Characterization of Phenotypic and Genotypic Regressors for Imaging

Study Overview
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Brief Summary
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The influence of genes on addictive and neuropsychiatric disorders is complex, especially given that multiple genes likely influence certain behaviors that are correlated with addiction. Researchers are interested in looking at the genetic information of individuals who are enrolled on National Institute for Drug Abuse studies to investigate specific genetic variants that may be related to substance abuse. Researchers will study the effects of genes on several aspects of thinking such as attention, memory, decision making, problem solving, learning, and emotional feelings, and investigate the ways in which genetic information affects addictive behaviors and substance abuse. In addition, researchers will study how genes may explain differences in imaging data in substance users. Objectives: - To collect genetic information for research on genetic aspects of addiction and substance abuse. Eligibility: Adults age 18 or older (1) healthy, non-drug-using nonsmokers, (2) healthy smokers, (3) healthy individuals dependent on other commonly abused drugs, and (4) individuals with other psychiatric disorders. Participants must be enrolled in another National Institute on Drug Abuse, Intramural Research Program imaging protocol. Design: This study involves one to two visits to National Institute on Drug Abuse, Intramural Research Program that may be separate from the participant's current research protocol study visits or on the same day as those visits. Participants will provide a blood sample and complete questionnaires about mood, memory, and learning. Participants may also be asked to do a few tasks, such as playing computer games involving coin tosses and money management, or responding to questions on a computer screen.

Detailed Description
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Objective: To determine genetic variants as well as behavioral measures across different study group populations. Results of these will be used as regressors to help explain inter-individual differences in data collected across IRP protocols. Study Population: The study population will include 1) healthy non-smoking, participants with no substance use disorders 2) healthy individuals with nicotine use disorder 3) healthy individuals with other substance use disorders 4) individuals with other psychiatric disorders and 5) treatment-seeking individuals with substance use disorders. Participants must be under evaluation for another NIDA-IRP protocol, generally healthy, and age 18 or older. Design: The main study will require approximately 5-8 hours. Main study procedures may be done in 1 visit or multiple visits, and may be done in conjunction with another NIDA-IRP study. After being consented into the main study, the participant will be asked to submit a blood sample, an MRI scan, complete various questionnaires, characterization instruments and several behavioral tasks. Blood will only be drawn once, provided there are no technical problems (such as sample damage during collection, preparation, shipping or assay) requiring a repeat draw. If participants enroll in other NIDA-IRP imaging protocols, they will be asked to repeat a few of the time- sensitive questionnaires in this protocol during the MRI visits of the other protocols. Data acquired in this protocol will be compared to data acquired in other NIDA-IRP protocols. An arm of this protocol will be used to pilot test a phenotyping battery developed by the NIDA CTN. This battery overlaps with several of the assessments in the main protocol. Participants in the NIDA CTN pilot study who also meet criteria for the main study may participate in the main study as well. The CTN Pilot procedures require approximately 4-6 hours to complete. Outcome Measures: The primary outcome measures in this study are the genetic, behavioral and phenotypic factors that are related to addiction. Secondary outcome measures are to compare the genetic, behavioral and phenotypic factors to imaging and behavioral data acquired across other IRP protocols.

Official Title
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Characterization of Phenotypic and Genotypic Regressors

Conditions
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Healthy Volunteers, Substance Use Disorders

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Main Study All participants must be: -under evaluation for another NIDA-IRP study or the NIDA CTN pilot portion of this study. Justification: data acquired under other studies will be compared to data collected in this protocol. -> 18 years of age. Justification: Some NIDA-IRP studies have included teens, aged 13 17, but no current studies include them so we will only include adults in this study for now. EXCLUSION CRITERIA: Main Study. History of neurological illnesses that per the study clinicians would be significant enough to impair ability to tolerate the procedure or alter neuronal activity, including but not limited to CVA, CNS tumor, head trauma with significant sequelae, Multiple Sclerosis or other demyelinating diseases, epilepsy, movement disorders, or migraine in treatment. Assessment tool: phone screen and history and physical (H and P). Rationale: Neurological illnesses may impair ability to tolerate the procedures and alter neuronal activity, adding noise to the data. Cognitive impairment (unless this population of subjects is included in another IRP protocol in which the subject is also participating). Assessment tool: self-report during H&P of special education classes, history of specific learning disability or mental retardation, validated IQ test, such as Wechsler Abbreviated Scale of Intelligence (WASI) or Shipley-2. Rationale: Cognitive impairment may impair ability to tolerate the procedures and alter neuronal activity, adding noise to the data. Current major mood, anxiety or psychotic disorder (unless this population of subjects is included in another IRP protocol in which the subject is also participating). Assessment tool: self-report, H&P, a structured or semi-structured psychiatric interview such as the computerized SCID with follow up clinical interview (or full interviewer-administered) and/or the Mini International Neuropsychiatric Interview (M.I.N.I). Rationale: Current major mood or psychotic disorders may impair ability to tolerate the procedures and alter neuronal activity, adding noise to the data. Pregnancy. Assessment tool: Urine pregnancy test. Rationale: fMRI is not accepted as a safe procedure purely for research purposes during pregnancy. HIV -positive individuals. Assessment tool: oral HIV test with serum confirmation of positive results. Rationale: potential liver/metabolic/vascular disease can interfere with the physiological transduction mechanisms for fMRI (i.e. making the measurement unreliable). Unable to undergo MRI scanning due to possible pregnancy, metallic devices in the body, claustrophobia or body morphometry. Currently using respiratory, cardiovascular or anticonvulsant medications that may interfere with the BOLD MRI signal.. Non-English speaking. Assessment tool(s): self-report. Rationale: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing study procedures. The inability to effectively communicate safety procedures in a language other than English could compromise the safety of non-English speaking participants. Suspected or confirmed active SARS-CoV-2 infection. Assessment tool: 2019 Novel Coronavirus (COVID-19) patient screening tool administered by phone prior to participant arrival. The current version of the screening tool to be used is available at http://intranet.cc.nih.gov/hospitalepidemiology/emerging_infectious_diseases.html). Viral testing looking for SARS-CoV-2 in a specimen deemed appropriate by NIH such as nasopharyngeal or midturbinate swab. We reserve the right to change the specimen type as NIH approves new test procedures. This test may be carried out in-house at NIDA, NIH, at a community testing site or through a commercial vendor. Anyone with a positive symptom screen without a clear alternative explanation or a positive viral test will be excluded until they recover or (for asymptomatic cases) are no longer infectious. Additionally, participants will be asked about any lingering neurological and psychiatric symptoms such as difficulty with memory or concentration, changes in mood or new anxiety symptoms that may be a result of COVID- 19 exposure. The MAI will evaluate any lingering symptoms to determine whether the potential impact on data is compatible with continuing in the study. MAI will also retain the ability to exclude for a suspicious symptom screen without positive viral test. Rationale: Covid-19 is extremely infectious and can have serious consequences. Allowing participants with active infection would alter the risk:benefit ratio for non-treatment studies without a primary focus on SARS-CoV-2 to an unacceptable level of risk. In addition, Covid-19 can have cognitive consequences which would add unnecessary noise to the study data. Screening and testing will continue as long as public health officials and/or NIDA medical personnel deem it appropriate. Other health conditions that would impact safety of participation or scientific integrity of data collection. Inclusion criteria: NIDA CTN Pilot Study All participants must: Either have a current DSM-5 diagnosis for at least one of the following substance use disorders: nicotine, cocaine, marijuana, opiate; or 2) no current DSM-5 substance use disorder (control participants). Justification: These criteria are consistent with the scope of this study to pilot this battery of tests for future use in similar populations enrolled in the NIDA CTN studies. Be greater than or equal to 18 years of age. Justification: The NIDA CTN will use this battery in adults. Exclusion criteria: NIDA CTN Pilot Study A DSM-5 major psychiatric diagnoses unrelated to a substance use disorder including but not limited to bipolar disorder and schizophrenia. Diagnoses secondary to substance use disorder will be allowable providing the participant s symptoms do not interfere with the ability to complete assessments. Assessment tool: self-report, H&P, structured or semi-structured psychiatric interview. Rationale: Current major mood or psychotic disorders may impair ability to complete the assessments and would add unnecessary noise to the data. Cognitive impairment. Assessment tool: self-report during H&P of special education classes, history of specific learning disability or mental retardation, WASI. Rationale: Cognitive impairment may impair ability to complete the assessments and would add unnecessary noise to the data. Non-English speaking. Assessment tool(s): self-report. Rationale: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing study procedures. The inability to effectively communicate safety procedures in a language other than English could compromise the safety of non-English speaking participants. Suspected or confirmed active SARS-CoV-2 infection. Assessment tool: 2019 Novel Coronavirus (COVID-19) patient screening tool administered by phone prior to participant arrival. The current version of the screening tool to be used is available at http://intranet.cc.nih.gov/hospitalepidemiology/emerging_infectious_diseases.html). Viral testing looking for SARS-CoV-2 in a specimen deemed appropriate by NIH such as nasopharyngeal or mid- turbinate swab. We reserve the right to change the specimen type as NIH approves new test procedures. This test may be carried out in-house at NIDA, NIH, at a community testing site or through a commercial vendor. Anyone with a positive symptom screen without a clear alternative explanation or a positive viral test will be excluded until they recover or (for asymptomatic cases) are no longer infectious. MAI will also retain the ability to exclude for a suspicious symptom screen without positive viral test. Rationale: Covid-19 is extremely infectious and can have serious consequences. Allowing participants with active infection would alter the risk:benefit ratio for non- treatment studies without a primary focus on SARS-CoV-2 to an unacceptable level of risk. In addition, Covid-19 can have cognitive consequences which would add unnecessary noise to the study data. Testing will continue as long as public health officials and/or NIDA medical personnel deem it appropriate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| controls<br>healthy non-smoking, participants with no substance use disorders | |
| psychiatric disorders<br>individuals with other psychiatric disorders | |
| smokers<br>healthy individuals with nicotine use disorder | |
| substance use disorders<br>healthy individuals with other substance use disorders | |
| treatment seeking individuals<br>treatment seeking individuals with substance use disorders | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measures are the genetic, behavioral and phenotypic factors that are related to addiction. | To determine whether genetic polymorphisms, phenotypic measures and behavioral characterization instruments can explain variance in structural and functional imaging data and in behavioral outcome measures such as treatment outcome or substance use trajectories or patterns as collected under other NIDA IRP protocols and clinical trials conducted in the NIDA CTN. | each visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome measures are to compare the genetic, behavioral and phenotypic factors to imaging and behavioral data acquired across other IRP protocols. | To compare the genetic, behavioral and phenotypic factors to imaging and behavioral data acquired across other IRP protocols | each visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genotype, Phenotype, Characterization, fMRI, Natural History