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.We will test the overall hypothesis 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. Investigators 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. To capture a wide range of illness severity, investigators will include subthreshold depression and cannabis use on ≥20 days of the past 30 days. Comprehensive clinical evaluations, a computerized reward task, and blood tests for CD4+ count, VL, and serum THC will be performed at baseline, 6- and 12 months. fMRI (resting-state, RFT, RPET, pain task) and cognitive tests will be done at baseline.
To elucidate mechanisms of substance use disorders (SUD) and comorbid mental illnesses in people living with HIV (PLWH), the investigators propose to investigate reward and pain circuitry in cannabis use and depression comorbidity, two highly prevalent conditions in PLWH. The study will take place in our health system in The Bronx-a persistent epicenter of the HIV epidemic due to profound poverty and health disparities. The focus is on young adults (ages 18-34) to minimize HIV chronicity effects and due to the high rates of SUD and reduced adherence to HIV treatments in this age group; among >31,000 diagnosed young PLWH in The Bronx in 2019, less than 70% had suppressed (<200 copies/mL) viral load (VL).