SNPMiner Trials by Shray Alag


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Report for Mutation V158M

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 26 clinical trials

Clinical Trials


1 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 Major Depression 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

2 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 Postoperative Pain Drug: Placebo 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

3 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 Antisocial Behavior Psychopathology Substance Use HIV Infections 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

4 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 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

5 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 Schizophrenia Schizoaffective Disorder Behavioral: Cognitive Remediation 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

6 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 Alcohol Craving Mood Changes 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

7 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 Schizophrenia Drug: Memantine 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

8 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 Opioid-related Disorders Opiate Dependence Opiate Addiction Opiate Abuse 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

9 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 Schizophrenia Cannabis Abuse Cannabis Dependence Dual Diagnosis Drug: Clozapine 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

10 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 Down Syndrome (DS) 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

11 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 Postoperative Nausea and Vomiting Vomiting Drug: Placebo Drug: Dexamethasone 3 mg Drug: Dexamethasone 6 mg 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

12 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 Healthy Drug: Tolcapone 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

13 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 Healthy Young and Older Adults Procedure: tDCS Drug: Citalopram 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

14 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 Mild Cognitive Impairment (MCI) Device: tDCS 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

15 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 Healthy Older Adults Device: tDCS 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

16 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 Healthy Young Adults Device: tDCS 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

17 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 Bulimia Nervosa Eating Disorders Dopamine Reward Catechol-O-methyltransferase Drug: AMPT/ Demser Drug: Diphenhydramine 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

18 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 Fatigue 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

19 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 Parkinson's Disease 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

20 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 Pain 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

21 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 Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Lymphoblastic Lymphoma Acute Leukemia Other: Educational Intervention Other: Educational Intervention Other: Quality-of-Life Assessment 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

22 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 Primary Dysmenorrhea Device: Active tDCS 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

23 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 Primary Dysmenorrhea Device: Active tDCS 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

24 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 Major Depressive Disorder Perinatal Depression 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.

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

26 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 Psychotic Disorders Behavioral: Cognitive remediation therapy (CR) Behavioral: Supported education (SE) 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)


HPO Nodes


HP:0000716: Depressivity
Genes 390
PDGFRB PFN1 DNAJC13 LIMK1 TRNS1 HTT LMAN2L CLN6 TSC2 FMR1 PSAP FGFR1 CPOX GBA GNAS DRD2 EPCAM NOTCH3 KISS1 ELN GABRG2 CLRN1 PON1 AARS2 PINK1 TBP ATRX RRM2B MAPT GPR35 UCHL1 PSEN1 SPRY4 PPARGC1A TACR3 FGF17 GNA11 C19ORF12 SNCA CP GLA HLA-DRB1 CHMP2B KCTD17 ND4 PDGFB MLH3 MSH2 NR4A2 USH2A ATP1A3 GIGYF2 PRNP TCF4 USH1C TRNQ DNMT1 RUNX1 HLA-DQB1 NEK1 ZC3H14 CLIP1 CACNA1G PDGFRB COQ2 TOR1A POLG GNAS OPTN MECP2 MAN2B1 GABRG2 C9ORF72 UNC13A GNRHR COX3 WDR11 GRN KCNT1 FMR1 ARVCF FBXO31 VPS13C MED25 SQSTM1 SLC6A4 MST1 MAPK1 MAPT MBOAT7 TRAPPC9 GBA ARSA ERBB4 UBQLN2 WFS1 MED23 SLC18A2 SQSTM1 PRNP ARMC5 TBP OCRL ATXN8OS TRNS1 USH1G ADGRV1 HS6ST1 GNAS GTF2IRD1 UFD1 TWNK TRNH C9ORF72 CCNF SGCE MAPT TARDBP RFC2 PLA2G6 TTC19 POLG XPR1 SNCAIP LRRK2 PRKCG DCTN1 PDGFRB PROKR2 TREM2 CLIP2 COMT GABRA1 XK TBC1D7 DNMT1 PRKACA JMJD1C NEFH SOD1 FRRS1L TRNL2 PRSS12 KDM5B DMPK CEP78 HIRA PPOX BCR VCP TARDBP EPM2A DNAJC5 COX1 PGAP1 MSH6 PMS1 MAN1B1 ND5 PRKAR1A RSRC1 DUSP6 HBB ST3GAL3 IQSEC1 CISD2 GSN ND6 EHMT1 TOR1A POLG ALMS1 LMNB1 CHD7 STX16 PRNP CHMP2B CFAP410 BCS1L PER3 TK2 TBX1 TUSC3 FA2H RPS20 AIMP1 FGF14 COX2 TREM2 DNA2 CLCN4 CPOX EDC3 CRBN GDAP2 SEC24C PAH FLT4 EPHA4 TMEM106B FGF8 EIF4G1 NSMF SLC2A1 AMACR SLC25A4 TRNL1 KISS1R FGF14 PAH RRM2B CBL ATP13A2 CHCHD10 DAO ATXN10 ADH1C CRADD PDGFB PMS2 TRNF PON2 LINS1 SYNJ1 ATXN8OS FUS PLA2G6 AP2S1 HNRNPA1 MSTO1 SNCA CACNA1H ND1 RREB1 PROK2 MYO7A SLC45A1 FUS JPH3 PODXL GLE1 SGCE GPR101 SPAST MATR3 MAN2B1 PON3 WHRN PRNP COASY PDCD1 LRRK2 GBA DCPS PDZD7 GNAS PPT1 COQ2 AIP GLT8D1 TGFBR2 MYO7A SMPD1 WFS1 PIGC KCNJ2 TWNK ANOS1 HTR2A POLG ATXN8 ABCA7 SARS1 AFG3L2 ANXA11 POLG PTPN22 RPS6KA3 SEMA4A TWNK PARK7 CC2D1A POLG2 GCH1 DGUOK HTRA2 BAZ1B TRNS2 TAF15 VPS35 ASXL1 ATXN2 HTT C12ORF4 CDH23 PCDH15 GP1BB PANK2 CACNA1G EZR HARS1 PIK3CA FAN1 FMO3 ATP1A3 MSTO1 NSUN2 PANK2 ARSG TNIK PINK1 PER2 TET3 TWNK SNCA CSF1R CLCN4 VCP GRIK2 GTF2I BMPR1A ATXN2 TET2 TBK1 TAC3 TRNN TBK1 FMN2 ATP7B SRPX2 THOC2 CRKL GRIN2A PTS VCP FIG4 NHLRC1 ARMC5 PRPH CDH23 TRNL1 CTSF ATXN10 TRNW JRK C9ORF72 CHCHD10 TBX1 GABRB3 CASR MLH1 PRKN SRSF2 CYP27A1 KRAS DCTN1 B3GALNT2 NDST1 PRNP HNMT HLA-DQB1 ANG TSC1 VAPB SLC20A2 METTL23 WASHC4 TBL2 CIB2 HMBS HMBS C9ORF72 DCTN1 PPP2R2B KCTD17 ESPN VCP POLG C9ORF72 PDE11A CBS GNRH1 PRNP TECR IDUA GNAS TRNS2 USP8 GLUD2 DNAJC6
Protein Mutations 4
A1298C C677T V158M V66M
HP:0002013: Vomiting
Genes 284
PPM1D SHANK3 ABCC8 KMT2E SLC6A8 NDUFAF5 BCKDHB KCNJ1 CPT2 ELP1 NEUROG3 RANBP2 CPOX NAGS SLC25A13 MVK COX1 MPI SLC22A5 STK11 ND2 CPS1 POLG SCNN1A ALG11 NDUFV1 TRNF CTNS RELA OTC PNPLA8 ND3 PCCB ACAT1 ATP6V0A4 CLMP BOLA3 DBT SERPING1 TYMP TRNC SCNN1B HSD3B2 NEUROG3 MTRR PDCD10 SAA1 HADH DBH ALG11 SERPING1 ACY1 NFIX TRNK TRNL1 ND1 ND4 NDUFS3 RRM2B NDUFV2 ALDOB SCNN1A ALDH18A1 HIBCH ND1 PHGDH ADNP COQ2 NAXD POLG COX3 TRNQ MPV17 RET MMUT SLC7A7 NDUFB11 TCN2 CFI NDUFS1 MRAP FARSB SUGCT PDSS2 CYTB PCCA TRNV CYP11A1 TIMMDC1 NDUFAF8 NDUFB10 HMGCL KCNJ11 ALDOB COX3 ASL ACADVL ATP6 ACADL F12 TNFRSF1A ABCC8 CYP11B2 MLYCD DGAT1 ATRX OPLAH GLA MTHFD1 CYP11A1 NDUFS6 SSR4 EGFR FOXRED1 CDH23 NBAS TRNS2 CCM2 ND1 GALC NDUFS4 NDUFAF4 TRNQ AQP2 GK BCKDHA SERPING1 CACNA1A SPP1 ETFA TXNRD2 ASS1 FBP1 MET TRNS1 MRPS7 CTNNB1 ACAT1 PMM2 COA8 AVPR2 ND5 ESR1 TP53 MVK TRNH NDUFS8 NAGS NDUFAF3 TMEM126B ACSF3 STAR PIGY GALT RARS1 AIMP1 ETFB HLCS MMAA COX2 TRNF CDK8 HNF1A HFE SAR1B ALG3 TRNW MCCC1 GCDH FLNA DGUOK MC2R MMAB ALAD DHCR7 POLG ACP2 GALC BRAF SCNN1G STAT4 NDUFA6 KCNJ11 SLC25A15 D2HGDH ST3GAL5 INHBA IVD NDUFS2 NDUFV1 CFH TRNS2 UCP2 APC NNT HNF4A ARG1 ACSF3 SYT1 NDUFS4 COX1 TRNW TNF TYMP ND5 NDUFA1 ACADM MSX2 SLC25A15 NDUFA11 IRAK1 MEN1 CYP24A1 ALX4 ZEB2 LPL HMGCS2 ND6 SLC12A3 PPOX CYTB ETFDH ND5 SLC22A5 HMGCL NDUFAF1 SLC1A3 ND4 ASPA SMPD1 AVP NDUFAF2 C11ORF95 FOXP3 NR3C2 HMBS TRNL1 NDUFS1 DLD ND3 ACADVL HELLPAR ALPL TRNK SLC12A1 TRNW NDUFB3 ND6 ND2 OXCT1 TRNS1 NDUFB9 COX2 GHSR AIP HPRT1 ACTG2 SLC7A7 TRNV PSAP EDNRA TRMU CDH23 SCNN1G CD46 CD55 PYCR2 SAR1B KRIT1 CYP11B1 ACAD8 ALG8 BTD GALE ND6 MCCC2 PMM2 TRNL1 NDUFS7 ACADM SCNN1B LIPA ND1 NUBPL
Protein Mutations 3
S253N V158M Y129S
SNP 1
rs4680
HP:0012378: Fatigue
Genes 398
PFN1 SOX3 ATRX VHL LBR BIRC3 BLNK GNAS CD79A SH2B3 STAT5B EPCAM NF1 MEFV IL12A-AS1 CTLA4 MLX PON1 PNPLA8 RPL5 RUNX1 KCNQ1 RRM2B GPR35 ELANE PPARGC1A IGH GLA DBH CCR1 MLH3 XPC MSH2 CCND1 KLRC4 ATP7A KCNQ3 PSTPIP1 PALLD HLA-B TCF4 CDKN2A RUNX1 BCOR ALB AGK GBA NEK1 CFI IRF2BP2 ALAS2 MRAP OPTN MYD88 CAV3 NKX2-1 BCL2 CCDC78 PALB2 C9ORF72 UNC13A DNAJC6 SDHA SMAD4 TBX19 C4A ATM PDE8B RPS28 NUMA1 SCN8A MMACHC NFKB2 PRKAR1A MST1 HBA1 RPL11 SOX3 SLC25A11 SCNN1A ERBB4 UBQLN2 SLC18A3 PODXL HFE SQSTM1 ARMC5 HLA-DPB1 PRRT2 MET NPM1 SLC26A4 NAGS FAS CCNF TSHR STAR SDHD IL12A SPIB PREPL RET POU1F1 WIPF1 DLST LHX4 TSC1 HNF1A TET2 DCTN1 STEAP3 FOXE1 TREM2 NABP1 FGFR1 PYGM HESX1 WAS SLC5A5 INSR NEFH KCNN4 IL23R SOD1 HESX1 ERAP1 RPS27 RPS7 FOXP1 STAT6 CALR CFH DMPK DUOX2 BRCA1 VCP TARDBP GCK DYSF TBL1XR1 CCND1 MSH6 PMS1 COL1A2 ACADM BCR SDHB IGLL1 MEN1 EPOR PRTN3 UNC93B1 MDH2 DNMT3A HLA-B BRCA2 JAK2 HMGCL DDB2 RPS17 CHMP2B CFAP410 IL12RB1 PAX8 LHX4 CPT1A ERCC2 RPL35A MMEL1 RPS20 PRKACA COL5A2 RET RPL31 PYGL RPL15 IRF5 NKX2-5 HLA-DRB1 EPHA4 ABL1 ERCC4 RPL27 DNM1L SLC25A4 SMAD3 POU1F1 HAVCR2 OPA1 PLEC SLC26A4 JAK2 KCNE1 CBL SDHB KIT ATP13A2 RPS24 PGM1 DAO GATA1 NAB2 SDHB SDHAF2 VHL DMD PDGFRA PMS2 ALB ERCC5 SLC11A1 PON2 CPT2 IGHM RPS26 PROP1 PML PIGT AP2S1 SCNN1B HNRNPA1 SLC18A2 PROP1 TSHR POMGNT1 COQ2 RPL26 RPS29 SDHC MALT1 SDHD HESX1 FUS SDHC FH SCN2A GLE1 C1QBP GPR101 LHX3 MATR3 RPS10 CPT2 PON3 CHRND BCL10 BCL6 ZBTB16 AIP GLT8D1 TAZ TGFBR2 KRAS SERPINA6 HLA-B TWNK IKZF1 UBAC2 ABCC2 RARA MORC2 MYH7 ANXA11 POLG EPAS1 CDH23 SLC2A10 PTPN22 TFR2 SEMA4A POLG2 GCH1 PROKR2 KCNQ2 TLR3 TAF15 TRAF3 FIP1L1 ASXL1 CDC73 SOX2 TNPO3 ATXN2 TXNRD2 TRNK HLA-DPA1 LRRC8A MPL TSC2 DUOXA2 TLR4 CTNNB1 PIK3CA NLRP3 FAN1 PIGA IGH TWNK KIT TICAM1 PROP1 RPS15A NR3C1 TPO XPA PRKAR1A BMPR1A ERCC3 TET2 KIF23 TBK1 TSHB MC2R MEN1 ATP13A2 TK2 CDC73 IL10 IL12B TET2 RPL18 STAT4 MMADHC POU2AF1 FIG4 STAT3 ARMC5 VPS13A MPL PRPH TSR2 NNT HNF4A TP53 CDH23 COL5A1 BTNL2 GLI2 PTPN22 PAX8 FOXA2 CHCHD10 PTPN3 TMEM127 CD79B GATA2 IL12A MLH1 TBK1 ADA2 SRSF2 SLC12A3 IGH KRAS ARNT2 IYD TG SLC3A1 PHKG2 SMAD3 PDE11A COL1A1 ANG VAPB SLC40A1 NLRP3 OTX2 NR3C1 RPL35 HELLPAR MAX KIF1B FGF23 TCF3 PIEZO1 PIK3R1 AIP PHKA2 SDHA OTX2 HLA-DRB1 SLC25A26 TNXB CDH23 RPS19 CD46 BTK SLC4A1 SYNJ1 FTL TNFSF15 SCNN1G VHL USP8 TET2 TET2 JAK2 HBA2
Protein Mutations 3
T25W V158M V18M
SNP 0
HP:0000726: Dementia
Genes 290
C9ORF72 HNRNPA2B1 DNAJC13 HTT CHCHD10 HNRNPA1 CLN6 FMR1 PSAP ATXN10 TOMM40 GBA ATXN3 PSEN1 ADH1C GBA2 CHMP2B COX1 TREM2 POLG NOTCH3 PLAU TRNF AARS2 PINK1 VPS13C TBP SYNJ1 MAPT ATXN8OS UCHL1 PSEN1 SNCA FUS TYMP SLC13A5 TRNC PLA2G6 MATR3 EPM2A SNCA C19ORF12 PANK2 SNCA CP PPP2R2B CHMP2B HTT TRNK TRNL1 ND1 ND4 PDGFB RRM2B NR4A2 ERCC8 MPO VPS13A LRRK2 SERPINI1 JPH3 PODXL GIGYF2 ITM2B WDR45 PRNP COX3 TRNQ DNMT1 SPAST SDHB ABCD1 C9ORF72 PRNP GBA PSEN2 NPC2 LRRK2 SQSTM1 GBA TRPM7 CYTB SNCA TRNV MAPT RNF216 HTRA1 COX3 COL4A1 CYP27A1 GRN FTL FMR1 TUBA4A TWNK APP ALDH18A1 MMACHC VPS13C MAPT MBTPS2 TMEM106B SQSTM1 ATP13A2 SPG21 ATN1 APTX GBA HEXA ATP6V0A2 PARK7 ALDH18A1 WDR45 DGUOK HTRA2 ARSA NOTCH2NLC TRNS2 ROGDI MAPT KCTD7 WFS1 TREM2 CISD2 TRNQ VPS35 APOE GBA PRNP PSEN2 HTT TBP HFE CLN3 NHLRC1 TRNS1 UBQLN2 GRN CHCHD10 PNPLA6 TRNH VCP SDHD HTRA1 TYROBP ZFYVE26 HNRNPA2B1 NPC1 TREM2 C9ORF72 SLC2A3 PSEN1 MAPT TYROBP TARDBP CP TREM2 PANK2 DNMT1 RNF216 PINK1 MATR3 ATP6V1A PLA2G6 SNCA SDHAF1 MAPT GRN CSF1R TTR XPR1 COX2 TRNF SDHA VCP SNCAIP SORL1 LRRK2 GRN ATXN2 TARDBP SCARB2 TRNW ATP7B APP GM2A PRDM8 TBK1 PDGFRB PRICKLE1 ATP13A2 IRF6 APOE ROGDI POLG PSEN1 ATXN2 CHMP2B PSEN1 APP PRKAR1B VCP ATP13A2 PRNP ITM2B ATP6 NHLRC1 ATP13A2 TBK1 TRNS2 ASAH1 NOS3 APP A2M EPM2A CSTB DNAJC5 COX1 CTSF CERS1 CHMP2B SQSTM1 WFS1 TRNW TUBB4A APP ATN1 PRNP ND5 C9ORF72 JPH3 SPG21 RAB39B PRKN ND6 MAPT ATXN2 DCTN1 ND5 ABCA7 APP SNCB CUBN PRNP PRNP FBXO7 ERCC4 HLA-DQB1 PSEN1 NDP C9ORF72 TREX1 DCTN1 PRDX1 PPP2R2B VCP TMEM106B SNCA CFAP43 PSEN1 VCP TRNE GBA2 APP NOTCH3 TRNS1 COX2 ATP6V1E1 TREM2 TIMM8A FTL VCP CHMP2B MAPT MECP2 ATP6 MAPT TMEM106B EIF4G1 DNM1L ND6 ADA2 ASAH1 GBE1 TRNL1 CST3 ND1 GLUD2 OPA1 DNAJC6
Protein Mutations 1
V158M
SNP 0
Protein Mutations 1
V158M
SNP 0
HP:0001268: Mental deterioration
Genes 478
PDGFRB HEPACAM DNAJC13 GLB1 HTT CHD2 SYNJ1 CLN6 FMR1 PSAP TOMM40 GBA SLC13A5 COX1 DAOA XPA TREM2 NOTCH3 PLAU ATP1A3 CNKSR2 AARS2 PINK1 SLC1A2 VPS13C TBP MAPT UCHL1 CHD2 PSEN1 TYMP SLC13A5 TRNC MAPT SCN8A EPM2A C19ORF12 SYNJ1 SNCA CP CHMP2B WWOX TRNK TRNL1 ND4 PDGFB TRAK1 APOL2 NR4A2 ERCC8 VPS13A LRRK2 HSD17B10 GIGYF2 WDR45 PRNP TRNQ DNMT1 SDHB TTPA GABRA2 SCO2 NDUFS2 GBA KMT2A PSEN2 PDGFRB SPG11 TLR3 TRPM7 SNCA GCH1 MAPT CACNA1B UBAP1 COX3 GRN FTL FMR1 TUBA4A HGSNAT ERCC2 ALDH18A1 VPS13C MAPT SQSTM1 PLP1 CUX2 FA2H APTX MAPT GBA ALDH18A1 ARSA TBP ROGDI MAPT GALC KCTD7 WFS1 CISD2 TRNQ APOE GBA MFSD8 PRNP PSEN2 JAM2 TBP HFE DCAF17 CLN3 QDPR NHLRC1 EEF1A2 TRNS1 KCNB1 UBQLN2 GNAS CHCHD10 ARSA TRNH SDHD HTRA1 ZFYVE26 HNRNPA2B1 NPC1 CTC1 C9ORF72 SLC2A3 CACNA1A MAPT TARDBP DARS2 CP DNMT1 RNF216 PSAP PLA2G6 SDHAF1 MAPT GABRG2 CLN5 XPR1 SGPL1 MYORG HNF1A SNCAIP LRRK2 PRKCG GRN TRNW ATP7B CLTC PRDM8 SUMF1 ADA2 PDGFRB IRF6 COMT ATXN2 GALC CHMP2B HTR2A NECAP1 SZT2 CLN6 DNMT1 AARS1 UBA5 ATP13A2 TRNS2 DMPK UCP2 NOS3 PSAP RBM28 A2M EPM2A YWHAG CSTB DNAJC5 COX1 CHMP2B WFS1 ATN1 ND5 PRKAR1A PARS2 JPH3 RBM28 TIMM8A RAB39B IDUA ND6 RRM2B MAPT GALC PTS KCNA2 LMNB1 COL18A1 APP ATXN7 PRNP FBXO7 ERCC4 PSEN1 NDP GRN PRDX1 ERCC6 SNCA FA2H NOTCH3 COX2 FGF12 NDUFAF3 TREM2 DHDDS RAB27A TIMM8A FTL GDAP2 PAH CTNS MAPT MECP2 ATP6 TMEM106B SNORD118 EIF4G1 AP5Z1 KCNA2 NBN HCN1 DNM1L ND6 RTN4R ADA2 ASAH1 TRNL1 SYNGAP1 CST3 ND1 OPA1 C9ORF72 HNRNPA2B1 DNM1 GBA DRD3 CTSD CHCHD10 HNRNPA1 TREX1 SCN3A ATXN10 NDUFB8 ATXN3 PSEN1 ADH1C GBA2 CHMP2B CHI3L1 PDGFB ACTL6B POLG CSF1R UBTF TRNF SURF1 ATP6V1A SYNJ1 ATXN8OS SNCA MAPT FUS PLA2G6 RRM2B MATR3 SNCA PANK2 ARSA PPP2R2B KCNC1 HTT PDE10A ND1 NRAS SPG11 RRM2B GALC BSCL2 SCN1A MTHFR MPO HIBCH SERPINI1 CPLX1 JPH3 NTRK2 PODXL ITM2B COX3 SPAST ABCD1 DISC2 C9ORF72 PRNP CLN8 COASY CSTB NPC2 LRRK2 SQSTM1 GBA CYTB NAGLU TRNV PPT1 RNF216 KCNJ11 HTRA1 RNASEH1 COL4A1 CYP27A1 TWNK ABCC8 PLEKHG4 APP AP2M1 MMACHC MBTPS2 TMEM106B ATP13A2 SPG21 ATN1 MFN2 SYN2 HEXA ATP6V0A2 PARK7 WDR45 DGUOK HTRA2 NOTCH2NLC TRNS2 CYFIP2 TBC1D24 TREM2 PRDM8 VPS35 HTT SYNJ1 TRNK AP3B2 GRN APOL4 PNPLA6 STXBP1 VCP TYROBP NUS1 TREM2 PSEN1 TYROBP TBK1 TREM2 PANK2 PINK1 MATR3 ATP6V1A SNCA BSCL2 GRN GRIN2D CSF1R TTR DNM1 COX2 MAPT TRNF SDHA VCP SORL1 ATXN2 TARDBP SCARB2 SLC6A1 APP GM2A TBK1 PRICKLE1 ATP13A2 APOE ROGDI POLG TK2 PSEN1 NDUFA6 PSEN1 APP PRKAR1B VCP ATP13A2 PRNP ITM2B ATP6 NHLRC1 SQSTM1 TINF2 CLN8 TBK1 ARV1 SMC1A ASAH1 ACTB HNF4A GBA APP HEXB CTSF CERS1 SQSTM1 TRNW TUBB4A APP PRNP C9ORF72 C19ORF12 CNTNAP2 SPG21 PRKN TIMMDC1 ATXN2 DCTN1 ND5 ABCA7 PPP3CA SNCB GABRB2 CUBN PRNP HLA-DQB1 SLC20A2 C9ORF72 TREX1 DCTN1 PPP2R2B VCP TMEM106B FA2H CFAP43 PSEN1 VCP TRNE GABRB3 GBA2 APP SCN1A TRNS1 ATXN7 ATP6V1E1 PDE11A SUMF1 PSAP GABRA5 VCP CHMP2B MAPT MAPK10 PLA2G6 MCOLN1 GBE1 ATP1A2 PRNP GLUD2 DNAJC6
Protein Mutations 3
K56M V158M V66M
HP:0002015: Dysphagia
Genes 485
DNAJC13 LBR NEB FMR1 KCNAB2 GBA ATXN8OS SLC6A9 ADCY6 NEB SACS TBP SYT14 RRM2B TK2 PRPH GNAQ SLC52A3 TYMP CHMP1A MAPT CHD7 PDP1 SNCA ADD3 CLCN1 PCNA CCR6 CHRNA1 GFPT1 VAPB NCAPG2 NR4A2 MEGF10 SLC5A7 VPS13A TGM6 NUP62 ATP1A3 GIGYF2 COLQ HLA-B ATXN3 SCO2 NDUFS2 KMT2A SETBP1 CACNA1G SEMA3E POLG COL13A1 MYMK REEP1 GCH1 STUB1 MECP2 COL7A1 PABPN1 HLA-DQA1 IRF5 TRAPPC12 SDHD DNAJB6 FTL KIAA0319L HGSNAT COQ4 FLCN TPM2 EXOSC9 LRP12 SCARB2 SQSTM1 PLP1 WFS1 LAMA2 ATXN1 MYH8 MAPT DDHD2 SKI GBA VARS1 GEMIN4 AR NECTIN1 SELENON TAF1 KY PUS3 MYO9A MMP1 CNTNAP1 PLEC TBP DGUOK ATXN8OS COLQ FARS2 PFN1 QDPR TUBB4A TAF1 UBQLN2 ND5 CHCHD10 ZFYVE26 NPC1 HLA-DQB1 TBC1D23 C9ORF72 MAPT ALS2 TARDBP MYO9A SCN4A RARS1 PSAP SLC52A2 IRF5 AGRN ACTA1 SNAP25 MYORG MACF1 SLC9A6 CAV1 SNCAIP LRRK2 PRKCG ATP7B RNASEH1 ANKRD11 SPG7 MAP2K2 ATXN2 CHMP2B PYGM DDHD2 CHRNE HLA-DRB1 PLAA NOP56 NEK1 SPG7 ERLIN2 DMPK MSX1 SOD1 DKK1 STXBP1 CARS2 POLG MMP1 SLC25A1 ECM1 COL7A1 SLC19A3 TIMM8A TPM3 RERE DNAJB6 IRF2BPL RRM2B TRAPPC12 POLG PTS LMNB1 KCNK9 ATXN7 ACTA1 RYR1 ASPA FBXO7 PRKRA KIT MFF ATP6 SDHB TRNL1 NDUFS1 KCNC3 TANGO2 ND3 SLC18A3 SPG7 TK2 SNCA TRNW CAV1 CDH1 ND6 SLC52A3 FA2H HPCA NOTCH3 PIGN ASCC1 NDUFAF3 HPRT1 CAVIN1 TIMM8A NGLY1 FTL SPECC1L GDAP2 ALDH18A1 CTNS MAPT MGME1 TPM2 EIF4G1 DLX4 GRHL3 SYT2 LAMB2 DNM1L COL7A1 SLC25A4 SON POLR3A COL7A1 TUBB6 SDHC BRAF OPA1 DCTN1 IRF6 LIFR RRM2B GBA SDHB KIT TRIP4 KLHL7 NEFH CHRNA1 CHCHD10 VAMP1 SCN4A NUP62 ATXN10 NDUFB8 ATXN3 ADH1C SLC1A4 NGLY1 PDGFRA POLG SDHB POLR3A UBTF TOP3A REEP1 SCN4A ERLIN2 SURF1 ATXN8OS IDH2 MAPT FUS PRDM16 PLA2G6 NEUROD2 ATP1A3 MATR3 PANK2 NEB VAC14 GNS SDHC TPM3 SPG11 SLC9A6 GNAO1 RRM2B KLHL41 GALC CHRNE KCNK9 ATXN3 SDHC ND1 ADNP PIK3R5 XRCC1 HTT VAMP1 CHRND CHRND ACOX1 HLA-DRB1 PLEC LINGO1 RHBDF2 NPC2 RERE SQSTM1 YY1 NEB NRXN1 ACTA1 MYOT ADAR TAF1 COQ2 POLR3B KIF5A AFG3L2 ALS2 RNASEH1 MED17 ATP6 CYP27A1 FXN TWNK IKZF1 ATXN8 CYP7B1 POLR3A TTBK2 SPG21 PRKRA CARMIL2 POLG PMP22 ACTA1 DMPK POLG2 GBA2 DGUOK FLAD1 GRM1 VPS35 CHAT GJB1 CDC73 SERPING1 TP63 ATXN3 SYNJ1 REPS1 ATP7A MYOT REV3L UBTF PANK2 NONO CACNA1G GRIN2D MYH7 EPRS1 DLG1 PIGA QDPR ATP1A3 NDUFAF2 ARHGAP29 TANGO2 PANK2 CRYAB TWNK DYSF KIT MATR3 ATN1 SNCA CACNA1A CRLF1 PLXND1 B4GALNT1 YARS2 MAPT PANK2 GBA MID1 KLHL41 LMX1B VAMP1 SCN4A ATXN2 TARDBP POLR3B SLC25A22 TBK1 MECR KBTBD13 ATP13A2 TPM3 TK2 CDC73 TP63 IRX5 NDUFA6 PSEN1 PTS APP PNKD GRHL2 LMOD3 HOXB1 NECTIN1 CACNA1A PRPS1 NDUFS3 NF1 TBK1 KLHL40 MYPN SMC1A KAT6B ASAH1 ALS2 RLIM ACTB GBA PUF60 FRG1 MPZ SPART ITGB4 TUBB4A COL7A1 PRNP VAMP1 NOS1 ARX NOP56 ATXN8 C19ORF12 EBF3 SPG21 IDH1 NDUFA9 ND4 FBXL4 CNTNAP2 KLHL40 GUCY1A1 CCN2 CHAT OPTN UBB SLC5A7 TRNK BMP4 LMNB1 GABRD TBCD SETX FERMT1 MSX1 ND2 VCP AFG3L2 PEX16 POLG ATXN7 STUB1 ACTA1 GMPPA SDHA ACTG2 TRNV DAB1 PYROXD1 ATXN1 C12ORF65 CCR6 SIK1 RAI1 PDE8B TPM3 SCN3A PLA2G6 ALS2 KCND3 KLHL41 CCN2 ERLIN2 PLAA IRF6 SYT14 SETX GLUD2
Protein Mutations 1
V158M
SNP 0