Investigating the genetic factors influencing addiction and neuropsychiatric disorders

Characterization of Phenotypic and Genotypic Regressors

This study is trying to see how our genes might affect addiction and mental health by comparing healthy people with those who have substance use disorders through tests and brain scans.

Quick facts

• Study type: Observational
• Enrollment: 2625 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT01148381 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the relationship between genetic variants and behaviors associated with addiction and substance abuse. Participants, including healthy individuals and those with substance use disorders, will undergo genetic testing, MRI scans, and complete various questionnaires and behavioral tasks. The goal is to identify how genetic information may explain differences in cognitive functions and imaging data related to substance use. Data collected will be compared across different populations to enhance understanding of addiction mechanisms.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 or older, both healthy non-smokers and those with substance use disorders.

Not a fit: Patients with significant neurological illnesses or those unable to tolerate the study procedures may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding of the genetic factors influencing addiction, potentially guiding personalized treatment approaches.

How similar studies have performed: Other studies have shown promise in linking genetic factors to addiction behaviors, suggesting that this approach may yield valuable insights.

Eligibility criteria

* 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. Participants may also be asked about any lingering neurological and psychiatric symptoms that may be a result of COVID-19 infection. The Medical Advisory Investigator (MAI) will assess the severity in relation to the potential impact on data. Assessment tool: History and physical (H\&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 for which the subject is also under consideration). Assessment tool: self-report during H\&P of special education classes, history of specific learning disability or mental retardation. A validated IQ test such as the Shipley-2 may also be administered. 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 for which the subject is also under consideration). 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). 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.
* Other health conditions that would impact safety of participation or scientific integrity of data collection.

Inclusion criteria: NIDA CTN Pilot Study

All participants must:

1. 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.
2. 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

1. 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.
2. Cognitive impairment. Assessment tool: self-report during H\&P of special education classes, history of specific learning disability or mental retardation. A validated IQ test such as the Shipley-2 may also be administered. Rationale: Cognitive impairment may impair ability to complete the assessments and would add unnecessary noise to the data.
3. 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.

Where this trial is running

Baltimore, Maryland

• National Institute on Drug Abuse, Biomedical Research Center (BRC) — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Betty Jo Salmeron, M.D. — National Institute on Drug Abuse (NIDA)
• Study coordinator: NIDA IRP Screening Team

Conditions Healthy Volunteers; Substance Use Disorders; Genotype; Phenotype; Characterization; fMRI; Natural History