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The Neural Underpinnings of Depression and Cannabis Use in Young PLWH

年轻感染者抑郁症和大麻使用的神经基础

基本信息

批准号：
10677848
负责人：
Vilma Gabbay
金额：
$ 81.82万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677848
关键词：
Adherence Age Amygdaloid structure Analgesics Anhedonia Anterior Anxiety Appointment Binding Blood Tests Brain CD4 Lymphocyte Count CNR1 gene Cannabis Chronic Clinic Complex Corpus striatum structure Data Depressed mood Development Diagnosis Diagnostic Discipline Disease Epidemic Evaluation Expectancy Functional Magnetic Resonance Imaging Functional disorder Future Gender Goals HIV HIV/AIDS Habenula Health Health system Hypersensitivity Image Insula of Reil Learning Light Machine Learning Maps Measures Mental Depression Mental Health Mental disorders Methodology Methods Modeling Morbidity - disease rate Neurons New York Nucleus Accumbens Outcome Pain Participant Pattern Persons Play Population Poverty Process Research Resolution Rest Rewards Risk Behaviors Role Self Assessment Serum Severities Severity of illness Sex Orientation Signal Transduction Sleep Structure Substance Use Disorder System Testing Tetrahydrocannabinol Thalamic structure Trauma Ventral Tegmental Area Viral Viral Load result Work addiction age group behavioral construct causal model cognitive function cognitive testing cohort comorbid depression comorbidity computerized depressive symptoms design disorder control follow-up graph theory health disparity imaging modality improved indexing machine learning classification marijuana use marijuana use disorder marijuana user midbrain central gray substance mood symptom neural neural circuit neuroimaging neuromechanism nicotine use novel novel therapeutic intervention pain processing pain scale pain sensitivity pain symptom research clinical testing response reward anticipation reward circuitry reward processing specific biomarkers substance use subthreshold depression suicidal young adult

项目摘要

PROJECT SUMMARY / ABSTRACT In response to RFA-DA-21-012, “Elucidation of mechanisms underlying complex morbidities of SUD and other mental Illnesses in people living with HIV/AIDS” (PLWH), we propose to investigate reward and pain circuitry in cannabis use and depression comorbidity, two highly prevalent conditions in PLWH. We will focus on young adults (ages 18-34) to minimize HIV neuronal chronicity effects and in light of the high rates of substance use and reduced adherence to HIV treatment in this age group. Our proposed model is: 1) Both reward dysfunction (deficits in reward learning, expectancy, attainment, positive prediction errors) and pain hypersensitivity (pain sensitivity, aversion, negative prediction errors) contribute to cannabis use and depression comorbidity in young PLWH. 2) The habenula (Hb), a small limbic hub, plays a pivotal regulatory role in these processes by inhibiting ventral tegmental area (VTA) reward signals to the nucleus accumbens (NAc) following pain and loss. 3) THC, a major component of cannabis, exerts its psychoactive analgesic effects by binding to cannabinoid 1 receptors in the reward and pain systems, including the anterior cingulate (ACC), periaqueductal gray (PAG), thalamus, amygdala, VTA, NAc, and Hb, creating temporary relief of mood and pain symptoms but resulting in long-term alterations in reward circuitry that exacerbate depression and substance use. 4) Capitalizing on improvements in fMRI resolution, our novel imaging methods overcome prior technical constraints to study the Hb and other small structures critical to reward and pain processing. Supporting data from PLWH ages 18-34 in our health system show that 43% have depression, 21% have cannabis use disorders, and only 68% had undetectable HIV viral load (VL). Using the reward flanker (RFT) and reward prediction error (RPET) fMRI tasks, we documented distinct brain activity during reward anticipation, attainment and prediction error, which predicted future depression severity. Further, we detected Hb activation during RPET and a pain task, and mapped Hb intrinsic functional connectivity (iFC) with regions critical to reward (VTA), pain (insula, PAG), or both circuits (NAc, ACC). Distinct Hb iFC were documented in relation to depression, anhedonia and cannabis use. We hypothesize that cannabis use and depression in young PLWH have an additive effect, inducing both reward deficits and pain hypersensitivity and that this pattern will predict worse outcomes at 1 year follow-up. We will utilize a 2×2 factorial design: 1) 70 depressed cannabis users; 2) 70 depressed cannabis non-users; 3) 70 non-depressed cannabis users; and 4) 70 non-depressed cannabis non-users. Participants will have comprehensive evaluations at baseline, 6- and 12-months including depression, substance, reward, pain, anxiety, trauma, HIV treatment, CD4+ count, and VL. Baseline cognitive testing and fMRI (resting-state, RFT, RPET, pain) will be performed. Analytical approaches will include machine learning classifications.

项目摘要/摘要