SNPMiner Trials by Shray Alag


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Report for SNP rs6971

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 28 clinical trials

Clinical Trials


1 PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [(11)C]PBR28 in Patients With Multiple Sclerosis (MS)

This study will use positron emission tomography (PET) to measure a brain protein called peripheral benzodiazepine receptor (PBR) in patients with multiple sclerosis. PBR is created during the inflammation process, and brain inflammation is a key feature of multiple sclerosis (MS). PBR usually affects one type of brain cell, but it can also cause damage to surrounding areas of the brain in patients with MS. PET studies of PBRs and brain inflammation may help elucidate the role of these brain cells in patients with MS. Healthy normal volunteers and patients with MS between 18 and 70 years of age may be eligible for this study. Patients with MS must have had onset of disease between 18 and 40 years of age. Patients with MS undergo the following procedures: Visit 1: Medical history, physical examination, blood tests and magnetic resonance imaging (MRI). Visit 2: Blood tests and PET scan. Visits 3 and 4: MRI and physical examination. Visit 5: PET scan and blood tests. Visit 6: MRI and physical examination. Healthy volunteers undergo the following: Visit 1: Medical history, physical examination, blood tests. Visits 2 and 3: PET and blood tests. Magnetic Resonance Imaging MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that can slide in and out of the scanner (a metal cylinder), wearing earplugs to muffle loud knocking noises that occur during the scanning process. The procedure lasts about 90 minutes; the patient is asked to lie still for up to 25 minutes at a time. The subject can communicate with the MRI staff at all times during the scan. During part of the scan a contrast agent is administered through a catheter (plastic tube) placed in an arm vein to enhance the images. Positron Emission Tomography (PET) The PET scan gives information on brain and body chemistry and function. The subject lies on a bed that slides in and out of the doughnut-shaped scanner. A catheter is placed in a vein in the arm and another is placed in an artery in the wrist or elbow area. The catheter in the arm is used for injecting a radioactive material that the scanner detects, and the other is used to collect blood samples. A custom-molded plastic mask is used to support the head and prevent it from moving during the procedure. The subject may be asked to perform various tasks during the PET scan or to lie quietly. The scan lasts about 2.5 hours.

NCT00432900 Multiple Sclerosis Radiation: [(11)C]PBR28
MeSH:Multiple Sclerosis Sclerosis

- Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene).

HEALTHY VOLUNTEERS - EXCLUSION CRITERIA: Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene).

Primary Outcomes

Measure: Correspondence between increased PBR expression measured by [11C]PBR28 PET and gadolinium-enhancing lesions on MRI.

Time: At time of dosing

Measure: Correspondence between increased PBR expression and previously and/or persistently gadolinium-enhancing lesions on MRI.

Time: At time of dosing

Secondary Outcomes

Measure: Correspondence between PBR expression and other MRI defined pathology including T2-weighted hyperintense and T1-weighted hypointense lesions.

Time: Follow-up (~Month 4)

Measure: Correspondence between PBR expression and normal appearing white and gray matter on MRI.

Time: Follow-up (~Month 4)

2 Phase 0 Clinical Protocol: A Longitudinal and Multimodal Exploratory Study to Evaluate a Neuroinflammatory Hypothesis in Patients With Schizophrenia Compared to Young Healthy Subjects

Previous research has suggested central nervous system inflammatory activity to be critically involved in disease development and progression in schizophrenia, with a complex interplay of inflammatory mechanisms leading to the development of brain abnormalities and medical symptoms related to schizophrenia. However, the mutual interactions of different inflammatory pathways and their relation to disease course have not been sufficiently studied. This study therefore aims to explore the interaction of neuroinflammatory mechanisms in patients with schizophrenia and to assess whether the inflammatory activity in schizophrenia is state-dependent and occurs mainly during psychotic episodes.

NCT02009826 Schizophrenia Psychosis Radiation: [18F]-PBR111 Positron Emission Tomography (PET) Behavioral: Cognitive and psychomotor tasks Biological: Blood sampling
MeSH:Schizophrenia Psychotic Disorders Mental Disorders
HPO:Psychosis Schizophrenia

- Low affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at Screening - Use of benzodiazepines for 3x the half-life prior to PET-scan - Presence of irremovable magnetic materials in or on the body - Has a medical history of organic brain disease - Has a medical history of traumatic brain injury - Has a medical history of allergic reaction to any of the substances in the tracer fluid.

Primary Outcomes

Description: Regional distribution volume in tissue (VT) of 2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide (PBR111) labelled with fluorine-18 (18F) in schizophrenia patients and age- , gender-, and translocator protein (TSPO) binding profile- matched healthy controls

Measure: Regional VT of [18F]PBR111

Time: 2 years

Secondary Outcomes

Description: Levels and ratios of inflammatory and neurotoxicity markers in blood samples of schizophrenia patients compared to healthy age- and gender-matched healthy controls.

Measure: Peripheral markers

Time: 2 years

3 Non-Invasive Characterization in Cardiac Sarcoidosis

In a study of Cardiac sarcoidosis, a serious heart condition, a radiotracer is being used to examine inflammation.

NCT02017522 Cardiac Sarcoidosis Device: 11C-PBR PET
MeSH:Sarcoidosis

If you have two copies of a genetic variation called rs6971 which will prevent this tracer from generating high-quality images you may not participate.

Primary Outcomes

Description: The primary outcome of this study will be the ratio of 11C-PBR28 PET activity in myocardial regions with inflammation indicated by FDG PET and/or edema indicated by increased T2 signal with cardiac MRI compared to the 11C-PBR28 PET activity in myocardial segments which appear normal on FDG PET and cardiac MRI. The primary outcome is thus the intensity of uptake in abnormal regions as a percentage of the intensity of uptake in normal segments.

Measure: Ratio of 11C-PBR28 in the Myocardium

Time: 1 hour scan

Secondary Outcomes

Description: As a secondary outcome of this study we will evaluate the ratio of 11C-PBR28 PET activity in regions with fibrosis indicated by decreased myocardial perfusion on 82Rb PET and/or late gadolinium enhancement on cardiac MRI without imaging signs of active inflammation compared to 11C-PBR28 PET activity in myocardial segments which appear normal on 82Rb PET, FDG PET and cardiac MRI. This outcome will thus be expressed by 11C-PBR28 PET uptake in fibrotic regions as a percentage of uptake in normal segments We will also evaluate the concordance between extracardiac activity seen in 11C-PBR28 and FDG PET, and when available, histopathology of contemporaneous biopsy specimens.

Measure: The Ratio of 11C-PBR28 PET Activity in Cardiac Regions With Fibrosis

Time: 1 hour scan

4 Reproducibility of the 11C-PBR28 PET Signal

The Translocator Protein (TSPO) is a protein which reaches very high levels when there is inflammation in the brain. Recently, radioligands have been developed which attach to the TSPO (a radioligand is a drug which has been tagged with radioactivity). Using positron emission tomography (PET) imaging, the radioligand can be detected following injection into a patient. However, it is difficult to accurately measure the amount of TSPO using PET at the moment. This is because the brain does not have a "reference region" for TSPO (ie an area in the brain with no TSPO at all). "Reference regions" are very useful to help work out how much of a PET signal represents "specific binding" (of the radioligand to the target of interest), and how much represents "non specific binding" (of the radioligand to many other structures which are not of interest). In the absence of a reference region, non specific binding can be estimated by giving a drug which binds to the TSPO. The drug prevents the radioligand binding the TSPO and (in a manner of speaking) "creates" a temporary reference region so non specific binding can be measured. To do this, we will use XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor) to bind TSPO and block binding of the PET ligand ([11C]PBR28), a TSPO ligand from the phenoxyarlyacetamide class. Most TSPO PET studies (and in one of our previous studies approved by West London REC) quantify the signal using a ratio of specific binding in the brain to radioactivity in the blood. This requires arterial line insertion which is burdensome for subjects, and increases variability. In this study we aim to determine the ratio of specific binding in the brain to nonspecific binding in the brain by using the temporary reference region. For more accuracy the participants will repeat the scanning procedure so determine test-retest variability of the amount of TSPO.

NCT02086240 Neurodegenerative Disorders Drug: XBD173
MeSH:Neurodegenerative Diseases
HPO:Neurodegeneration

Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.. To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.. Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients.

Primary Outcomes

Description: Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.

Measure: TSPO Binding Status

Time: Baseline/Screening visit

Other Outcomes

Description: Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients. Subjects will receive a baseline 11C-PBR28 scan, and then a repeat scan following an oral dose of 90mg XBD173 (Emapunil). Both VT and BPND will be determined. Subjects will then return approximately 10 days later for a repeat of these procedures.

Measure: To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.

Time: 1st and 2nd Study Visit (approximately 10 days after the 1st study visit)

5 Assessment of [11C]ER-176 to Image Translocator Protein in Brain and Whole-Body of Healthy Subjects

Background: - A protein called translocator protein may play a role in brain inflammation. Sometimes it is present at higher levels in the lungs than in the brain. Researchers want to see if a drug called [11C]ER176 can provide an image of this protein in the brain. Objective: - To test the ability of a drug to image a protein, and test how it is distributed in the body. Eligibility: - Healthy adults over age 18. Design: - Participants will be screened with medical history, physical exam, and blood and urine tests. - Participants will have a PET scan of the brain using [11C]ER176. It will be injected through an intravenous tube into 1-2 arm veins. A tube may also be put into an artery at the wrist or elbow. Some participants will also have a lung scan. - For the PET, participants will lie on a bed that slides in and out of a doughnut-shaped scanner. A plastic mask will be molded to their face and head. They may be wrapped with restraining sheets. The scan will last about 120 minutes. Blood may be taken during the scan. - Blood and urine will be taken before and after the scan. - During another visit, participants will have an MRI scan of the brain. Participants will lie on a table that slides in and out of a metal cylinder. A strong magnetic field and radio waves will take pictures of the brain. The scanner makes loud knocking noises. Participants will be given earplugs. - Some participants will have only a whole-body PET scan using [11C]ER176.

NCT02147392 Pharmacokinetics Adult Drug: [11C]ER-176

Although [(11)C]PBR28 has high in vivo specific signal, it is very sensitive to the high and low affinity states of TSPO, which are caused by the rs6971 single nucleotide polymorphism (SNP) in the fourth exon of the TSPO gene resulting in a nonconservative alanine-to-threonine substitution in position 147 of the encoded TSPO protein.

Primary Outcomes

Measure: The identifiability and time stability of distribution volume calculated with compartmental modeling and evaluate the genotype sensitivity of [11C]ER-176

Time: 1 year

Secondary Outcomes

Measure: Whole-body biodistribution and dosimetry of [11C]ER-176.

Time: 1 year

6 Brain Inflammation and Function in Alcoholism

Background: - Brain inflammation due to high alcohol intake may affect thinking, memory, and concentration. Researchers want to measure this using positron emission tomography (PET). Objective: - To study how excessive alcohol consumption affects brain function. Eligibility: - Adults 30-75 years old who are moderate or severe alcohol drinkers. - Healthy volunteers. Design: - Participants will be screened with medical history, physical exam, interview, and blood and urine tests. Their breath will be tested for alcohol and recent smoking. - Phase 1: - Participants will stay in the hospital 3 days. They will have blood and heart tests and daily urine tests. - A small plastic tube will be inserted by needle in each arm. One will go in a vein, the other in an artery. - Participants will have 2 PET scans with 2 different radioactive compounds. Participants will lie on a bed that slides in and out of the scanner with a cap on their head. - Participants will have magnetic resonance imaging (MRI) scans. Participants will lie in the scanner either resting with their eyes open or while performing an attention task. - Participants will have tests of memory, attention, concentration, and thinking. They may answer questions, take tests, and perform simple actions. - Phase 2 of the study will only be done if Phase 1 results show brain inflammation. - Phase 2 will repeat Phase 1. - For healthy volunteers, Phase 2 will begin 3 weeks after Phase 1. - Other volunteers must not have alcohol for at least 3 weeks and stay in a hospital up to 4-6 weeks between Phase 1 and Phase 2. After Phase 2, they will have 5 follow-up calls over 3 months.

NCT02233868 Alcohol Use Disorder (AUD) Other: connectivity Other: neuroinflammation Drug: neurofunction
MeSH:Encephalitis Inflammation Alcoholism Alcohol Drinking
HPO:Encephalitis

Homozygosity for the rs6971 polymorphism on TSPO that results in LB (Owen et al 2011) (genotyping results).

Primary Outcomes

Description: To assess if there is inflammation detected in the brain of alcoholics subjects as measured with [11C]PBR28 as compared to healthy controls.

Measure: To assess inflammation in the brain

Time: end of study

Description: To assess if there is neuroinflammation detected in the brain of alcoholics subjects as measured with [11C]PBR28 as compared to healthy controls and if it recovers with at least 3 weeks of abstinence.

Measure: To determine if there is neuroinflammation in the brain.

Time: end of study

Description: We want to see whether [11C] PBR28 uptake in the brain reflects levels similar to controls after at least 3 weeks of alcohol abstinence.

Measure: To assess between group differences in inflammation in the brain of AUD subjects in Phase II who either abstain from alcohol for at least 3 weeks or relapse (continue to drink alcohol) for at least 3 weeks.

Time: end of study

Secondary Outcomes

Description: to assess if neuroinflammation is associated with markers of brain function and to evaluate if neuroinflammation predicts relapse in AUD over a 3 month follow-up period.

Measure: To assess the impact of neuroinflammation on brain function (assessed with PET and 18FDG and with MRI for fMRI with task activation and for functional connectivity).

Time: end of study

7 Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder

The purpose of this study is to determine if translocator protein total distribution volume (TSPO VT) is elevated in major depressive disorder that is not responding to medication and if adding minocycline can affect TSPO VT. Many remain treatment resistant with common antidepressant treatments and the investigators think it may be due to poor targeting of brain pathologies.

NCT02362529 Major Depressive Disorder Drug: Minocycline Drug: Placebo Drug: Celecoxib
MeSH:Depressive Disorder Depression Depressive Disorder, Major
HPO:Depressivity

The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA.

Primary Outcomes

Description: TSPO VT will be measured using [18F]FEPPA positron emission tomography brain scans. Eligible MDE participants will be randomized to either minocycline or placebo. Following 8 weeks of either minocycline or placebo treatment, MDE participants will have a second PET scan .

Measure: Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects

Time: Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans

Description: Compare baseline TSPO VT prior to treatment between MDE group and healthy group

Measure: Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects

Time: Pre-treatment scan will take place up to 8 weeks from initial assessment

Secondary Outcomes

Description: Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.

Measure: Change in Hamilton Depression Rating Scale Score

Time: Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment).

Other Outcomes

Description: To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.

Measure: Hopkins Verbal Learning Test-Revised

Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

Description: To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.

Measure: Brief Visuospatial Memory Test-Revised

Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

Description: To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.

Measure: Comprehensive Trails Making Test

Time: Pre- and post-minocycline or placebo treatment.

Description: The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA. The genetic sample will also be used to study sequences of genes that are believed to affect TSPO expression, inflammation, mood and conditions that may predispose to mood disorders.

Measure: Genetic sample

Time: Phase 1-single sample

Description: Analyses will include complete blood cell count (CBC), ESR, hepatic and renal function. Peripheral marker analyses will include proteins related to TSPO expression and inflammation. Plasma minocycline and celecoxib levels will be analyzed.

Measure: Blood samples (serum and plasma)

Time: Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).

8 Imaging and BioFluid Biomarkers in Amyotrophic Lateral Sclerosis

This is a multicenter, 18-month study, which aims to identify imaging and biofluid biomarkers in people with ALS to expand the understanding of ALS pathology, treatment targets, disease progression, and anatomical differences between different disease phenotypes. This pilot project is tailored to produce imaging tools that will allow researchers to conduct future ALS clinical trials more efficiently which may in turn impact the pace for ALS drug discovery.

NCT02559869 Amyotrophic Lateral Sclerosis (ALS) Drug: [18F] GE-180
MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis
HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to SI judgment 7. Pregnant women or women currently breastfeeding 8. Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study In addition, any subject meeting any of the following criteria during screening evaluations will be excluded from entry into the PET portion of the study: 1. Radiation exposure that exceeds the site's current guidelines 2. Low affinity TSPO binders determined by having a Thr/Thr polymorphism in the TSPO gene (rs6971) at the Screening Visit Women of Childbearing Potential (WOCBP) For the purposes of this study, women of child bearing potential are defined as all women who are capable of becoming pregnant, unless they meet one of the following criteria: - 12-months post-menopausal - Post-hysterectomy - Surgically sterile Inclusion Criteria Study subjects meeting all of the following criteria will be allowed to enroll in the study: 1.

The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to SI judgment 7. Pregnant women or women currently breastfeeding 8. Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study In addition, any subject meeting any of the following criteria during screening evaluations will be excluded from entry into the PET portion of the study: 1. Radiation exposure that exceeds the site's current guidelines 2. Low affinity TSPO binders determined by having a Thr/Thr polymorphism in the TSPO gene (rs6971) at the Screening Visit Women of Childbearing Potential (WOCBP) For the purposes of this study, women of child bearing potential are defined as all women who are capable of becoming pregnant, unless they meet one of the following criteria: - 12-months post-menopausal - Post-hysterectomy - Surgically sterile Amyotrophic Lateral Sclerosis (ALS) Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis In this trial, approximately 200 subjects will participate in this study from 2 Northeast ALS Consortium (NEALS) centers in the United States.

Primary Outcomes

Description: Aim 1 will be accomplished by obtaining [18F] GE-180 PET imaging from 25 people with ALS compared to 25 age, gender, and binding affinity matched healthy volunteers.

Measure: Measure & localize brain inflammation in people with ALS via [18F] GE-180 PET imaging.

Time: 12 months

Description: Aim 1 will be accomplished by obtaining state of-the-art MRI acquisition sequences from 50 people with ALS compared to 50 MRI age- and gender-matched healthy volunteers.

Measure: Define anatomical, structural, and functional changes in the brain via MRI of ALS Subjects vs. Healthy Controls at Baseline

Time: 12 months

Description: Blood from 100 subjects will be studied to quantitate circulating pro- and anti-inflammatory monocyte/macrophage and T cells, with results to be correlated with neuroimaging and evaluated as potential biomarkers of disease progression.

Measure: Determine systemic inflammatory factors that may modify the progression or other clinical or imaging correlates of ALS.

Time: 12 months

Secondary Outcomes

Description: Clinical and [18F] GE-180 PET imaging data will be collected every 6 months from the 25 people with ALS for at least 12 months.

Measure: Determine the longitudinal changes in brain inflammation in people with ALS in correlation with ALS severity and rate of progression.

Time: 12 months

Description: Clinical and MRI data will be collected every 3 months from 50 people with ALS for at least 12 months.

Measure: Determine the longitudinal changes in the anatomical, structural, and functional measures in people with ALS, and build ALS prediction models using the clinical and MRI data.

Time: 12 months

9 A [C-11]-PBR28 Positron Emission Tomography Study to Evaluate the Effect of ABT-555 on Central Nervous System Inflammation in Subjects With Relapsing Forms of Multiple Sclerosis

This open-label positron emission tomography (PET) study is designed to determine the effect of ABT-555 on translocator protein expression level in participants with relapsing forms of multiple sclerosis.

NCT02606630 Multiple Sclerosis Drug: ABT-555
MeSH:Multiple Sclerosis Sclerosis

Inclusion Criteria: Diagnosis of relapsing-remitting MS (RRMS) or relapsing secondary progressive MS (SPMS) Neurologically stable at Screening, in the investigator's judgment and not actively experiencing or recovering from a recent relapse in the 30 days preceding the Screening Visit A Kurtzke Expanded Disability Status Scale (EDSS) score of 1.0 to 6.0, inclusive at the Screening Visit High or mixed affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at screening Exclusion Criteria: Diagnosis of primary progressive or non-relapsing secondary progressive MS Smoking more than 10 cigarettes per day or use of a nicotine patch Known history of, or positive screening test result for hepatitis C virus or hepatitis B virus Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening Any type of live virus vaccine from 4 weeks before randomization History of abnormal laboratory results Inclusion Criteria: Diagnosis of relapsing-remitting MS (RRMS) or relapsing secondary progressive MS (SPMS) Neurologically stable at Screening, in the investigator's judgment and not actively experiencing or recovering from a recent relapse in the 30 days preceding the Screening Visit A Kurtzke Expanded Disability Status Scale (EDSS) score of 1.0 to 6.0, inclusive at the Screening Visit High or mixed affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at screening Exclusion Criteria: Diagnosis of primary progressive or non-relapsing secondary progressive MS Smoking more than 10 cigarettes per day or use of a nicotine patch Known history of, or positive screening test result for hepatitis C virus or hepatitis B virus Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening Any type of live virus vaccine from 4 weeks before randomization History of abnormal laboratory results Multiple Sclerosis Multiple Sclerosis Sclerosis null

Primary Outcomes

Description: Compare 2 dynamic positron emission tomography scans to examine the effect of a single administration of ABT-555 on translocator protein expression

Measure: Change in translocator protein expression

Time: Day 0 and 109 days

10 Pilot Study of Positron Emission Tomography (PET) Imaging: Correlations With Advanced Magnetic Resonance Imaging in Multiple Sclerosis

Traditional Magnetic Resonance Imaging (MRI) in Multiple Sclerosis (MS) has enabled clinicians to measure disease activity but there are inherent limitations. Clinical/radiographic dissociation can be seen in some patients and the abnormalities are not specific. This pilot study is an opportunity to determine the relationship between quantitative advanced MRI measures and OCT with PET measurements of microglial activation and myelin health.

NCT02869360 Multiple Sclerosis
MeSH:Multiple Sclerosis Sclerosis

- Aged 18 to 60 - High or mixed affinity binder to rs6971 TSPO polymorphism Exclusion Criteria: - Pregnant or breastfeeding - Suffering from an unstable medical condition - Have a neurological or ocular disorder other than MS - Any contra-indications to MRI Inclusion Criteria: - Diagnosed with Multiple Sclerosis according to the 2011 McDonald criteria.

- Aged 18 to 60 - High or mixed affinity binder to rs6971 TSPO polymorphism Exclusion Criteria: - Pregnant or breastfeeding - Suffering from an unstable medical condition - Have a neurological or ocular disorder other than MS - Any contra-indications to MRI Multiple Sclerosis Multiple Sclerosis Sclerosis null

Primary Outcomes

Measure: Whole Brain PBR28 binding

Time: Baseline

Secondary Outcomes

Measure: Lesional PiB binding

Time: Baseline

Measure: Myelin Water Imaging

Time: Baseline

Measure: MR Spectroscopy (Total NAA, NAA/Cr, mI)

Time: Baseline

Measure: Optical Coherence Tomography (RNFL thickness)

Time: Baseline

11 Targeting Microglial Activation for Treatment of Autism Spectrum Disorder (ASD): A Proof-of-Concept, Target-Engagement Study

Autism spectrum disorders (ASD) are highly disabling, persistent neurodevelopmental disorders. There are no available treatments for core symptoms of ASD or biologically-based clinical biomarkers. Emerging evidence indicates that levels of brain inflammation are increased in ASD. In particular, recent work implicates hyperactivity of microglial cells, the resident immune cells of the brain. However, the functional consequences of microglial activation remain unknown. This study will measure microglial activation in ASD using positron emission tomography (PET) brain imaging. Adult males with ASD (n=15) and healthy controls (n=15) will be recruited for this study and undergo comprehensive clinical and behavioral baseline assessment. All subjects will then undergo baseline PET imaging using a radiotracer that labels activated microglia. Subjects with ASD will then undergo 12-week open label treatment with minocycline, an FDA-approved antibiotic thought to block microglial activation. PET imaging will be repeated at 12 weeks to confirm target engagement. A subset of control subjects will also undergo repeat PET imaging to determine test-retest reliability. During minocycline treatment, ASD subjects will be evaluated every 2 weeks for safety, clinical impression, behavioral functioning, and measures of cognition. Results will provide important information regarding the relationship between levels of brain inflammation, cognitive and behavioral function in ASD.

NCT03117530 Autism Spectrum Disorder Drug: Minocycline
MeSH:Autistic Disorder Autism Spectrum Disorder
HPO:Autism Autistic behavior

hepatic, neurologic, renal disease) to increase risk to the subject 3. Presence of severe behavioral disturbance likely to require initiation of treatment during the course of the protocol 4. Clinical judgment of the study physician of inability to perform the requirements of the study 5. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, or benzodiazepines 6. Homozygous genotype for minor allele of rs6971 7. History of recent febrile illness in past 30 days 8. History of allergic reactions to tetracycline antibiotics 9. Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change 10.

hepatic, neurologic, renal disease) to increase risk to the subject 4. Presence of current or lifetime severe psychopathology potentially confounding assessment of TSPO binding (psychosis, severe depression, bipolar disorder, Obsessive-Compulsive Disorder) 5. Current prescribed medication likely to confound assessment of TSPO binding 6. Clinical judgment of the study physician of inability to perform the requirements of the study 7. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, benzodiazepines, or psychotropic medications likely to confound assessment of TSPO binding 8. Homozygous genotype for minor allele of rs6971 9. SRS-2 T-score score of >59 10.

Primary Outcomes

Measure: Evaluate differences in CNS microglial activation in adults with ASD versus healthy volunteers via in vivo CNS binding of [11C]-DAA1106

Time: Data will be collected at PET scan #1, which will take place during screening (Days -28 to 0) for the study

Measure: Evaluate the effect of 12-weeks of minocycline exposure on CNS microglial activation in adults with ASD by measuring change in [11C]-DAA1106 binding pre- and post- treatment

Time: Data will be collected at PET scan #1 (between days -28 and 0 before intervention) and at PET scan #2 during Week 12 of intervention

Secondary Outcomes

Measure: Effect of minocycline exposure on cognition across seven cognitive domains before and after low dose intervention and regular dose intervention as measured by MCCB (MATRICS Consensus Cognitive Battery) subdomain scores

Time: Data will be collected at baseline and during Weeks 6 and 12 of intervention

Measure: Effect of minocycline exposure on self-rated anxiety and emotion regulation as measured by ADAMS (Anxiety and Depression Mood Scale)

Time: Data will be collected at baseline and during Weeks 6 and 12 of intervention

Measure: Effect of minocycline exposure on peripheral inflammatory cytokine profiles as measured by DNA and RNA expression in blood samples

Time: Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)

Other Outcomes

Measure: Change in clinician-rated global improvement as measured by CGI

Time: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention

Measure: Change in self-reported symptoms of ASD with minocycline treatment as measured by SRS-2

Time: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention

Measure: Change in informant-reported symptoms of ASD with minocycline treatment as measured by ABC-CV

Time: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention

12 Brain Microglial Activation in the Early Stage of the Parkinson's Disease: a Predictive Biomarker of the Evolution?

Phase II, Open-labeled, Prospective, Multi-center study of assessing the link between microglial activation and dopaminergic denervation kinetics in the early stage of Parkinson disease, by using the imaging of [18F]DPA-714 a new ligand of Translocator Protein-18 kDa (TSPO) by Positron Emission Tomography (PET).

NCT03230526 Parkinson Disease Drug: [18F]DPA-714 PET scan
MeSH:Parkinson Disease

Exclusion Criteria: - Pregnant woman - Minor - Adult protected by the law - Contraindication to PET-scan - Contraindication to brain MRI - History of inflammatory or dysimmune chronic disease - History of psychiatric disease or drug addiction - History of cognitive disorders (MMS<26) - Hypersensibility to iodine derivates or one of these components - Long-term Treatments which can interfere in neuroinflammation process - Treatments / substances susceptible to interfere with the 18F-DPA-714 - TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder) - Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome Inclusion Criteria: - Patients having a Parkinson's disease diagnosed according to the criteria UKPDSBB.

Exclusion Criteria: - Pregnant woman - Minor - Adult protected by the law - Contraindication to PET-scan - Contraindication to brain MRI - History of inflammatory or dysimmune chronic disease - History of psychiatric disease or drug addiction - History of cognitive disorders (MMS<26) - Hypersensibility to iodine derivates or one of these components - Long-term Treatments which can interfere in neuroinflammation process - Treatments / substances susceptible to interfere with the 18F-DPA-714 - TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder) - Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome Parkinson Disease Parkinson Disease The Parkinson's disease ( MP) is a frequent but heterogeneous neurodegenerative disease in term of clinical presentation(display) and evolutionary profile.

Primary Outcomes

Description: Coefficient of correlation between the striatal microglial activation level measured by PET imaging [binding potential (BP) of 18F-DPA-714 in the striatum] and dopaminergic denervation kinetics obtained from two 123I-FP-CIT (DaTscan) scans

Measure: Coefficient of correlation between level of microglial striatal activation and the And the dopaminergic denervation kinetics

Time: 36 months

Secondary Outcomes

Description: Will be estimated by imaging PET with [18F]DPA-714

Measure: Analyze the relationship between the level of microglial activation in the black substance at the early stage of MP and the dopaminergic denervation kinetics

Time: 36 months

Description: The equivalent dose of cumulative L-Dopa

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: baseline

Description: The equivalent dose of cumulative L-Dopa

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 18 months

Description: The equivalent dose of cumulative L-Dopa

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 36 months

Description: MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: Baseline

Description: MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 18 Months

Description: MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 36 Months

Description: MDS-UPDRS scale (part IV)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: baseline

Description: MDS-UPDRS scale (part IV)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 18 months

Description: MDS-UPDRS scale (part IV)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 36 months

Description: QUIP RS

Measure: Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Time: baseline

Description: QUIP RS

Measure: Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Time: 18 months

Description: QUIP RS

Measure: Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Time: 36 months

Description: MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: baseline

Description: MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 18 months

Description: MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 36 months

Description: MDS-UPDRS scale (part II : 2.13 and part III : 3.11)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: baseline

Description: MDS-UPDRS scale (part II : 2.13 and part III : 3.11)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 18 months

Description: MDS-UPDRS scale (part II : 2.13 and part III : 3.11)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 36 months

Description: MDS-UPDRS scale (part I)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: MDS-UPDRS scale (part I)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: MDS-UPDRS scale (part I)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: NMS SCALE

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: baseline

Description: NMS SCALE

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: NMS SCALE

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Scopa-Aut Score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: baseline

Description: Scopa-Aut Score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Scopa-Aut Score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Evaluation of constipation according to Rome III criteria

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Evaluation of constipation according to Rome III criteria

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Evaluation of constipation according to Rome III criteria

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Detection of hypotension

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Detection of hypotension

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Detection of hypotension

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Epworth's Sleepiness Scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Epworth's Sleepiness Scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: Epworth's Sleepiness Scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: UPSIT test

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: baseline

Description: UPSIT test

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: MoCA score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: MoCA score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: MoCA score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: MATTIS scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: MATTIS scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: MATTIS scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: Anxiety symptoms assessed using Beck's anxiety inventory

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Anxiety symptoms assessed using Beck's anxiety inventory

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Anxiety symptoms assessed using Beck's anxiety inventory

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: Symptoms of depression assessed using the Beck Depression

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Symptoms of depression assessed using the Beck Depression

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: Symptoms of depression assessed using the Beck Depression

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: Dopaminergic denervation at inclusion will be measured by the binding potential (BP) of ioflupane (123I-FP-CIT) by regions of interest in the caudate and putamen of the striatum

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic denervation at baseline (DaTscan initial)

Time: Baseline

Description: MDS-UPDRS scale

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: QUIP questionnaire

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: NMS questionnaire

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: Scopa-Aut Score

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: Rome III criteria

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: The level of cortical microglial activation measured by fixation of the radioligand 18F-DPA-714, on some volumes of interest in the brain

Measure: Evaluate the link between the level of striatal microglial activation and the level of activation in other brain regions (black substance, bridge and cortex)

Time: 36 months

Description: Neurologic Evaluation

Measure: Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Time: baseline

Description: Neurologic Evaluation

Measure: Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Time: 18 months

Description: Neurologic Evaluation

Measure: Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Time: 36 months

Description: The serum levels of 13 cytokines will be analyzed

Measure: Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation

Time: Baseline

Description: The serum levels of 13 cytokines will be analyzed

Measure: Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation Evaluate the relationship between the level of nigrostriatal microglial activation

Time: 18 months

Description: The serum levels of 13 cytokines will be analyzed

Measure: Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation

Time: 36 months

Description: Measurement of serum uric acid

Measure: Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Time: Baseline

Description: Measurement of serum uric acid

Measure: Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Time: 18 months

Description: Measurement of serum uric acid

Measure: Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Time: 36 months

13 Development of Minocycline as a Neuroimmune Therapy for Alcohol Use Disorder

The objective of this proposal is to advance medication development for alcohol use disorder by examining the efficacy and mechanisms of action of minocycline, a neuroimmune modulator, as a potential treatment. This study has important clinical implications, as the available treatments for alcohol use disorder are only modestly effective and testing novel medications is a high research priority.

NCT03244592 Alcohol Use Disorder Inflammation Neurocognitive Dysfunction Craving Alcohol Drinking Drug: Minocycline Drug: Sugar pill
MeSH:Inflammation Alcoholism Alcohol Drinking Cognitive Dysfunction
HPO:Cognitive impairment Mental deterioration

15. low affinity rs6971 genotype Inclusion Criteria: 1. Ages 25 - 45 2. Meet DSM-5 diagnostic criteria for an AUD [n.b., only participants with moderate or severe AUD will be enrolled] 3. Drink ≥ 48 standard drinks in a 30-day period before enrollment Exclusion Criteria: 1. Currently in treatment for AUD, a history of treatment in the 30 days before enrollment, or currently treatment seeking 2. Current (last 12 months) DSM-V diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine 3. Lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder 4. Positive urine screen for narcotics, amphetamines, or sedative hypnotics 5. Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised 6. Pregnancy, nursing, or refusal to use reliable method of birth control (if female) 7. A medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes) 8. AST, ALT, or GGT ≥ 3 times upper normal limit 9. Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year 10.

15. low affinity rs6971 genotype Alcohol Use Disorder Inflammation Neurocognitive Dysfunction Craving Alcohol Drinking Inflammation Alcoholism Alcohol Drinking Cognitive Dysfunction The research objective of this project is to advance medication development for AUD by conducting a randomized, double blind, placebo-controlled, neuroimaging study to examine the effects of minocycline on neuroinflammation, alcohol cue reactivity, neurocognitive performance, and alcohol use.

Primary Outcomes

Description: Level of [11C]DAA1106 binding during PET imaging

Measure: Microglial Activation

Time: Change from baseline after 28 days of medication dosing

Description: Alcohol Urge Questionnaire (AUQ)

Measure: Cue-Induced Alcohol Craving

Time: Change from baseline after 28 days of medication dosing

Description: Total drinks consumed

Measure: Alcohol consumption

Time: Day 28 of medication dosing period

Description: Hopkins Verbal Learning Test

Measure: Verbal Learning and Memory

Time: Change from baseline after 28 days of medication dosing

Description: Wisconsin Card Sorting Test

Measure: Set-Shifting

Time: Change from baseline after 28 days of medication dosing

Description: Stop Signal Task

Measure: Response Inhibition

Time: Change from baseline after 28 days of medication dosing

Description: Grooved Pegboard Test

Measure: Manipulative Dexterity

Time: Change from baseline after 28 days of medication dosing

Description: Digit Symbol Substitution Test

Measure: Executive Function

Time: Change from baseline after 28 days of medication dosing

Description: Digit Span

Measure: Memory

Time: Change from baseline after 28 days of medication dosing

Description: WAIS Vocabulary

Measure: Vocabulary

Time: Change from baseline after 28 days of medication dosing

Description: Rey Complex Figure Copy

Measure: Executive Function

Time: Change from baseline after 28 days of medication dosing

Secondary Outcomes

Description: Serum level of cytokines and innate immune receptors

Measure: Peripheral Proinflammatory Marker levels

Time: At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing

Description: Symptom count from the alcohol module for the Structured Clinical Interview for DSM-5

Measure: Alcohol Use Disorder Severity

Time: At baseline (day zero) and after 28 days of medication dosing

14 Brain Function and Connectivity in Methamphetamine Dependence: The Link to Neuroinflammation and the Effects of Ibudilast

Addiction to methamphetamine is a serious health problem in the United States. Right now, there are no medications that a doctor can give someone to help them stop using methamphetamine. More research is needed to develop drugs for methamphetamine addiction. Ibudilast (the study drug) is a drug that could help people addicted to methamphetamine.

NCT03341078 Methamphetamine-dependence Drug: Ibudilast Drug: Placebo Oral Tablet

Pre and post differences in brain function will be assessed.. Effects of ibudilast on overall cognitive battery score.. Pre and post differences in overall cognitive battery score will be assessed.. Inclusion Criteria: - abstinent from all drugs and have a negative urine drug screen on test days - Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders Exclusion Criteria: - Known sensitivity to ibudilast - Left handed - MRI contraindications - Clinically significant neurological, endocrine, renal, hepatic, or systemic diseases that would compromise safe participation or confound outcomes - Any psychiatric diagnoses or primary psychotic or mood disorders (past depression diagnoses allowed) - Any drug use disorder diagnosis besides methamphetamine or tobacco - Any recreational or prescriptive use of psychotropic medications - Claustrophobia - Women who are pregnant or breast-feeding - Neurodegenerative diseases that present with neuroinflammation - More than 4 weeks abstinent from methamphetamine - rs6971 genotype that confers low translocator protein (TSPO) binding affinity to prevent unnecessary radiation exposure - Liver disease requiring medication or medical treatment and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit - Participation in any drug study in the last 3 months Inclusion Criteria: - abstinent from all drugs and have a negative urine drug screen on test days - Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders Exclusion Criteria: - Known sensitivity to ibudilast - Left handed - MRI contraindications - Clinically significant neurological, endocrine, renal, hepatic, or systemic diseases that would compromise safe participation or confound outcomes - Any psychiatric diagnoses or primary psychotic or mood disorders (past depression diagnoses allowed) - Any drug use disorder diagnosis besides methamphetamine or tobacco - Any recreational or prescriptive use of psychotropic medications - Claustrophobia - Women who are pregnant or breast-feeding - Neurodegenerative diseases that present with neuroinflammation - More than 4 weeks abstinent from methamphetamine - rs6971 genotype that confers low translocator protein (TSPO) binding affinity to prevent unnecessary radiation exposure - Liver disease requiring medication or medical treatment and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit - Participation in any drug study in the last 3 months Methamphetamine-dependence Addiction to methamphetamine is a serious health problem in the United States.

Primary Outcomes

Description: Pre and post differences in brain neuroinflammation will be assessed.

Measure: Effects of ibudilast on neuroinflammation as assessed by magnetic resonance spectroscopy (MRS)

Time: 6 weeks

Description: Pre and post differences in brain neuroinflammation will be assessed.

Measure: Effects of ibudilast on neuroinflammation as assessed by positron emission tomography (PET)

Time: 6 weeks

Description: Pre and post differences in brain function will be assessed.

Measure: Effects of ibudilast on brain function as assessed by magnetic resonance imaging (MRI)

Time: 6 weeks

Secondary Outcomes

Description: Pre and post differences in overall cognitive battery score will be assessed.

Measure: Effects of ibudilast on overall cognitive battery score.

Time: 6 weeks

15 Effect of Modulating Gamma Oscillations by Transcranial Alternating Current Stimulation on Brain Structure and Function in Humans

This study aims to implement an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.

NCT03412604 Alzheimer Disease Device: Transcranial Alternating Current Stimulation (tACS)
MeSH:Alzheimer Disease
HPO:Alzheimer disease

- Contraindication for undergoing MRI or receiving TMS or tACS, - >50 mSv of radiation exposure for research within the past year (PET imaging exclusion) - Presence of the Thr/Thr polymorphism in the TSPO gene (rs6971) due to low affinity binding for the PBR 28 (microlgia) PET scan - History of fainting spells of unknown or undetermined etiology that might constitute seizures.

Primary Outcomes

Description: Adverse Events as a result of tACS stimulation will be reported

Measure: Incidence of Treatment-Emergent Adverse Events

Time: Up to 12 weeks

Description: Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions

Measure: PET amyloid burden

Time: up to 12 weeks

Description: Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions

Measure: PET tau deposition

Time: up to 12 weeks

Secondary Outcomes

Description: Changes in the microglia activation observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions

Measure: PET Microglia activation

Time: up to 12 weeks

Other Outcomes

Description: Change in Adas-Cog score will be reported, to document a potential clinical benefit of tACS. The scale ranges from a total score of 0-70 with higher score indicating greater cognitive impairment.

Measure: Alzheimer's Disease Assessment Scale -Cog Score

Time: up to 12 weeks

16 UAB Neuroinflammation in Parkinson's Disease - TSPO-PET Substudy

The primary objective of this substudy is to measure the concentration and the regional brain distribution of activated brain microglia/macrophages using the PET (Positron Emission Tomography) ligand [18F]DPA-714 in participants enrolled in the UAB Neuroinflammation in PD study. The PET tracer [18F]DPA-714 binds to the 18 kDa translocator protein (TSPO, also known as the peripheral benzodiazepine receptor) in the mitochondria of activated microglia/macrophages and provides a non-invasive measure of neuroinflammation. The amount and distribution of [18F]DPA-714 in the brain will be correlated to clinical data acquired through the separate ongoing Neuroinflammation in PD study. The primary objective of this study is to determine if patients with PD have higher levels of neuroinflammation than healthy controls as measured with [18F]DPA-714-PET/MRI.

NCT03457493 Parkinson Disease Drug: DPA-714-PET/MRI
MeSH:Parkinson Disease

3. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.

4. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Primary Outcomes

Description: Estimates of brain TSPO concentrations measured with PET will serve as a marker for neuroinflammation. TSPO-PET measures will be compared between PD patients and healthy controls. We expect the PD patients to have higher measures of neuroinflammation than healthy controls.

Measure: Comparison of TSPO-PET measures of neuroinflammation between PD patients and healthy controls.

Time: 2 years

Description: The estimates of neuroinflammation measured with TSPO-PET will be correlated with clinical assessments of PD severity and biospecimens collected through the UAB Neuroinflammation in PD study.

Measure: Correlation of DPA-714-PET/MRI with demographics, clinical and biospecimen assessments from Neuroinflammation in PD study

Time: 2 years

17 The Relationship Between Neuropsychological Testing and MRI, PET and Blood Biomarkers in Neurodegenerative Disease (COBRE - Project 1): AIM 2

The complex pathological cascades leading to both Alzheimer's disease (AD) and Parkinson's disease (PD) involve, at various points, inflammation. Since inflammation is a treatable symptom, understanding how and when it impacts the brain, and where specifically in the brain, would offer important guidance in the development of new treatments, sorely needed in both diseases. Microglia play an important anti-inflammatory role, and produce a substance, mitochondrial translocator protein (TSPO), whose presence can be used as a marker of regional inflammation. GE180 is a newly developed PET ligand which binds to TSPO and hence can be used in imaging studies to analyze regional inflammation in living patients. In prior studies it has shown regional specificity in multiple sclerosis and brain injury. In the current study, the investigators will be using GE180 to analyze regional and global inflammation in the brains of patients with AD and PD at two time points. The results of the current study will provide enriched understanding of inflammation in these conditions, and potentially provide preliminary data to inform design of future interventional trials.

NCT03702816 Alzheimer Disease Parkinson Disease Inflammation Diagnostic Test: GE180 PET Scan
MeSH:Parkinson Disease Alzheimer Disease Inflammation
HPO:Alzheimer disease

For MCI patients, fit criteria based in Movement Disorders Task Force or NIA Exclusion Criteria: 1. Significant neurological disorders other than AD or PD; 2. Unstable medical conditions 3. History of major psychiatric diseases 4. MRI evidence of infarction or other focal lesion or multiple lacunes 5. Clinically significant abnormalities in B12 or TSH 6. Identified as having a common polymorphism (rs6971) in the TSPO gene which has been shown to reduce binding affinity of tracers similar to GE180.

Primary Outcomes

Description: We will use a linear regression model to assess whether regional microglial activation is predictive of cognitive performance in domains of memory, visuospatial function, language, and executive functioning. These differing units of measurement collected through neuropsychological evaluation will be aggregated into one model in order to assess the correlations between regional activation and cognitive performance in any different domains.

Measure: Linear Regression Model Assessing Cognitive Performance and Regional Microglial Activation

Time: Baseline

Description: We will use repeated measures analyses to asses whether there is a significant change in microglial activation between year 1 scan and year 2 scan. We will then assess if this change in microglial activation over this time period relates to changes in cognitive measures.

Measure: Repeated Measures Analyses to Asses Change in Microglial Activation Over Time

Time: Baseline (Year 1) compared to Year 2

Description: We will use a linear regression model to assess whether global microglial activation is predictive of overall cognitive performance (as assessed with scores on the Dementia Rating Scale (DRS) and Montreal Cognitive Assessment (MoCA)).

Measure: Linear Regression Model Assessing Cognitive Performance and Global Microglial Activation

Time: Baseline

18 Positron Emission Tomography (PET) Imaging Study in Relapsing-Remitting and Primary-Progressive Multiple Sclerosis (MS): Correlations With Advanced MRI in MS

While both conventional and advanced MRI techniques offer important insights into MS pathophysiology, important aspects of this inflammatory disorder are undetectable with existing MRI technology. In Multiple Sclerosis (MS), there is growing interest in PET as an imaging modality that can increase the investigator's understanding of the disease processes and may add to an understanding of MS phenotype, particularly when combined with advanced MRI techniques such as myelin water imaging.

NCT03787446 Multiple Sclerosis
MeSH:Multiple Sclerosis Sclerosis

- Mixed affinity binder according to rs6971 TSPO polymorphism1.

Exclusion Criteria: - Low and high affinity binders according to rs6971 TSPO polymorphism - Subject pregnant or breastfeeding.

A separate pre-screening consent form will be issued for the TSPO rs6971 polymorphism and eGFR blood samples, a separate pre-screening step.

Eligible participants, according to their TSPO rs6971 polymorphism will be presented a separate study consent form to continue into the clinical trial.

Primary Outcomes

Description: To show an increase in 11C-PBR28 binding in all sub-types of MS compared to healthy controls.

Measure: Whole Brain PBR28 binding

Time: January 2020

Secondary Outcomes

Description: To quantitatively measure the brain levels of water located within myelin

Measure: Myelin Water Imaging by MRI

Time: January 2020

Description: To correlate brain levels of inflammation measured by 11C-PBR28 with Retinal Nerve Fiber Layer (RNFL) thickness on Optical Coherence Tomography (OCT).

Measure: Optical Coherence Tomography

Time: January 2020

Description: To correlate brain levels of inflammation and myelin measured by PET with cognitive dysfunction in MS patients.

Measure: MS Spectroscopy

Time: January 2020

19 Imaging the Neuroimmune Effects of Acute Opioid Administration

In this study, a novel human laboratory model will be evaluated. Preclinical research indicates acute opioid administration evokes an immune response in the periphery and brain. Here, we will translate those preclinical findings to healthy human volunteers and quantify the neuroimmune response to a morphine challenge (Specific Aim). To measure the neuroimmune system, we will use [11C]PBR28 positron emission tomography (PET) imaging to quantify 18kDa translocator protein (TSPO) availability. TSPO is an imaging marker of the neuroimmune system shown to scale with microglia levels. Up to twenty healthy volunteers will complete two 120-minute [11C]PBR28 PET scans. Subjects will complete one scan prior to, and one scan 2-hr after, a single morphine injection (0.07 mg/kg i.m.). Specific Aim: To determine whether an acute morphine injection increases TSPO availability in healthy volunteers. Hypothesis: Relative to baseline, morphine will significantly increase whole-brain TSPO availability, consistent with a neuroimmune response.

NCT03801629 Drug Effect Drug: Intramuscular Morphine

8. 'Low affinity binding' individuals based on rs6971 polymorphism (<10% of the population).

Primary Outcomes

Description: The percentage change in 18kDa translocator protein (TSPO) availability from pre-Morphine to post-Morphine measured via PET [11C]PBR28 scans

Measure: Morphine-induced Change in TSPO availability

Time: One 120-minute PET [11C]PBR28 scan before and the other ~2 hours after morphine challenge

Secondary Outcomes

Description: The percentage change in Cogstate memory performance

Measure: Morphine-induced Change in Memory Proficiency

Time: The Cogstate Battery will be administered twice: once before and once ~1 hours after the morphine challenge

20 An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis

In multiple sclerosis (MS) cells of the immune system attack the brain causing tissue damage. In secondary progressive MS (SPMS) these repeated immune attacks have stopped but despite this new damage continues to appear. TSPO is a protein found in the brain and cells of the immune system, whose levels increase during MS. The investigators would like to know whether drugs that bind TSPO could dampen the immune responses in patients with SPMS. The investigators will be testing two drugs that affect TSPO; etifoxine and XBD173. Subjects with SPMS will be recruited from neurology clinics at hospitals associated with Imperial College Healthcare NHS Trust. Healthy volunteers will also be recruited in order to provide a comparison to these patients. The volunteers recruited will be invited to the clinical research facility (CRF) at Hammersmith Hospital. The volunteers will take one of the two drugs every day for 7 days. The researchers will perform blood tests before the first dose and after the last dose to investigate the effects of the drugs, including the expression of genes and immune cell activity. This will allow the researchers to explore which of the two drugs produces the greatest changes in the amount of TSPO in the blood in MS patients relative to healthy controls.

NCT03850301 Multiple Sclerosis Drug: XBD173 Drug: Etifoxine
MeSH:Multiple Sclerosis Sclerosis

b To explore the potential dependence of these pharmacodynamic responses on variation at rs6971 (a common polymorphism influencing ligand binding affinities in the TSPO protein) in the TSPO gene.

Primary Outcomes

Description: Plasma cytokine concentrations

Measure: Monocyte phenotye - Tissue necrosis factor-α

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotye - Interferon-γ

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 1β

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 16

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 17

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 23

Time: 7 days

Description: Transforming growth factor-β

Measure: Immunomodulatory factor -Transforming growth factor-β

Time: 7 days

Description: Interleukins -4

Measure: Immunomodulatory factor - Interleukins -4

Time: 7 days

Description: Interleukins - 10

Measure: Immunomodulatory factor - Interleukins - 10

Time: 7 days

Description: Flow

Measure: Relative proportions of WBC subsets

Time: 7 days

Secondary Outcomes

Description: Genome, proteome, metabolome

Measure: Monocyte phenotype - 'omic analyses

Time: 7 days

Description: Plasma levels of neurofilament

Measure: Neurofilament

Time: 7 days

21 Neuroinflammation After Myocardial Infarction - Imaging Substudy

The purpose of the study is to see if positron emission tomography and magnetic resonance imaging (PET/MRI) with an investigational drug called [18F]DPA-714 will show inflammation in the brain after a heart attack. This study may help physicians and researchers better understand the role of brain inflammation in heart disease and develop new treatments to protect the brain.

NCT03968445 Myocardial Infarction Drug: [18F]DPA-714-PET/MRI
MeSH:Myocardial Infarction Infarction
HPO:Myocardial infarction

English speaking with at least 8th grade education 4. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.

Diagnosis of dementia 12. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Primary Outcomes

Description: The regional brain concentrations of [F-18]DPA-714, a PET imaging marker of neuroinflammation, will be compared between study participants who have recently been hospitalized for acute myocardial infarction (AMI) and a control group undergoing elective percutaneous coronary interventions (PCI).

Measure: TPSO-PET measurement of neuroinflammation after acute myocardial infarction

Time: 2 years

22 PBR28 Brain PET Imaging With Lipopolysaccharide (LPS) Challenge for the Study of Microglia Function in Alzheimer's Disease

To examine the differences in the capacity to activate microglia in patients with Alzheimer's Disease (AD) compared to age-comparable cognitively normal subjects and younger healthy controls.

NCT04057807 Alzheimer Disease Drug: LPS
MeSH:Alzheimer Disease
HPO:Alzheimer disease

- BMI > 35 or < 19 - Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or Intrauterine Device (IUD) - Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population) - Patients on antiplatelet and anticoagulant medications will be excluded.

Primary Outcomes

Description: Th primary outcome is MARI (calculated in the parietal ROIs) in AD patients compared to elderly controls. The investigators will use 7 AD and 7 comparably aged cognitively normal successfully scanned subjects to calculate the microglial activation reserve index. It is expected that there will be significant differences between the two groups suggesting Altered reactivity of the microglia in AD.The result would be an exciting one suggesting at least one mechanism by which some patients with significant amyloid load have progressive dementia while comparable others are either cognitively normal or have stable MCI. It will also suggest avenues for intervention in amyloid positive MCIs to prevent progression to Alzheimer's dementia

Measure: An altered reactivity of microglia

Time: 180 minutes post intervention

Secondary Outcomes

Description: The investigators will evaluate the effects of aging on MARI. Comparisons will be made for MARI between cognitively normal elderly and the 8 healthy individual to whom the researchers applied this protocol in an earlier study. The reactivity of microglia is reported to change with age (11) and so MARI is expected to change in the cognitively normal elderly. However, it is expected that the differences between the young and elderly cognitively normal subjects to be small relative to the comparison of AD and elderly normal controls.

Measure: Effects of aging on MARI

Time: 180 minutes post intervention

Description: The investigators will look at the relationship of regional and global amyloid load to MARI. The presence of a relationship suggests that one of the reasons for altered microglial reactivity might be interactions of microglia with pathologic amyloid.

Measure: Effects of amyloid on MARI

Time: 180 minutes post intervention

Description: The investigators will explore whether MARI would correlate with measure of disease stage, with higher MARIs associated with worse neuropsychological score and more severe disease. The investigators will look for correlations between MARI and the individual neuropsychological scores. This would determine if disease severity is correlated with microglial activation reserve.

Measure: Effects of MARI on cognition

Time: 180 minutes post intervention

23 An Open-label, Adaptive Design Study in Patients With Amyotrophic Lateral Sclerosis (ALS) to Characterize Safety, Tolerability and Brain Microglia Response, as Measured by TSPO Binding, Following Multiple Doses of BLZ945 Using Positron Emission Tomography (PET) With the Radioligand [11C]-PBR28

It is an open label study to evaluate safety, tolerability and brain microglia response in ALS patients following multiple doses of BLZ945.

NCT04066244 Amyotrophic Lateral Sclerosis Drug: BLZ945
MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis
HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

8. High-affinity binders (HAB) or mixed-affinity binders (MAB) to TSPO as evaluated by genotyping for the rs6971 polymorphism in the TSPO gene at the screening visit.

Primary Outcomes

Description: Volume of distribution (Vt) in different brain regions for each [11C]-PBR28 PET scan, and change after BLZ945 treatment, compared to baseline. Evaluate brain microglial reduction, as measured by reduction in TSPO binding following oral doses of BLZ945 in ALS subjects by using PET imaging with [11C]-PBR28.

Measure: Change from baseline in volume of distribution (Vt) in different brain regions for [11C]-PBR28 PET scan

Time: Day -42, up to Day 22

Secondary Outcomes

Description: Measured by Cmax - The maximum plasma concentration of BLZ945

Measure: Plasma Pharmacokinetics (PK) of BLZ945 - Cmax

Time: Day 1; up to Day 17

Description: Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of BLZ945

Measure: Plasma Pharmacokinetics (PK) of BLZ945 - Tmax

Time: Day 1; up to Day 17

Description: Measured by AUC - Area under the curve of BLZ945

Measure: Plasma Pharmacokinetics (PK) of BLZ945 - AUC

Time: Day 1; up to Day 17

Description: Measured by T1/2 - The elimination half-life of BLZ945

Measure: Plasma Pharmacokinetics (PK) of BLZ945 - T1/2

Time: Day 1; up to Day 17

Description: Urine renal clearance (CLR) of BLZ945

Measure: Renal Clearance (CLR) of BLZ945

Time: Day 1; up to Day 7

Description: To assess the CYP2C8 pharmacogenomic-pharmacokinetic relationship; CYP2C8 genotyping and BLZ945 plasma PK parameters

Measure: CYP2C8 genotyping and BLZ945 plasma PK parameters

Time: Day 1; up to Day 17

24 Imaging the Neuroimmune System in PTSD With PET

In this study, individuals with and without post-traumatic stress disorder (PTSD) will undergo one positron emission tomography (PET) scan using the radiotracer [11C]PBR28, which binds to the 18kDa translocator protein (TSPO). A subset of individuals who complete the first PET [11C]PBR28 scan will be invited to complete an inflammatory challenge and second PET [11C]PBR28 scan. Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral biomarker levels will be assayed periodically throughout the experimental session. Specific aims: 1) Determine if individuals with PTSD exhibit neuroimmune system disruption relative to well-matched comparators at baseline. 2) Determine if individuals with PTSD exhibit a disrupted neuroimmune response after a classical immune stimulus relative to well-matched comparators. 3) Determine if LPS differentially alters cognitive function, subjective response, or physiological markers in individuals with PTSD compared to well-matched comparators. Hypothesis: Individuals with PTSD will exhibit a suppressed neuroimmune system at baseline and an attenuated neuroimmune response following LPS challenge.

NCT04236986 Post Traumatic Stress Disorder Drug: Lipopolysaccharide
MeSH:Stress Disorders, Traumatic Stress Disorders, Post-Traumatic

Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population) Inclusion Criteria: 1. Men and women, aged 18-55 years 2. Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis) 3. Able to read and write English and to provide voluntary, written informed consent Exclusion Criteria: 1.

Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population) Post Traumatic Stress Disorder Stress Disorders, Traumatic Stress Disorders, Post-Traumatic null

Primary Outcomes

Description: Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.

Measure: Baseline TSPO Availability

Time: Before LPS administration (baseline)

Description: Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.

Measure: Post-LPS TSPO Availability

Time: 3-hours after LPS administration (1.0 ng/kg; IV)

Secondary Outcomes

Description: Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall). Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).

Measure: Baseline Cogstate Cognitive Battery performance

Time: Before LPS administration

Description: Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall). Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).

Measure: Post-LPS Cogstate Cognitive Battery performance

Time: Approximately 1-hour after LPS administration

25 Measuring the Neuroimmune Response to Alcohol

This study uses positron emission tomography imaging of the 18-kDa translocator protein to measure the brain's immune response to alcohol.

NCT04251221 Alcohol Drinking Alcohol Use Disorder Drug: Oral Alcohol Challenge
MeSH:Alcoholism Alcohol Drinking

Specifically, we will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal or b) have a score of > 8 on the Clinical Institute Withdrawal Assessment scale at intake - Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population).

Primary Outcomes

Description: This is the percent change in [11C]PBR28 distribution volume post-alcohol relative to baseline. As a percent change, it could range from -10% to 200%.

Measure: Neuroimmune Response to Alcohol

Time: Measured 1-4 hours after oral alcohol challenge ends - Will require ~120 minutes

Description: This is the percent change in scores across the cogstate battery. These values could realistically vary much more widely, from -1000% to 1000% (although this extent is not expected).

Measure: Working Memory

Time: The morning following alcohol challenge - Will require ~30 minutes

Description: The percent change score in performance on the probabilistic response task. These values could realistically vary much more widely, from -300% to 300% (although this extent is not expected).

Measure: Anhedonia

Time: The morning following alcohol challenge - Will require ~30 minutes

26 Evaluation of in Vivo Neuroinflammation in Alzheimer's Disease Using Novel Positron Emission Tomography (PET/CT) Imaging

This research study is being done to learn more about inflammation in the brain using Positron Emission Tomography/Computed Tomography (PET/CT) imaging in people with Alzheimer's Disease/Mild Cognitive Impairment or healthy controls. If the subject agrees to be in this study, she/ he will have two types of PET/CT scans on the same day. The subject may have a screening visit before the PET/CT scan visit if the investigator needs to confirm the subject is able to be in the study. A blood sample will be taken before the scans. Additional blood samples will be taken during the PET scans. Subjects must also agree to have an MRI scan for this research study if she/he has not had a recent scan that the study doctor decides can be used for this study.

NCT04274998 Alzheimer Disease Healthy Volunteer Drug: [11C]PBR28 and[18F]NOS
MeSH:Alzheimer Disease
HPO:Alzheimer disease

3. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be negative by the study PI. 4. High affinity carrier of the rs6971 TSPO polymorphism (whole genome sequencing is available from the UPenn ADC research cohort and will be interrogated for this polymorphism) 5. Mini-mental status exam (MMSE) score of 28 or higher per ADC database.

3. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be positive by the study PI. 4. High affinity carrier of the rs6971 TSPO polymorphism (whole genome sequencing is available from the UPenn ADC research cohort and will be interrogated for this polymorphism) 5. Mini-mental status exam (MMSE) score of 14-27 per ADC database.

Primary Outcomes

Description: The primary outcome measure will be comparison of whole brain GM binding between controls and the MCI/AD group. the investigator will compare groups with a t-test. the investigator will evaluate the correlation of whole brain GM binding of 11C-PBR28 and 18F-NOS.

Measure: understanding the uptake of [18F]NOS in the human brain in AD/MCI and Healthy Controls and compare to same-day [11C]PBR28 uptake using PET/CT scan

Time: 3 years

Secondary Outcomes

Description: Secondary outcome measures for will include regional and voxel-wise comparisons between binding of the tracers. Correlation between regional 11C-PBR28 or 18F-NOS binding and either amyloid PET SUVR (calculated with cerebellar gray matter reference) or GM volumetric measurements will be evaluated using Pearson's r and rank sum correlation initially using false discovery rate (FDR)-corrected<0.05 statistical thresholds.

Measure: Comparing the patterns of [18F]NOS and [11C]PBR28 brain uptake with patterns of cerebral amyloidosis and neurodegeneration using PET/CT

Time: 3 years

27 Molecular Imaging Probes to Inform Heterogeneity in Idiopathic Pulmonary Fibrosis

The purpose of the study is to see if imaging with [18F]FDG and [18F]DPA-714 using positron emission tomography and computed tomography (PET/CT) will show lung inflammation and fibrosis in patients diagnosed with idiopathic pulmonary fibrosis (IPF). This study may help physicians and researchers better understand how best to treat patients with IPF in the future.

NCT04362644 Idiopathic Pulmonary Fibrosis Drug: PET/CT using PET ligands [F-18]FDG and [F-18]DPA-714
MeSH:Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis
HPO:Pulmonary fibrosis

4. Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) >0.70. 5. High or mixed affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Primary Outcomes

Measure: Correlate quantitative PET measures of lung inflammation with [F-18]FDG and [F-18]DPA-714 to pulmonary function tests.

Time: screening to 48 hours post 2nd imaging visit.

28 Neuroinflammation and Age-associated Brain Pathology: Two Potential Mechanisms of Cognitive Impairment in Breast Cancer

This study will use a PET/MRI scanner and an investigational radioactive drug called [F-18]DPA-714 that measures inflammation in the brain, also called neuroinflammation, before chemotherapy and after 3 to 6 cycles of chemotherapy given as part of your clinical care. In addition, this study will use a PET/MRI scanner with an investigational radioactive drug called [C-11]PiB that measures the amount of abnormal protein (called beta-amyloid) in the brain that is a marker of Alzheimer's disease pathology. One of the most common complaints among breast cancer survivors is cognitive or memory problems especially in older adults. Researchers need to better understand the mechanisms and risk factors for cognitive problems in order to address this problem. This study seeks to examine two mechanisms, neuroinflammation and amyloid deposition, that have been suggested in other age-related cognitive disorders. This study may help physicians and researchers develop new treatments to protect the brain in cancer patients. UAB plans to enroll 20 participants in this study.

NCT04364672 Breast Cancer Drug: [11C]PiB and 18F-labeled DPA-714 PET scan
MeSH:Breast Neoplasms Cognitive Dysfunction
HPO:Breast carcinoma Cognitive impairment Mental deterioration Neoplasm of the breast

Stage IIIA may also be a tumor larger than 50mm that has spread to 1 to 3 axillary lymph nodes (T3, N1, M0). 4. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.

12. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Primary Outcomes

Measure: Measure neuroinflammation by calculating the concentration and regional distribution of activated brain microglia/macrophages using PET ligand [F-18]DPA-714.

Time: Pre-study visit through 3-6 cycles of chemotherapy (each cycle is typically 2 weeks)

Secondary Outcomes

Measure: Measure cognitive impairment by calculating the concentration and regional brain distribution of pathologic amyloid deposition using the PET tracer [C-11]PiB in participants prior to starting chemotherapy.

Time: After pre-study visit and before starting chemotherapy


HPO Nodes


HP:0001268: Mental deterioration
Genes 461
SMC1A FUS PDE11A PLEKHG4 CTC1 SPG11 FA2H PLA2G6 SYNJ1 C9ORF72 HTT UBAP1 ND5 HEXB PTS MAPT TRNS2 PDGFB APOL2 TWNK GBA FGF12 JPH3 KCNB1 NOTCH3 APOE PAH MAPK10 CNTNAP2 APP COL4A1 ABCC8 MCOLN1 RAB27A CLN6 ERCC6 COX3 GRN APOE ADH1C BSCL2 FMR1 TRNS1 UCP2 PRNP VPS13C GLUD2 TBK1 GBA KCNA2 DISC2 CSTB WFS1 ATP6 HSD17B10 MAPT FTL VCP CSF1R C9ORF72 CYTB NDUFA6 PDGFRB PRKCG ZFYVE26 CSTB HTR2A JPH3 PSEN2 GDAP2 MAPT EPM2A C9ORF72 APP PODXL LRRK2 C19ORF12 HNRNPA2B1 CACNA1A SERPINI1 CP CFAP43 PRNP HLA-DQB1 SNCA ND1 SGPL1 DNM1 CPLX1 VPS35 NDUFB8 C9ORF72 ATXN3 SNCA GABRA5 CHMP2B TIMM8A ATN1 LRRK2 PARK7 DNMT1 TTR ASAH1 SCN1A GIGYF2 APP CHD2 ATP13A2 COX2 UBQLN2 HNRNPA1 ATN1 VPS13A CHMP2B TYROBP SLC2A3 ACTB SQSTM1 CST3 HCN1 ERCC2 SDHB ATP13A2 CHCHD10 SPG21 GRN MAPT GCH1 PSEN1 PNPLA6 SPG21 IDUA TRNL1 SYN2 ITM2B GBA C9ORF72 CHI3L1 MAPT PSAP GBA SZT2 CLN8 ATXN2 TREM2 TREM2 MMACHC NPC1 CTNS PDGFRB PLAU AP2M1 DNM1 TRPM7 HFE SNORD118 SNCA NDUFS2 TBK1 NDP SQSTM1 DAOA SLC6A1 YWHAG SUMF1 TREX1 GLB1 FTL DNAJC6 TRNQ UBA5 CNKSR2 HGSNAT UBTF NUS1 MFN2 PSAP ALDH18A1 COX1 TMEM106B ARV1 ASAH1 TARDBP TLR3 SYNJ1 MAPT STXBP1 EIF4G1 HNRNPA2B1 HNF1A MAPT VCP PSEN1 PANK2 ATP13A2 CYFIP2 AARS1 PSEN1 HNF4A PRDM8 COMT ND6 PSEN1 GRN NOTCH3 ALDH18A1 ATP7B DNMT1 GRN ATP13A2 PPT1 RAB39B CYP27A1 TRNC CUX2 GABRA2 SDHD PRDM8 ACTL6B PSEN2 APOL4 MBTPS2 CTSD TRAK1 HEXA CLTC ATXN10 SNCAIP ATXN7 RTN4R POLG SUMF1 SQSTM1 TMEM106B GM2A PSEN1 NDUFAF3 MECP2 PRKN TK2 CLN8 DNMT1 POLG PRDX1 CISD2 GRN TREM2 LMNB1 NRAS SNCA SCO2 PSAP CHMP2B APP TUBA4A SLC1A2 RBM28 UCHL1 ATXN2 TBP TRNF MAPT GABRB3 PPP2R2B PRNP XPR1 CHD2 MAPT NOS3 COL18A1 DNM1L HEPACAM XPA TYROBP SNCA SLC20A2 CSF1R PRNP TRNW PRNP SDHA WFS1 SNCB SCN9A RRM2B ARSA SURF1 MAPT C19ORF12 CHMP2B APP RBM28 SNCA ADA2 GABRB2 AP5Z1 TBC1D24 ATP1A2 TREM2 DGUOK ATXN2 MAPT ERCC8 HTRA2 QDPR DCTN1 TMEM106B HTRA1 GBA2 NBN PLA2G6 PLA2G6 DARS2 CP APP AARS2 VCP WDR45 MATR3 HTRA1 MAPT MATR3 HTT PDE10A PANK2 TUBB4A GBA2 PRICKLE1 NR4A2 GALC ADA2 WDR45 NHLRC1 ST3GAL5 RNASEH1 SQSTM1 VCP ERCC4 KCNA2 DNAJC13 TRNK AMN EEF1A2 TIMMDC1 HTT TOMM40 PRNP ATP6V1A CLN3 KCNJ11 CACNA1B SDHAF1 PRNP GRIN2D ROGDI FBXO7 APP PLP1 TRNV TINF2 NPC2 BSCL2 ABCD1 ATP6V1A GBA FA2H COASY CERS1 APTX TREM2 RNF216 CLN6 VPS13C GBA CLN5 TBK1 PPP3CA MYORG PDGFB PRKAR1A GBE1 DNAJC5 MAPT TTPA TRNE GBA RRM2B EPM2A FA2H SYNGAP1 TYMP PPP2R2B TREX1 MPO KMT2A OPA1 MFSD8 ATXN7 PINK1 PSEN1 CFAP43 LRRK2 CTSF AP3B2 DHDDS ARSA NAGLU SPAST RNF216 FMR1 ITM2B IRF6 TIMM8A TBP HIBCH RRM2B KCNC1 GABRG2 ATXN8OS PSEN1 SLC13A5 WWOX SCN8A PINK1 PRNP SLC13A5 ATP6 PDGFRB SCARB2 SORL1 DRD3 CUBN ATP6V0A2 GNAS PARS2 ROGDI NOTCH2NLC NTRK2 KCTD7 DCAF17 SPG11 SCN3A ABCA7 VCP VCP ARSA SYNJ1 NHLRC1 SCN1A CHCHD10 A2M PRKAR1B TBP NECAP1 ATP1A3 MTHFR CHMP2B ATP6V1E1 TRNK DCTN1 TARDBP
Protein Mutations 3
K56M V158M V66M
HP:0000729: Autistic behavior
Genes 559
MID2 PTCHD1 SARS1 AP1S2 SYNJ1 FMN2 UBE3A CXORF56 ST3GAL5 NAA10 OTUD6B FGF12 STXBP1 KCNB1 ASH1L NDUFAF3 PAH MAPK10 SDHD CNTNAP2 PIGC HNF1B GABRD PWRN1 TRNL1 ZC3H14 SETD5 PSMD12 PRODH TUBB3 FMR1 HCFC1 PPP2CA VPS13C PDE4D CTNNB1 KCNA2 USP9X STS B3GALNT2 MAPT NDST1 VCP ANK3 HDAC8 PDE4D NAGA DCPS TCF4 C9ORF72 POLA1 NLGN3 TSPAN7 TBX1 NR2F1 SCN1B ND1 DEAF1 MED13L MAPK8IP3 SCN1A KMT2A NEUROD2 PIGG NDUFS1 COX2 GABRD CLCN4 MEF2C SIM1 GNAO1 MED12 UFD1 RARS1 RNF135 PODXL IL1RAPL1 SATB2 SMG9 CACNA1A C12ORF4 CHD8 SH2B1 SNRPN TBC1D23 IQSEC2 PGAP3 ACOX1 RSPRY1 TRNQ NDP JMJD1C MEIS2 CC2D1A DNM1 RSPRY1 IFNG TRIM8 DPYD CC2D2A ND3 SNORD116-1 AP3B2 CTCF RPL10 TBR1 IPW GABRA5 FTSJ1 FRMPD4 TMEM216 ACSL4 PARK7 NDUFS2 KDM6B WASHC4 NUS1 TRNS1 ALMS1 FGFR1 TSC1 NTRK2 CHD2 PIGL SEC24C PIGQ SDHC ALG13 SMC1A FBXO31 HERC1 SLC9A6 TRRAP THOC2 ANKRD11 HCN1 GAMT ADNP IQSEC2 CUX2 SDHB METTL23 MECP2 UPF3B TCF4 PAK3 GRIA3 WARS2 SNORD115-1 SPATA5 NDUFAF4 TBCK EP300 HIVEP2 UBTF SYP EXT2 COMT POMT1 CRADD BCKDK SZT2 NAA10 CDKL5 SCN9A ZNF41 PIGY AP2M1 CARS2 RERE STS MAN1B1 DNM1 STXBP1 CLP1 OPHN1 COX1 HCN1 DEAF1 AGTR2 MEF2C SLC6A1 YWHAG PTEN ND5 ND4 PTEN IREB2 PIGP ZNF423 MED25 DNAJC6 NSUN2 UBA5 CNKSR2 MAGEL2 DMD ELN NONO NUS1 CAMTA1 CASK USF3 EXT2 ARV1 RREB1 NDUFA11 SRY MTOR SPECC1L NDUFAF2 HCN1 KLLN MBOAT7 NDUFB9 STXBP1 DDX3X RAI1 FOXRED1 NDUFS7 TECR LMAN2L HERC2 GP1BB PSEN1 CYFIP2 AARS1 SETD2 RFC2 NDUFAF1 PCDH19 COG5 FRMPD4 PUF60 TWNK AUTS2 PLXND1 ND6 SYT1 EZR WFS1 EP300 NFIB GRN SLC25A22 ZNF81 NLGN4X RSRC1 CUX2 GABRA2 CXORF56 KCNA1 TRNF MKRN3-AS1 ACTL6B GJA8 MICOS13 NDUFA6 NAGA TRAK1 CDH15 NDUFAF4 USP7 CLTC PRDM16 ND2 SMC3 ALDH5A1 TBX1 ZFPM2 CNTNAP2 SLC35A3 ARHGEF6 TMEM106B PCDH19 FOXG1 SKI PDE4D MECP2 KCNAB2 PRKN SIN3A CHD7 IL1RAPL1 ST3GAL3 CTCF PPM1D LIMK1 SNCA ATRX LHX1 TBL2 SHANK3 SLC1A2 UCHL1 CEP290 ZBTB20 GABRB3 DYRK1A RPS23 TM4SF20 CHD2 TAF1 SCN2A MEIS2 TBR1 YY1 RERE NDUFS4 ALG11 SLC9A7 NDUFS3 SOX2 ALG13 HERC2 NEUROD2 SLC6A8 WFS1 PIGW HNRNPH2 ARNT2 HIRA DEPDC5 REV3L IQSEC2 SNX14 SH2B1 NDUFS6 SHANK3 RAD21 GABRB2 GDI1 ACADL SLC35C1 NDUFAF3 TREM2 STAG1 ATP1A3 SIM1 SCN2A CLIP2 NDUFV1 MED12 HTRA2 TRAPPC9 SEC23B GABRA1 ALDH18A1 PIGO SETD5 RAB11B NIPBL SIK1 GRIK2 ST3GAL3 PCGF2 NRXN1 TMEM126B MECP2 GFM1 AHDC1 MED23 SCN1B ASXL3 DHCR7 GJA5 CNKSR2 AUTS2 GRIA3 EHMT1 TMEM138 TMLHE TIMMDC1 TAF1 HECW2 NDUFAF5 TBC1D24 PROKR2 DHCR7 SYNGAP1 MED13L MECP2 ST3GAL5 SQSTM1 ADGRV1 SLC35A3 CLCN4 KMT5B ADSL KCNA2 ALG13 NHS EHMT1 KDM5B NDUFS8 ND1 ADNP MSTO1 AGTPBP1 SYN1 EEF1A2 TBX2 EDC3 PGAP1 TMEM237 SLC6A8 MKRN3 SON ATP6V1A CACNA1B DLG3 SCN1B PIGP AIMP1 GRIN2D LINS1 PIK3CA CHRNA7 NDN NDUFB10 DPYD UBA5 SMAD4 SLC45A1 HESX1 MCTP2 TCF20 C12ORF4 NEXMIF SNX14 EGF NALCN PRSS12 TSC2 CDKL5 AKT1 TLK2 DOCK7 CLCN4 PIGV TSC2 PPP3CA BCORL1 NLGN4X FOXP2 NDUFS4 CHD1 NDUFB11 AFF2 OTUD6B ARVCF GTF2I KCNT1 FTSJ1 RORA TRNW COX3 PIGL GABRG2 NAA15 CDKL5 PRKAR1A ARFGEF2 SYNGAP1 ARID1B BCOR PACS2 GPHN TRNH NDUFA13 KMT2C NLGN3 GNAQ TCF12 LRRK2 PPP2R5D CRBN MBOAT7 CLIP1 TBX1 PUF60 AP3B2 DHDDS PTCHD1 SLC25A12 TRNS2 USP27X HDAC4 PGAP2 WDR26 NUBPL SNRPN TRIO PWAR1 GATM STAG2 POGZ ARX PACS1 FLCN MAN1B1 MAOA NPAP1 FRRS1L GABRG2 BAZ1B HNMT WWOX POLA1 NDUFV2 GATAD2B SCN8A GABRG2 PINK1 KDM5C TUSC3 SLC13A5 SCN9A EXTL3 KPTN CACNA1C DYM ZNF711 PARS2 IQSEC1 OTX2 NEXMIF NTRK2 SOX3 SCN2A GRIN1 ARX TNIK SCN1A PNKP SLC25A1 NDUFB3 RAB39B CHD2 FOXP1 TMEM231 SCN3A RPS6KA3 STX1B FMR1 MECP2 CACNA2D2 SCN8A SEMA3E SCN1A NDUFA1 RERE CNNM2 NECAP1 GTF2IRD1 CHMP2B CREBBP TSC1 SH2B1
Protein Mutations 1
S1009A
SNP 1
rs6971
HP:0000716: Depressivity
Genes 381
TRNF ARSG FUS ANG PDE11A GLE1 SARS1 PLA2G6 NEK1 SLC18A2 HLA-DRB1 FMN2 TRNS2 XK SMPD1 HTT CHD7 ATXN10 SNCAIP TCF4 ATP1A3 GPR101 DRD2 PDGFB OPTN TWNK RRM2B GBA KCNT1 BCR JPH3 NOTCH3 PDCD1 PAH PIGC HTR2A PRKN DNMT1 TRNL1 ZC3H14 ST3GAL3 USH1G LMNB1 LIMK1 SNCA ADH1C ATRX OCRL PRKACA TBL2 FMR1 PRNP CPOX USP8 PPARGC1A UCHL1 VPS13C GLUD2 KCNJ2 TBK1 MST1 TWNK MSTO1 MAPT B3GALNT2 PPP2R2B PROKR2 PRNP XPR1 RPS20 POLG SQSTM1 ARMC5 NDST1 TRNN TARDBP USH2A TRNL2 GNAS DCPS STX16 TTC19 ATXN10 SLC20A2 TBX1 CSF1R GSN ND1 ATP7B CDH23 TAC3 MYO7A WFS1 TWNK PDGFRB HS6ST1 PRKCG ESPN COX2 HIRA GNAS CLCN4 CASR ARSA GABRA1 GCH1 DNA2 MAPT UBQLN2 GDAP2 FGF8 TOR1A SEMA4A TK2 UFD1 FUS DGUOK EPM2A HARS1 C9ORF72 POLG UNC13A PODXL TBK1 LRRK2 CLIP2 HTRA2 DCTN1 TRAPPC9 C19ORF12 PLA2G6 MATR3 C12ORF4 GRIK2 SLC6A4 PRNP MECP2 CP HLA-DQB1 CFAP410 CACNA1G MED23 AARS2 VCP TRNQ PRNP JMJD1C SRPX2 VAPB MYO7A SGCE CC2D1A VPS35 ABCA7 CCNF EHMT1 C9ORF72 SNCA MLH1 PANK2 DUSP6 CEP78 GABRB3 FIG4 NR4A2 BMPR1A PTPN22 PARK7 MECP2 DNMT1 WASHC4 TRNS1 CACNA1G AMACR VCP ALMS1 IDUA CHMP2B PMS1 GIGYF2 KISS1R TSC1 RPS6KA3 COQ2 ERBB4 KDM5B POLG2 SEC24C SLC2A1 COQ2 DNAJC13 MSTO1 MSH6 FBXO31 RRM2B CHMP2B HTT POLG EDC3 PGAP1 NSMF SLC25A4 ATXN2 PIK3CA THOC2 PER2 GLA CACNA1H TBC1D7 PAH SQSTM1 POLG GNAS PRNP AIMP1 ARMC5 CIB2 LINS1 GABRG2 FGFR1 C9ORF72 CDH23 METTL23 TACR3 EPCAM TRNS1 PPOX KRAS ANOS1 SLC45A1 WARS2 POLG FA2H COASY HLA-DQB1 GNAS TRNL1 PRSS12 CLN6 GBA PMS2 C9ORF72 CLCN4 HBB TSC2 PDGFB AIP PRKAR1A COMT MAPT DNAJC5 CRADD ATXN8 ATXN2 ATP13A2 ARVCF GTF2I WHRN GBA TRNW COX3 KISS1 TREM2 TGFBR2 PDZD7 AFG3L2 PDGFRB BCS1L MAN1B1 SNCA VCP NEFH TRNH COX1 ATP1A3 DAO CPOX PINK1 LRRK2 HMBS CRBN DCTN1 CTSF GPR35 CLIP1 TBX1 ND5 TAF15 ND4 PTS PON3 MED25 DNAJC6 TRNS2 NSUN2 FMO3 SPAST HMBS FGF17 ELN PON1 CBS CYP27A1 FGF14 PSAP FMR1 TMEM106B KCTD17 RREB1 CHCHD10 TWNK TBP AP2S1 ATXN8OS FRRS1L ATXN8OS BAZ1B HNMT FAN1 ADGRV1 PINK1 HNRNPA1 PRPH TUSC3 MBOAT7 PRNP PANK2 FGF14 GABRG2 KCTD17 PDGFRB TECR LMAN2L EIF4G1 GNAS CLRN1 EPHA4 GP1BB JRK IQSEC1 TREM2 MSH2 PSEN1 RFC2 PON2 MAPK1 SGCE PER3 PROK2 GRIN2A TNIK PFN1 MLH3 GRN ND6 CRKL ANXA11 C9ORF72 GNRHR EZR VCP USH1C GNRH1 TOR1A WFS1 POLG NHLRC1 CISD2 CHCHD10 WDR11 SPRY4 PPT1 PCDH15 TBP GTF2IRD1 SOD1 RSRC1 GLT8D1 DCTN1 GNA11 TARDBP
Protein Mutations 4
A1298C C677T V158M V66M