Cerebrospinal fluid levels of 5-HIAA and dopamine in people with HIV and depression.

Depression is a common illness in people with HIV (PWH) and is associated with substantial morbidity and mortality. The mechanisms that underpin depression in PWH remain incompletely elucidated, and more research is therefore needed to develop effective treatments. One hypothesis is that neurotransmitter levels may be altered. These levels could be influenced by the chronic inflammation and viral persistence that occurs in PWH. We examined a panel of cerebrospinal fluid (CSF) neurotransmitters in PWH on suppressive antiretroviral therapy (ART), many of whom had a current depression diagnosis. CSF monoamine neurotransmitters and their metabolites were measured from participants in studies at the Emory Center for AIDS Research (CFAR). Only participants on stable ART with suppressed HIV RNA from both plasma and CSF were analyzed. Neurotransmitter levels were measured with high-performance liquid chromatography (HPLC). Neurotransmitters and their metabolites included dopamine (DA), homovanillic acid (HVA, a major metabolite of dopamine), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA, a major metabolite of serotonin), and 4-hydroxy-3-methoxyphenylglycol (MHPG, a major metabolite of norepinephrine). Multivariable logistic regression was used to evaluate factors associated with depression. There were 79 PWH with plasma and CSF HIV RNA levels < 200 copies/mL at the time of the visit, and 25 (31.6%) carried a current diagnosis of depression. Participants with depression were significantly older (median age 53 years versus 47 years, P = 0.014) and were significantly less likely to be African American (48.0% versus 77.8%, P = 0.008). Participants with depression had significantly lower dopamine levels (median 0.49 ng/mL versus 0.62 ng/mL, P = 0.03) and significantly lower 5-HIAA levels (median 12.57 ng/mL versus 15.41 ng/mL, P = 0.015). Dopamine and 5-HIAA were highly correlated. In the multivariable logistic regression models, lower 5-HIAA was significantly associated with the depression diagnosis when accounting for other significant demographic factors. The associations between lower 5-HIAA, lower dopamine, and depression in PWH suggest that altered neurotransmission may contribute to these comorbid conditions. However, the effects of antidepressants on neurotransmitters cannot be ruled out as a factor in the 5-HIAA results.

Alcohol and cannabis use in Urban, African American, first-episode schizophrenia-spectrum patients: associations with positive and negative symptoms.

OBJECTIVE: On the basis of limited prior research on associations between symptoms and substance use in first-episode psychosis, a retrospective chart review was conducted to test 2 hypotheses: (1) the presence of positive symptoms is associated with alcohol use prior to admission and (2) the absence of prominent negative symptoms is associated with cannabis use prior to admission. METHOD: Eligible patients included those admitted for a first episode of psychosis in a public-sector, university-affiliated hospital that serves a predominantly African American, socially disadvantaged, urban population. The 72 patients included in the analysis were 18 to 40 years of age, and all were African American. Using a structured data collection instrument, discharge summaries of consecutively admitted patients from January 2002 to March 2005 were reviewed to extract data on basic demographic and clinical characteristics, the presence of 11 symptoms, and alcohol and cannabis use within 6 months prior to hospitalization. RESULTS: Alcohol use in the 6 months prior to hospitalization was associated with a higher frequency of positive psychotic symptoms among first-episode patients. Cannabis use was associated with a lower likelihood of having prominent negative symptoms. These associations remained even after controlling for relevant covariates in logistic regression models. CONCLUSION: Although the direction of causality cannot be established, the association between positive psychotic symptoms and alcohol use may represent a self-medication effect, whereas the association between lesser negative symptoms and cannabis use may result from the fact that interpersonal deficits and reduced hedonic capacity minimize drug-seeking activities.