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：
10331210
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/10331210
关键词：
AIDS/HIV problem Adherence Age Amygdaloid structure Analgesics Anhedonia Anterior Anxiety Appointment Binding Blood Tests Brain CD4 Lymphocyte Count CNR1 gene Cannabis Chronic Classification 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 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 Play Population Poverty Process Research Resolution Rest Rewards Risk Behaviors Role 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 marijuana use marijuana use disorder marijuana user midbrain central gray substance mood symptom neural circuit neuroimaging neuromechanism nicotine use novel pain processing pain scale pain sensitivity pain symptom relating to nervous system research clinical testing response reward anticipation reward circuitry reward processing specific biomarkers substance use subthreshold depression treatment strategy 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.

项目概要/摘要针对 RFA-DA-21-012，“阐明 SUD 和其他疾病复杂发病机制” “艾滋病病毒感染者/艾滋病患者的精神疾病”（PLWH），我们建议调查奖励和疼痛回路大麻使用和抑郁症合并症是艾滋病毒感染者中非常普遍的两种疾病，我们将重点关注年轻人。成人（18-34 岁）应尽量减少 HIV 神经元慢性影响并考虑到物质使用率较高我们提出的模型是：1）功能障碍奖励。（奖励学习、期望、成就、积极预测错误方面的缺陷）和疼痛超敏反应（疼痛敏感性、厌恶、负面预测错误）会导致年轻人使用大麻和抑郁症合并症 2) PLWH。缰核（Hb）是一个小的边缘中枢，通过抑制在这些过程中发挥着关键的调节作用。疼痛和丧失后腹侧被盖区 (VTA) 向伏隔核 (NAc) 发出奖励信号 3) THC，大麻的主要成分，通过与大麻素 1 受体结合发挥其精神镇痛作用奖励和疼痛系统，包括前扣带回 (ACC)、导水管周围灰质 (PAG)、丘脑、杏仁核、VTA、NAc 和 Hb，可暂时缓解情绪和疼痛症状，但会产生长期影响奖赏回路的改变会加剧抑郁和药物滥用 4) 利用改进。在功能磁共振成像分辨率方面，我们的新颖成像方法克服了先前的技术限制来研究 Hb 和其他对奖励和疼痛处理至关重要的小结构，来自 18-34 岁感染者的健康数据。系统显示，43% 的人患有抑郁症，21% 的人患有大麻使用障碍，只有 68% 的人患有无法检测到的艾滋病毒使用奖励侧翼（RFT）和奖励预测误差（RPET）fMRI 任务，我们记录了病毒载量（VL）。在奖励预期、获得和预测错误期间，大脑活动不同，从而预测未来此外，我们在 RPET 和疼痛任务期间检测了 Hb 激活，并绘制了 Hb 内在图谱。功能连接（iFC）与对奖赏（VTA）、疼痛（岛叶、PAG）或两个回路（NAc、ACC）至关重要的区域。记录了不同的 Hb iFC 与抑郁症、快感缺失和大麻使用有关的情况。吸食大麻和年轻感染者抑郁症会产生累加效应，导致奖励不足和痛苦超敏反应，并且这种模式将预测 1 年随访时的更差结果，我们将使用 2×2 阶乘。设计：1) 70 名抑郁症大麻使用者；2) 70 名抑郁症非大麻使用者；3) 70 名非抑郁症大麻者使用者；和 4) 70 名非抑郁症非使用者将在以下时间接受全面评估。基线、6 个月和 12 个月，包括抑郁、物质、奖励、疼痛、焦虑、创伤、HIV 治疗、CD4+ 将进行基线认知测试和功能磁共振成像（静息状态、RFT、RPET、疼痛）。方法将包括机器学习分类。