Defining Neurobiological Links Between Substance Use and Mental Illness

Major Depressive Disorder Clinical Trial

Official title: Defining Neurobiological Links Between Substance Use and Mental Illness

Status Recruiting

Clinical Trial Summary

Background: Nicotine dependence leads to about 480,000 deaths every year in the United States. People with major depressive disorder (MDD) are twice as likely to use nicotine compared to the general population. They have greater withdrawal symptoms and are more likely to relapse after quitting compared with smokers without MDD. More research is needed on how nicotine affects brain function in those with MDD. Objective: To understand how nicotine affects symptoms of depression and related brain function. Eligibility: People aged 18 to 60 years with and without MDD who do not smoke cigarettes or use other nicotine products. Design: Participants will have 2 or 3 study visits over 1 to 3 months. Participants will have 2 MRI scans at least 1 week apart. Each scan visit will last 5 to 7 hours. At each scan, they will have urine and breath tests to screen for recent use of alcohol, nicotine, and illegal drugs. Before each scan, they will take 1 of 2 medications: nicotine or placebo. Participants will receive each medication once. They will not know which medication they are receiving at each scan. For each MRI scan, they will lie on a table that slides into a cylinder. Sometimes they will be asked to lie still. Sometimes they will complete tasks on a computer. Tasks may include identifying colors or playing games to win money. Each scan will take about 2 hours. Participants will answer questions about their thoughts, feelings, and behaviors before and after each scan. They will have a blood test after each scan.

Clinical Trial Description

Study Description: Tobacco smoking leads to 480,000 deaths and a loss of $300 billion a year in the U.S. Individuals with major depressive disorder (MDD) are more vulnerable for experiencing these burdens as they are twice as likely to use nicotine versus the general population. The current work will explain the neurobiological basis of this enhanced risk and will define potential targets for lessening the impact of nicotine on those with MDD. This research plan will take the innovative approach of evaluating nicotine s effects in non-smokers with and without MDD. In contrast to focusing on nicotine dependent individuals, which introduces confounds due to chronic use, this design will directly show the domains in which the neurobiological impact of nicotine is greater in those with MDD, providing a mechanistic framework for enhanced risk. Objectives: The primary objective is to determine the differential neurobiological impact of a nicotinic agonist on those with and without current major depressive disorder. Whether such effects are linked with specific symptoms of MDD will be assessed as will the potential modifying influence of biological sex. Those with a lifetime history of MDD will be assessed as well given evidence that reduced reward responsivity is a trait that persists even when one no longer meets current MDD criteria. Endpoints: Brain function will be assessed in several ways: 1) Resting-state fMRI will determine pharmacologically mediated group-specific differences in functional brain organization and inherent dynamic functioning 2) Task-based fMRI will determine pharmacologically mediated group-specific differences in reward function, affective processing, and interceptive awareness. These same measures will further be assessed considering specific symptoms of MDD and biological sex. ;

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Mental Disorders
• Normal Physiology
• Substance Use Disorder
• Substance-Related Disorders

• NCT number: NCT05538910
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: NIDA IRP Screening Team
• Phone: (800) 535-8254
• Email: researchstudies@nida.nih.gov
• Status: Recruiting
• Phase: N/A
• Start date: February 2, 2023
• Completion date: December 31, 2027