SNPMiner Trials by Shray Alag

rs12979860 (38) rs6971 (31) rs9939609 (11) rs6265 (11) rs738409 (11) rs7903146 (8) rs4680 (8) rs8099917 (8) rs11200638 (6) rs429358 (6) rs10490924 (6) rs7412 (6) rs16969968 (5) rs25531 (5) rs1801133 (5) rs1800497 (5) rs1799971 (4) rs4244285 (4) rs2832407 (4) rs1045642 (4) rs1544410 (4) rs10033464 (3) rs1761667 (3) rs6166 (3) rs1042713 (3) rs2023239 (3) rs1051730 (3) rs174537 (3) rs1006737 (3) rs2230199 (3) rs1128503 (3) rs2231142 (3) rs10455872 (3) rs6313 (3) rs1061170 (3) rs776746 (3) rs4588 (3) rs2069514 (2) rs1799963 (2) rs9332739 (2) rs2032582 (2) rs3745274 (2) rs6295 (2) rs12936231 (2) rs6280 (2) rs7103572 (2) rs35599367 (2) rs13266634 (2) rs1410996 (2) rs6025 (2) rs4129267 (2) rs70991108 (2) rs174547 (2) rs1127354 (2) rs362331 (2) rs53576 (2) rs35705950 (2) rs641153 (2) rs1695 (2) rs2234246 (2) rs10741657 (2) rs1800955 (2) rs2106261 (2) rs4149056 (2) rs2234237 (2) rs362307 (2) rs3808607 (2) rs1828591 (2) rs1800470 (2) rs1024611 (2) rs12785878 (2) rs3751143 (2) rs762551 (2) 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rs2248949 (1) rs222797 (1) rs1643649 (1) rs4803455 (1) rs2853564 (1) rs780094 (1) rs2231137 (1) rs6434222 (1) rs3825942 (1) rs112735431 (1) rs751402 (1) rs9701796 (1) rs1202167 (1) rs1202168 (1) rs1202169 (1) rs12472215 (1) rs4311 (1) rs2279238 (1) rs3766404 (1) rs7349683 (1) rs3781727 (1) rs1800450 (1) rs7157609 (1) rs529802001 (1) rs2257401 (1) rs3817198 (1) rs1217414 (1) rs1045485 (1) rs2278392 (1) rs2476601 (1) rs7993418 (1) rs13181 (1) rs4673 (1) rs2097432 (1) rs324011 (1) rs1079598 (1) rs1800566 (1) rs1800682 (1) rs603965 (1) rs993607 (1) rs1790349 (1) rs1044396 (1) rs3742376 (1) rs6592052 (1) rs9332377 (1) rs16111115 (1) rs11559024 (1) rs1149222 (1) rs11870474 (1) rs25331 (1) rs2929116 (1) rs2929115 (1) rs7961953 (1) rs2242480 (1) rs4532 (1) rs222747 (1) rs105173 (1) rs2165241 (1) rs1800795 (1) rs2075606 (1) rs11648486 (1) rs35874116rs (1) rs4795541 (1) rs2282679 (1) rs7853758 (1) rs1504982 (1) rs1176713 (1) rs11249433 (1) rs12467815 (1) rs10524523 (1) rs4880 (1) rs12760457 (1) rs2062305 (1) rs3828057 (1) rs3790515 (1) rs11687951 (1) rs1800896 (1) rs254093 (1) rs4994 (1) rs4633 (1) rs1885988 (1) rs11099592 (1) rs6843082 (1) rs17611 (1) rs2228171 (1) rs1042173 (1) rs41432149 (1) rs926198 (1) rs12992677 (1) rs2305619 (1) rs1800888 (1) rs61729512 (1) rs2266782 (1) rs1653624 (1) rs664393 (1) rs2246704 (1) rs11959427 (1) rs4848306 (1) rs3765467 (1) rs2246709 (1) rs2089760 (1) rs2180439 (1) rs2242447 (1) rs2981582 (1) rs12654788 (1) rs5275 (1) rs1053230 (1) rs1906591 (1) rs2010963 (1) rs11102930 (1) rs2601126 (1) rs2854116 (1) rs2854117 (1) rs16944 (1) rs17778257 (1) rs16942 (1) rs1801282 (1) rs5751876 (1) rs762251 (1) rs3803662 (1) rs10264272 (1) rs28399433 (1) rs230561 (1) rs12654778 (1) rs4364254 (1) rs10177833 (1) rs2238071 (1) rs1801275 (1) rs10766197 (1) rs704010 (1) rs10937405 (1) rs2228480 (1) rs9526240 (1) rs17570669 (1) rs10407022 (1) rs4612666 (1) rs6746030 (1) rs889312 (1) rs243866 (1) rs2740565 (1) rs1558902 (1) rs8192620 (1) rs10865801 (1) rs58542926 (1) rs3789604 (1) rs1801260 (1) rs2273773 (1) rs10757274 (1) rs573112 (1) rs2244613 (1) rs10757278 (1) rs6330 (1) rs1056892 (1) rs11931074 (1) rs2075252 (1) rs1297860 (1) rs28459296 (1) rs2380205 (1) rs780094s (1) rs9557195 (1) rs11045585 (1) rs1801253 (1) rs1801132 (1) rs11569562 (1) rs2104772 (1) rs15524 (1) rs2854275 (1) rs2066842 (1) rs12255372 (1) rs6323 (1) rs1057910 (1) rs1051375 (1) rs544684689 (1) rs2234237r25r (1) rs6318 (1) rs9826 (1) rs7120118 (1) rs12356193 (1) rs8111699 (1) rs7270101 (1) rs17042171 (1) rs1062033 (1) rs553668 (1) rs185670819 (1) rs1405655 (1) rs6311 (1) rs518147 (1) rs10401969 (1) rs4516035 (1) rs33996649 (1) rs10276036 (1) rs1465952 (1) rs2232618 (1) rs549927573 (1) rs41308230 (1) rs2293152 (1) rs2237060 (1) rs5215 (1) rs4820059 (1) rs12329760 (1) rs12676 (1) rs11083519 (1) rs16874954 (1) rs35597368 (1) rs1799983 (1) rs5573 (1) rs2229774 (1) rs2731886 (1) rs5574 (1) rs2302616 (1) rs12221497 (1) rs4973768 (1) rs5569 (1) rs2032892 (1) rs13281615 (1) rs4820268 (1) rs10079250 (1) rs1799750 (1) rs9366637 (1) rs4148738 (1) rs10456542 (1) rs25648 (1) rs9984723 (1) rs766996587 (1) rs2398162 (1) rs7291050 (1) rs1011970 (1) rs4253728 (1) rs12143842 (1)

SNPMiner SNPMiner Trials (Home Page)


Report for SNP rs6265

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

There are 11 clinical trials

Clinical Trials


1 Epigenetic Regulation of Brain-Derived Neurotropic Factor (BDNF) in Patients With Major Depression

The investigators will (1) detect the associations between brain-derived neurotrophic factor (BDNF) DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive disorder (MDD) patients, (2) check the correlation between blood BDNF protein and RNA and BDNF rs6265 gene, and (3) discuss the possible mechanisms of epigenetic regulation of BDNF in Taiwanese major depressive patients.

NCT01182103
Conditions
  1. Major Depressive Disorder
MeSH:Depression Depressive Disorder Depressive Disorder, Major
HPO:Depressivity

Epigenetic Regulation of BDNF in Major Depression The investigators will (1) detect the associations between brain-derived neurotrophic factor (BDNF) DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive disorder (MDD) patients, (2) check the correlation between blood BDNF protein and RNA and BDNF rs6265 gene, and (3) discuss the possible mechanisms of epigenetic regulation of BDNF in Taiwanese major depressive patients.

Primary Outcomes

Description: averaged percentage of methylation at each CpG site listed

Measure: Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls

Time: 2 years

Description: Chromatin immunoprecipitation (ChIP) was used to measure histone modification. The unit of our given machine is relative quantification, and a higher value indicated increased histone modification. The detailed method could be found in: Huebert DJ, Kamal M, O'Donovan A, Bernstein BE: Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 2006; 40: 365-369.

Measure: Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls

Time: 2 years

Secondary Outcomes

Description: Serum BDNF levels were measured. MDD patients received antidepressant treatment, a standard biological management. Nothing novel (such as experimental drugs or management) is introduced in the treatment, so the research design is observational (of standard treatment). The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.

Measure: BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls

Time: 2 years

2 The Influence of 5-HTTLPR and BDNF Polymorphisms on Anxiety and Mood After Acute Exercise

The Influence of 5-HTTLPR and BDNF Polymorphisms on Anxiety and Mood After Acute Exercise. Introduction: The 5-HTTLPR (SLC6A4) and BDNF (Val66Met) polymorphism presents an action on the modulation of human behavior and has received great attention as a risk factor for several psychiatric disorders. In recent years, a growing number of studies have evaluated the association between these polymorphisms and personality traits related to anxiety and depression. Objectives: To determine the frequencies of 5-HTTLPR and BDNF polymorphisms in a college students population; To determine the influence of 5-HTTLPR and BDNF polymorphisms on mood states and anxiety after acute physical exercise. Material and Methods: Four hundred (400) College students will be assessed. In the first phase of the study, the following procedures will be performed: Screening, Aerobic Fitness Assessment (Step Test), Questionnaires (PAR-Q, Habitual Physical Activity Level, Beck Anxiety and Depression Scale, State-Trait Anxiety, and Perceived Stress Scale), blood sample collection and genotyping. In the second phase of the study, two (2) groups with or without polymorphisms will be selected (for each gene). These groups will be submitted to four conditions (three experimental conditions and one control condition), carried out randomly and separated by an interval of 1 week. In the experimental Conditions the volunteers will perform treadmill exercises sessions (30 minutes) in three different intensities (light, moderate and vigorous) and will respond to the Borg Scale at 10, 20 e 30 minutes. In the control condition the volunteers will be instructed to remain seated (quiet rest), relaxed and silent for 30 minutes. In both conditions, the volunteers will complete the Profile of Mood States (POMS) and State-Anxiety (STAY), 05 (five) minutes before and, 5 (five) and 20 (twenty) minutes following the interventions.

NCT03556176
Conditions
  1. Polymorphisms
  2. Exercise
  3. Mood
Interventions
  1. Behavioral: Exercise
  2. Behavioral: Quiet rest
MeSH:Anxiety Disorders

PCR will be performed with the following primers forward (GGCGTTGCCGCTCTGAATGC) and reverse (GAGGGACTGAGCTGGACAACCAC).. Detection of the polymorphism BDNF Val66Met SNP rs6265 genotype (G196A).

The BDNF Val66Met SNP rs6265 genotype (G196A) will be obtained, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with forward (5'-ACTCTGGAGAGCGTGAAT-3') and reverse (5'-ATACTGTCACAC ACGCTC-3') primers, and further digestion of the PCR product with NlaIII enzyme (Cat.

Primary Outcomes

Description: The POMS questionnaire is an instrument to evaluate mood states. It has 65 items and 6 domains: tension-anxiety, depression, anger-hostility, vigour-activity, fatigue, and confusion- bewilderment. The total mood disturbance score is derived by subtracting the vigour-activity score from the the sum of scores from the other subscales. The iceberg profile is characterized by low raw scores on the tension, depression, anger, fatigue, and confusion scales and above norms (the "water line") on vigor.

Measure: Response of mood states after interventions

Time: Change from 5 minutes before the treatments to 5 and 20 minutes after three exercise intensities and quiet rest

Description: Anxiety Inventory-STAI trait-state. The scales encompasses 20 items and provides a one-dimensional measurement of anxiety. Range of scores for each subtest is 20-80, the higher score indicating greater anxiety. A cut point of 39-40 has been suggested to detect clinically significant symptoms.

Measure: Response of anxiety after interventions

Time: Change from 5 minutes before the treatments to 5 and 20 minutes after three exercise intensities and quiet rest

Secondary Outcomes

Description: The Physical Activity Readiness Questionnaire (PAR-Q) was originally designed as a screening questionnaire to be self-administered before beginning physical activity. It has been designed to identify the small number of adults for whom physical activity may be inappropriate or those who should have medical advice concerning the type of activity most suitable for them.The people who to answer yes to one or more of seven questions will be advised to consult their doctors before increasing their physical activity. Those who to answer no to all questions will be included in the protocol study.

Measure: Evaluation safety or possible risk of exercising

Time: baseline

Description: Habitual Physical Activity Level (BAECKE):The Baecke Questionnaire was developed to measure habitual physical activity. The questionnaire includes items about household activities, sport, and leisure time activities over the past year. The Sport Index is divided into four categories (<1 h; 1-2 hrs; 2-3 hrs; 3-4 hrs and > 4 hrs) and each of these categories has an appropriate coefficient (0.5; 1.5; 2.5; 3.5 and 4.5) Usual daily activity and leisure activity are scored in a range of from 0 to 5. Global PA will be the sum of 3 indexes.

Measure: Habitual Physical Activity Level

Time: Baseline

Description: Beck Inventory Anxiety and Depression: The Beck Depression and Anxiety Inventory consists of a self-report questionnaires. These instruments are used to measure the severity of depressive and anxiety episodes.These instruments are widely used by health professionals and researchers in a variety of clinical and research settings. In the Beck Depression Inventory normal score are between 0 and 15; medium depression scores from 15 to 20 (dysphoria), and high depression scores over 20, and in the Beck Anxiety Inventory: 0-9: normal to minimal anxiety;10-18: mild to moderate anxiety;19-29: moderate to severe anxiety and 30-63: severe anxiety.

Measure: Evaluation of depression and anxiety symptoms

Time: Baseline

Description: McArdle Step Test was developed to estimate the aerobic capacity of university students. For the test the individual must ascend and descend a step during 3 min with different stepping rates for women and men (22 and 24 steps/min, respective

Measure: Estimation the aerobic capacity

Time: Baseline

Description: The detection of the polymorphism in the SLC6A4 gene will be done by the PCR-RFLP method: restriction fragment length polymorphism (RFLP), in which the PCR amplification of the flanking region of the SNP is followed by the digestion reaction with a specific restriction enzyme. The polymorphism of the SLC6A4 gene will be determined by the Polymerase Chain Reaction (PCR) and subsequent gel electrophoresis. PCR will be performed with the following primers forward (GGCGTTGCCGCTCTGAATGC) and reverse (GAGGGACTGAGCTGGACAACCAC).

Measure: Detection of the polymorphism in the SLC6A4

Time: Baseline

Description: The BDNF Val66Met SNP rs6265 genotype (G196A) will be obtained, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with forward (5'-ACTCTGGAGAGCGTGAAT-3') and reverse (5'-ATACTGTCACAC ACGCTC-3') primers, and further digestion of the PCR product with NlaIII enzyme (Cat. No. R0125S, New England Biolabs). From the five possible restriction fragments for this Val66Met amplicon, the genotype will be identified by the size and distribution of three bands: 243 bp for the G variant (Val), 168 bp and 75 bp bands for the A variant (Met), and these three bands for GA heterozygotes (Val/Met), on 2.5% (w/v) agarose gel electrophoresis.

Measure: Detection of the polymorphism BDNF Val66Met SNP rs6265 genotype (G196A)

Time: Baseline

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

6 Clinical, Psychological and Genetic Characteristics of Patients With Atopic Dermatitis and Psoriasis

Atopic dermatitis (AD) and psoriasis (PS) are chronic, relapsing dermatological disorders with a high rate of psychiatric co-morbid pathology represented with depression. Brain Derived Neurotrophic Factor (BDNF) belongs to the neurotrophin family and widely studied in pathophysiology of psychiatric and dermatological disorders. A biological stress response system by altered hypothalamic-pituitary-adrenal (HPA) axis as well hypothalamic-pituitary-gonadal (HPG) axis may contribute to dermatoses and psychiatric disorders development. Various factors including gender, genetic, psychological stress, socioeconomic factors also affect the course of dermatoses. A 10-week, case-control study evaluate clinical, psychological and biochemical parameters in AD and PS patients, and healthy control volunteers (HC) depending on gender and BDNF rs6265 gene polymorphism. All parameters are evaluated twice: at disease exacerbation (study baseline) and week 10. The following methods are conducted: assessment of dermatological status, using Scoring of Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI); assessment of depression and anxiety according to DSM-V criteria and with Hamilton Depression Rating Scale (HAM-D) and with Hamilton Anxiety Rating Scale (HAM-A); analysis of serum BDNF (ng/ml), cortisol (nmol/L), testosterone (ng/dL) and IgE levels (IU/ml, AD only); DNA extraction and genotyping of BDNF variants.The study will last during 4-5 months.

NCT03831646
Conditions
  1. Atopic Dermatitis
  2. Psoriasis
MeSH:Dermatitis, Atopic Psoriasis Dermatitis Eczema
HPO:Atopic dermatitis Eczema Eczematoid dermatitis Inflammatory abnormality of the skin Palmoplantar pustulosis Psoriasiform dermatitis

A 10-week, case-control study evaluate clinical, psychological and biochemical parameters in AD and PS patients, and healthy control volunteers (HC) depending on gender and BDNF rs6265 gene polymorphism.

DNA extraction and genotyping the BDNF rs6265 (Val66Met) gene polymorphism in AD, PS and HC.

Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC in accordance with BDNF rs6265 gene polymorphism and gender.

Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC divided into BDNF rs6265 gene polymorphism (Val/Val; Val/Met; Met/Met) and gender (males, females) at study baseline and week 10.

Correlation analysis of dermatological, psychological and biochemical parameters in EAD, IAD and PS patients, and HC divided into groups in accordance with BDNF rs6265 gene polymorphism (Val/Val; Val/Met; Met/Met) and gender (males, femaes).

This study evaluate clinical, psychological and biochemical parameters in AD and PS patients depending on gender and BDNF rs6265 gene polymorphism.

Primary Outcomes

Description: Assessment of atopic dermatitis severity is conducted using Scoring of Atopic Dermatitis (SCORAD) index. SCORAD index formula is: A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The maximum SCORAD score is 103. SCORAD <23 - mild AD; SCORAD from 23 to 63 - moderate AD; SCORAD> 63 - severe AD.

Measure: Assessment of change in the severity of atopic dermatitis after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and at week 10

Description: Assessment of the psoriasis severity is conducted using Psoriasis Area and Severity Index (PASI). The patient's body is divided into four sections (head (H) (10% of a person's skin); arms (A) (20%); trunk (T) (30%); legs (L) (40%)). The percent of skin lesions of each area is assessed as follows: 0 (0% of involved area); 1 (< 10%); 2 (10-29%); 3 (30-49%); 4 (50-69%); 5 (70-89%); 6 (90-100%). Further, for each region, the intensity of 3 clinical signs is evaluated - redness, thickness and scaling and assessed as follows: 0 - no lesions,1 - easy, 2 - moderate, 3 - severe, 4 - very severe. The sum of all three severity parameters is calculated for each section, multiplied by the area score for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 0.3 for body, 0.4 for legs). PASI range is from 0 (no disease) to 72 (maximum disease). The severity of psoriasis is assessed as follows: PASI <20 - mild; PASI from 20 to 50 - moderate; PASI> 50 - severe

Measure: Assessment of change in the severity of psoriasis after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and at week 10

Description: Depression is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Depression Rating Scale (HAM-D) using the following ranges: absence, ≤7; mild, 8-16; moderate, 17-27; severe, ≤28

Measure: Assessment of change in the severity of depression in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and week 10

Description: Depression is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Depression Rating Scale (HAM-D) using the following ranges: absence, ≤7; mild, 8-16; moderate, 17-27; severe, ≤28

Measure: Assessment of the severity of depression in healthy controls (HC)

Time: At disease onset (study baseline)

Description: Anxiety is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Anxiety Rating Scale (HAM-A) using the following ranges: ≤17, easy; 18-24, moderate; over 25, medium-severe

Measure: Assessment of change in the severity of anxiety in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10

Time: At disease onset (study baseline) and week 10

Description: Anxiety is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Anxiety Rating Scale (HAM-A) using the following ranges: ≤17, easy; 18-24, moderate; over 25, medium-severe

Measure: Assessment of the severity of anxiety in HC

Time: At disease onset (study baseline)

Description: The total IgE levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 0.000-100.0 IU/ml

Measure: Evaluation of changes in serum immunoglobulin E (IgE, IU/ml) levels from study onset (baseline) at week 10 in atopic dermatitis patients

Time: At disease onset (study baseline) and week 10

Description: The total IgE levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 0.000-100.0 IU/ml

Measure: Analysis of serum IgE (IU/ml) levels in HC

Time: At disease onset (study baseline)

Description: Serum BDNF levels are analyzed using a solid-phase, sandwich, two-site, ELISA (Promega, US; G7610). No measurement scale is used

Measure: Evaluation of changes in serum Brain Derived Neurotrophic Factor (BDNF, ng/ml) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients

Time: At disease onset (study baseline) and week 10

Description: Serum BDNF levels are analyzed using a solid-phase, sandwich, two-site, ELISA (Promega, US; G7610). No measurement scale is used

Measure: Analysis of serum BDNF (ng/ml) levels in HC

Time: At disease onset (study baseline)

Description: The total cortisol levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 138-690 nmol/L

Measure: Evaluation of changes in cortisol (nmol/L) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients

Time: At disease onset (study baseline) and week 10

Description: The total cortisol levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 138-690 nmol/L

Measure: Analysis of serum cortisol (nmol/L) levels in HC

Time: At disease onset (study baseline)

Description: The total testosterone levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: men 20-49 years - 72 -853ng/dL; men≥50 years -129-767 ng/dL; women ovulating - 0.010-73.0 ng/dL; women postmenopausal - 0.010-43.0 ng/dL.

Measure: Evaluation of changes in testosterone (ng/dL) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients

Time: At disease onset (study baseline) and week 10

Description: The total testosterone levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: men 20-49 years - 72 -853ng/dL; men≥50 years -129-767 ng/dL; women ovulating - 0.010-73.0 ng/dL; women postmenopausal - 0.010-43.0 ng/dL.

Measure: Analysis of serum testosterone (ng/dL) levels in HC

Time: At disease onset (study baseline)

Description: DNA extraction and genotyping the BDNF rs6265 (Val66Met) gene polymorphism in AD, PS and HC

Measure: DNA extraction in AD, PS and HC

Time: At disease onset (study baseline)

Secondary Outcomes

Description: EAD and IAD patients will be divided into subgroups in accordance with BDNF gene polymorphism and gender with following assessment of SCORAD scores compared with baseline after conventional treatment at week 10 in each group using unpaired t-test

Measure: Assessment and comparison (Unpaired t-test) of SCORAD scores in extrinsic atopic dermatitis (EAD, IgE level above the normal) and intrinsic atopic dermatitis (IAD, normal IgE level) patients compared with baseline after conventional treatment at week 10

Time: At disease onset (study baseline) and week 10

Description: Psoriasis patients will be divided into subgroups in accordance with BDNF gene polymorphism and gender with following assessment of PASI scores compared with baseline after conventional treatment at week 10 in each group.

Measure: Assessment and comparison (Unpaired t-test) of PASI scores in psoriasis patients compared with baseline after conventional treatment at week 10 in accordance with BDNF gene polymorphism (Val/Val; Val/Met;Met/Met) and gender(males, females)

Time: At disease onset (study baseline) and week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of HAM-D scores in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of HAM-D scores in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-D scores in EAD, IAD, PS and HC

Time: At disease onset (study baseline) and week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of HAM-A scores in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of HAM-A scores in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-A scores in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of serum BDNF(ng/ml) levels in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of serum BDNF levels in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum BDNF (ng/ml) levels in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for comparisons of serum cortisol (nmol/L) levels in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of serum cortisol levels in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum cortisol (nmol/L) levels in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of serum testosterone (ng/dL) levels in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of serum testosterone levels in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum testosterone (ng/dL) levels in EAD, IAD,PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC divided into BDNF rs6265 gene polymorphism (Val/Val; Val/Met; Met/Met) and gender (males, females) at study baseline and week 10

Measure: Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC in accordance with BDNF rs6265 gene polymorphism and gender

Time: At disease onset (study baseline) and at week 10

Description: Unpaired, two-way ANOVA and Bonferroni means separation tests will be used for multiple comparisons of testosterone/cortisol ratio in EAD, IAD and PS patients and HC divided into subgroups in accordance with BDNF gene polymorphism and gender at disease onset (baseline) and week 10. Comparisons will include assessment of testosterone/cortisol ratio in all patients at baseline and week 10 compared with HC, and assessment of data changes at week 10 compared with baseline

Measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of testosterone/cortisol ratio in EAD, IAD, PS and HC

Time: At disease onset (study baseline) and at week 10

Description: Correlation analysis of dermatological, psychological and biochemical parameters in EAD, IAD and PS patients, and HC divided into groups in accordance with BDNF rs6265 gene polymorphism (Val/Val; Val/Met; Met/Met) and gender (males, femaes)

Measure: Correlation analysis of studied parameters in dermatological patients and HC

Time: At disease onset (study baseline) and week 10

7 Efficacy and Effectivity of Long Term Home Based tDCS in Fibromyalgia: an Explanatory Randomized Clinical Trial

Fibromyalgia(FM) is a widespread musculoskeletal pain syndrome characterized by fatigue, sleep disorders, cognitive impairment, depressive symptoms and neuro-vegetative symptoms. It is a multivariable and complex neurobiological process. FM worldwide prevalence according to American College of Rheumatology (ACR) 2010 diagnostic criteria is estimated under 5,4%. In USA the burden caused by FM is estimated at 29 billions every year, due to assistance, health care costs and retirement to loss of productivity. It is known that conventional pharmacological approaches present poor therapeutic response in more than 50% of these patients. It is conceivable that this limited results, at least in part, due to the lack of a complete elucidation of its pathophysiology. Our hypothesis is that tDCS has a superior effect on clinical outcomes, functional capacity, cortical excitability, and psycho-affective functions compared to simulated treatment. In order to respond to the objectives of this study, a randomized, parallel-blinded clinical trial will be conducted. FM patients will be randomized to receive tDCS with anodic pole on the primary motor cortex and the cathode pole on the contralateral prefrontal cortex.

NCT03843203
Conditions
  1. Fibromyalgia
  2. Transcranial Direct Current Stimulation
Interventions
  1. Device: Transcranial Direct Current Stimulation - tDCS
MeSH:Fibromyalgia Myofascial Pain Syndromes

Blood samples will be collected at baseline in order to determine BDNF gene polymorphism for the G allele (rs6265).

Primary Outcomes

Description: Change from before and after the First phase of treatment on Pain scores assessed by a visual analogue scale (VAS 0 to 100mm) (0 means no pain - 100 means the worst pain imaginable)

Measure: Change in pain level - first phase

Time: 1 month

Description: Change from before and after the First phase of treatment on Total score on the Brazilian Profile of Chronic Pain: Screen (BPCP:S) (range from 0 to 93; high numbers means more pain severity, interference in daily activities and emotional burden)

Measure: Change in functional capacity - first phase

Time: 1 month

Secondary Outcomes

Description: Change from before and after the Second phase of treatment on Pain scores assessed by a visual analogue scale (VAS 0 to 100mm) (0 means no pain - 100 means the worst pain imaginable)

Measure: Change in pain level - second phase

Time: 3 months

Description: Change from before and after the First phase of treatment on Total score on the Brazilian Profile of Chronic Pain: Screen (BPCP:S) (range from 0 to 93; high numbers means more pain severity, interference in daily activities and emotional burden)

Measure: Change in functional capacity - second phase

Time: 3 months

Description: Change from before and after the First phase of treatment on the score in a numerical pain scale (NPS 0-10) for a moderate heat pain stimulus to the right arm (ventral region) during a conditioned pain modulation task (CPM-task), where participant keeps the counter-lateral hand in an iced cold water (0 to 1º Celsius)

Measure: Change in Function of modulatory descending system

Time: 1 month

Description: Change from before and after the First phase of treatment on measures of motor threshold (MT), motor evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP) assessed with transcranial magnetic stimulation (TMS).

Measure: Change in Function of corticospinal pathway

Time: 1 month

Description: Blood samples will be collected at baseline and after the First phase of intervention in order to determine BDNF serum levels using a standardized kit

Measure: Change in levels of Brain derived neurotrophic factor - BDNF

Time: 1 month

Description: Blood samples will be collected at baseline in order to determine BDNF gene polymorphism for the G allele (rs6265)

Measure: Polymorphism of Brain derived neurotrophic factor - BDNF

Time: 10 minutes

8 Interventional Study of Expiratory Muscle Strength Training as a Treatment in Neuromuscular Disorders

The purpose of this study is to investigate the impact of expiratory muscle strength training (EMST) on the swallowing, breathing, oral intake, quality of life and cough function of people with oculopharyngeal muscular dystrophy (OPMD).

NCT04009408
Conditions
  1. Oculopharyngeal Muscular Dystrophy
  2. Muscular Dystrophies
  3. Myopathy; Hereditary
Interventions
  1. Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
MeSH:Muscular Dystrophies Muscular Diseases Muscular Dystrophy, Oculopharyngeal Neuromuscular Diseases
HPO:Muscular dystrophy Myopathy

We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status.

Primary Outcomes

Description: Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. A lower score is a better outcome.

Measure: Global Swallowing Function

Time: Change in score from week 0 to week 5

Secondary Outcomes

Description: Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening.

Measure: Global Swallowing Function

Time: Change in score from week 0 to week 15; change in score from week 5 to week 15.

Description: MEP is a measure of respiratory muscle strength and is assessed with a handheld manometer, measured in centimetres of water (cmH2O). A higher score is a better outcome.

Measure: Maximum expiratory pressure (MEP)

Time: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.

Description: Measure of cough strength that is assessed using a spirometer, measured in litres per minute (L/min). A higher score is a better outcome.

Measure: Volitional cough strength (peak cough flow)

Time: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.

Description: Measure of how much air is exhaled during forced exhalation and is assessed with a spirometer, measured in litres. A higher score is a better outcome.

Measure: Forced vital capacity (FVC)

Time: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.

Description: A measure daily nutritional and hydration consumption. Oral intake is assessed using the Functional Oral Intake Scale (FOIS), a validated 7-point ordinal scale (1 = no oral intake; 2 = tube dependent with minimal/inconsistent oral intake; 3 = tube supplements with consistent oral intake; 4 = total oral intake in single consistency; 5 = total oral intake of multiple consistencies requiring special preparation; 6 = total oral intake with no special preparation, but must avoid specific foods or liquid items; 7 = total oral intake with no restrictions). A higher score is a better outcome.

Measure: Oral Intake

Time: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.

Description: Will be measured using the Eating Assessment Tool-10 (EAT-10), a self-administered, symptom-specific outcome instrument for dysphagia. The EAT-10 allows patients to rate their swallowing symptoms on scale of 0 = no problem to 4 = severe problem. A lower score is a better outcome.

Measure: Self-perceived swallowing impairment

Time: Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.

Description: An optional blood sample will be collected for biomarker analysis, to identify correlations with clinical response. We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status. For these 5 genetic biomarkers, participants will be scored as having zero, one, or two alleles. This information will be used in subgroup analyses for the primary and secondary outcomes.

Measure: Biomarker analyses

Time: Baseline measurement (week 0)

9 Stroke Rehabilomics Study: Epigenetics and Genetics Characterization of the BDNF and SLC6A4 Genes in Patients Undergoing Robotic Rehabilitation Treatment

Stroke is associated with disability and impaired quality of life. Persistent motor impairment is common with incomplete recovery of motor function after rehabilitation, mainly in the upper limbs (UL). Robot-mediated therapy (RMT) has been proposed as a viable approach for the rehabilitation of the UL, but more rigorous studies are needed to tailor rehabilitation and to better address the treatment. Brain-derived neurotrophic factor (BDNF) and the serotonin transporter gene (SLC6A4) have been shown to play an important role in post-stroke recovery. After ischemic stroke, disruption and subsequent reorganization of functional brain connections occur both locally and far from the lesion, with the latter possibly contributing to function recovery. This project aims to assess whether epigenetic and genetic variations of BDNF and SLC6A4 can occur in stroke patients after robotic rehabilitation treatment. This study will allow to identify potential genetic and epigenetic biomarkers in post-stroke rehabilitation that could be used to predict the response to a specific rehabilitation treatment and to choose the optimal treatment for the patient (Rehabilomics).

NCT04223180
Conditions
  1. Stroke
Interventions
  1. Device: Robotic assisted intervention
MeSH:Stroke
HPO:Stroke

Presence/absence of rs6265 in the BDNF.

BDNF rs6265 polymorphism will be analyzed using HpyCH4IV restriction enzyme which identifies homozygous Valine/Valine, heterozygous Valine/Methionine and homozygous Methionine/Methionine.

Moreover, the investigators will also detect BDNF rs6265 and SLC6A4 5-HTTLPR polymorphisms.

Moreover, BDNF rs6265 polymorphism will be analyzed using HpyCH4IV restriction enzyme which identifies homozygous Valine/Valine, heterozygous Valine/Methionine and homozygous Methionine/Methionine.

Primary Outcomes

Description: BDNF rs6265 polymorphism will be analyzed using HpyCH4IV restriction enzyme which identifies homozygous Valine/Valine, heterozygous Valine/Methionine and homozygous Methionine/Methionine

Measure: Presence/absence of rs6265 in the BDNF

Time: Baseline (T0)

Description: SLC6A4 5-HTTLPR polymorphism will be analyzed by a specific protocol that identifies gene polymorphisms according to the polymerase chain reaction (PCR) fragment sizes: short [S; 486 base pairs (bp), 14 repeats], long [L; 529bp, 16 repeats], or extra-long [XL; 612 or 654bp, 20 or 22 repeats].

Measure: Presence/absence of 5-HTTLPR in the SLC6A4

Time: Baseline (T0)

Secondary Outcomes

Description: Promoter methylation of BDNF using pyrosequencing analysis with PyroMark Q24 (Qiagen, Germany).

Measure: Change in promoter methylation levels of BDNF gene

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: Promoter methylation of SLC6A4 using pyrosequencing analysis with PyroMark Q24 (Qiagen, Germany).

Measure: Change in promoter methylation levels of SLC6A4 gene

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Other Outcomes

Description: The FMA-UL is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, sensation and joint functioning in patients with post-stroke hemiplegia. The upper limb portion of the FMA-UL ranges from 0 (hemiplegia) to 66 points (normal upper limb motor performance).

Measure: Change in Fugl-Meyer Assessment of Motor Recovery after Stroke for Upper Extremity portion (FMA-UL)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The BI is designed to assess the ability of an individual with a neuromuscular or musculoskeletal disorder to care for him/herself. It ranges from 0 to 100, with a higher number meaning better performance in activities of daily living.

Measure: Change in Modified Barthel Index (BI)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The Motricity Index is used to measure strength in upper extremities and ranges from 0 to 100, with higher scores meaning higher strength.

Measure: Change in Motricity Index (MI)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: SDMT evaluates information processing speed. It consists of a simple task of replacing symbols with numbers. Using a reference key, the patient has 90 seconds to match a sequence of symbols with the correspondent numbers as rapidly as possible. Both written or oral administration can be used.

Measure: Change in Symbol Digit Modalities Test (SDMT)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The TOL test is a tool to assess strategic decision and problem solving. The patient is required to move different colored balls on the three pegs of different lengths, according to a model and a number of established moves. The maximum time for each configuration is 60 seconds.

Measure: Tower of London (TOL)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The ROCF is a neuropsychological assessment for evaluation of visuospatial abilities, memory, attention, planning, working memory and executive functions. The patient is required to copy a complex figure freehand (recognition), and then draw it from memory (recall). The score is assigned based on the correctness of each line (from 0 to 2).

Measure: Change in Rey-Osterrieth Complex Figure Test (ROCF).

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The DS is a test that measures the verbal memory span (digit memory). The patient is required to correctly repeat the sequence of number listened. It is composed by two different tests: the Digits Forward and the Digit Backward. The range for Digit Forward is from 6 to -1.

Measure: Change in Digit Span (DS)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The SCWT is a neuropsychological test used to assess the cognitive interference. The patient is required to read three different tables as fast as possible (in 30 seconds): the first contains 100 names of colors ink in black; the second contains 100 shapes of different colors (red, blue, green); the third contains 100 color-words are printed in an inconsistent color ink (for instance the word "red" is printed in green ink).

Measure: Change in Stroop and Color Word test (SCWT)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Description: The BBT is a tool to measure unilateral gross manual dexterity. Patients are seated at a table, in front of a rectangular box with a partition in the middle. 150 colored, wooden blocks are placed in one compartment. Patients are required to move as many blocks as possible, one at time, from one compartment to the other in a period of 60 seconds. BBT is scored by counting the number of blocks carried over from a compartment to the other one. At the beginning, patients perform a one-minute trial period. Patients have to perform the BBT with both hands.

Measure: Change in Box and Block test (BBT)

Time: Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

10 University of Iowa Interventional Psychiatry Service Patient Registry

The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and autonomic nervous system measures (i.e. "fight-or-flight" response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient ("personalized medicine").

NCT04480918
Conditions
  1. Treatment Resistant Depression
  2. Major Depressive Episode
  3. Major Depression
  4. Major Depressive Disorder
  5. Bipolar Disorder
  6. Bipolar Depression
Interventions
  1. Device: Electroconvulsive Therapy (ECT)
  2. Device: Transcranial Magnetic Stimulation (TMS)
  3. Drug: Ketamine
  4. Drug: Esketamine
MeSH:Disease Depression Depressive Disorder Depressive Disorder, Major Bipolar Disorder Depressive Disorder, Treatment-Resistant
HPO:Bipolar affective disorder Depressivity Mania

Data on genetic polymorphisms (differences) that have been demonstrated or hypothesized to play a functional role in major depression, e.g. the brain derived neurotrophic factor (BDNF) rs6265 (val66met) single nucleotide polymorphism, will be obtained.

Primary Outcomes

Description: The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms.

Measure: Montgomery-Åsberg Depression Rating Scale (MADRS) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Secondary Outcomes

Description: The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of "not assessed." Item 3 is rated on a 4-point Likert scale from "none" to "outweighs therapeutic effect." Items 1 and 3 are assessed in relation to last clinical encounter (if possible).

Measure: Clinical Global Impression/Severity (CGI) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The GAD-7 is the self-reported anxiety questionnaire which scores each of the 7 symptoms of Generalized Anxiety Disorder in the last two weeks on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("over half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."

Measure: Generalized Anxiety Disorder, 7-item (GAD-7) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The MoCA is a 30-point screening instrument for detecting cognitive dysfunction. It is used to assess the following cognitive domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed (short-term memory recall), and orientation.

Measure: Montreal Cognitive Assessment (MoCA) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The PHQ-9 is the self-reported depression module of the PHQ, which scores each of the 9 symptoms of a major depressive episode on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("more than half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."

Measure: Patient Health Questionnaire, 9-item (PHQ-9) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The TCI is a 240-item questionnaire. It operates with seven dimensions of personality traits, i.e. four so-called temperaments: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS), and three so-called characters: Self-Directedness (SD), Cooperativeness (CO) and Self-Transcendence (ST). Each of these traits has a varying number of subscales.

Measure: Temperament and Character Inventory (TCI) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Other Outcomes

Description: The patient will be asked to continuously wear a Fitbit wristband to monitor gross motor activity, e.g. foot steps. Changes in gross motor activity throughout the day will also provide data on circadian rhythmicity (sleep-wake cycles).

Measure: Actigraphy Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, and DNA will be isolated and extracted. Data on genetic polymorphisms (differences) that have been demonstrated or hypothesized to play a functional role in major depression, e.g. the brain derived neurotrophic factor (BDNF) rs6265 (val66met) single nucleotide polymorphism, will be obtained. These genotypes (genetic data) will then be correlated with antidepressant response.

Measure: Candidate Gene (DNA) Polymorphisms

Time: The genetic specimen will be obtained within approximately 1 week of starting treatment (likely with the baseline epigenetic sample.

Description: The investigators will obtain task-free ("resting state") rs-EEG [detecting electrical signals in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.

Measure: Electroencephalography (EEG) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, at baseline and in response to interventional treatments for treatment-resistant depression. DNA will be isolated and extracted. Data on epigenetic (experience-based) modifications to the DNA that have been demonstrated or hypothesized to play a functional role in major depression, e.g. global methylation changes, will be obtained. Changes in epigenetic status, e.g. global DNA methylation changes pre- and post-treatment, will then be correlated with antidepressant response.

Measure: Epigenetic (Experience-Based) DNA Modifications Pre-Post Change

Time: The initial specimen will be obtained within approximately 1 week of starting treatment. The post-specimen will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: Facial recognition software, FaceX (FaceX LLC) will be used to record and analysis facial features at rest and evoked by interview questions and emotionally provocative videos.

Measure: Facial Expression Analysis Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: Galvanic skin response as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.

Measure: Galvanic Skin Response Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: Heart rate variability as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.

Measure: Heart Rate Variability Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The NIH Toolbox is a comprehensive set of neurobehavioral assessments that assess multiple neuropsychiatric domains. We will perform the cognitive and emotional batteries in this study.

Measure: National Institutes of Health (NIH) Toolbox(R) Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: Pupillometry (pupil diameter measurements) as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.

Measure: Pupillometry Pre-Post Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The investigators will obtain task-free ("resting state") rs-fMRI [detecting blood oxygen-level dependent (BOLD) signal in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.

Measure: Resting State Functional Magnetic Resonance Imaging (rs-fMRI) Pre-Post Change

Time: The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The investigators will obtain structural brain imaging at baseline and in response to interventional treatments for treatment-resistant depression.

Measure: Structural Magnetic Resonance Imaging (MRI) Pre-Post Change

Time: The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).

Description: The patient will be asked to read standardized passages, i.e. Grandfather Passage and Rainbow Passage, and answer questions about daily life and interests while being recorded. These recordings will be transcribed and analyzed for vocal tone, inflection, word choice, etc.

Measure: Vocal Pattern Detection Pre, During and Post-Change

Time: Pre-assessment will be obtained within approximately 1 week of starting treatment. Interim assessments will occur weekly during treatment. Post-assessment will be obtained as close as possible following completion of treatment course.

11 A Virtual Reality Intervention to Improve Attention in Heart Failure Patients

Heart failure is a prevalent and serious public health concern with the growing aging population. Patients with heart failure often experience attention impairment that decreases their ability to perform self-care and diminishes their health-related quality of life. In past studies, 15 - 27% of heart failure patients had attention impairment. Attention is fundamental to human activities including self-care management of heart failure. However, cognitive interventions focusing on attention are scarce in heart failure literature. This study focuses on developing a novel cognitive intervention specifically targeting improved attention and testing its efficacy on improving attention, self-care, and health-related quality of life. The investigators in this study are asking the following 3 questions: 1) does the newly developed cognitive intervention using immersive virtual reality technology (Nature-VR) improve attention compared with the control condition (Urban-VR)?; 2) does Nature-VR intervention improve HF self-care and health-related quality of life compared with Urban-VR control condition?; and 3) are selected biological factors associated with attention function in HF? The virtual reality-based cognitive intervention (Nature-VR) can be an efficacious intervention for the patients to use and enjoy without burdening already reduced attention. This study has great potential to improve attention and prevent attention impairment, thereby leading to healthier lives among heart failure patients.

NCT04485507
Conditions
  1. Heart Failure
  2. Cognitive Dysfunction
Interventions
  1. Other: Nature-VR
  2. Other: Urban-VR
MeSH:Heart Failure Cognitive Dysfunction
HPO:Abnormal left ventricular function Cognitive impairment Congestive heart failure Mental deterioration Right ventricular failure

The frequency of BDNF Val66Met genotype (e.g., rs6265) will be examined and attention will be examined by the genotype.. Apolipoprotein (APOE) gene.

Primary Outcomes

Description: Performances on the computerized cognitive test of Multi-Source Interference Task will be examined in terms of speed and accuracy. Participants are instructed to identify the target number, which is different than the other 3 numbers provided on the computer screen. There are two types of trials, congruent and incongruent. Congruent trials have a target number that is always matched its position on the button (e.g., 100, 020, or 223), in contrast, incongruent trials have the target number that is never matched with it position in the button (e.g., 010, 233, or 232). Faster response time and lower error rates indicate better attention.

Measure: Changes in attention - Multi-Source Interference Task

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Description: Participants are instructed to remember the sequence of numbers the data collector told and repeat the numbers right after the instructor finished talking. This test has 2 subsets, Forward-repeat exactly the same sequence, and Backward-repeat the numbers in the backward from last to the first. More digits correctly repeated indicate better attention.

Measure: Changes in attention - Digit Span Test

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Description: This traditional cognitive test of attention is a paper-pencil based measure and has 2 parts. Part A requires participants to connect a series of randomly arrayed, distinct circles numbered 1 to 25 in correct order as quickly as possible. Part B requires participants to connect a series of 25 circles numbered 1 to 13 randomly intermixed with letters from A to L, alternating between numbers and letters, and proceeding in ascending order (e.g., 1-A-2-B-3 and so on). Faster response time in seconds indicates better attention.

Measure: Changes in attention - Trail Making Test

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Description: Stroop Test is a color-word test measuring the ability to processe different visual features and ignore distractions. The test has 2 parts of reading letters of color names and colors of color names using 4 color names (i.e., red, blue, yellow, and green). Congruent trials have the same letters and colors of the color names (i.e., red in red color). Incongruent trials have different letters and colors of the color names (i.e., red in blue color). Faster response time and lower error rates indicate better attention.

Measure: Changes in attention - Stroop Test

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Description: This self-reported questionnaire has 13 items on 0 to 10 response scales asking effectiveness in behaviors requiring attention. Higher scores indicate better subjective attention

Measure: Changes in attention - Attentional Function Index

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Secondary Outcomes

Description: This self-reported questionnaire consists of 29 items divided into 3 scales measuring self-care maintenance, symptom perception, and self-care management. In addition, self-care confidence is measured by additional 10 items. Each scale is scored separately and standardized to achieve a possible score of 0 to 100. Higher scores indicate better self-care of HF.

Measure: Changes in the Self-Care of Heart Failure Index (SCHFI)

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Description: Minnesota Living with Heart Failure Questionnaire will be used to measure health-related quality of life. This self-report questionnaire consists of 21 items on which patients are asked to rate how their HF condition impacted their physical and emotional health. Lower scores indicate better HRQL.

Measure: Changes in Minnesota Living with Heart Failure Questionnaire (LHFQ)

Time: Baseline, 4 weeks, 8 weeks, and 26 weeks

Other Outcomes

Description: Venipuncture will be performed to draw the blood by following Indiana University general laboratory safety guidelines. Changes in the serum BDNF levels (ng/ml) and its associations with attention will be examined.

Measure: Changes in serum brain-derived neurotrophic factor levels (serum BDNF)

Time: Baseline and 4 weeks

Description: Venupucture will be performed to draw the blood for the possible genetic biomarker. The frequency of BDNF Val66Met genotype (e.g., rs6265) will be examined and attention will be examined by the genotype.

Measure: BDNF gene

Time: Baseline

Description: Venupucture will be performed to draw the blood for the possible genetic biomarker. The 3 common allele of APOE (i.e., e2, e3, and e4) will be examined. The frequency of APOE genotypes (e.g., rs7412, rs429358) will be examined and attention will be examined by the genotype.

Measure: Apolipoprotein (APOE) gene

Time: Baseline

Description: Venupucture will be performed to draw the blood for the possible genetic biomarker. Specifically, dopamine receptor gene 4 (e.g., 48 bp VNTR) polymorphism and its association with attention will be examined.

Measure: Dopamine receptor gene

Time: Baseline

Description: Venupucture will be performed to draw the blood for the possible genetic biomarker. The dopamine transporter gene (DAT1) (e.g., rs28363170 - 40 bp VNTR) polymorphism and its association with attention will be examined.

Measure: Dopamine transporter gene

Time: Baseline


HPO Nodes


HP:0000716: Depressivity
Genes 461
EZR TGIF1 ND6 PROK2 COL7A1 NODAL TOR1A CACNA1G VPS35 NSUN2 GTF2IRD1 SLC20A2 CHD7 COL7A1 TACR3 SHH ST3GAL3 ARVCF NR4A2 CEP85L RREB1 AARS2 GNA11 ATXN10 FMO3 TCF4 POLG ATXN8OS AIMP1 C9ORF72 LRRK2 PSAP FGF8 CYP27A1 DCTN1 GAS1 GBA TGFBR2 PODXL FOXH1 CLIP2 VPS13C TBK1 HIRA CC2D1A GP1BB GNAS PDGFRB VAPB ABCA7 MEN1 COX1 DLL1 HARS1 SEC24C SIX3 GABRG2 ELN PIK3CA PAH POLG GNAS TWNK GNRH1 THOC2 MBOAT7 VCP PMS2 FOXH1 SLC6A4 GABRG2 POLG PDGFB CBL CDON AP2S1 GAS1 MAPT TARDBP TRNW TMEM106B MATR3 TTC19 DNAJC5 TRNL1 BCS1L CBS FRRS1L KRAS JRK GLA CDON PDGFRB SHH DISP1 PRPH ZIC2 AMACR DISP1 SLC25A4 MAN1B1 DNA2 GBA GSN FOXH1 GNRHR TDGF1 KDM5B FAN1 ADH1C VPS13A XK CEP78 TRNS1 GLI2 FGF8 TRNH ATP13A2 NEFH CSF1R COASY FMR1 ATXN8 ATXN2 FGFR1 ARSA CLCN4 USP8 TRNS2 TBC1D7 ND1 ND4 HTR2A DISP1 PANK2 STAG2 CCNF GPR101 SIX3 TRNQ PRNP ZC3H14 DCPS CISD2 HTT HNMT SLC2A3 MSH6 USH1C DNMT1 VCP ZIC2 CACNA1H MSTO1 C9ORF72 KCNJ2 HMBS MSH2 MED23 FGF8 KCNT1 PER2 SHH USH2A USH1G DRD2 PTPN22 NODAL ERBB4 PPT1 PTCH1 DAO ZIC2 TRNF CDH23 THOC2 MED25 HTT DLL1 LINS1 WASHC4 TRNS2 TUSC3 TET3 PLA2G6 MYO7A CDON CHCHD10 PSEN1 EPM2A PINK1 ARSG EPHA4 CHCHD10 CHMP2B ANOS1 CDKN1B PDZD7 MAN2B1 PTCH1 SLC45A1 DNAJC6 GLI2 PER3 ATXN10 TAF15 ADGRV1 SNCA HLA-DQB1 SLC2A1 FGF8 C19ORF12 TSC2 PRKN OPTN POLG2 MAPK1 CARS1 POLG WDR11 PDCD1 FGFR1 PPP2R2B PCDH15 FLT4 TECR SGCE DNAJC13 COQ2 B3GALNT2 RPS20 GLE1 SQSTM1 SPRY4 CACNA1G FA2H CDKN2C NHLRC1 SNCA UNC13A DGUOK CPOX TBK1 CDH23 FGF14 PFN1 PRNP MAPT CLRN1 JMJD1C RSRC1 TBX1 FBXO31 PTS EPCAM PON2 TNIK TBL2 TBX1 PDGFRB ATRX TAC3 PANK2 TARDBP FMR1 EHMT1 PRNP CLIP1 RFC2 DCTN1 SARS1 TRAPPC9 FGF14 SNCA RRM2B LIMK1 KISS1 NOTCH3 XPR1 FIG4 TWNK SIX3 CRBN GLI2 SMPD1 HLA-DQB1 CRKL PMS1 CDKN2B HTRA2 SPAST HS6ST1 PDE11A C9ORF72 MST1 SLC18A2 FGFR1 RPS6KA3 WFS1 CDON DNMT1 SRSF2 LMNB1 PRSS12 GABRB3 EDC3 POLG TRNS1 ZIC2 CLCN4 KCTD17 GBA TK2 CFAP410 MLH1 VCP COX2 GABRA1 FOXH1 PARK7 SYNJ1 COX3 EIF4G1 PON1 HNRNPA1 LRRK2 IDUA FGF8 GRIK2 POLG PRKCG NDST1 TGIF1 DUSP6 ATXN2 RRM2B SMC1A WFS1 PRNP TDGF1 TSC1 STX16 GIGYF2 ATP1A3 PTCH1 ATP1A3 HMBS GLI2 ARMC5 KCTD17 SEMA4A GLUD2 GAS1 HTT TET2 TBP GAS1 ASXL1 DMPK CASR PDGFB PRNP CIB2 UFD1 COQ2 TGIF1 GLT8D1 TREX1 VCP ARMC5 GTF2I MECP2 TWNK KISS1R LMAN2L GRIN2A PTCH1 RUNX1 ANG PIGC NSMF GNAS TWNK TDGF1 ANXA11 SGCE GCH1 FUS AIP TGIF1 BMPR1A UBQLN2 CTSF OCRL PON3 CHMP2B METTL23 ESPN CLN6 TDGF1 TRNL2 IQSEC1 TRNL1 PRKACA PRNP C9ORF72 DLL1 GRN PGAP1 GDAP2 TRNN SHH MSTO1 SIX3 SNCAIP MLH3 ND5 SRPX2 STAG2 NEK1 WHRN TBP TREM2 GNAS MMP1 C12ORF4 FMN2 PPARGC1A SQSTM1 HLA-DRB1 PINK1 ATP7B TREM2 BCR TOR1A SOD1 C9ORF72 NODAL GNAS DCTN1 PRKAR1A AFG3L2 GPR35 BAZ1B DLL1 PLA2G6 CDKN1A MAN2B1 COMT CRADD PROKR2 MAPT FUS MYO7A JPH3 NODAL FGF17 PAH UCHL1 DISP1 ATXN8OS
HP:0003198: Myopathy
Genes 485
TRNH CHRNA1 PGAM2 NODAL ND6 CSRP3 TRNL1 HSPG2 ACTN2 BAG3 PSEN1 ACADS TRNK NDUFAF4 GTF2IRD1 TRNC NEB HNRNPA2B1 PUS1 SLC25A4 FGFR1 COL6A2 FKRP TRNS2 SHH SDHD STIM1 TRNP AKT1 ALG14 CACNA1S ND1 HADHA RYR1 NEB TMEM43 FKTN ACTA1 TRIM32 SYNE1 LARGE1 PLOD1 POMT2 PLEC DLL1 COL6A1 DOK7 COX3 CLIP2 SCN4A TAZ CHRND RAF1 LAMB2 TRNT B3GALNT2 TKFC CRYAB EMD COX1 MUSK ELN DSG2 PTEN MYH7 POLG TCAP ND4L VCP CFL2 CHRNA1 ND2 KLHL41 MYH2 TRIM32 COL9A1 BIN1 ND6 CHKB COLQ TPM2 RNR1 KLHL41 SQSTM1 TRIP4 ATP6 SDHAF1 MYH6 TXNRD2 TRNL1 MYOT TRNW NEB SUFU ABHD5 TPM2 TRNF TDGF1 GK CYTB CHRNE SELENON AK9 ACTA1 GNE TRNW TNPO3 MYBPC3 SLC5A7 CHRNB1 MYF6 FKTN COL13A1 AGL CHST14 RMND1 TRNL1 TRMU ND5 MAP3K20 SIL1 FKTN VMA21 GFER CHRNE SLC25A4 COL6A2 DNA2 DNAJB6 PRKAR1A CHRNB1 MYOT CAP2 VPS13A XK TTN TRNS1 TRNH ORAI1 COX1 TNNT1 ADGRG6 COMP PDE8B LMNA ND4L DES DNM1L RYR1 FHL1 CASQ1 USP8 COL12A1 ND1 NEFH LMNA ND4 ND5 LAMA4 LDB3 COL12A1 TRNF LMOD3 SIL1 SLC25A4 PANK2 TTN MTAP PPARG COL6A3 TRNQ PGK1 CFL2 RYR1 TRNS1 BSCL2 UNC80 GK RET TPM3 TRNQ FLAD1 HNRNPA2B1 TRAPPC11 VAMP1 STIM1 ISCU MSTO1 CYTB FKBP14 GMPPB DPM3 HADHB DES SLC22A5 HACD1 MYBPC3 NEXN STIM1 SELENON TRNK TAZ TNNT2 CAV3 TRNF LMNA CHRND SCN4A VCP B4GALT1 FGF8 SCN4A ND1 TNNT1 SCN4A SCN4A LAMP2 TRNS2 CDON FKRP GIPC1 RBM20 SGCB LMNA FOXH1 GATAD1 DNM2 GMPPB MYH7 TIA1 DYSF TTN TNNC1 ABHD5 GAS1 MYPN RYR1 MAN2B1 TPM3 MGME1 ANO5 EPG5 TNNI3 TBCE B4GALT1 AGRN SQSTM1 COL9A2 ATP6 ANKRD1 SYNE2 DISP1 TTN CACNA1S TRNP POLG2 POLG ACTA1 SAR1B TPM2 SLC18A3 DSE ND5 DNM2 TRNI ERGIC1 MYOT MYMK ZIC2 CRYAB KLHL40 VAMP1 CAPN3 MYH7 SCN5A NUBPL NDUFA11 TRNE MYBPC1 FKBP14 ACTA1 TTN CDH23 RAPSN CHRND OPA1 CRYAB ND2 PDE11A LMNB2 CPT2 POMT1 SGCG MYOD1 POMT1 ACTA1 TBL2 ZBTB20 PLEC FKTN INPP5K CYTB CTNS TRNF PNPLA2 TTN PLN RFC2 NDUFS2 GYG1 SDHB TPI1 KLHL41 ND4 RRM2B LMNA LIMK1 FLNC MYO18B NEB TPM3 SDHA TWNK NDUFAF1 GCLC CASQ1 POMGNT1 UBA1 SGCD ACTC1 TMPO ND6 FHL1 HAND2 TGIF1 TK2 ALDOA TPM3 MYOT FLNC ND1 MYH14 COL6A1 OPA1 MTMR14 TRNQ FKRP CISD2 ITGA7 PRDM16 AGL POLG CHRNB1 PRKAG2 MYPN TK2 ITGA7 TAF1A TK2 PPCS COLQ COX2 CCDC174 HADHA CHRNE ND6 CHRNB1 COX3 AGK ACAD9 ACTA1 GFPT1 RERE POLG HADHB MTTP TPM1 GNE XDH TRNE SKI LARGE1 ALG2 MYH7 RRM2B ALPL SCN4A SDHD GLI2 BAG3 CHAT SLC25A1 ANO5 YARS2 FHL2 TIA1 GABRD ACTA1 LMNA PNPLA2 TRNS2 PTCH1 COX3 LRP4 SGCA C1QBP PTEN KBTBD13 ACACA DHX16 DPAGT1 TRNK GTF2I MYH7 TWNK MYH7 MYO9A ACADM TRNV RYR1 POMT1 COL13A1 PSEN2 COX2 COL6A3 TRAPPC11 CAV3 ATP6 TTN EMD VCL SIX3 ND5 ND4 COL9A3 CENPF VCP PRKACA TRNL1 DOLK HNRNPA1 KLHL9 AGRN PGK1 SLC25A3 MYL2 NEB MYMK PABPN1 ND5 SYT2 MTMR14 COX1 AP1S2 KBTBD13 FXR1 PRDM16 NARS2 AGK FXR1 ORAI1 LRP12 BIN1 WFS1 SNAP25 STIM1 ABCC9 BAZ1B CRPPA ADSS1 TANGO2 HNRNPA1 NDUFB3 COX3 NEBL GCLC LDB3 DYSF DMD KCNAB2 SELENON HNRNPDL TRNS1 NALCN SDHA
Protein Mutations 0
HP:0001635: Congestive heart failure
Genes 264
TLL1 DSP PLN SLC25A26 BSCL2 DSP NDUFB11 ACTC1 RET TRNL1 JUP CAV1 TRNK SGCD ACTC1 KCNJ5 GTF2IRD1 TRNC FXN WRN HBA2 TTN CAVIN1 VHL ATP6V1A PPA2 FGFR3 MYH7 TRNS2 EYA4 PLOD1 LMNA BMP2 KIF1B SLC2A10 NDUFB8 GNA11 CACNA1S ND1 HADHA TCF4 GAA TRNK VCL GATA6 TBL2 MYL3 PLOD1 ABCC6 GNPTAB SDHD STRADA PNPLA2 ENG LMNA CLIP2 RFC2 TAZ TPI1 COL1A2 BAG3 LIMK1 DSP GTPBP3 DES IRF5 NDUFAF1 ELN SELENON PSMB8 HJV MYD88 MYH6 AGGF1 EYA4 ATP5F1A TET2 ND6 HFE DMD MST1 MAPRE2 DLST DNMT3A TNNI3K TUBB TNNT2 EFEMP2 TRIP4 DNAJC19 XYLT1 TRNQ SDHB GDNF ADCY5 EPAS1 GDF2 PRKAG2 PSEN2 CCR6 AFF4 COL1A1 CDH23 CITED2 ENPP1 RAB3GAP2 BCHE FLNC GLA SF3B1 TRNW HADHA DES IFIH1 MECP2 TMEM70 GATAD1 ACAD9 HBB ACVRL1 HADHB MTTP RASA1 TMEM127 FGF23 NF1 PRDM16 SDHAF2 PRKAR1A FGD1 LMNA NDUFAF3 TNNI3 RBM20 VHL IKBKG VPS33A XYLT2 MYH6 SDHD TRPM4 GLB1 ALMS1 SDHD COX1 TPM1 AGPAT2 SCN5A CLIC2 SCO2 LMNA CAV1 SDHA LMNA HAMP RYR1 CASR MYH7 TRIM37 KIF1B LMNA PTEN SURF1 ACTN2 MYH7 RET LMNA ATXN7 LMNA SLC19A2 GTF2I RPS19 MYH7 TRNF STAT1 GTPBP3 PPARG TRNV TMEM127 LDB3 MAX TBX20 TRNS1 COX2 MDH2 SCO1 MYLK2 GJA1 HFE NDUFS2 GK TTN ELAC2 HNRNPA2B1 IDS TBX20 TRNE MAX NSMCE2 ACAD9 TRNK CYTB GATA4 ND5 GLA ADCY5 HBA1 HADHB SNAP29 MYH7 NKX2-5 SLC22A5 SDHC HBB CITED2 HLA-DRB1 HNRNPA1 ABCC6 SDHB SLC25A3 ALMS1 CP VCP SCN4A HBB FH FBN1 DTNA FOS PRKAR1A TF SDHB COG7 VHL TLL1 PPARG FLNA ENG PSEN1 CCN2 MYPN GPR35 BAZ1B JUP EPG5 SLC25A11 RET CLIC2 COX3 FBLN5 SLC17A5 CAV3 NKX2-5 CEP19 TMEM43 PEX7 SMAD4 PHYH CYTB SCN1B MYSM1 ADAMTSL2 PRKAR1A TRNL1
HP:0011123: Inflammatory abnormality of the skin
Genes 508
PSMB4 ALOXE3 ABCA12 NFE2L2 COL7A1 NFKB2 TREX1 CACNA1G DHCR7 CASP8 COL7A1 CD247 TRAF6 KRT16 PSENEN SPINK5 IFNG KIT ARVCF EGFR LAMA3 HLA-C JAK3 ZNF341 RREB1 LMBRD1 GJC2 NLRP3 HPGD GNA11 BTK BTNL2 PEPD PIK3CD TGM1 HLA-DPA1 RAC1 KRT10 GJB6 ZAP70 H6PD KRT1 MRTFA ABCA12 CYP4F22 TRAF3IP2 WAS NLRP3 GJB2 CYBC1 TGM1 RAG1 TARS1 SMARCA2 TTC7A CLEC7A HIRA FLI1 GP1BB MORC2 BRAF TGM1 FERMT3 SEC24C EXTL3 MCCC2 IL36RN PAH PIGA HLCS CYBA HLA-DPB1 NLRP12 SIK3 HPGD FOXP3 SLC30A2 ABCA12 AP3B1 LIPN CD28 CASP10 CARD14 TCF3 LMBRD1 IL17RA NOD2 LACC1 SHOC2 IL10RA WNT4 IL7 TGM5 CTLA4 ADAMTS3 PAPSS2 DOCK8 HLA-B KRT14 PCCA LIG4 BLM PLA2G7 RNU4ATAC KNSTRN KDF1 GJC2 KIT SMARCAD1 ZNF750 TNFRSF1B PTPN22 ERCC2 IL7R KRT10 FECH CHST14 CIITA KIT STX11 MEFV LIG4 DNAJC21 IL2RA ALOXE3 ENPP1 ACADVL IKBKG PRTN3 SP110 TKT RFX5 EPB42 MEFV NOD2 NOD2 GJA1 FCGR2B RAG1 MVK CTLA4 TREX1 ZAP70 ECM1 MSMO1 SMARCC2 ALOX12B IFIH1 CCBE1 TFRC NFKB1 GJB4 TAF1 NLRP3 USP8 BTD DOCK8 LACC1 TCIRG1 CDK10 STING1 FLI1 ESR1 EDA STAT1 AIRE SRP54 MBTPS2 GATA3 MYD88 RMRP HLA-DRB1 GPR101 C4A DNAJC21 AP1B1 BTK PDGFRA CYP4F22 HPGD RAC1 MEFV CCBE1 RBCK1 ADA RNASEH2B PRMT7 PSMB9 CTSC TNFAIP3 PRF1 SLC4A1 STAT1 MBTPS2 MIF TGM1 SPP1 MYD88 LBR NCF2 IL17F FOXP3 TMC6 CSTA FGFR2 IRF2BP2 CTLA4 SDHA RBP4 RAG1 SMARCA2 KANSL1 SBDS CARD14 RFXAP GJB2 IL6ST PTPN22 ACP5 XIAP ESR1 TTC7A UROS RNASEH2A IL2RG SPTB POLR3A BTK KRT5 DNASE1L3 KRT1 FLT4 TP63 LRRC8A IL12A-AS1 SCNN1B LPIN2 C5 EPG5 LBR MS4A2 ANK1 CTLA4 IL12A GFI1 KANSL1 TP63 NIPAL4 IL17RC POMP MYSM1 SLCO2A1 DSE SDHB TMC8 LYZ NLRP3 CHD7 DSG1 NSUN2 FERMT1 NCF4 B2M SRP54 HLCS WIPF1 LYST MEIS2 SLC39A4 GATA1 EBP POLE MNX1 CDH23 ITGB4 SLC29A3 VEGFC TRPM4 TNFRSF1A DDX41 RAG2 JAK1 PGM3 SULT2B1 JMJD1C SDR9C7 MSN NIPAL4 HYOU1 TBX1 MYSM1 IL10 TBX1 GINS1 NCF4 IL4R COX4I2 RFXANK WIPF1 KRT1 NCF2 TNFRSF1B MPLKIP FOXP1 PSTPIP1 AGA LAMC2 RAG2 FECH RNASEH2C IL17F NCSTN DCLRE1C WAS PEPD IL6 NCF1 CD3D ERCC3 ERCC4 PSMB8 IL7R CTSC STAT3 SH3PXD2B STAT4 SPTA1 IL17RA SAMHD1 IGLL1 PSEN1 COL7A1 SLC6A19 CERS3 NSUN2 TRAF3IP2 TBX1 RNF113A IGHM CD79A PIK3R1 PIK3CA KRT10 FAM111B KDSR SCNN1G ADAM17 CD79B LRRC32 KRT17 BCL11B IVNS1ABP HLA-DRB1 CYBB KRT5 ERCC2 CD3E PTPRC IL23R SRD5A3 TEK FLG SPINK5 CYBA CARD11 CD3G LSS TREX1 CYBB IL10RB LPIN2 STAT3 CLEC7A ITGA6 PGM3 MBL2 STAT3 RTTN SREBF1 HDAC4 CARD9 RFX5 CHST14 DCLRE1C TLR4 MPDU1 NCF1 CYBC1 FGA SUOX IL2RG MEFV GJB3 EGFR OTULIN WAS CASR WNT4 CD247 CFI SAMHD1 UFD1 NSMCE3 RFXAP TREX1 CARMIL2 ABCC6 TNFRSF1A MEFV SHANK3 STAT4 IL6R LAMB3 GTF2H5 APOA1 GJB2 IL1RN IRAK1 KANSL1 GTF2H5 IFIH1 FAT4 RIPK1 RNASEH2C CIITA CCR1 KIF11 ALOX12B UBAC2 UBE2A RNU4ATAC AIP XYLT1 PNPLA1 RBM8A FAS NLRC4 HLA-DQB1 NEK9 HSPA9 PCCB MTHFD1 CTLA4 PSTPIP1 KRT1 EDARADD TGFB1 NR3C1 ERAP1 WDR1 CD28 PRKACA ADA2 CIB1 LYST TBCK ADAR POR ELANE STAT5B MBTPS2 PNPLA1 RFXANK EFL1 KLRC4 FOXC2 DNASE1 MMP1 KRT9 RRAS2 HLA-DRB1 AIRE LIG4 NFKB2 AK2 DCLRE1C NAXD SCNN1A LHCGR HSD3B2 LRBA ELANE GTF2E2 SH3PXD2B COMT EDAR FOXN1 BLNK IL2RG IL7R ERCC3 NIPAL4 ERCC2 RAG2 AP1S3 SDHC ADA FCGR2A AUTS2 PAH ERCC5 CTSB BTNL2 ADAM17 KDF1 HLA-B BTD MVK
Protein Mutations 4
G2545R H2507Q T454A V66M
SNP 1
rs6265
HP:0001268: Mental deterioration
Genes 500
SPG11 WDR45 NOTCH2NLC EEF1A2 ALDH18A1 ND6 TIMM8A TUBA4A TRNL1 TRNK VPS35 PNPLA6 TRNC SLC20A2 DRD3 NECAP1 ERCC6 HNRNPA2B1 CNKSR2 HFE GABRG2 APP RRM2B UCP2 TRNS2 NR4A2 GRN APP ATP13A2 MYORG TTR AARS2 DNM1 STXBP1 ITM2B ATXN10 ND1 KCNJ11 ARSA IRF6 ATXN8OS SYNJ1 C9ORF72 CSTB AARS1 ATP6 LRRK2 PSAP COMT PRDX1 GBA NDUFA6 PODXL VPS13C TBK1 PDGFRB SQSTM1 CYP27A1 TREX1 COX1 PMPCA TIMM8A TYROBP PRKAR1B HCN1 GNAS GCH1 ATN1 MTHFR CLTC VCP PSEN1 L1CAM GABRA5 PDGFB PTS ATP6V0A2 C9ORF72 SUMF1 UBQLN2 SLC1A2 PANK2 PSEN1 ATP6 SDHAF1 GABRB2 MAPT TRNW MAPT KMT2A TMEM106B NOTCH2NLC DNAJC5 SNCA MPO SCN1A NTRK2 CLN3 PDGFRB CDK19 TRNW RRM2B CST3 ATP6V1E1 GRN ITM2B MFSD8 CHMP2B SQSTM1 CHD2 GALC ROGDI HNF4A ADA2 ACTL6B MATR3 GALC PRDM8 SNCA RNF216 ERCC8 ATP1A3 KCNB1 CTC1 GBA PSAP FA2H SCARB2 ABCA7 YWHAG PSEN2 ADH1C VPS13A RNF216 APOE TRNS1 TRNH ABCD1 COX1 CSF1R COASY FMR1 TREM2 ATXN2 SCO2 ATXN2 ARSA FTL DCAF17 MATR3 DNM1L FBXO7 ND1 ATXN7 DAOA ND4 NRAS AP2M1 TRNF AUH MBTPS2 APP DALRD3 GRN PANK2 KCNA2 QDPR TRNQ APP TOMM40 PRNP HNF1A HTRA1 RBM28 TRNS1 PSEN1 A2M HTT SLC2A3 ERCC8 PLP1 BSCL2 DNMT1 HNRNPA2B1 MECP2 SLC44A1 NOTCH3 CHMP2B JAM2 TRNK TBK1 CYTB C9ORF72 TREM2 GABRA2 SUMF1 HMBS MMACHC ABCC8 NPC1 CUBN PSEN2 SYNGAP1 SNCB GBA CREBBP AP3B2 ZFYVE26 APP PPT1 TRNF VPS13C NPC2 NUS1 NHLRC1 VCP HTT IDUA TUBB4A FGF12 SQSTM1 EPM2A TRNS2 DNM1 TREM2 PLA2G6 CHCHD10 PSEN1 EPM2A TYROBP PINK1 SNORD118 TYMP VCP SLC13A5 PLAU SNCA C19ORF12 DNAJC6 CLN5 SNCA HLA-DQB1 SCN8A JPH3 C19ORF12 HTR2A PRKN ACTB APP CUX2 IDS SPG21 CHMP2B PPP2R2B CHI3L1 NDP DNAJC13 ARSA GALC SQSTM1 AP5Z1 PLP1 SORL1 FA2H MAPT CSTB SLC13A5 NHLRC1 SNCA DGUOK COL4A1 CHMP2B PSAP RBM28 TARDBP TTPA POLG PRNP CACNA1A MAPT MAPT GBA MAPT TRPM7 NDUFB8 CREBBP KCTD7 APOL4 ATP6V1A TMEM106B CFAP43 VPS13A PDGFRB RRM2B WWOX ATP13A2 SYNJ1 ATXN2 MAPT TARDBP FMR1 SPG11 ATP1A2 DISC2 CTNS SYNJ1 TBK1 TBP DCTN1 SDHB RNASEH1 ROGDI GBA2 SGPL1 GCDH SNCA ADA2 NOTCH3 XPR1 APOL2 CTSD ATP7B DARS2 MAPT EP300 ATP6V1A BSCL2 ARV1 PDE10A SYN2 HTRA2 SPAST SZT2 ND6 SPG21 LRRK2 ATP13A2 PDE11A PPP2R2B TK2 MMACHC DNMT1 GBE1 IDS LMNB1 SMC1A FTL OPA1 CACNA1B TRNQ C9ORF72 HEXB RAB39B CISD2 ERCC2 PLA2G6 MTHFR ALDH18A1 GBA MFN2 HEPACAM VCP COX2 SERPINI1 KCNC1 PARK7 GRN SYNJ1 COX3 EIF4G1 GRIN2D LRRK2 CLN6 CERS1 MCOLN1 NBN PRKCG MAPT TRNE RTN4R MAPT TIMMDC1 NDUFAF3 PRDM8 WFS1 PRNP FA2H PSEN1 SDHD ERCC6 GIGYF2 APTX DLAT UBTF PRNP CNTNAP2 GLUD2 HTT CSF1R PPP3CA TBP DMPK WDR45 PSAP PRICKLE1 PDGFB PRNP SURF1 GABRB3 APP HEXA PSEN1 TREX1 VCP GBA TWNK HGSNAT CYFIP2 KCNA2 TRNV TRAK1 MAPK10 UBA5 ATP13A2 DNMT1 COX2 FUS CHD2 NDUFS2 PARS2 HIBCH HTRA1 MAPT SCN1A CTSF ND5 CHMP2B DHDDS ATXN3 CLN6 VCP PLEKHG4 NAGLU GBA2 POLG TRNL1 TLR3 PRNP GRN GDAP2 HNRNPA1 LYST GBA SNCAIP ATN1 CLN8 TMEM106B GALC CP XPA ND5 ATXN7 HSD17B10 COL18A1 TBP COX6B1 MAPT PRNP TINF2 PSEN1 APOE TREM2 PINK1 UBAP1 TREM2 GM2A SCN3A GLB1 C9ORF72 WFS1 ASAH1 DCTN1 PRKAR1A PLA2G6 TREM2 MAPT NOS3 COX3 JPH3 RAB27A SLC6A1 ERCC4 PRNP PAH UCHL1 ABCD1 CHCHD10 ASAH1 CLN8 SDHA
Protein Mutations 3
K56M V158M V66M