatigue / interference)

Measure: Measurement of fatigue severity

Time: Baseline, 3 weeks, 4 weeks and 7 weeks

Other Outcomes

Description: Investigators will collect and store saliva samples so, should significant OLPI effects be obtained, we can evaluate whether a potential biomarker (COMT Val158Met variant) associates with placebo responsiveness.

Measure: Test for the presence of a COMT Val158Met/Val or Val/Val variant gene

Time: Baseline

2 Clinical Studies of Mental Illness Not Involving Treatment Development, Efficacy, or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression

Late-life depression (LLD) and cognitive impairment (CI) are significant public health problems among older adults, and their co-occurrence markedly increases disease burden and dementia risk. This highlights the importance of identifying and treating CI in LDD; however, current lack of reliable prognostic information from clinical, neuroimaging, and genetic data impedes research on targeted prevention and treatment. Two critical ways to close current knowledge gaps in predicting cognitive diagnostic outcomes of LLD involve: 1) increasing the number of diagnostic cases available to existing studies, and 2) using those studies to identify clinical, imaging, and genetic predictors that will improve future diagnosis. We intend to do both in the current proposal. We plan to study the following SPECIFIC AIMS: Aim 1: Identify baseline clinical-behavioral predictors of cognitive diagnostic outcomes in LLD. Working hypothesis: During acute LLD, CN will be associated with more frequent EOD and higher negative life stress than PCI and AD; PCI will be associated with EOD and higher frailty than CN and AD; AD will be associated with LOD, greater appetite loss, lower anxiety, and greater memory impairment than CN and PCI. Aim 2: Use multimodal neuroimaging at baseline to identify patterns associated with cognitive diagnostic outcomes in individuals with LLD. Working Hypothesis: CN will be associated with greater white matter integrity compared with PCI and AD; PCI will be associated with lower white matter integrity and network abnormalities in anterior cingulate cortex compared with CN; AD will be associated with lower hippocampal volume compared with CN and PCI. Aim 3: (exploratory): Explore interrelationships among candidate genes, cognitive diagnostic outcomes, and proposed phenotypic components relevant to LLD. Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss.

NCT00570583
Conditions
  1. Major Depression
  2. Dementia
MeSH:Dementia Depression Depressive Disorder
HPO:Dementia Depressivity

Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss. --- val158met ---

Specifically, CN individuals will have earlier first onset of depression (EOD) relative to AD, more negative life stress during acute depression compared with AD and PCI, and greater white matter integrity; CN will also be associated with the AA genotype of the COMT val158met polymorphism, which may confer both neuroprotection and higher stress sensitivity. --- val158met ---

Primary Outcomes

Measure: Change in Depression status (measured by Montgomery Asberg Depression Rating Scale)

Time: Minimum of once per year, up to 21 years

Measure: Change in Cognitive impairment (as measuring using cognitive tests including those found in the CERAD battery)

Time: Once per year, up to 21 years

Measure: Development of dementia (Determined by Clinical Consensus Conference)

Time: once per year, up to 14 years

Secondary Outcomes

Measure: Change in Cognition (as measured by tests including those in the CERAD battery) Change in Brain MRI markers (e.g., volume of white matter and gray matter lesions)

Time: once per year, up to 21 years

Measure: Change in Impairment in Instrumental or Basic Activities of Daily Living

Time: at least once per year, up to 21 years

Measure: Packing density of prefrontal cortex neurons with pyramidal morphology in post-mortem neuroanatomical studies

Time: once post-mortem

3 Genetic Association Study Between Single Nucleotide Polymorphisms (SNPs) and Cognitive Performance in Young Bipolar Type I Patients: LICAVALGENE

This is a genetic association study of cognitive impairment in young bipolar disease type I patients without medications in mania, depression, hypomania or mixed states.

NCT00969930
Conditions
  1. Bipolar

Methods: 80 patients with BD type I (SCID DSM-IV), age from 18 to 35 years old, currently on mania, depression, hypomania or mixed state after medication wash out will be submitted to complete neuropsychological evaluation and genotyped for COMT (val158met, rs165599, -287, rs737865), ApoE (epsilon 4) and BDNF (val66met)and 80 healthy controls. --- val158met ---

Primary Outcomes

Measure: Cognitive deficits in BD patients are associated with COMT, ApoE and BDNF polymorphisms

Time: 18 months

4 The Role of Sex Steroids and Serotonin Brain Dynamics in Perinatal Mental Health

Hormonal transitions such as across pregnancy and postpartum may trigger depressive episodes in some women. It is not known why, but estrogen sensitivity may play a critical role. A preclinical human risk model showed that depressive symptoms induced by pharmacological sex-hormone manipulation is linked to increases in serotonin transporter (SERT) brain binding, which lowers serotonergic brain tone. It is currently unknown if these findings translates to women across pre- to postpartum transitions. This longitudinal project studies a group of women who will deliver by planned caesarian, thus permitting the collection of cerebrospinal fluid (csf) containing central markers of serotonergic signaling, at the latest point in pregnancy. The women are followed across late pregnancy, delivery and 6 months postpartum to illuminate relations between sex-hormones, stress-regulation, estradiol sensitivity, csf markers of neurotransmission, serotonin transporter genotype variance, and potential development of subclinical or manifest depressive symptoms. Further, markers of relevance for the infant brain development and stress-regulation will be obtained from placenta tissue and umbilical cord blood. A subgroup of 70 women will participate in a brain imaging program early postpartum (week 3-5), which includes an evaluation of brain activity and structure and in vivo molecular brain imaging serotonergic markers. Thus, serotonergic markers in csf can be combined with postpartum molecular brain imaging of key features of serotonin signaling. Women in the imaging program are selected based on variation in their level of mental distress immediately postpartum (day 2-5). The study's main hypothesis is that women with high-expressing SERT genotypes are more sensitive to peripartum hormonal transition in terms of changes in serotonergic tone and emergence of depressive symptoms and that such an association will be stronger in the presence of candidate gene transcript biomarkers of oestrogen sensitivity. A further hypothesis is that in vivo molecular brain imaging and csf based serotonergic markers will be associated with depressive symptoms both early and later postpartum. Ideally, this project will provide a rationale for future targeted prevention and/or treatment of perinatal depression in women at high risk, which holds grand potential to protect not only mother but also infant brain health long-term.

NCT03795688
Conditions
  1. Major Depressive Disorder
  2. Perinatal Depression
Interventions
  1. Other: Pregnancy
MeSH:Depressive Disorder Depressive Disorder, Major
HPO:Depressivity

val158met (rs4680) status, binary variable, i.e. "val/val, val/met" vs "met/met" variants. --- val158met ---

Primary Outcomes

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Total group

Measure: Depressive symptoms

Time: Week 3-6 postpartum

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Week 3-6 postpartum

Description: 116 a priori defined gene transcripts, which where differentially expressed in third trimester of women who later developed perinatal depression with postpartum onset relative to pregnant women who did not and to other depressed (reference Mehta et al, 2014, Psychological Medicine) and confirmed to be coupled to estrogen fluctuations (Mehtaet al. 2018 British Journal of Psychiatry) will be evaluated in the total group. Also DNA methylation of the genes of these transcripts will be determined and analysed in terms of their predictive value (above chance) for perinatal depression.

Measure: Gene transcript and DNA methylation markers of estrogen sensitivity

Time: Prior to caesarean section

Description: Latent variable construct of brain 5-HT4R level based on quantification of 5-HT4R binding from 11C-SB207145 positron emission tomography in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Assessed in imaging group.

Measure: Cerebral serotonin 4 receptor binding postpartum

Time: Week 3-6 postpartum

Description: Assessed in total group

Measure: CSF levels of GABA

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of serotonin metabolite (5-HIAA)

Time: On day of caesarean section

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Week 3-6 postpartum

Description: Provides an estimate of cortisol exposure up to 6 months prior to delivery, total group

Measure: Hair cortisol level mothers

Time: On day of caesarean section.

Description: Provides an estimate of fetal cortisol exposure, infants from total group

Measure: Hair cortisol level newborns

Time: Day 0-5 postpartum.

Description: Hippocampal brain volume (including hippocampus) from structural MRI, imaging group.

Measure: Hippocampal volumes

Time: Week 3-6 postpartum.

Description: fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli. Assessed in imaging cohort

Measure: functional MRI response to reward

Time: Week 3-6 postpartum.

Description: rsfMRI based spontaneous co-fluctuations in low frequency BOLD signal, (functional connectivity). Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake. Assessed in imaging group.

Measure: Resting state functional connectivity MRI

Time: Week 3-6 postpartum

Description: Change in epigenetic SERT status from late pregnancy to postpartum week 3-6.

Measure: Change in epigenetic SERT status

Time: From just before delivery to 3-6 weeks postpartum

Description: Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Concentration of inflammatory markers, i.e hsCRP and immunoactive cytokines, in peripheral blood

Time: At week 3-6

Description: fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli. Assessed in imaging cohort.

Measure: functional MRI response to emotional faces

Time: Week 3-6 postpartum.

Secondary Outcomes

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Day 3-5 postpartum

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Week 12 postpartum

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in total group

Measure: Depressive symptoms

Time: Day 3-5 postpartum

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in all

Measure: Depressive symptoms

Time: 6 months postpartum

Description: Assessed in total group

Measure: CSF levels of serotonin

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of dopamine metabolites

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of noradrenaline metabolites

Time: On day of caesarean section

Description: Composite measure of IFN-c, IFN-alfa TNF-alfa og IL-6, in total group

Measure: CSF levels of inflammatory markers

Time: On day of caesarean section

Description: Estradiol level in peripheral blood, total group

Measure: Estradiol level

Time: Prior to caesarean section.

Description: Estradiol level peripheral blood, total group

Measure: Estradiol level

Time: At week 3-6 postpartum.

Description: Estradiol change pre- to postpartum, peripheral blood total group

Measure: Change in estradiol level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Progesterone level in peripheral blood

Measure: Progesterone level

Time: Prior to caesarean section.

Description: Progesterone level in peripheral blood

Measure: Progesterone level

Time: At week 3-6 postpartum.

Description: Progesterone change pre- to postpartum, peripheral blood total group

Measure: Change in progesterone level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Allopregnanolone level in peripheral blood

Measure: Allopregnanolone level

Time: Prior to caesarean section.

Description: Allopregnanolone level in peripheral blood

Measure: Allopregnanolone level

Time: At week 3-6 postpartum.

Description: Change in allopregnanolone level in peripheral blood

Measure: Change in allopregnanolone level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Cortisol change pre- to postpartum, peripheral blood total group

Measure: Change in cortisol level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Week 12 postpartum

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Prior to caesarean section

Description: Change in cortisol awakening response, from caesarean section to 3-6 weeks postpartum.

Measure: Change in cortisol awakening response

Time: ´From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the SERT gene, total group

Measure: DNA methylation of the SERT gene

Time: Prior to caesarean section

Description: DNA Methylation status for the SERT gene, total group

Measure: DNA methylation of the SERT gene

Time: Week 3-6 postpartum

Description: Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

Measure: DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: Prior to caesarean section.

Description: Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

Measure: DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the FK506-binding protein 51 (FKBP5) gene from late pregnancy to postpartum week 3-6.

Measure: Change in DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the glucocorticoid receptor gene, total group

Measure: DNA methylation of the glucocorticoid receptor gene

Time: Prior to caesarean section.

Description: Methylation status for the glucocorticoid receptor gene, total group

Measure: DNA methylation of the glucocorticoid receptor gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the glucocorticoid receptor gene from late pregnancy to postpartum week 3-6.

Measure: Change in DNA methylation of the glucocorticoid receptor gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the COMT gene, total group

Measure: DNA methylation of the COMT gene

Time: Prior to caesarean section.

Description: Methylation status for the COMT gene, total group

Measure: DNA methylation of the COMT gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the COMT gene from just before delivery to 3-6 weeks postpartum

Measure: Change in DNA methylation of the COMT gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the MAO-A gene, total group

Measure: DNA methylation of the MAO-A gene

Time: Prior to caesarean section.

Description: Change in methylation status for the MAO-A gene, total group

Measure: Change in DNA methylation of the MAO-A gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the MAO-A gene, total group

Measure: DNA methylation of the MAO-A gene

Time: Week 3-6 postpartum

Description: Methylation status for the oxytocin receptor gene, total group

Measure: DNA methylation of the oxytocin receptor gene

Time: Prior to caesarean section.

Description: Methylation status for the oxytocin receptor gene, total group

Measure: DNA methylation of the oxytocin receptor gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the oxytocin receptor gene, total group

Measure: Change in DNA methylation of the oxytocin receptor gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the oxytocin gene, total group

Measure: DNA methylation of the oxytocin gene

Time: Prior to caesarean section.

Description: Methylation status for the oxytocin gene, total group

Measure: DNA methylation of the oxytocin gene

Time: Week 3-6 postpartum

Description: Change methylation status for the oxytocin gene, total group

Measure: Change in DNA methylation of the oxytocin gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Systemic inflammation peripheral blood hsCRP and immunoactive cytokines

Time: Prior to caesarean section.

Description: Change in composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Change in systemic inflammation peripheral blood hsCRP and immunoactive cytokines

Time: From baseline (caesarean section to week 3-6 postpartum

Description: Family History Assessment Module (OS-FHAM). Number of first degree relatives with a history of depressive episodes or bipolar disorder. Total group.

Measure: Self reported family history of mood disorders

Time: Day 3-5 postpartum or before

Description: Barratt Impulsiveness Scale (BIS-11), self-reported. Range: 30-120. Total group.

Measure: Self reported impulsiveness score

Time: Day 3-5 postpartum or before

Description: NEO-PI-R - Revised NEO Personality Inventory, self-reported. Participants may score 20-80 for each of the personality traits: openness, conscientiousness, extraversion, agreeableness, and neuroticism. The higher the score, the more prominent is the personality trait. Total group.

Measure: Self reported Neuroticism score from NEO personality questionnaire

Time: Day 3-5 postpartum or before

Description: Parental bonding instrument (PBI), both parents, self-reported. Total group.

Measure: Self reported parental bonding quality

Time: Day 3-5 postpartum or before

Description: Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Self-reported perceived stress

Time: Day 3-5 postpartum

Description: Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Self-reported perceived stress

Time: Week 3-6 postpartum

Description: Change in Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Change in self-reported perceived stress

Time: Change from day 3-5 to week 3-6 postpartum

Description: Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Self-reported anhedonia

Time: Day 3-5 postpartum

Description: Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Self-reported anhedonia

Time: Week 3-6 postpartum

Description: Change in Snaith-Hamilton Pleasure Scale (SHAPS) score, range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Change in self-reported anhedonia

Time: Change from day 3-5 to week 3-6 postpartum

Description: Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Self-reported rumination

Time: Day 3-5 postpartum

Description: Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Self-reported rumination

Time: Week 3-6 postpartum

Description: Change in Rumination Response Scale (RRS) score, range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Change in elf-reported rumination

Time: Change from day 3-5 to week 3-6 postpartum

Description: Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Self-reported mood

Time: Day 3-5 postpartum

Description: Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Self-reported mood

Time: Week 3-6 postpartum

Description: Change in Profile of Mood States (POMS) score, range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Change in self-reported mood

Time: Change from day 3-5 to week 3-6 postpartum

Description: Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Self-reported sleep quality

Time: Day 3-5 postpartum

Description: Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Self-reported sleep quality

Time: Week 3-6 postpartum

Description: Change in Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Change in self-reported sleep quality

Time: Change from day 3-5 to week 3-6 postpartum

Description: Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Self-reported psychiatric symptoms

Time: Day 3-5 postpartum

Description: Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Self-reported psychiatric symptoms

Time: Week 3-6 postpartum

Description: Change in Brief symptom Inventory-53 item (BSI-53) score, range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Change in self-reported psychiatric symptoms

Time: Change from day 3-5 to week 3-6 postpartum

Description: WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Self-reported well-being

Time: Day 3-5 postpartum

Description: WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Self-reported well-being

Time: Week 3-6 postpartum

Description: Change in WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Change in self-reported well-being

Time: Change from day 3-5 to week 3-6 postpartum

Description: State Trait Anxiety Inventory (STAI-AD-D), state and trait subscales each have a range of 20-80, 20 means no anxiety. Total group.

Measure: Self-reported anxiety

Time: Day 3-5 postpartum

Description: State Trait Anxiety Inventory (STAI-AD-D), state subscale range 20-80, 20 means no anxiety. Total group.

Measure: Self-reported anxiety

Time: Week 3-6 postpartum

Description: Change in State Trait Anxiety Inventory (STAI-AD-D) score, state subscale range 20-80, 20 means no anxiety. Total group.

Measure: Change in self-reported anxiety

Time: Change from day 3-5 to week 3-6 postpartum

Description: Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Self-reported obsessive and compulsive symptoms

Time: Day 3-5

Description: Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Self-reported obsessive and compulsive symptoms

Time: Week 3-6 postpartum

Description: Change in Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Change in self-reported obsessive and compulsive symptoms

Time: Change from day 3-5 to week 3-6 postpartum

Description: Performance on Simple Reaction Time, in imaging cohort.

Measure: Performance on Simple Reaction Time

Time: Week 3-6 postpartum

Description: Gray matter brain volume prefrontal cortex and anterior cingulate cortex

Measure: Gray matter brain volume prefrontal cortex and anterior cingulate cortex

Time: At week 3-6 postpartum

Description: Composite measure of serotonin, tryptophan og tryptofan hydroxylase levels relative to 5-HIAA, in placenta sample. Infants from total group

Measure: Serotonergic turnover in placenta

Time: At delivery.

Description: 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta. Infants from total group

Measure: 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta

Time: At delivery

Description: Composite measure of methylation status for the FKBP5, glucocorticoid receptor, 11-beta hydroxysteroid dehydrogenase type 2 genes. Infants from total group

Measure: Methylation status of genes relevant for stress-hormone regulation in placenta

Time: At delivery

Description: Composite measure of the methylation status for monoamine oxidase, serotonin receptor and serotonin transporter genes. Infants from total group

Measure: Methylation status of genes related to serotonergic signaling in placenta

Time: At delivery

Description: Composite measure of methylation status and gene transcript profiles of Glucocorticoid receptor, FKBP5, oxytocin and oxytocin receptors, Brain-derived neurotrophic factor (BDNF) genes. Assessed in blood from umbilical cord blood sample from infants, total group.

Measure: Methylation status and gene transcript profiles of relevance for early brain development and stress regulation in newborn infants

Time: At delivery.

Other Outcomes

Description: val158met (rs4680) status, binary variable, i.e. "val/val, val/met" vs "met/met" variants

Measure: COMT-genotype (rs4680) variant, i.e met/met vs other polymorphisms

Time: Prior to caesarean section.

Description: BDNF val66met (rs6265) status, binary variable, i.e. "val/val" versus "met-carrier" status

Measure: BDNF genotype (rs6265) status, i.e. val/val versus met-carrier variants

Time: Prior to caesarean section.

Description: 5-HTTLPR genotype status (binary), i.e. high-expressing LALA vs low-expressing (S or LG) variants, based on SLC6A4, i.e. L or S variants, and further subtyping on rs25531 haplotype L(A)L(A) vs LGLA, LGLG or variants containing as S as specified above.

Measure: 5-HTT genotype status, i.e LALA vs low-expressing (S or LG) variants

Time: Prior to caesarean section.

Description: In house interview based on Kennerley Maternity Blues Questionnaire, range: 0-28, higher score indicates more severe postpartum blues symptoms. High blues score is associated with greater risk for perinatal depression at week 3-6.

Measure: Postpartum blues symptoms

Time: Day 3-5 postpartum.

Description: In house interview based on Stein's Maternity Blues Scale, range 0-26. High blues score is associated with greater risk for perinatal depression at week 3-6.

Measure: Postpartum blues symptoms

Time: Day 3-5 postpartum.

5 Modulation of Cognitive Flexibility by Transcranial Direct Current Stimulation, Tyrosine Administration and Polymorphisms in the COMT Gene

The current study would examine whether increases in endogenous dopaminergic activity via tyrosine and the (presumed) excitation of these by anodal tDCS of the dlPFC could causally be related to cognitive flexibility as measured by task switching and reversal learning. Additionally, the study will test whether the Val158Met-polymorphism in the catechol- O-methyltransferase (COMT) gene could also predict the effect of TYR supplementation, as this gene is involved in DA degradation in the prefrontal cortex.

NCT03845920
Conditions
  1. Modulation of Cognitive Flexibility by Transcranial Direct Current Stimulation, Tyrosine Administration and Polymorphisms in the COMT Gene
Interventions
  1. Combination Product: tdcs (sham/anodal) + drug (placebo/tyrosine)

Additionally, the study will test whether the Val158Met-polymorphism in the catechol- O-methyltransferase (COMT) gene could also predict the effect of TYR supplementation, as this gene is involved in DA degradation in the prefrontal cortex. --- Val158Met ---

Primary Outcomes

Description: Measuring change in perseverative errors in the WCST

Measure: Wisconsin Card Sorting Test (WCST) performance

Time: Measured twice in each session (4 arms): at time 0 and 80 minutes into testing.

Description: Measuring change in reversal errors in the WCST

Measure: Probabilistic Reversal Learning (PRL) performance

Time: Measured twice in each session (4 arms): at time 0 and 80 minutes into testing.

Description: Measuring change in conflict cost (defined as the difference in reaction time between congruent and incongruent responses)

Measure: Flanker Task performance

Time: Measured twice in each session (4 arms): at time 0 and 80 minutes into testing.

6 Biomarker Strategies for Medication-Enhanced Cognitive Training in Schizophrenia

Cognitive training is moderately effective at reducing symptoms and improving life function in schizophrenia patients. The present application develops a strategy for increasing the effectiveness of cognitive training through the use of pro-cognitive medications. Specific biomarkers will be studied that identify patients most sensitive to these pro-cognitive medications, to test the feasibility of using these biomarkers in a large clinical trial of medication-enhanced cognitive training in schizophrenia.

NCT01555697
Conditions
  1. Schizophrenia
Interventions
  1. Drug: Memantine
  2. Drug: Placebo
MeSH:Schizophrenia
HPO:Schizophrenia

PPI-enhancing effects of MEM in healthy subjects are associated with: 1) increased WM; and 2) phenotypes linked to the high activity Val158Met COMT polymorphism. --- Val158Met ---

Primary Outcomes

Description: Prepulse inhibition of the startle reflex is the automatic reduction in startle magnitude (assessed here by EMG of orbicularis oculi) when a startling stimulus (here a 40 ms 118 dB(A) noise burst; "PULSE") is preceded (here 10 - 120 msec) by a weak stimulus (here a 20 msec burst 16 dB over background "PREPULSE"). A %PPI metric is calculated based on the relative startle magnitude on (PREPULSE + PULSE) trials vs. PULSE alone trials. Possible maximal inhibition is 100%; there is no maximal "negative" value of inhibition. There is no clear "advantage" or "disadvantage" for lower or higher %PPI values, though on average, schizophrenia patients demonstrate lower % values compared to matched healthy subjects.

Measure: Prepulse Inhibition

Time: approx 45 minutes

Secondary Outcomes

Description: MATRICS Consensus Cognitive Battery Performance: This is a standardized neurocognitive battery that assesses performance in 7 domains of neurocognition. Primary data are recorded based on normalized T-scores; a separate score is provided for each domain, and a Comprehensive score (Primary measure here) is also calculated across domains. Possible T-score range is 0 - 100; higher score reflects better performance.

Measure: MATRICS

Time: approx 1 hour

7 Normalization of dyrk1A and APP Function as an Approach to Improve Cognitive Performance and Decelerate AD Progression in DS Subjects: Epigallocatechin Gallate as Therapeutic Tool

Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, is postulated to modulate dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and amyloid beta precursor protein (APP) gene overexpression in the brains of Down syndrome mouse models. The clinical study is aimed at demonstrating that normalization of Dyrk1A and APP functions is a therapeutic approach to improve cognitive performance and decelerate AD (Alzheimer's disease) like progression.

NCT01699711
Conditions
  1. Down Syndrome (DS)
Interventions
  1. Dietary Supplement: Epigallocatechin-3-gallate (EGCG)
MeSH:Down Syndrome

COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman). --- val158met ---

Primary Outcomes

Description: a.Intelligence Quotient [Kaufman (K-BIT)], b.Attention [Spatial Span direct series (SSP), Choice Reaction Time (CRT) CANTAB battery]c. Psychomotor Speed [ (MOT) CANTAB battery] d.Episodic Memory [visuospatial: Paired Associates Learning (PAL) and visual: Pattern Recognition Memory (PRM) CANTAB battery; visuospatial learning Cued Recall Test (CRT) ] e.Executive Functions [working memory: SSP CANTAB battery; verbal semantic fluency; inhibition: Cats and Dogs; planning: Tower of London-Drexel (TOLDX) mental flexibility: Weigl Card Sorting Test ] f.Language:[ Expressive language: Boston naming test (BNT) ; Receptive language: Token Test (TT) g.Functional, quality of life and neuropsychiatric evaluation [Adaptative Behaviour Assessment System (ABAS-II): Dementia Questionnaire for People with Intellectual Disabilities (DMR): Neuropsychiatric Inventory (NPI); quality of life: Kidscreen; semi-structured interview to evaluate subjective effects concerning relevant changes.

Measure: Change in Cognitive Evaluation

Time: From predose baseline to 19 months (end of treatment)

Description: APP derived amyloid peptides in plasma (INNO-BIA)

Measure: Change in Amyloidosis Biomarkers

Time: From predose baseline to 19 months (end of treatment)

Secondary Outcomes

Measure: Treatment compliance

Time: Predose baseline 3, 7, 13 months

Description: LDL (Low density lipoproteins), HDL (High density lipoprotein, cholesterol, triglycerides oxidized-LDL (Pentra Autoanalyzer, and ELISA Mercodia for LDLox

Measure: Change in Biomarkers of lipid oxidation

Time: Predose baseline: 3, 7, 13 months

Description: Plasma homocysteine (Abbot AxyM), transthyretrin (ELISA) FOXO1 (DNA-binding ELISA nuclear extract from lymphocytes)

Measure: Change in DYRK1A activity biomarkers

Time: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).

Measure: COMT val158met genetic polymorphism (catechol methyl transferase) (Taqman)

Time: Predose baseline

Measure: Change in AST (SGOT -serum glutamic oxaloacetic transaminase-) and ALT (SGPT- Serum Glutamic Pyruvate Transaminase-) (Pentra Autoanalyzer, and ELISA Mercodia for LDLox)

Time: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).

Measure: Change in Body Composition by electrical impedance (TANITA-MC-180)

Time: Predose baseline 4 , 7 and 13 and 19 moths (end of treatment plus 6 months).

Description: Parameters to be evaluated: (i) Motor threshold at Rest (MTR) for the Abductor Pollicis Brevis ( APB) muscle determination (ii) Basal single pulse response at rest for the APB at 110 of the MTR required, and (iii) Percentage of increase and decrease of the amplitude of the APB after double pulse, short and long pulse interval after transcranial magnetic stimulation (TMS).

Measure: Changes in Neurophysiology

Time: Predose baseline: 7, 13 months

Description: Regional brain morphology and volume (FLAIR) sequence to assess possible white matter tissue macroscopic lesions), brain function in disease-specific neural systems: Intrinsic functional organization (i.e., functional connectivity) in the resting-state within the neural systems.

Measure: Changes in Neuroimaging

Time: Predose baseline: 7, 13 months

8 A Pharmacotherapy Study: A Dose Response Effect of Atomoxetine on Alcohol-elicited Craving and Sensitivity to the Acute Effects of Alcohol

This two-stage study will examine the effects of a 5 day course of atomoxetine (placebo, 40, 60 or 80 mg/day; Strattera) (a selective NE transporter (NET) inhibitor) on alcohol-elicited craving and sensitivity to alcohol. The novelty of this study is that of atomoxetine and the fact that it targets NET, neither of which has heretofore been examined in the context of alcohol dependence. It is hopeful that this pilot study, of 86 total individuals, will provide the PI with sufficient preliminary data to submit a subsequent R01 application to study atomoxetine and the involvement of specific single nucleotide polymorphisms within the NET gene on alcohol-related phenotypes in alcohol dependent and non-dependent populations. The long-term objective of this research is to develop more efficacious treatment interventions for alcohol abuse and dependence. Hypothesis 1: It is hypothesized that subjects who receive 40, 60 or 80 mg/day of atomoxetine for 5 days will demonstrate significantly less alcohol-elicited craving than subjects who receive a placebo. Hypothesis 2: It is hypothesized that subjects who receive 40, 60 or 80 mg/day of atomoxetine for 5 days will be less sensitive to the acute effects of alcohol (subjective intoxication) than subjects who receive a placebo.

NCT01408589
Conditions
  1. Alcohol Craving
  2. Mood Changes
Interventions
  1. Drug: Atomoxetine, Strattera

COMT Val158Met (G/A), Val > Met 2-4x plasma activity DBH -1021 C/T, C/C has 3x more plasma activity NET gene variants were also examined. --- Val158Met ---

Primary Outcomes

Description: Alcohol craving and sensitivity were measured with the AUQ, ARS, POMS, BAES and SHAS

Measure: Alcohol Craving

Time: Day 5 of medication

Secondary Outcomes

Description: To determine whether two functional SNPs within the COMT and DBH genes moderate the effects of EtOH and or atomoxetine. COMT Val158Met (G/A), Val > Met 2-4x plasma activity DBH -1021 C/T, C/C has 3x more plasma activity NET gene variants were also examined

Measure: Genetic moderation

Time: day 5 of medication

9 Dexamethasone for the Treatment of Established Postoperative Nausea and Vomiting - a Randomised, Placebo-controlled, Dose-finding Study

Postoperative nausea and vomiting (PONV) are frequent after surgery and anaesthesia. Dexamethasone is widely used as antiemetic for the prevention of PONV. Little is known about the efficacy of antiemetic drugs for the treatment of established PONV symptoms. No single randomised trial has been published so far that tests the efficacy of dexamethasone for the treatment of established PONV symptoms. In this trial the investigators want to test the antiemetic efficacy of three different doses of intravenous dexamethasone for the treatment of established PONV symptoms. In adjunct protocols of this study the investigators aim to establish a novel method to quantify the anti-nausea efficacy of an antiemetic drug, to study pharmacogenetics of PONV, and to further our understanding on the smoking status as a predictive factor of PONV.

NCT01975727
Conditions
  1. Postoperative Nausea and Vomiting
  2. Vomiting
Interventions
  1. Drug: Placebo
  2. Drug: Dexamethasone 3 mg
  3. Drug: Dexamethasone 6 mg
  4. Drug: Dexamethasone 12 mg
MeSH:Nausea Vomiting Postoperative Nausea and Vomiting
HPO:Nausea Vomiting

The COMT enzyme possesses a frequent non-synonymous polymorphism that encodes for the substitution of valine (Val) by methionine (Met) at codon 158 (Val158Met). --- Val158Met ---

The COMT Val158Met polymorphism (rs4680) will be genotyped using a commercially available TaqMan® SNP genotyping assay (C_25746809_50, Applied Biosystems, Warrington, UK). --- Val158Met ---

Primary Outcomes

Description: Complete absence of any nausea and/or vomiting (including retching) in a previously nauseated or vomiting patient within 24 hours after administration of the study treatment.

Measure: Treatment efficacy of Dexamethasone for established PONV

Time: 24 hour follow up

Secondary Outcomes

Description: Free from PONV during the first 6 hours

Measure: Short term efficacity

Time: 6 hours

Description: Number of patients staying PONV free after rescue antiemetic during the first 24 postoperative hours

Measure: PONV free after rescue antiemtic

Time: 24 hour follow up

Description: quality of sleep during the first postoperative night (numerical rating scale ranging from 0 = no sleep at all to 10 = excellent sleep)

Measure: Quality of sleep

Time: 24 hour follow up

Description: any minor or major adverse effects during 24h.

Measure: Minor or major adverse effects

Time: 24 hour follow up

10 A Randomized, Double-blind, Placebo-controlled Examination of the Effects of Tolcapone (TASMAR) on Vigilance in Healthy Volunteers After Sleep Deprivation

In this study, pharmacologic effects of COMT inhibition during sleep deprivation in healthy subjects in dependence of their Val158Met genotype of COMT are studied. Potential effects are identified by measurement of vigilance and cognitive performance as well as EEG measurements during wake and sleep. - Trial with medicinal product

NCT02080715
Conditions
  1. Healthy
Interventions
  1. Drug: Tolcapone
  2. Drug: Placebo

Role of the Catechol-O-methyltransferase (COMT) in the Physiological Regulation of Vigilance In this study, pharmacologic effects of COMT inhibition during sleep deprivation in healthy subjects in dependence of their Val158Met genotype of COMT are studied. --- Val158Met ---

Primary Outcomes

Description: Vigilance is measured subjectively (questionnaires and visual analogue scales) and objectively (e.g., psychomotor vigilance task: reaction times and number of lapses; waking EEG: spectral power) at 3-hour intervals during 40 hours prolonged wakefulness in 30 healthy male adults.

Measure: Evolution of vigilance during prolonged wakefulness after intake of tolcapone when compared to placebo

Time: Participants will be studied during two weeks

11 Mechanism of tDCS-induced Learning Enhancement - the Role of Serotonin

The aim of this study is to assess whether the application of a selective serotonin reuptake inhibitor (SSRI) enhances and prolongs the learning enhancement achieved by anodal transcranial direct current stimulation (atDCS). For this, young and older healthy subjects will be tested with a well established learning paradigm. Results of this study may help to support the application of atDCS also in patients, e.g. with dementia or mild cognitive impairment.

NCT02092974
Conditions
  1. Healthy Young and Older Adults
Interventions
  1. Procedure: tDCS
  2. Drug: Citalopram
  3. Other: sham-tDCS + placebo

To assess predictors of SSRI-enhanced brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF, Val66Met, COMT, Val158Met, KIBRA, rs17070145, 5-Hydroxytryptamine transporter).. Inclusion Criteria: - right handedness - unobtrusive neuropsychological screening - ability to provide written informed consent - no pathological findings in head MRI - age: 18 to 35 years (young adults) or 50-80 years (older adults) - Highly effective contraception (Pearl Index < 1) or reliable abstinence from any heterosexual relationships in women of childbearing potential Exclusion Criteria: - severe internal or psychiatric disease (especially depression or suicidal thoughts) - epilepsy - cognitive impairment (< SD under age adjusted norm in neuropsychological testing) - concurrent taking of serotonin precursors (tryptophan, 5-HTP) or MAO inhibitors - concurrent taking of tramadol or triptans - concurrent taking of pimozide or linezolid - concurrent taking of other drugs prolonging the QT-interval - long-QT-syndrome - hypokalemia or hypomagnesemia - known intolerance of the study medication - claustrophobia or metallic implants, tattoos (MRI exclusion criteria) - pregnancy or lactation - participation in another drug-interventional clinical trial within the last month or during the entire study - probands that are placed in an institution due to official or judicial order - non-agreement to save and transmit pseudonymised study data within the clinical trial Inclusion Criteria: - right handedness - unobtrusive neuropsychological screening - ability to provide written informed consent - no pathological findings in head MRI - age: 18 to 35 years (young adults) or 50-80 years (older adults) - Highly effective contraception (Pearl Index < 1) or reliable abstinence from any heterosexual relationships in women of childbearing potential Exclusion Criteria: - severe internal or psychiatric disease (especially depression or suicidal thoughts) - epilepsy - cognitive impairment (< SD under age adjusted norm in neuropsychological testing) - concurrent taking of serotonin precursors (tryptophan, 5-HTP) or MAO inhibitors - concurrent taking of tramadol or triptans - concurrent taking of pimozide or linezolid - concurrent taking of other drugs prolonging the QT-interval - long-QT-syndrome - hypokalemia or hypomagnesemia - known intolerance of the study medication - claustrophobia or metallic implants, tattoos (MRI exclusion criteria) - pregnancy or lactation - participation in another drug-interventional clinical trial within the last month or during the entire study - probands that are placed in an institution due to official or judicial order - non-agreement to save and transmit pseudonymised study data within the clinical trial Healthy Young and Older Adults null --- Val66Met --- --- Val158Met ---

Primary Outcomes

Description: Recall score immediately after learning phase (=training of visual-spatial abilities) under tDC stimulation + SSRI application compared to learning under tDC stimulation + placebo.

Measure: Recall score after learning under tDC stimulation + SSRI compared to learning under tDC stimulation + placebo.

Time: immediately after end of learning phase (approx. 1 hour)

Secondary Outcomes

Description: Measurement of recall scores on the evening of the same day after the learning phase (+tDCS + SSRI), the morning of the day after and 1 week later in order to assess the prolongation of atDCS induced learning enhancement by the SSRI.

Measure: prolongation of the atDCS induced learning enhancement by SSRI

Time: 1 week

Description: Measurement of recall scores directly after learning phase after application of atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo.

Measure: Increase of learning enhancement by atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo

Time: immediately after learning phase (approx. 1 hour)

Description: Measurement of recall scores on the evening of the same day of learning phase, the morning of the day after and 1 week later under application of atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo, in order to assess prolongation of learning enhancement by SSRI.

Measure: prolongation of learning enhancement by atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo

Time: 1 week

Description: To assess predictors of SSRI-enhanced brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF, Val66Met, COMT, Val158Met, KIBRA, rs17070145, 5-Hydroxytryptamine transporter).

Measure: genotyping of learning related polymorphisms

Time: once

12 COMT Val158Met Polymorphism in Opiate-using Subjects Without Lifetime Opiate Dependence

The main objective is to compare the genotypes of the COMT Val158Met polymorphism between opiate-users and opiate-dependent subjects. The secondary objective is to constitute a sample of opiate-users without any lifetime opiate dependence.

NCT01570699
Conditions
  1. Opioid-related Disorders
  2. Opiate Dependence
  3. Opiate Addiction
  4. Opiate Abuse
Interventions
  1. Genetic: COMT polymorphism
MeSH:Opioid-Related Disorders

COMT Val158Met Polymorphism in Opiate-using Subjects Without Lifetime Opiate Dependence. --- Val158Met ---

Variation of COMT Val158Met Polymorphism Between COM-ON Patients and METHADOSE Patients The main objective is to compare the genotypes of the COMT Val158Met polymorphism between opiate-users and opiate-dependent subjects. --- Val158Met ---

Variation of COMT Val158Met Polymorphism Between COM-ON Patients and METHADOSE Patients The main objective is to compare the genotypes of the COMT Val158Met polymorphism between opiate-users and opiate-dependent subjects. --- Val158Met --- --- Val158Met ---

Inclusion Criteria: - Patient over 18 years old - Caucasian patients - Clinical diagnosis of lifetime opiate-using disorder (consumption over 10 times of illicit opiates (heroin, buprenorphine, methadone or morphine)) - Not lifetime history of opioid dependence (DSMIV) - Patients with health insurance coverage - Patient was treated with opioids analgesics to alleviate 2 or 3 in their lives Exclusion Criteria: - Non-Caucasian patients - Patients who cannot give their consent and/or who refuse the collection of genetic data - Patients with no health insurance coverage Inclusion Criteria: - Patient over 18 years old - Caucasian patients - Clinical diagnosis of lifetime opiate-using disorder (consumption over 10 times of illicit opiates (heroin, buprenorphine, methadone or morphine)) - Not lifetime history of opioid dependence (DSMIV) - Patients with health insurance coverage - Patient was treated with opioids analgesics to alleviate 2 or 3 in their lives Exclusion Criteria: - Non-Caucasian patients - Patients who cannot give their consent and/or who refuse the collection of genetic data - Patients with no health insurance coverage Opioid-related Disorders Opiate Dependence Opiate Addiction Opiate Abuse Opioid-Related Disorders The COMT enzyme enables the degradation of brain monoamines such as Dopamine and is encoded by a single gene for which several polymorphisms are known, including the Val158Met polymorphism which has been widely studied in various psychiatric disorders, including addictions, as well as in impulsivity. --- Val158Met ---

Primary Outcomes

Measure: Number of subjects with each COMT genotype (Val/Val, Val/Met and Met/Met) in the opiate-users' group and in the opiate-dependent subjects' group

Time: Day 0

Secondary Outcomes

Measure: Score on the M.I.N.I. (Mini-International Neuropsychiatric Interview) on the day of the inclusion

Time: Day 0

Measure: Score on the BIS (Barratt Impulsivity Scale) on the day of the inclusion

Time: Day 0

Measure: Score on the TCI (Cloninger's Temperament and Character Inventory) on the day of the inclusion

Time: Day 0

Measure: Score on the WURS (Wender Utah Rating Scale) on the day of the inclusion

Time: Day 0

Measure: Score on the ASRS(Self-Report Scale) on the day of the inclusion

Time: Day 0

Measure: Score on the MOPS (Measure Of Parental Style) on the day of the inclusion

Time: Day 0

Measure: Score on the Questionnaire of family breakdowns on the day of the inclusion

Time: Day 0

Measure: Score on the CD-RISC (Connor-Davidson Resilience scale) on the day of the inclusion

Time: Day 0

Measure: Score on the CTQ (Childhood trauma questionnaire) on the day of the inclusion

Time: Day 0

13 Modulation of Visual-Spatial Learning in Healthy Young Adults by Transcranial Direct Current Stimulation - Proof of Principle and Mechanisms

The aim of this study is to investigate whether a combination of intensive training of visual-spatial abilities (LOCATO task) with anodal transcranial direct current stimulation (tDCS) leads to an improvement of learning and memory in healthy young adults and to examine the underlying neuronal mechanism.

NCT02110407
Conditions
  1. Healthy Young Adults
Interventions
  1. Device: tDCS
  2. Behavioral: training

To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).. Inclusion Criteria: - right handednesss - unobtrusive neuropsychological screening - age: 18-35 years Exclusion Criteria: - severe internal or psychiatric disease - epilepsy - other severe neurological disease, e.g. --- Val66Met --- --- Val158Met ---

Primary Outcomes

Description: Investigation whether the combination of intensive visual-spatial training (LOCATO task) and tDCS leads to improvement of visual-spatial learning and memory measured by the performance in LOCATO task after end of a 3 day period of training compared to sham stimulation.

Measure: performance in LOCATO task (visual-spatial learning and memory) after a combination of intensive visual-spatial training and tDCS

Time: immediately after end of a 3 day period of training in tDCS condition vs sham condition

Secondary Outcomes

Description: long term effetcs measured by performance in LOCATO task after end of training and after 1 month compared to control conditions

Measure: long term effects

Time: after 1 month vs baseline

Description: Connectivity (measured by resting-state fMRT and correlation analysis) at baseline compared to end of training

Measure: functional changes: Connectivity

Time: after end of 3-day cognitive training vs baseline

Description: cortical excitability measured by transcranial magnetic stimulation (TMS)

Measure: cortical excitability

Time: at baseline

Description: quality of life as measured by standardized questionaire at baseline compared to quality of life measured 1 month after intervention (training and stimulation vs. training and sham-stimualtion)

Measure: Quality of Life

Time: after 1 month vs baseline

Description: memory performance tested at baseline compared to memory performance after the end of a 3-day cognitive training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: memory

Time: immediately after end of 3-day of cognitive training, after 1 month vs. baseline

Description: To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).

Measure: genotyping of learning related polymorphisms

Time: once

14 Modulation of Visual-Spatial Learning in Healthy Older Adults by Transcranial Direct Current Stimulation - Proof of Principle and Mechanisms

The aim of this study is to investigate whether a combination of intensive training of visual-spatial abilities (LOCATO task) with anodal transcranial direct current stimulation (tDCS) leads to an improvement of learning and memory in healthy older adults and to examine the underlying neuronal mechanism.

NCT02110056
Conditions
  1. Healthy Older Adults
Interventions
  1. Device: tDCS
  2. Behavioral: training

To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).. Inclusion Criteria (old healthy controls): - right handedness - unobtrusive neuropsychological screening - age: 50-90 years Exclusion Criteria: - severe internal or psychiatric disease - epilepsy - other severe neurological diseases, e.g. --- Val66Met --- --- Val158Met ---

Primary Outcomes

Description: Investigation whether the combination of intensive visual-spatial training (LOCATO task) and tDCS leads to an improvement of visual-spatial learning and memory measured by performance in LOCATO task after end of a 3 day training period compared to sham stimulation.

Measure: Performance in LOCATO task (Visual-Spatial learning and memory) after a combination of intensive visual-spatial training and tDCS

Time: immediately after the end of a 3 day training period in tDCS condition compared to sham condition

Secondary Outcomes

Description: long term effects measured by performance in LOCATO task after end of training and after 1 month compared to control condition

Measure: long term effects

Time: after 1 month vs baseline

Description: Connectivity (measured by resting-state fMRT and correlation analysis) at baseline compared to end of 3 day period of training

Measure: functional changes: Connectivity

Time: after end of 3-day period of training vs baseline

Description: measured by transcranial magnetic stimulation (TMS) at baseline

Measure: cortical excitability

Time: at baseline

Description: quality of life as measured by standardized questionaire at baseline compared to quality of life measured 1 month after intervention (training and stimulation vs. training and sham-stimualtion)

Measure: Quality of life

Time: after 1 month vs baseline

Description: memory performance tested at baseline compared to memory performance after the end of a 3-day cognitive training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: memory

Time: immediately after end of 3-day of cognitive training, after 1 month vs. baseline

Description: affective state measured at baseline compared to affective state measured after the end of a 3-day cognitve training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: affective state

Time: immediately after the end of 3-day cognitive training, after 1 month vs. baseline

Description: To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).

Measure: genotyping of learning related polymorphisms

Time: once

15 Modulation of Visual-Spatial Learning in Patients With Mild Cognitive Impairment (MCI) by Transcranial Direct Current Stimulation - Proof of Principle and Mechanisms

The aim of this study is to investigate whether a combination of intensive training of visual-spatial abilities (LOCATO task) with anodal transcranial direct current stimulation (tDCS) leads to an improvement in learning and memory in patients with mild cognitive impairment (MCI) and to examine the underlying neuronal mechanism.

NCT02110043
Conditions
  1. Mild Cognitive Impairment (MCI)
Interventions
  1. Device: tDCS
  2. Behavioral: training
MeSH:Cognitive Dysfunction
HPO:Cognitive impairment Mental deterioration

To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).. Inclusion Criteria (MCI patients): - right handedness - amnestic and amnestic plus MCI with: 1. subjective memory impairment; 2. objective memory difficulties, at least 1 SD below gender, age and education adjusted standard values; 3. relatively normal performance in other cognitive domains; 4. no constraints in activities of daily livings 5. age: 50-90 years Exclusion Criteria: - severe internal or psychiatric disease - epilepsy - other severe neurological diseases, e.g. --- Val66Met --- --- Val158Met ---

Primary Outcomes

Description: Investigation whether the combination of intensive visual-spatial training (LOCATO task) and tDCS leads to improvement of visual-spatial learning and memory measured by performance in LOCATO task after end of a 3 day period of training compared to sham stimulation.

Measure: Performance in LOCATO task (Visual-spatial learning and memory) after a combination of intensive visual-spatial training and tDCS

Time: immediately after end of a 3-day period of training in tDCS condition vs sham condition

Secondary Outcomes

Description: long term effects measured by performance in LOCATO task in tDCS condition after end of cognitve training and after 1 month compared to control conditions

Measure: long term effects

Time: after 1 month vs baseline

Description: Connectivity (measured by resting-state fMRT and correlation analysis) at baseline compared to end of 3 day period of training

Measure: functional changes: Connectivity

Time: end of 3-day cognitive training vs baseline

Description: cortical excitability measured by transcranial magnetic stimulation (TMS)

Measure: cortical excitability

Time: at baseline

Description: quality of life as measured by standardized questionaire at baseline compared to quality of life measured 1 month after intervention (training and stimulation vs. training and sham-stimualtion)

Measure: Quality of Life

Time: after 1 month vs baseline

Description: memory performance tested at baseline compared to memory performance after the end of a 3-day cognitive training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: memory

Time: immediately after end of 3-day of cognitive training, after 1 month vs. baseline

Description: affective state measured at baseline compared to affective state measured after the end of a 3-day cognitve training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: affective state

Time: immediately after the end of 3-day cognitive training, after 1 month vs. baseline

Description: To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).

Measure: genotyping of learning related polymorphisms

Time: once

16 Efficacy of Transcranial Direct Current Stimulation for Severe Refractory Primary Dysmenorrhea: Translational and Genetic Neuroimaging Studies

Primary Dysmenorrhea (PDM), defined as menstrual pain without discernable organic causes, is inexorably common in adolescent women, about 40-90% of women may suffer from it, and 20% of them can be severe in the context of being refractory to medication, daily function impairment, and having pain of severe degree. Novel therapeutic method is in need for pain alleviation for this particular phenotype. We have previously reported that PDM females may engage motor-cortex based descending pain modulation system in our resting-state functional Magnetic Resonance Imaging (rs-fMRI) and thermal pain-activation fMRI studies. Based on the reported analgesic efficacy of transcranial Direct Current Stimulation (tDCS) on the motor cortex for various experimental painful conditions and clinical pain disorders, we reason that tDCS can be effective for the severe and medication-refractory PDM patients. This study aim to investigate the analgesic efficacy of tDCS in severe PDMs and to elucidate the dynamic brain neuroplasticity in the context of functional connectivity (FC) of pain matrix after tDCS intervention. We will recruit 30 severe PDMs and randomly allocate them to either real or sham group in a triple-blind manner. rs-fMRI for functional connectivity analysis will be performed before and after the tDCS intervention. The imaging data will be correlated with behavioral and psychological measurements. This is the first study in the literature investigating the tDCS efficacy for severe PDM. The result can promise a new possibility for clinical application.

NCT03594916
Conditions
  1. Primary Dysmenorrhea
Interventions
  1. Device: Active tDCS
  2. Device: Sham tDCS
MeSH:Dysmenorrhea
HPO:Dysmenorrhea

To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen. --- Val66Met --- --- Val158Met ---

Primary Outcomes

Description: pain scale; from 0 to 10; score 0: no pain, score 10: unbearable pain

Measure: Visual Analog Scale (VAS)

Time: change from baseline (1st menstrual phase, before tDCS) at one month (2nd menstrual phase, with tDCS), change from baseline (1st menstrual phase, before tDCS) at two months (3rd menstrual phase)

Description: Resting-state functional magnetic resonance imaging (rs-fMRI) is a well established method of functional magnetic resonance imaging (fMRI) that is used to evaluate regional interactions in the brain that occur in a resting (task-negative) state, when a subject is not performing an explicit task. Functional connectivity is the connectivity between brain regions that share functional properties, it can be defined as the correlation between spatially remote neurophysiological events, expressed as the neural networks of brain.

Measure: Functional connectivity of rs-fMRI Imaging

Time: change from baseline (before tDCS, before 2nd menstrual phase) at one week (after tDCS completion), change from baseline (before tDCS, before 2nd menstrual phase) at four weeks (before the 3rd menstrual phase)

Secondary Outcomes

Description: To assess the threshold of thermal sensation (cold, cold-pain, heat, heat-pain; from 0 to 50 centigrade temperature), according to the established protocol of an ascending limit approach for heat pain and a descending limit approach for cold pain.

Measure: Quantitative sensory testing (QST)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 20 to 80; score 20: not anxious, score 80: extremely anxious

Measure: Spielberger State-Trait Anxiety Inventory (STAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 0 to 63; score 0: not anxious, score 63: extremely anxious

Measure: Beck Anxiety Inventory (BAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess depressive symptoms; from 0 to 63; score 0: not depressed, score 63: extremely depressed

Measure: Beck Depression Inventory (BDI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain-maladaptive psychological status; from 0 to 52; score 0: not pain Catastrophizing , score 52: extremely pain Catastrophizing

Measure: Pain Catastrophizing Scale (PCS)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain status; from 0 to 78; score 0: not painful, score 78: extremely painful

Measure: Long-form McGill Pain Questionnaire (MPQ)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess quality of life; he SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. From 0 to 100; score 0: equivalent to maximum disability, score 100: no disability.

Measure: Short-Form Health Survey (SF-36)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess testosterone, progesterone, estrogen

Measure: Blood Hormones Measurement

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase)

Description: To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen

Measure: Genotyping

Time: baseline

Description: To assure blinding efficacy; Patients do self-assessment about whether they receive real tDCS or sham tDCS. Assessment questionnaire:1 or 0. 1: real tDCS; 0: sham tDCS.

Measure: Efficacy of tDCS blinding

Time: At 1 months after tDCS intervention

17 Cognitive Remediation and Supported Education in Psychotic Disorders: a Randomized Controlled Trial on the Efficacy and the Best Predictors of Academic Functioning

This trial aims to assess the added value of cognitive remediation therapy to supported education intervention in young adults with a psychotic disorder. The objectives of this study are threefold: The first objective is to evaluate the efficacy of supported education and cognitive remediation therapy for young adults with psychotic disorders in terms of academic outcome (primary outcome) and cognitive, neurobiological, and psychological outcomes (secondary outcomes). The second objective is to explore mechanisms of change in academic outcomes using a multidimensional approach (cognitive, psychological and biological characteristics) in youth with psychotic disorders. The third objective is to investigate the patients' perspectives regarding their appreciation of the supported education programs. Academic outcomes, cognitive performance as well as psychological and genetic variables will collected at baseline (T0). Participants will then be randomized either to the experimental condition (Cognitive remediation + Supported education + Treatment as usual) or the control condition (Supported education + Treatment as usual) for three months. Directly after the end of treatment (T1) and three months following the end of treatment (T2), the same measures as baseline will be repeated. One year post-treatment (T3), a last assessment will be conducted for academic outcomes.To assess qualitative experience of patients enrolled in supported education, we will recruit a subsample of the randomized controlled trial to participate in a photovoice activity.

NCT04040829
Conditions
  1. Psychotic Disorders
Interventions
  1. Behavioral: Cognitive remediation therapy (CR)
  2. Behavioral: Supported education (SE)
  3. Other: Treatment as usual (TAU)
MeSH:Mental Disorders Psychotic Disorders
HPO:Psychosis

Presence or absence of a genetic variant (Met66Met) of the BDNF gene (Val66Met).. Presence or absence of the Val158Met polymorphism on the Catechol-O-Methyltransferase (COMT) gene. --- Val66Met --- --- Val158Met ---

Single nucleotide polymorphisms (SNP) in the 3' end of the COMT gene and the Val158Met polymorphism. --- Val158Met ---

Presence or absence of the Val158Met polymorphism on the Catechol-O-Methyltransferase (COMT) gene. --- Val158Met ---

Primary Outcomes

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree. The School subscale assesses the ability to meet deadlines, punctuality and school performance.

Measure: Mean change from baseline on the First-Episode Social Functioning Scale (School subscale)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree. The School subscale assesses the ability to meet deadlines, punctuality and school performance.

Measure: Mean change from baseline on the First-Episode Social Functioning Scale (School subscale)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree. The School subscale assesses the ability to meet deadlines, punctuality and school performance.

Measure: Mean change from baseline on the First-Episode Social Functioning Scale (School subscale)

Time: Baseline (T0; moment of enrollment in the study) to 1-year post-treatment (T3; one year following the end of the intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree. Relationships and social activities at school subscale assesses relationships with professors and students as well as participation in class.

Measure: Mean change from baseline on the First-Episode Social Functioning Scale (Relationships and social activities at school subscale)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree. Relationships and social activities at school subscale assesses relationships with professors and students as well as participation in class.

Measure: Mean change from baseline on the First-Episode Social Functioning Scale (Relationships and social activities at school subscale)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree. Relationships and social activities at school subscale assesses relationships with professors and students as well as participation in class.

Measure: Mean change from baseline on the First-Episode Social Functioning Scale (Relationships and social activities at school subscale)

Time: Baseline (T0; moment of enrollment in the study) to 1-year post-treatment (T3; one year following the end of the intervention)

Description: The Rubric tool assesses six domains of academic functioning, namely contributions, attitude, preparedness, focus on the task, professionalism and effort, and a composite score from those six scales. Based on the rating of several questions, a mean score of each domain, as well as a total score, will be obtained using a Likert scale that ranges from 1 (lowest the student can achieve) to 4 (highest the student can achieve).

Measure: Mean change from baseline on the Rubric tool

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Rubric tool assesses six domains of academic functioning, namely contributions, attitude, preparedness, focus on the task, professionalism and effort, and a composite score from those six scales. Based on the rating of several questions, a mean score of each domain, as well as a total score, will be obtained using a Likert scale that ranges from 1 (lowest the student can achieve) to 4 (highest the student can achieve).

Measure: Mean change from baseline on the Rubric tool

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Rubric tool assesses six domains of academic functioning, namely contributions, attitude, preparedness, focus on the task, professionalism and effort, and a composite score from those six scales. Based on the rating of several questions, a mean score of each domain, as well as a total score, will be obtained using a Likert scale that ranges from 1 (lowest the student can achieve) to 4 (highest the student can achieve).

Measure: Mean change from baseline on the Rubric tool

Time: Baseline (T0; moment of enrollment in the study) to 1-year post-treatment (T3; one year following the end of the intervention)

Secondary Outcomes

Description: The CVLT-II assesses verbal episodic memory. The test includes the learning of a list of words, followed by an immediate and a delayed recall.

Measure: Raw score change from baseline on the California verbal learning test-II (CVLT-II) (delayed recall).

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The CVLT-II assesses verbal episodic memory. The test includes the learning of a list of words, followed by an immediate and a delayed recall.

Measure: Raw score change from baseline on the California verbal learning test-II (CVLT-II) (delayed recall).

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Rey complex figure test assesses visual episodic memory. The test includes the copy of a complex figure, followed by an immediate and a delayed recall.

Measure: Raw score change from baseline on the Rey Complex Figure test (delayed recall).

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Rey complex figure test assesses visual episodic memory. The test includes the copy of a complex figure, followed by an immediate and a delayed recall.

Measure: Raw score change from baseline on the Rey Complex Figure test (delayed recall).

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The digit span subtest backward assesses verbal working memory. A series of number are read to the participant. The participant has to recall the numbers backward.

Measure: Raw score change from baseline on the digit span subtest backward of the Wechsler Adult Intelligence Scale-IV (WAIS-IV)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The digit span subtest backward assesses verbal working memory. A series of number are read to the participant. The participant has to recall the numbers backward.

Measure: Raw score change from baseline on the digit span subtest backward of the Wechsler Adult Intelligence Scale-IV (WAIS-IV)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The coding subtest assesses speed of processing. The participant has to match as many numbers as possible with symbols based on a key.

Measure: Raw score change from baseline on the coding subtest of the Wechsler Adult Intelligence Scale-IV (WAIS-IV)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The coding subtest assesses speed of processing. The participant has to match as many numbers as possible with symbols based on a key.

Measure: Raw score change from baseline on the coding subtest of the Wechsler Adult Intelligence Scale-IV (WAIS-IV)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The spatial span subtest backward assesses visual working memory. A board with blocks are presented to the participant. The assessor point series of blocks and the participant has to point the blocks backward.

Measure: Raw score change from baseline on the spatial span subtest backward of the Wechsler Memory Scale

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The spatial span subtest backward assesses visual working memory. A board with blocks are presented to the participant. The assessor point series of blocks and the participant has to point the blocks backward.

Measure: Raw score change from baseline on the spatial span subtest backward of the Wechsler Memory Scale

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The HRT-BC assesses sustained attention. Letters appear on a computer screen and the participant has to press the space bar as fast as possible, except when the letter is an "X". The HRT-BC reflects the reaction time between the six conditions of the CPT-3. In each condition, the letters are presented at a different rate. A higher HRT-BC score indicates a decrease of efficiency in information processing, which suggest difficulties in sustained attention.

Measure: Raw score change from baseline on the Hit Reaction Time Block Change (HRT-BC) of the Continuous Performance Test-3 (CPT-3)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The HRT-BC assesses sustained attention. Letters appear on a computer screen and the participant has to press the space bar as fast as possible, except when the letter is an "X". The HRT-BC reflects the reaction time between the six conditions of the CPT-3. In each condition, the letters are presented at a different rate. A higher HRT-BC score indicates a decrease of efficiency in information processing, which suggest difficulties in sustained attention.

Measure: Raw score change from baseline on the Hit Reaction Time Block Change (HRT-BC) of the Continuous Performance Test-3 (CPT-3)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The fourth condition of the Trail Making Test assesses cognitive flexibility. Letters and numbers are presented on a page.The participants has to connect these letters in alphabetical order and the numbers in numerical order while alternating between the numbers and letters

Measure: Raw score change from baseline on the fourth condition of the Trail Making Test (Delis-Kaplan Executive Function System; D-KEFS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The fourth condition of the Trail Making Test assesses cognitive flexibility. Letters and numbers are presented on a page.The participants has to connect these letters in alphabetical order and the numbers in numerical order while alternating between the numbers and letters

Measure: Raw score change from baseline on the fourth condition of the Trail Making Test (Delis-Kaplan Executive Function System; D-KEFS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The third condition of the color-word interference assesses inhibition. Name of color written in a different color of ink are presented to the participant. The participant has to name the color of the ink for each word as fast as possible.

Measure: Raw score change from baseline on the third condition of the color-word interference (Delis-Kaplan Executive Function System; D-KEFS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The third condition of the color-word interference assesses inhibition. Name of color written in a different color of ink are presented to the participant. The participant has to name the color of the ink for each word as fast as possible.

Measure: Raw score change from baseline on the third condition of the color-word interference (Delis-Kaplan Executive Function System; D-KEFS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The first condition of the verbal fluency subtest assesses phonemic fluency. The participant has to name as many word as possible in one minute that start by a given letter.

Measure: Raw score change from baseline on the verbal fluency subtest (first condition) (Delis-Kaplan Executive Function System; D-KEFS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The first condition of the verbal fluency subtest assesses phonemic fluency. The participant has to name as many word as possible in one minute that start by a given letter.

Measure: Raw score change from baseline on the verbal fluency subtest (first condition) (Delis-Kaplan Executive Function System; D-KEFS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Tower of London assesses planning and organization. For this test, the assessor produces different models on his board using three beads (green, blue and red). The participant has to replicate the model using as few moves as possible.

Measure: Raw score change from baseline on the Tower of London (total item completed with the minimum movement)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Tower of London assesses planning and organization. For this test, the assessor produces different models on his board using three beads (green, blue and red). The participant has to replicate the model using as few moves as possible.

Measure: Raw score change from baseline on the Tower of London (total item completed with the minimum movement)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Matrix reasoning subtest assesses perceptual reasoning. Series of complex patterns are presented to the participant. The participant has to choose the logical end to each pattern.

Measure: Raw score change from baseline on the Matrix subtest of the Wechsler Adult Intelligence Scale-IV (WAIS-IV)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Matrix reasoning subtest assesses perceptual reasoning. Series of complex patterns are presented to the participant. The participant has to choose the logical end to each pattern.

Measure: Raw score change from baseline on the Matrix subtest of the Wechsler Adult Intelligence Scale-IV (WAIS-IV)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Combined stories test assesses theory of mind. Short stories are presented to the participant and questions regarding the mental states of the characters are asked.

Measure: Raw score change from baseline on the Combined Stories test

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Combined stories test assesses theory of mind. Short stories are presented to the participant and questions regarding the mental states of the characters are asked.

Measure: Raw score change from baseline on the Combined Stories test

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Social Knowledge test assess social perception. Situations of daily life are presented to the participant. The participant is asked to state the emotion that would be felt by most people in that situation.

Measure: Raw score change from baseline on the Social Knowledge test

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Social Knowledge test assess social perception. Situations of daily life are presented to the participant. The participant is asked to state the emotion that would be felt by most people in that situation.

Measure: Raw score change from baseline on the Social Knowledge test

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Penn Emotion Recognition task assesses emotion recognition. Faces expressing emotions are presented on a computer screen. The participant has to determine the emotion expressed by the character among the seven choices.

Measure: Raw score change from baseline on the Penn Emotion Recognition task

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Penn Emotion Recognition task assesses emotion recognition. Faces expressing emotions are presented on a computer screen. The participant has to determine the emotion expressed by the character among the seven choices.

Measure: Raw score change from baseline on the Penn Emotion Recognition task

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The Échelle de Répercussion Fonctionnelle assesses functional impact of cognitive deficits in daily living using a semi-structured interview. The severity of the functional impact is rated on a Likert scale from 1= no impact to 7=important impact.

Measure: Raw score change from baseline on the Échelle de Répercussion Fonctionnelle

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The Échelle de Répercussion Fonctionnelle assesses functional impact of cognitive deficits in daily living using a semi-structured interview. The severity of the functional impact is rated on a Likert scale from 1= no impact to 7=important impact.

Measure: Raw score change from baseline on the Échelle de Répercussion Fonctionnelle

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The PANSS is a semi-structured interview that assess clinical symptoms of psychotic disorder, including positive symptoms, negative symptoms and general psychopathology.

Measure: Raw score change from baseline on the Positive And Negative Syndrome Scale (PANSS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The PANSS is a semi-structured interview that assess clinical symptoms of psychotic disorder, including positive symptoms, negative symptoms and general psychopathology.

Measure: Raw score change from baseline on the Positive And Negative Syndrome Scale (PANSS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The SERS assesses self-esteem. The questionnaire includes 20 questions rated on a Likert scale from 1=Never to 7=Always

Measure: Raw score change from baseline on the Self-Esteem Rating Scale (SERS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The SERS assesses self-esteem. The questionnaire includes 20 questions rated on a Likert scale from 1=Never to 7=Always

Measure: Raw score change from baseline on the Self-Esteem Rating Scale (SERS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The SSTICS assesses metacognitive knowledge, i.e., participant' perceptions of his cognitive abilities. The questionnaire includes 21 questions rated on a Likert scale ranging from 0=Never to 4=very often.

Measure: Raw score change from baseline on the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The SSTICS assesses metacognitive knowledge, i.e., participant' perceptions of his cognitive abilities. The questionnaire includes 21 questions rated on a Likert scale ranging from 0=Never to 4=very often.

Measure: Raw score change from baseline on the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree

Measure: Raw score change from baseline on the First-Episode Social Functioning Scale (FESFS)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The FESFS assesses different aspect of functioning including social functioning, productive activities and instrumental activities of daily living. Each question is rated on a Likert scale ranging from 1=Totally disagree to 4= Completely agree

Measure: Raw score change from baseline on the First-Episode Social Functioning Scale (FESFS)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: The CTQ assesses adverse events experienced during childhood and adolescence. The CTQ includes 70 items rated on a Likert scale ranging from 1=Never true to 5=very often true

Measure: Raw score change from baseline on the Childhood Trauma Questionnaire (CTQ)

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: The CTQ assesses adverse events experienced during childhood and adolescence. The CTQ includes 70 items rated on a Likert scale ranging from 1=Never true to 5=very often true

Measure: Raw score change from baseline on the Childhood Trauma Questionnaire (CTQ)

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: Presence or absence of a genetic variant (Met66Met) of the BDNF gene (Val66Met).

Measure: Presence or absence of a genetic variant (Met66Met) of the Brain-derived neurotrophic factor (BDNF) gene (Val66Met) at baseline

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: Presence or absence of a genetic variant (Met66Met) of the BDNF gene (Val66Met).

Measure: Presence or absence of a genetic variant (Met66Met) of the Brain-derived neurotrophic factor (BDNF) gene (Val66Met) at baseline

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

Description: Single nucleotide polymorphisms (SNP) in the 3' end of the COMT gene and the Val158Met polymorphism

Measure: Presence or absence of the Val158Met polymorphism on the Catechol-O-Methyltransferase (COMT) gene

Time: Baseline (T0; moment of enrollment in the study) to Post-treatment (T1; directly after the 3-months period of intervention)

Description: Single nucleotide polymorphisms (SNP) in the 3' end of the COMT gene and the Val158Met polymorphism

Measure: Presence or absence of the Val158Met polymorphism on the Catechol-O-Methyltransferase (COMT) gene

Time: Baseline (T0; moment of enrollment in the study) to 3-months post-treatment (T2; three months following the end of the intervention)

18 Neuronal Correlates of Catecholamine Depletion in Patients With Bulimia Nervosa Off Medication and Healthy Controls

Bulimia nervosa is a severe psychiatric disorder characterized by recurrent binge eating episodes followed by inappropriate compensatory behavior to prevent weight gain such as self-induced vomiting. With this project, the investigators want to investigate the role of the neurotransmitter dopamine in bulimia nervosa. Dopamine is reported to have an important influence on the neural reward system and is involved in the processing of gains and losses. The reward system is functionally connected to the individual perception of rewards in the environment. A previous study revealed that under catecholamine depletion including dopamine depletion women suffering from bulimia nervosa in their past reported mild bulimic symptoms and their reward processing became dysfunctional: their ability to use rewarding stimuli for task solving was diminished. The aim of this study is to investigate the role of reduced dopamine availability in the development or maintaining of bulimia nervosa and in the dysfunctional processing of rewarding stimuli and negative visual information. Therefore, the investigators hypothesize that catecholamine depletion achieved by oral administration of alpha-methyl-paratyrosine (AMPT) will induce mild bulimic symptoms in females suffering from bulimia nervosa in their past. In addition, they will reveal dysfunctions in reward and emotional processing under catecholamine depletion. Using functional magnetic resonance imaging, the investigators propose that a reduced activation of the nucleus accumbens, a neural structure of the reward system, will be the neural correlate of this dysfunctional reward processing. Furthermore, the amygdala, a neural structure that is involved in emotional processing, will show a higher activation under catecholamine depletion. Genetic factors additionally have an influence on the dopaminergic system. Therefore, the investigators hypothesize that genetic factors, for example the COMT val-158-met polymorphism may have an effect on the behavioral and neural response to catecholamine depletion. In sum, this investigation may help to understand which changes in reward and emotional processing may lead to a reoccurrence of bulimic symptoms. In future, the findings of this study may help to develop individual pharmacological and psychotherapeutical interventions to enhance the outcome of treatment.

NCT02179814
Conditions
  1. Bulimia Nervosa
  2. Eating Disorders
  3. Dopamine
  4. Reward
  5. Catechol-O-methyltransferase
Interventions
  1. Drug: AMPT/ Demser
  2. Drug: Diphenhydramine
  3. Drug: Placebo
MeSH:Bulimia Feeding and Eating Disorders Bulimia Nervosa
HPO:Bulimia

Therefore, the investigators hypothesize that genetic factors, for example the COMT val-158-met polymorphism may have an effect on the behavioral and neural response to catecholamine depletion. --- val-158-met ---

The COMT val-158-met polymorphism was found to play a critical role for the activity of the enzyme catechol-O-methyltransferase (COMT) that metabolizes catecholamines after they have been released into the synaptic cleft. --- val-158-met ---

In addition this study provided preliminary evidence that COMT val-158-met polymorphism explains some of the variance in the behavioral response to catecholamine depletion. --- val-158-met ---

An additional goal is to examine the effect of the COMT val-158-met polymorphism on neural activity. --- val-158-met ---

3. Participants with homozygous val-158 alleles of the COMT val-158-met polymorphism will show an increased activation in the ventral striatum during a reward task. --- val-158-met ---

4. Participants with at least one met-158 allele of the COMT val-158-met polymorphism will show higher amygdala activation during the encoding of negative emotional visual information. --- val-158-met ---

Primary Outcomes

Measure: Number of participants with side effects

Time: 1 year

Secondary Outcomes

Measure: Performance differences in behavioral tasks after catecholamine depletion

Time: 4 years

Measure: Differences in neural activation assessed during functional magnetic resonance imaging (fMRI) in the different conditions

Time: 4 years

Measure: Differences in neural activation assessed during functional magnetic resonance imaging (fMRI) and in performance in behavioral tasks in the different conditions between the different genotypes

Time: 4 years

19 Clozapine for Cannabis Use Disorder in Schizophrenia

Many individuals with schizophrenia also suffer from marijuana addiction that worsens their problems related to schizophrenia. Most of the medications prescribed for schizophrenia have no effect on reducing marijuana use. Preliminary data suggests that clozapine, an atypical antipsychotic, may limit marijuana use in people diagnosed with schizophrenia, but it is not commonly used due to its side effects and is reserved for people who do not respond to other antipsychotic medications. In the proposed study, 132 individuals who are diagnosed with both schizophrenia and a cannabis use disorder will be randomized to a 12-week treatment course with either clozapine or risperidone (another commonly prescribed antipsychotic medication) to test the hypothesis that patient treated with clozapine will have decreased cannabis use as compared to patients treated with risperidone. Should this study indicate that clozapine will lessen marijuana use in persons diagnosed with schizophrenia more than risperidone, it will provide evidence needed to begin to shift clinical practice toward its use in this population.

NCT01639872
Conditions
  1. Schizophrenia
  2. Cannabis Abuse
  3. Cannabis Dependence
  4. Dual Diagnosis
Interventions
  1. Drug: Clozapine
  2. Drug: Risperidone
MeSH:Marijuana Abuse Schizophrenia
HPO:Schizophrenia

Finally, this study will explore whether those patients with the val/val genotype at the Catechol-O-methyltransferase (COMT) Val158Met locus are more likely to decrease cannabis use during CLOZ treatment than are those without the val/val COMT genotype. --- Val158Met ---

Primary Outcomes

Description: Intensity of cannabis use is obtained each week retrospectively as the number of joints smoked during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Measure: Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)

Time: 12 weeks

Description: Frequency of cannabis use is obtained each week retrospectively as the number of days of cannabis use during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Measure: Average Over Time of Frequency of Cannabis Use

Time: 12 weeks

20 Neuromodulation Effect of Transcranial Direct Current Stimulation in Severe Refractory Primary Dysmenorrhea: BDNF and MEG Study

Primary Dysmenorrhea (PDM), defined as menstrual pain without discernable organic causes, is inexorably common in adolescent women, about 40-90% of women may suffer from it, and 20% of them can be severe in the context of being refractory to medication, daily function impairment, and having pain of severe degree. Novel therapeutic method is in need for pain alleviation for this particular phenotype. It has been reported that PDM females may engage motor-cortex based descending pain modulation system in our resting-state functional Magnetic Resonance Imaging (rs-fMRI) and thermal pain-activation fMRI studies. Based on the reported analgesic efficacy of transcranial Direct Current Stimulation (tDCS) on the motor cortex for various experimental painful conditions and clinical pain disorders, it is plausible that tDCS can be effective for the severe and medication-refractory PDM patients. This study aim to investigate the analgesic efficacy of tDCS in severe PDMs and to elucidate the dynamic brain neuroplasticity in the context of experimental pain after tDCS intervention. Thirty severe PDMs will be recruited and randomly allocated to either real or sham group in a triple-blind manner. Experimental pain electrical stimulation will be performed before and after the tDCS intervention. The experimental pain-evoked magnetoencephamographic (MEG) data will be correlated with behavioral and psychological measurements. This is the first study in the literature investigating the tDCS efficacy for acute pain in severe PDM. The result can promise a new possibility for clinical application.

NCT03608215
Conditions
  1. Primary Dysmenorrhea
Interventions
  1. Device: Active tDCS
  2. Device: Sham tDCS
MeSH:Dysmenorrhea
HPO:Dysmenorrhea

To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen. --- Val66Met --- --- Val158Met ---

Primary Outcomes

Description: pain scale; from 0 to 10; score 0: no pain, score 10: unbearable pain

Measure: Visual Analog Scale (VAS)

Time: change from baseline (1st menstrual phase, before tDCS) at one month (2nd menstrual phase, with tDCS), change from baseline (1st menstrual phase, before tDCS) at two months (3rd menstrual phase)

Description: Somatosensory evoked magnetic fields (SEFs) is a well established magnetoencephalographic (MEG) cortical response evoked by electric stimulation. SEFs to experimental pain stimulation using electrical stimulator applied on the skin over the trajectory of median nerve will be used to evaluate pain-evoked cortical response.

Measure: Somatosensory evoked magnetic fields to experimental pain

Time: change from baseline (before tDCS, before 2nd menstrual phase) at one week (after tDCS completion), change from baseline (before tDCS, before 2nd menstrual phase) at four weeks (before the 3rd menstrual phase)

Secondary Outcomes

Description: To assess the threshold of thermal sensation (cold, cold-pain, heat, heat-pain; from 0 to 50 centigrade temperature), according to the established protocol of an ascending limit approach for heat pain and a descending limit approach for cold pain.

Measure: Quantitative sensory testing (QST)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 20 to 80; score 20: not anxious, score 80: extremely anxious

Measure: Spielberger State-Trait Anxiety Inventory (STAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 0 to 63; score 0: not anxious, score 63: extremely anxious

Measure: Beck Anxiety Inventory (BAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess depressive symptoms; from 0 to 63; score 0: not depressed, score 63: extremely depressed

Measure: Beck Depression Inventory (BDI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain-maladaptive psychological status; from 0 to 52; score 0: not pain Catastrophizing , score 52: extremely pain Catastrophizing

Measure: Pain Catastrophizing Scale (PCS)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain status; from 0 to 78; score 0: not painful, score 78: extremely painful

Measure: Long-form McGill Pain Questionnaire (MPQ)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess quality of life; he SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. From 0 to 100; score 0: equivalent to maximum disability, score 100: no disability.

Measure: Short-Form Health Survey (SF-36)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess testosterone, progesterone, estrogen

Measure: Blood Hormones Measurement

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase)

Description: To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen

Measure: Genotyping

Time: baseline

Description: To assure blinding efficacy; Patients do self-assessment about whether they receive real tDCS or sham tDCS. Assessment questionnaire:1 or 0. 1: real tDCS; 0: sham tDCS.

Measure: Efficacy of tDCS blinding

Time: At 1 months after tDCS intervention

21 Age-17 Follow-up of Home Visiting Intervention

This study is a longitudinal follow-up of 670 primarily African-American women and their 17-year-old firstborn children enrolled since 1990 in a highly significant randomized controlled trial (RCT) of prenatal and infancy home visiting by nurses. Nurses in this program are charged with improving pregnancy outcomes, child health and development, and maternal economic self-sufficiency. This follow-up examines whether earlier program effects on maternal and child functioning lead to less violent antisocial behavior, psychopathology, substance use and use-disorders, and risk for HIV; whether these effects are greater for those at both genetic and environmental risk; and whether program effects replicate those found with whites in an earlier trial.

NCT00708695
Conditions
  1. Antisocial Behavior
  2. Psychopathology
  3. Substance Use
  4. HIV Infections
Interventions
  1. Behavioral: Nurse Home Visiting
MeSH:HIV Infections

2. Effects on youth violent antisocial behavior, SUDs, and risky sexual behavior will be more pronounced among males with the MAOA-LPR low activity alleles compared to males with MAOA-LPR high activity alleles, and among both males and females with 2 copies of the high-activity Val allele of the COMT Val158Met polymorphism compared to those with 2 copies of the low-activity met allele or heterozygotes. --- Val158Met ---

Primary Outcomes

Description: Public benefit expenditures estimated from review of state administrative records and maternal report of all children's birth dates. Program effects on public-benefit expenditures hypothesized to be especially pronounced for mothers with higher psychological resources.

Measure: Maternal life-course (reflected in reduced total public benefit expenditures for SNAP, AFDC/TANF, and Medicaid).

Time: through first child age 18

Description: Direct tests of youth cognitive, language, and academic functioning. Program effects in this domain hypothesized to be most pronounced for children born to mothers with low psychological resources.

Measure: Cognitive, language, and academic functioning among first-born children.

Time: at youth age 18

Description: Measure of internalizing disorders based upon youth self-report.

Measure: Youth depression and anxiety

Time: at youth age 18

Description: Self-reported involvement with criminal justice system and antisocial behavior. Program effects on arrests and convictions hypothesized to be greater for females.

Measure: Youth gang membership, arrests, convictions, and self-reported antisocial behavior, especially for crimes involving interpersonal violence.

Time: at youth age 18

Description: Outcomes based upon self-report and urine assays for STI's and substance use.

Measure: Youth risk for HIV infection, pregnancies, births, use of substances, and SUDs.

Time: at youth age 18.

Secondary Outcomes

Description: Based upon maternal self-report of SUDs and depression.

Measure: Reduced maternal substance use disorders (SUDs) and depression.

Time: at youth age 18

Description: Based upon direct tests of risky decision making, impulsivity, facial recognition, verbal working memory) and records of high school graduation. Program effects in this domain hypothesized to be more pronounced for children born to mothers with low psychological resources.

Measure: Improved child executive cognitive functioning, and rates of high school graduation.

Time: at youth age 18

Other Outcomes

Description: Self-reported number of subsequent pregnancies, pregnancy outcomes, live births, low-birth weight newborns, and birth dates. Program effects on cumulative pregnancies and births hypothesized to be more pronounced among mothers with high psychological resources.

Measure: Cumulative subsequent pregnancies - mothers

Time: through youth age 18

Description: Self-reported pregnancies and pregnancy outcomes.

Measure: Pregnancies - youth

Time: through youth age 18

Description: Self-reported duration and quality of relationship, cohabitation, marriage, partner employment, and relationship to first-born child

Measure: Relationship with Current Partner

Time: at youth age 18

22 Remediation of Working Memory in Schizophrenia

The primary aim of the study is to test the efficacy of a novel cognitive remediation intervention that targets working memory-related functions. To accomplish this goal, 80 volunteer patients with schizophrenia will be enrolled and randomized to either a cognitive remediation condition that targets working memory or a computer skills training intervention that teaches computer applications. In both conditions participants will receive computer training three times a week for 4 months. The investigators hypothesize that patients who receive the cognitive remediation intervention will demonstrate significantly greater change on neuropsychological measures of working memory and executive abilities than patients who receive the computer skills course. In addition, the investigators hypothesize that the intervention-induced cognitive change will be associated with concurrent improvements in functional capacity and psychosocial functioning in the community. A second study goal is to examine the stability of the intervention-induced changes in cognition. Cognition and psychosocial functioning will be reassessed 4 and 8 months after treatment termination to examine the stability of treatment effects and to assess whether a less intense maintenance training (once a week sessions) provides any additional benefit to participants. Lastly, this study will examine in an exploratory manner whether there are individual differences in treatment response. The Val158Met polymorphism of the COMT gene has been found to be associated with working memory and prefrontal dysfunction in schizophrenia. The study will test whether the COMT polymorphism is predictive of response to cognitive remediation.

NCT00995553
Conditions
  1. Schizophrenia
  2. Schizoaffective Disorder
Interventions
  1. Behavioral: Cognitive Remediation
  2. Behavioral: Computer Skills
MeSH:Schizophrenia Psychotic Disorders
HPO:Psychosis Schizophrenia

The Val158Met polymorphism of the COMT gene has been found to be associated with working memory and prefrontal dysfunction in schizophrenia. --- Val158Met ---

Primary Outcomes

Description: The Working Memory and Attention indexes of the MATRICS Consensus Cognitive Battery was used to assess near generalization of training with untrained tasks that were conceptually similar to training tasks. Each scale provide an age and gender corrected T-score. Thus, scores can range from 0-100, with a higher score indicating better performance.

Measure: Cognitive Assessment - MATRICS Consensus Cognitive Battery

Time: Post-intervention, within 2 weeks of completion of the 4 month intervention

Secondary Outcomes

Description: The UPSA is a measure of the ability to apply cognitive skills to functional tasks. The total score from this scale was used. Scores may range from 0 - 100, with higher scores being better.

Measure: Functional Capacity - University of California, San Diego Performance-Based Skills Assessment

Time: Post-intervention, within 2 weeks of completion of the 4 month intervention

23 Reliability of Pupil Response to Acute Pain

The purpose of this research study is to test whether researchers can reliably measure the response pupils have when an acute painful stimulus is experienced. Changes in the size of the pupil of the eye can be an indicator of brain activity in a region of the brain that is important for feeling pain.

NCT02628314
Conditions
  1. Pain
  2. Osteoarthritis
MeSH:Acute Pain

Key secondary hypotheses: Compared to individuals homozygous for val at the val158met site of the catecholamine-O-methyltransferase (COMT) gene, those homozygous for met will show smaller pupil responses to noxious stimuli and weaker CPM. --- val158met ---

Primary Outcomes

Description: pupil diameter in response to 5 second presentation of noxious heat stimuli

Measure: Percentage of change in pupil diameter

Time: 8 weeks

Description: Verbal pain scores will be obtained during stimulus presentation

Measure: Change from Baseline Verbal Pain Scores

Time: 8 weeks

24 Prospective Study of Dysarthria, Swallowing Disorders and Respiratory in Parkinson's Disease

The investigators prospectively enrolled 64 early PD patients (less than 3 years after the first symptom) in order to prospectively assess the natural history of non-dopaminergic symptoms.

NCT02627664
Conditions
  1. Parkinson's Disease
Interventions
  1. Other: observational study
MeSH:Deglutition Disorders Parkinson Disease Dysarthria
HPO:Dysarthria Dysphagia Oral-pharyngeal dysphagia Spastic dysarthria

To evaluate of cognitive and profile correlation to the polymorphisms of COMT (catechol-O-methyltransferase: Val158Met COMT) of MAPT H1 / H2 (microtubule associated tau protein) and ApoE (Apolipoprotein-E-ε2, 3, 4 ). --- Val158Met ---

Primary Outcomes

Description: BECD (French battery of clinical evaluation of the dysarthria) is a validated scale for qualitative assessment of dysarthria severity in neurological disorders, especially PD

Measure: dysarthria severity assessed by the BECD scale

Time: 2 years

Secondary Outcomes

Description: pulmonary function tests include spirometry with standard spirometer and maximal inspiratory and expiratory flow volume curves . At least 3 reproductible F-V curves are necessary. Values of FCV, FEV, peak expiratory flow, peak inspiratory flow, forced expiratory flow, SNIP were measured 12 hours after last levodopa intake (off drug)

Measure: respiratory insufficiency detection

Time: 2 years

Description: 150 mL glass of water test video fluoroscopy of swallow in off drug condition face and profile incidences: qualitative analysis of oral, pharyngeal, aspiration if necessary blindly assessed by 2 ENT experts in PD

Measure: swallowing function

Time: 2 years

Description: SWS test rhythmic tests for differens imposed frequencies (upper lower limb and facial) kinematic analysis of gait parameters by VICON (oxford metrics)

Measure: gait axial function (freezing)

Time: 2 years

Measure: Mattis scale

Time: 2 years

Measure: LARS scale

Time: 2 years

Measure: MADRS scale

Time: 2 years

Measure: PAS scale

Time: 2 years

Measure: MoCA

Time: 2 years

Description: To evaluate of cognitive and profile correlation to the polymorphisms of COMT (catechol-O-methyltransferase: Val158Met COMT) of MAPT H1 / H2 (microtubule associated tau protein) and ApoE (Apolipoprotein-E-ε2, 3, 4 )

Measure: Genetic Polymorphisme

Time: 2 years

25 The Effect of Perioperative Intravenous Low-dose Ketamine on Acute and Chronic Neuropathic Pain After Major Back Surgery. A Randomised, Placebo-controlled, Double-blind Study

After a surgical operation, patients may suffer from chronic pain. Ketamine, a well known anesthetic acts on receptors in the spine (NMDA receptors), which are implied in the occurrence of chronic pain. The mechanism is called central sensation. It is known that Ketamine reduces immediate postoperative pain, but its effectiveness in the prevention of the chronic pain is still unknown. The investigators study will follow patients until one year after operation for the occurrence of chronic pain. The investigators hypothesis is that Ketamine reduces significantly chronic postoperative pain after major back surgery and improves patient outcome. There may be important inter-individual differences how persons react on a drug. These differences are partly determined by the genes of each individual. The investigators study includes therefore a genetic analysis. Psychological and social factors also influence the perception of pain. It is still not well understood who these "psychosocial factors" determine the appearance and perception of chronic pain. In the investigators study the investigators will therefore study these factors by questionnaires.

NCT00618423
Conditions
  1. Postoperative Pain
Interventions
  1. Drug: Placebo
  2. Drug: Ketamine
MeSH:Pain, Postoperative

As for pain sensitivity and morphine response variability, the met allele at the val158met polymorphisms in the catechol-O-methyltransferase gene (COMT), reduces the ability of the enzyme to metabolize catecholamines, and has been associated with a decrease in opioid consumption in cancer pain patients. --- val158met ---

Primary Outcomes

Measure: To evaluate the long-term (6 and 12 months) effect of perioperative intravenous low-dose ketamine on chronic neuropathic pain in patients undergoing major back surgery.

Time: one year

Secondary Outcomes

Measure: To evaluate the short-term (during hospitalisation) effect of perioperative intravenous low-dose ketamine in patients undergoing major back surgery: tolerability and safety, opioid-sparing effect, pain intensity, morphine-related adverse effects.

Time: one week

Measure: To study the potential impact of genetic variability of several enzymes (CYP2D6, CYP2C9, COMT) known to modulate pain sensitivity and/or metabolism of opioid and NSAIDs on analgesic consumption and ketamine response.

Time: immediate

Measure: To study psychosocial factors that may be involved in the perception of acute and chronic postoperative pain in patients with or without chronic back pain undergoing back surgery.

Time: one year

Measure: To study the pharmakokinetics of an intravenous low-dose ketamine infusion.

Time: one day

26 Improving Learning and School Functioning in Latino Children With Cancer

This randomized clinical trial studies how well a high-intensity intervention parenting program works in improving learning and school functioning in Latino children with acute leukemia or lymphoblastic lymphoma. A high-intensity intervention program may help doctors to see whether training parents or caregivers in specific parenting skills and "pro-learning" behaviors will result in better learning and school outcomes for Latino children with acute leukemia or lymphoblastic lymphoma. It is not yet known if a high-intensity intervention program is more beneficial than a standard of care lower intensity parenting intervention.

NCT03178617
Conditions
  1. Acute Lymphoblastic Leukemia
  2. Acute Myeloid Leukemia
  3. Lymphoblastic Lymphoma
  4. Acute Leukemia
Interventions
  1. Other: Educational Intervention
  2. Other: Educational Intervention
  3. Other: Quality-of-Life Assessment
  4. Other: Questionnaire Administration
MeSH:Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, Non-Hodgkin
HPO:Leukemia Lymphoma Non-Hodgkin lymphoma

EXPLORATORY OBJECTIVES: I. Explore the associations between neurocognitive performance and polymorphisms in candidate genes previously reported to explain cognitive variability in childhood cancer survivors (e.g., the catechol-O-methyltransferase Val158Met polymorphism and the nitric oxide synthase [NOS3] 894T allele) or involved in the stress response (e.g., the Serotonin transporter rs25531 and the Glucocorticoid receptor rs6190). --- Val158Met ---

Primary Outcomes

Description: Measured by the parent-reported Pediatric Quality of Life Inventory school domain.

Measure: Change in child's health-related quality of life school functioning

Time: Baseline up to 12 months

Description: Measured by the Efficacy scale from the Parent Knowledge, Beliefs and Behaviors Questionnaire-3rd Revision (PBQ-R3).

Measure: Change in parental efficacy

Time: Baseline up to 12 months

Secondary Outcomes

Description: Measured by WIAT: reading and math scores and classroom grades from school report cards.

Measure: Objective academic performance (Child)

Time: Up to 12 months

Description: Measured by the Conners Parent Report Attention subscale.

Measure: Attention performance (Child)

Time: Up to 12 months

Description: Measured by PBQ-R3 Behaviors Scale.

Measure: Frequency of pro-learning behaviors (Parent)

Time: Up to 12 months

Description: Measured by the Parents' weekly time spent with child in pro-learning behaviors and activities.

Measure: Frequency of pro-learning behaviors (Parent)

Time: Up to 12 months

Description: Measured by PBQ-R3 Knowledge scale.

Measure: Knowledge of pro-learning parenting (Parent)

Time: Up to 12 months

Measure: Children's scores on other neurocognitive tests as assessed by learning, memory, and processing speed

Time: Up to 12 months

Measure: Parental reports of their children's HRQOL as measured by the PedsQL parent proxy questionnaire

Time: Up to 12 months


HPO Nodes


HP:0000716: Depressivity
Genes 461
EZR TGIF1 ND6 PROK2 COL7A1 NODAL TOR1A CACNA1G VPS35 NSUN2 GTF2IRD1 SLC20A2 CHD7 COL7A1 TACR3 SHH ST3GAL3 ARVCF NR4A2 CEP85L RREB1 AARS2 GNA11 ATXN10 FMO3 TCF4 POLG ATXN8OS AIMP1 C9ORF72 LRRK2 PSAP FGF8 CYP27A1 DCTN1 GAS1 GBA TGFBR2 PODXL FOXH1 CLIP2 VPS13C TBK1 HIRA CC2D1A GP1BB GNAS PDGFRB VAPB ABCA7 MEN1 COX1 DLL1 HARS1 SEC24C SIX3 GABRG2 ELN PIK3CA PAH POLG GNAS TWNK GNRH1 THOC2 MBOAT7 VCP PMS2 FOXH1 SLC6A4 GABRG2 POLG PDGFB CBL CDON AP2S1 GAS1 MAPT TARDBP TRNW TMEM106B MATR3 TTC19 DNAJC5 TRNL1 BCS1L CBS FRRS1L KRAS JRK GLA CDON PDGFRB SHH DISP1 PRPH ZIC2 AMACR DISP1 SLC25A4 MAN1B1 DNA2 GBA GSN FOXH1 GNRHR TDGF1 KDM5B FAN1 ADH1C VPS13A XK CEP78 TRNS1 GLI2 FGF8 TRNH ATP13A2 NEFH CSF1R COASY FMR1 ATXN8 ATXN2 FGFR1 ARSA CLCN4 USP8 TRNS2 TBC1D7 ND1 ND4 HTR2A DISP1 PANK2 STAG2 CCNF GPR101 SIX3 TRNQ PRNP ZC3H14 DCPS CISD2 HTT HNMT SLC2A3 MSH6 USH1C DNMT1 VCP ZIC2 CACNA1H MSTO1 C9ORF72 KCNJ2 HMBS MSH2 MED23 FGF8 KCNT1 PER2 SHH USH2A USH1G DRD2 PTPN22 NODAL ERBB4 PPT1 PTCH1 DAO ZIC2 TRNF CDH23 THOC2 MED25 HTT DLL1 LINS1 WASHC4 TRNS2 TUSC3 TET3 PLA2G6 MYO7A CDON CHCHD10 PSEN1 EPM2A PINK1 ARSG EPHA4 CHCHD10 CHMP2B ANOS1 CDKN1B PDZD7 MAN2B1 PTCH1 SLC45A1 DNAJC6 GLI2 PER3 ATXN10 TAF15 ADGRV1 SNCA HLA-DQB1 SLC2A1 FGF8 C19ORF12 TSC2 PRKN OPTN POLG2 MAPK1 CARS1 POLG WDR11 PDCD1 FGFR1 PPP2R2B PCDH15 FLT4 TECR SGCE DNAJC13 COQ2 B3GALNT2 RPS20 GLE1 SQSTM1 SPRY4 CACNA1G FA2H CDKN2C NHLRC1 SNCA UNC13A DGUOK CPOX TBK1 CDH23 FGF14 PFN1 PRNP MAPT CLRN1 JMJD1C RSRC1 TBX1 FBXO31 PTS EPCAM PON2 TNIK TBL2 TBX1 PDGFRB ATRX TAC3 PANK2 TARDBP FMR1 EHMT1 PRNP CLIP1 RFC2 DCTN1 SARS1 TRAPPC9 FGF14 SNCA RRM2B LIMK1 KISS1 NOTCH3 XPR1 FIG4 TWNK SIX3 CRBN GLI2 SMPD1 HLA-DQB1 CRKL PMS1 CDKN2B HTRA2 SPAST HS6ST1 PDE11A C9ORF72 MST1 SLC18A2 FGFR1 RPS6KA3 WFS1 CDON DNMT1 SRSF2 LMNB1 PRSS12 GABRB3 EDC3 POLG TRNS1 ZIC2 CLCN4 KCTD17 GBA TK2 CFAP410 MLH1 VCP COX2 GABRA1 FOXH1 PARK7 SYNJ1 COX3 EIF4G1 PON1 HNRNPA1 LRRK2 IDUA FGF8 GRIK2 POLG PRKCG NDST1 TGIF1 DUSP6 ATXN2 RRM2B SMC1A WFS1 PRNP TDGF1 TSC1 STX16 GIGYF2 ATP1A3 PTCH1 ATP1A3 HMBS GLI2 ARMC5 KCTD17 SEMA4A GLUD2 GAS1 HTT TET2 TBP GAS1 ASXL1 DMPK CASR PDGFB PRNP CIB2 UFD1 COQ2 TGIF1 GLT8D1 TREX1 VCP ARMC5 GTF2I MECP2 TWNK KISS1R LMAN2L GRIN2A PTCH1 RUNX1 ANG PIGC NSMF GNAS TWNK TDGF1 ANXA11 SGCE GCH1 FUS AIP TGIF1 BMPR1A UBQLN2 CTSF OCRL PON3 CHMP2B METTL23 ESPN CLN6 TDGF1 TRNL2 IQSEC1 TRNL1 PRKACA PRNP C9ORF72 DLL1 GRN PGAP1 GDAP2 TRNN SHH MSTO1 SIX3 SNCAIP MLH3 ND5 SRPX2 STAG2 NEK1 WHRN TBP TREM2 GNAS MMP1 C12ORF4 FMN2 PPARGC1A SQSTM1 HLA-DRB1 PINK1 ATP7B TREM2 BCR TOR1A SOD1 C9ORF72 NODAL GNAS DCTN1 PRKAR1A AFG3L2 GPR35 BAZ1B DLL1 PLA2G6 CDKN1A MAN2B1 COMT CRADD PROKR2 MAPT FUS MYO7A JPH3 NODAL FGF17 PAH UCHL1 DISP1 ATXN8OS
HP:0002013: Vomiting
Genes 374
TGIF1 ACSF3 PNPLA8 MC2R TRNK CFI NAGS ND6 CTNNB1 MPI NDUFS4 GALC ALG11 TRNL1 NODAL DYRK1A COL1A1 TRNK DHCR7 TRNC PIGY NDUFB9 CDKN2C SCNN1G D2HGDH ND2 APC PMM2 SHH CPOX CPOX EGFR RRM2B LAMA3 PPOX UCP2 TRNS2 HPRT1 ND1 POLG ACSF3 TNFRSF1A NBAS NDUFS8 PDSS2 ND1 SCNN1B KCNJ11 SHANK3 ASS1 CDH23 GALT NDUFS6 AIMP1 ACY1 SI ZEB2 ETFDH STK11 MPV17 GALE FGF8 GAS1 FOXH1 LAMC2 NR3C2 NDUFS1 KRIT1 PHGDH MCCC1 OXCT1 CCM2 PMM2 COQ2 CYP11B2 BRAF SIX3 MEN1 COX1 ADNP DLL1 TXNRD2 SIX3 GLI2 CDK8 MCCC2 NDUFA6 SAA1 CDKN2B HLCS POLG ND6 NDUFS2 NDUFV2 NDUFAF5 STAT4 DLD ASL MSX2 ND3 AVP FOXH1 FOXP3 AVPR2 TRMU ND4 LPL CDON MLYCD CDON ALAD MEN1 HNRNPK SSR4 ALG8 NDUFV1 RANBP2 GAS1 CPOX SCNN1G TRNQ TRNW FBP1 ATRX NOTCH2NLC CPT2 MRAP SAR1B CFH SLC7A7 KCNJ11 NDUFS7 ZIC2 COL5A1 NDUFA1 ACP2 CDH23 PCCA NUBPL CD46 KMT2E GK COX2 CDON FOXH1 CPS1 TRNW KCNJ1 TYMP RARS1 SHH DISP1 NDUFB3 COX3 TRNV HADH ALDH18A1 FGF8 ZIC2 GALC NFIX SLC12A3 ACAD8 HNF4A F12 GHSR NDUFB10 MTTP SERPING1 PDCD10 DISP1 TGIF1 ESR1 ARG1 NAGS NDUFA11 NDUFS3 ALDOB FOXH1 ACADVL TDGF1 AIP HFE TRNW SMC1A ETFB HMGCL SLC25A13 TDGF1 TP53 TRNS1 ACAT1 GLI2 FGF8 TRNH TCN2 COX1 PTCH1 SLC22A5 C11ORF95 MVK PPM1D HMBS MEFV ALDOB GLI2 FGFR1 STAR ND2 GAS1 ND5 GAS1 NDUFAF2 SLC7A7 PSAP MET NDUFV1 TGIF1 ND1 ACADVL ND4 TNFRSF1A FOXRED1 LIPA ACAT1 DGUOK TRNF ATP6V0A4 SUGCT ELP1 LAMB3 DISP1 MMAB ZEB2 STAG2 OTC TMEM126B ACADM IRAK1 PTCH1 TRNV SIX3 TRNQ RECQL4 HNF1A SLC1A3 TDGF1 TRNS1 COX2 ALX4 SLC25A15 NEUROG3 SLC25A15 HNRNPK GK NDUFB11 BCKDHA HIBCH TGIF1 ZIC2 ZEB2 TIMM22 ASPA NDUFAF8 NLRC4 TNF SERPING1 PCCB NDUFAF4 MTHFD1 ND3 CYTB ND5 GLA HMGCS2 ALG3 NEUROG3 FGF8 MMUT ABCC8 ALPL SHH SLC22A5 TDGF1 FARSB NDUFS1 SPP1 POLG TRNL1 MMAA DLL1 CYP11B1 MRPS7 SHH NODAL CTNS SIX3 RELA PTCH1 ZIC2 TRNF MTRR SLC5A6 BCKDHB SYT1 CLMP ND5 STAG2 DLL1 HMGCL GFM2 FLNA CYP11A1 AQP2 SLC6A8 ND6 CYP11A1 ACADM ST3GAL5 BOLA3 TRNS2 TIMMDC1 RET CACNA1A ND1 OPLAH CD55 CDON ABCC8 SLC12A1 NAXD HELLPAR SCNN1A HSD3B2 NNT NODAL ACTG2 SCNN1B TYMP CDKN1B NDUFAF3 DBT SCN2A DLL1 EDNRA PYCR2 PTCH1 CDKN1A NDUFS4 NDUFAF1 GLI2 ANAPC1 COX3 ATP6 SMPD1 COL5A2 COA8 ETFA NODAL CTNS DBH SCNN1A SAR1B IVD CYTB DGAT1 ALG11 SERPING1 DISP1 CYP24A1 TRNL1 BTD FGFR1 MVK
Protein Mutations 3
S253N V158M Y129S
SNP 1
rs4680
HP:0012378: Fatigue
Genes 399
TLL1 SLC25A26 IGH SERPINA6 MEN1 COL1A1 NPM1 ZBTB16 ABCC2 DDB2 KIT SH2B3 IKZF1 MALT1 SOX3 ATM TCF4 HLA-DPA1 GATA6 TP53 SCNN1G NAB2 ALB DCTN1 PROKR2 TGFBR2 NLRP3 IGH TAZ HBA1 GNAS RARA ALAS2 VAPB SLC26A4 MORC2 TXNRD2 NKX2-5 TRAF3 PIK3CA MYD88 MYH6 TSC1 ATRX HLA-DPB1 KCNN4 SLC40A1 PMS2 DUOXA2 COL9A1 SLC22A4 CBL DLST TNPO3 MEN1 TCF3 DNMT3A HESX1 HESX1 AP2S1 PROP1 STAT5B TARDBP DNAJC6 CTLA4 EPAS1 TET2 MRAP MATR3 ERCC3 COL5A1 KCNE1 CDH23 CD46 CCDC78 BCL2 FOXP1 KRAS GLA CHRND PHKG2 NLRP3 PRPH NKX2-1 KIT SLC12A3 PYGM HNF4A NF1 IL12RB1 SDHAF2 SOX3 SLC25A4 PRKAR1A SLC18A2 CALR AIP FAN1 PRTN3 TET2 MDM4 SDHD SLC4A1 POU1F1 LHX4 ATP13A2 NEFH PDE8B HBA2 PREPL GATA2 ERCC2 STAR IYD BRCA1 DNM1L MET PODXL USP8 KIF1B ARNT2 PAX8 SCNN1A CCNF GPR101 C4A HNF1A MAX CCND1 INSR BTK MSH6 PDGFRA MEFV VCP PALLD TBX20 BCL10 TICAM1 TRNK BCL6 NUMA1 PADI4 GATA4 JAK2 KL MSH2 SDHC EIF2AK4 GBA CITED2 LBR HLA-DRB1 PTPN22 ERBB4 TNFSF15 SLC26A4 DAO SDHA CAV3 NLRP3 STAT6 CDC73 HAVCR2 HMGCL PTPN22 FGFR1 DUOX2 SDHB MMEL1 IL10 LRRC8A IL12A-AS1 EPHA4 CHCHD10 CHMP2B PIEZO1 TSHR NNT DMD KIF23 TSC2 TAF15 ERCC4 TSHB COL9A2 IL18BP TNXB IL12A NKX2-5 CD244 OPTN POLG2 SLC11A1 DBH IRF5 XPC SDHB NLRP3 NABP1 PNPLA8 PTPN22 MC2R CFI NAGS CTNNB1 RPS20 GLE1 ACTC1 OTX2 VHL PIGA UNC13A TBK1 CDH23 MYH7 PFN1 SPIB TRHR SLC2A10 PDE11A GLI2 CDH23 IL12B EPCAM XPA PON2 IL10 TBX19 ATP13A2 PLEC WIPF1 COMP SDHD FOXA2 PTPN3 BCOR LHX3 PROP1 PYGL RRM2B HESX1 FIG4 IL12A TWNK UNC93B1 MPL CDKN2A COL1A2 PMS1 CCND1 BRCA2 PROP1 MLX C9ORF72 SMAD3 IGLL1 MST1 TK2 SRSF2 IGHM CD79A PIK3R1 POMGNT1 OPA1 SDHB CD79B IVNS1ABP CFH CITED2 FTL CFAP410 MLH1 FOXE1 IL23R STAT3 PAX8 COQ2 STEAP3 PRKAR1A PON1 HNRNPA1 AGK SMAD4 GCK IGH TFR2 POLG OTX2 FGF23 ATXN2 NR3C1 HLA-B PIGT PGM1 TLR4 LHX4 ARMC5 SEMA4A SDHA BCR IRF2BP2 PALB2 TET2 ASXL1 WAS DMPK ERCC5 POU1F1 RET C1QBP TET2 ATP7A GLT8D1 KCNQ1 CARMIL2 ARMC5 SCNN1B KRAS JAK2 TSHR STAT4 TWNK SMAD3 TG ACADM TMEM127 RUNX1 SLC18A3 ANG TBX20 ANXA11 CCR1 GCH1 MDH2 UBAC2 HFE BIRC3 AIP EPOR PHKA2 BMPR1A MMADHC FAS CPT1A UBQLN2 NLRC4 PSTPIP1 SOX2 PON3 COL9A3 NR3C1 POU2AF1 ERAP1 PRKACA ALB TLR3 CDC73 SLC3A1 TET2 SLC5A5 PML VHL FIP1L1 MLH3 TBK1 ELANE JAK2 NEK1 TBL1XR1 TREM2 FH KLRC4 HLA-B PPARGC1A SQSTM1 HLA-DRB1 NFKB2 MPL VHL SOD1 TPO TLL1 HELLPAR ABL1 SYNJ1 GPR35 CIITA RUNX1 BLNK SLC25A11 FUS RET COL5A2 DYSF SDHC NFKBIL1 BTNL2 HLA-B
Protein Mutations 3
T25W V158M V18M
SNP 0
HP:0000726: Dementia
Genes 293
CHMP2B PPP2R2B WDR45 NOTCH2NLC NDP ALDH18A1 ND6 TUBA4A DNAJC13 TRNL1 TRNK SQSTM1 VPS35 PNPLA6 SORL1 TRNC HNRNPA2B1 SLC13A5 HFE NHLRC1 SNCA DGUOK COL4A1 CHMP2B APP RRM2B TRNS2 TARDBP NR4A2 POLG PRNP GRN APP ATP13A2 MAPT MAPT TTR GBA AARS2 MAPT TRPM7 ITM2B ATXN10 ND1 KCTD7 ATP6V1A TMEM106B IRF6 ATXN8OS CFAP43 C9ORF72 CSTB VPS13A ATP6 ATP13A2 LRRK2 ATXN2 PSAP MAPT TARDBP PRDX1 FMR1 GBA PODXL TBK1 VPS13C DCTN1 SDHB ROGDI GBA2 GCDH SNCA TBK1 NOTCH3 XPR1 SQSTM1 CYP27A1 TREX1 ATP7B MAPT COX1 TIMM8A TYROBP PRKAR1B ATN1 HTRA2 SPAST VCP ND6 PSEN1 SPG21 LRRK2 ATP13A2 PPP2R2B MMACHC ATP6V0A2 C9ORF72 DNMT1 GBE1 UBQLN2 PANK2 PSEN1 ATP6 SDHAF1 FTL OPA1 TRNQ TRNW MAPT C9ORF72 TMEM106B NOTCH2NLC RAB39B CISD2 DNAJC5 SNCA ALDH18A1 GBA MPO VCP COX2 SERPINI1 CLN3 PDGFRB TRNW CST3 PARK7 ATP6V1E1 GRN GRN ITM2B SYNJ1 COX3 EIF4G1 CHMP2B LRRK2 CERS1 ROGDI ADA2 MATR3 PRDM8 SNCA MAPT RNF216 TRNE GBA SCARB2 ABCA7 PSEN2 ADH1C WFS1 PRNP PSEN1 SDHD RNF216 APOE TRNS1 GIGYF2 TRNH APTX DLAT ABCD1 COX1 CSF1R PRNP FMR1 TREM2 ATXN2 ATXN2 ARSA FTL GLUD2 HTT TBP MATR3 DNM1L WDR45 PRICKLE1 PDGFB PRNP APP FBXO7 HEXA PSEN1 ND1 VCP ND4 TRNF TWNK AUH MBTPS2 APP PANK2 TRNV TRNQ APP TOMM40 PRNP HTRA1 ATP13A2 DNMT1 TRNS1 PSEN1 COX2 A2M HTT FUS ERCC8 HNRNPA2B1 HTRA1 MECP2 NOTCH3 MAPT CHMP2B CTSF CYTB C9ORF72 TREM2 ND5 CHMP2B ATXN3 MMACHC CLN6 VCP NPC1 CUBN PSEN2 GBA2 SNCB GBA POLG TRNL1 PRNP GRN HNRNPA1 ZFYVE26 LYST APP SNCAIP ATN1 TRNF VPS13C NPC2 NHLRC1 VCP TMEM106B CP ND5 TBP TUBB4A SQSTM1 EPM2A TRNS2 PRNP PSEN1 APOE TREM2 TREM2 PINK1 PLA2G6 TREM2 CHCHD10 PSEN1 EPM2A GM2A TYROBP PINK1 C9ORF72 WFS1 TYMP VCP ASAH1 DCTN1 PLAU SNCA DNAJC6 PLA2G6 TREM2 MAPT NOS3 COX3 SNCA HLA-DQB1 JPH3 C19ORF12 JPH3 PRKN ERCC4 APP UCHL1 CHCHD10 SPG21 SDHA
Protein Mutations 1
V158M
SNP 0
HP:0001268: Mental deterioration
Genes 500
SPG11 WDR45 NOTCH2NLC EEF1A2 ALDH18A1 ND6 TIMM8A TUBA4A TRNL1 TRNK VPS35 PNPLA6 TRNC SLC20A2 DRD3 NECAP1 ERCC6 HNRNPA2B1 CNKSR2 HFE GABRG2 APP RRM2B UCP2 TRNS2 NR4A2 GRN APP ATP13A2 MYORG TTR AARS2 DNM1 STXBP1 ITM2B ATXN10 ND1 KCNJ11 ARSA IRF6 ATXN8OS SYNJ1 C9ORF72 CSTB AARS1 ATP6 LRRK2 PSAP COMT PRDX1 GBA NDUFA6 PODXL VPS13C TBK1 PDGFRB SQSTM1 CYP27A1 TREX1 COX1 PMPCA TIMM8A TYROBP PRKAR1B HCN1 GNAS GCH1 ATN1 MTHFR CLTC VCP PSEN1 L1CAM GABRA5 PDGFB PTS ATP6V0A2 C9ORF72 SUMF1 UBQLN2 SLC1A2 PANK2 PSEN1 ATP6 SDHAF1 GABRB2 MAPT TRNW MAPT KMT2A TMEM106B NOTCH2NLC DNAJC5 SNCA MPO SCN1A NTRK2 CLN3 PDGFRB CDK19 TRNW RRM2B CST3 ATP6V1E1 GRN ITM2B MFSD8 CHMP2B SQSTM1 CHD2 GALC ROGDI HNF4A ADA2 ACTL6B MATR3 GALC PRDM8 SNCA RNF216 ERCC8 ATP1A3 KCNB1 CTC1 GBA PSAP FA2H SCARB2 ABCA7 YWHAG PSEN2 ADH1C VPS13A RNF216 APOE TRNS1 TRNH ABCD1 COX1 CSF1R COASY FMR1 TREM2 ATXN2 SCO2 ATXN2 ARSA FTL DCAF17 MATR3 DNM1L FBXO7 ND1 ATXN7 DAOA ND4 NRAS AP2M1 TRNF AUH MBTPS2 APP DALRD3 GRN PANK2 KCNA2 QDPR TRNQ APP TOMM40 PRNP HNF1A HTRA1 RBM28 TRNS1 PSEN1 A2M HTT SLC2A3 ERCC8 PLP1 BSCL2 DNMT1 HNRNPA2B1 MECP2 SLC44A1 NOTCH3 CHMP2B JAM2 TRNK TBK1 CYTB C9ORF72 TREM2 GABRA2 SUMF1 HMBS MMACHC ABCC8 NPC1 CUBN PSEN2 SYNGAP1 SNCB GBA CREBBP AP3B2 ZFYVE26 APP PPT1 TRNF VPS13C NPC2 NUS1 NHLRC1 VCP HTT IDUA TUBB4A FGF12 SQSTM1 EPM2A TRNS2 DNM1 TREM2 PLA2G6 CHCHD10 PSEN1 EPM2A TYROBP PINK1 SNORD118 TYMP VCP SLC13A5 PLAU SNCA C19ORF12 DNAJC6 CLN5 SNCA HLA-DQB1 SCN8A JPH3 C19ORF12 HTR2A PRKN ACTB APP CUX2 IDS SPG21 CHMP2B PPP2R2B CHI3L1 NDP DNAJC13 ARSA GALC SQSTM1 AP5Z1 PLP1 SORL1 FA2H MAPT CSTB SLC13A5 NHLRC1 SNCA DGUOK COL4A1 CHMP2B PSAP RBM28 TARDBP TTPA POLG PRNP CACNA1A MAPT MAPT GBA MAPT TRPM7 NDUFB8 CREBBP KCTD7 APOL4 ATP6V1A TMEM106B CFAP43 VPS13A PDGFRB RRM2B WWOX ATP13A2 SYNJ1 ATXN2 MAPT TARDBP FMR1 SPG11 ATP1A2 DISC2 CTNS SYNJ1 TBK1 TBP DCTN1 SDHB RNASEH1 ROGDI GBA2 SGPL1 GCDH SNCA ADA2 NOTCH3 XPR1 APOL2 CTSD ATP7B DARS2 MAPT EP300 ATP6V1A BSCL2 ARV1 PDE10A SYN2 HTRA2 SPAST SZT2 ND6 SPG21 LRRK2 ATP13A2 PDE11A PPP2R2B TK2 MMACHC DNMT1 GBE1 IDS LMNB1 SMC1A FTL OPA1 CACNA1B TRNQ C9ORF72 HEXB RAB39B CISD2 ERCC2 PLA2G6 MTHFR ALDH18A1 GBA MFN2 HEPACAM VCP COX2 SERPINI1 KCNC1 PARK7 GRN SYNJ1 COX3 EIF4G1 GRIN2D LRRK2 CLN6 CERS1 MCOLN1 NBN PRKCG MAPT TRNE RTN4R MAPT TIMMDC1 NDUFAF3 PRDM8 WFS1 PRNP FA2H PSEN1 SDHD ERCC6 GIGYF2 APTX DLAT UBTF PRNP CNTNAP2 GLUD2 HTT CSF1R PPP3CA TBP DMPK WDR45 PSAP PRICKLE1 PDGFB PRNP SURF1 GABRB3 APP HEXA PSEN1 TREX1 VCP GBA TWNK HGSNAT CYFIP2 KCNA2 TRNV TRAK1 MAPK10 UBA5 ATP13A2 DNMT1 COX2 FUS CHD2 NDUFS2 PARS2 HIBCH HTRA1 MAPT SCN1A CTSF ND5 CHMP2B DHDDS ATXN3 CLN6 VCP PLEKHG4 NAGLU GBA2 POLG TRNL1 TLR3 PRNP GRN GDAP2 HNRNPA1 LYST GBA SNCAIP ATN1 CLN8 TMEM106B GALC CP XPA ND5 ATXN7 HSD17B10 COL18A1 TBP COX6B1 MAPT PRNP TINF2 PSEN1 APOE TREM2 PINK1 UBAP1 TREM2 GM2A SCN3A GLB1 C9ORF72 WFS1 ASAH1 DCTN1 PRKAR1A PLA2G6 TREM2 MAPT NOS3 COX3 JPH3 RAB27A SLC6A1 ERCC4 PRNP PAH UCHL1 ABCD1 CHCHD10 ASAH1 CLN8 SDHA
Protein Mutations 3
K56M V158M V66M
HP:0002015: Dysphagia
Genes 639
TGIF1 ASCC1 PIGN NOS1 TRNK TIMM8A CLTC COL7A1 NODAL CACNA1G VPS35 KCNK9 CAVIN1 KAT6B PRPS1 NEB POLR3B COL7A1 SDHD SHH TUBB4A KIT PRKRA NTRK1 NGLY1 RLIM RRM2B NUTM2B-AS1 OPTN IKZF1 SPECC1L ND1 NR4A2 CAV1 CHRNE YY1 SLC5A7 MYORG STUB1 ATXN10 DNAJB6 REPS1 ATP1A3 NDUFAF2 ATXN3 DDHD2 DAB1 NEB MEGF10 NODAL ATXN8OS GUCY1A1 ACTA1 ARHGAP29 EPB41L1 DCX VARS1 PLEC FGF8 GAS1 KCNQ5 GBA NDUFA6 FOXH1 IRF6 SCN4A MSX1 ANKRD11 CHRND NEB MRPS25 LAMB2 KLHL41 TBK1 CCR6 BRSK2 CYP27A1 PNKD IRF5 QDPR TPM2 ADNP DLL1 SIX3 MYO9A TIMM8A POLG NUP62 GCH1 SATB2 DCTN1 PSEN1 GMPPA GNS FOXH1 GRIN2B ND4 ADD3 PTS CDON TAF1 CUX1 COLQ SON KLHL41 ADAR ACOX1 UBQLN2 PANK2 GAS1 CRLF1 MAPT TK2 MYOT AR NEB KMT2A SPG11 MYH8 SPECC1L TPM2 CCR6 SCN3A KDM5B ZC4H2 CDON RELN ACTA1 CHRND IRF2BPL SLC5A7 RARS1 SHH DISP1 SCN4A TRNV PUS3 KIT ZIC2 PYGM PFN1 SLC52A3 MATR3 GALC ZMYND11 DISP1 CHRNE MAP2K2 SLC25A4 KIT SHH DNAJB6 NCAPG2 FOXH1 EEF1A2 HPDL KCNC3 CDH15 LIFR TDGF1 ALS2 ADH1C VPS13A CACNG2 NGLY1 GLI2 FGF8 ATXN1 GAS1 KLHL40 ATXN8 SCN4A ECM1 ATXN2 SCO2 FGFR1 CAV1 SDHC FTL NECTIN1 ND5 KIF1A MATR3 IDH2 PUF60 PDP1 ATXN3 DNM1L UBE3A TAF1 AFG3L2 TAOK1 FBXO7 STXBP1 TDGF1 ATXN7 SLC52A2 PPP3CA ALS2 KCND3 DYNC1H1 ZIC2 UBB CAMK2A POLG DISP1 PANK2 ZEB2 STAG2 LMX1B QDPR SIX3 GJB1 SIX3 MRPS28 SLC2A3 PDGFRA PLP1 TPM3 ATXN8 EPRS1 GRIN2D FLAD1 MFF ZIC2 ASPA VAMP1 SLC44A1 NOTCH3 ADCY6 SLC25A22 ND3 POLR3A LAMA2 C9ORF72 REEP1 SACS NECTIN1 HMBS POLR3B TRPM3 FBXL4 FGF8 CYP7B1 NPC1 MED17 SHH GRM1 SYT14 CAMK2B CACNA1A DLG1 SIK1 NDUFS1 LBR CACNA1A NOP56 TBCD NODAL ATXN1 ZFYVE26 KIF5A ERLIN2 PTCH1 HTT ZIC2 SDHA SLC9A6 NPC2 PCNA SCN4A CDC73 HTT DLL1 SETX PEX16 TRAPPC12 TUBB4A SQSTM1 CIC ATP7A RNASEH1 MMP1 DEAF1 REEP1 PLAA PLA2G6 CDON CHCHD10 SLC6A9 TBC1D23 PDE8B PTCH1 TYMP POLR3A CCN2 HLA-DRB1 SNCA PTCH1 ARX TPM3 MGME1 SPG7 HLA-DQA1 C19ORF12 DGUOK STUB1 UBE3A FGF8 GLI2 SLC1A4 GLI2 AGRN BRAF SNCA CNTNAP1 POLG2 POLG ACTB VAPB APP SET SLC18A3 DLX4 SDHB TRNL1 PANK2 SPG21 FGFR1 MYH7 MYOT CHMP2B C12ORF65 RAI1 FERMT1 EXOSC9 MYMK FLCN DNAJC13 COQ2 CRYAB DKK1 LINGO1 DDHD2 LMNB1 SQSTM1 KLHL40 RHBDF2 VAMP1 CACNA1G PIK3R5 FA2H NONO ALDH18A1 MAPT WFS1 PIGA ND2 AFG3L2 DGUOK MID1 PSAP SIGMAR1 GBA2 TGM6 SCARB2 ASH1L HPRT1 TARDBP CNTNAP2 VAC14 KIAA0319L MAPT YARS2 NDUFB8 GBA MBD5 COL7A1 VAMP1 NRXN1 SLC19A3 PTS SDHC GEMIN4 COQ4 VPS13A CSNK2B RRM2B ATP13A2 PANK2 ATXN2 REV3L MAPT TARDBP FMR1 SPG11 CTNS SYNJ1 TBK1 STXBP1 SYNGAP1 ATXN3 RNASEH1 SLC9A6 NOP56 TP63 VAMP1 PLAA MADD GCDH KLHL41 SNCA RRM2B PAX7 CCN2 NOTCH3 TPM3 TWNK ATP7B SIX3 SPART TP63 GLI2 GNAO1 PYROXD1 TANGO2 SOD1 SPG21 IDH1 FARS2 MSX1 TK2 ATN1 SEMA3E CDON SRPX2 LMNB1 NDUFA9 NDUFS3 GRHL3 TGIF1 FXN NUP62 SMC1A ALS2 FTL TRIP4 SPG7 OPA1 TAF1 PRDM16 POLG UBE3A MYPN PLA2G6 ZIC2 ADGRG1 GBA TK2 DISP1 COLQ FOXH1 GFPT1 NF1 XRCC1 ACTA1 UBTF KCNK9 GRIN1 CHAMP1 EIF4G1 LRRK2 FGF8 ACTA1 RERE POLG DMPK PRKCG PLXND1 MACF1 SKI B4GALNT1 TTBK2 TGIF1 HLA-DQB1 WAC SETBP1 MAPT ACTA1 NDUFAF3 ERLIN2 RRM2B TRNW SMC1A KY CDON HLA-B CHAT TDGF1 DYSF SEC31A GIGYF2 ATP1A3 PMP22 UBTF SLC25A1 PTCH1 DOCK8 PRNP MPZ ATP1A3 HOXB1 FOXH1 MYT1L GLI2 GABRD GLUD2 TUBB6 GAS1 TBP GAS1 DMPK FIG4 NF2 DYRK1A SURF1 TOP3A TGIF1 KBTBD13 CARMIL2 VCP GBA MECP2 WARS2 EBF3 POLR3A TWNK HGSNAT PI4KA GNAQ MYO9A PTCH1 COL13A1 RYR1 KLHL7 TDGF1 PRKRA TRAPPC12 PLEC FUS NDUFS2 CARS2 TGIF1 ZEB2 KIRREL3 SELENON ATXN8OS NEK1 NEFH ALS2 ATXN3 SLC52A3 HSD17B10 HPCA TDGF1 SYT14 POLG CDC73 RAB11A DLL1 FRG1 GDAP2 HLA-DRB1 SDHB HIVEP2 SHH TPM3 SIX3 GBA SNCAIP RERE CHD7 NEUROD2 ERLIN2 TCF4 MECR GRHL2 STAG2 SYT2 ATXN7 TBP ND6 MMP1 MAPT MFF CHMP1A DLL1 MED12L LRP12 SPG7 LMOD3 NODAL GRM7 ACTG2 ASAH1 SNAP25 CHRNA1 ALS2 ATP6 DLL1 PABPN1 FUS TANGO2 MID1 GRIN1 ATP6 CDH1 SDHB BMP4 CLCN1 IRF6 ACOX1 IRF5 NODAL KCNAB2 SDHC PRPH SETX SERPING1 NEU1 CHAT ABCD1 IRX5 CHCHD10 ASAH1 ITGB4 OCA2 DISP1 ATXN8OS
Protein Mutations 1
V158M
SNP 0