IDU'S HIV-1 INFECTION, NEUROENDOCRINE RESPONSES

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from Applicant's Abstract): Growing evidence suggests that
injecting drug users (IDUs) and HIV+ IDUs exhibit abnormal neuroendocrinology
such as limbic-hypothalamo-pituitary-adrenocortical (HPA) activity. Thus, the
applicant's earlier investigations found attenuated norepinephrine (NE) and
ACTH responses to a cold pressor challenge in HIV-1+ individuals. This raised
the possibility that HIV-1 infection and IDU are associated with a lack of
adaptation to "stressors." These abnormalities could also be mediators of
mental disorders and negative medical outcomes in these populations. In order
to develop strategies for suitable interventions, it is necessary to identify
the HPA-specific neuroendocrine abnormalities in IDUs and HIV-1+ IDUs.

This 5-year proposal investigates the responses of the HPA axis and autonomic
system and their role as mediators in the pathogenesis of mental disorders
including anxiety, depressed mood, distress and cognitive-motor dysfunctions in
HIV-1+ IDUs. Two groups of IDUs (n=280), divided into HIV-1+ (n=140) and HIV-1-
(n-140), and a group of non-IDUs and HIV-1- normal (non-IDU) individuals
(n=140), will be investigated using a 2X3X3 cross-sectional design (men, women;
African-American, Hispanics and Caucasians; HIV-1+ IDUs, HIV-1- IDUs and HIV-1-
non-IDUs). HIV-1+ subjects will be recruited across the entire spectrum of
infection. Subjects will be examined for symptoms of mental disorders using
specific batteries and investigated for their neuroendocrine (ACTH, cortisol),
and NE and E responses to cold pressor, star tracing and oCRH challenges, as
well as expression of lymphocyte Type I and Type II corticosteroid receptor
transcripts. Findings will be useful in explaining the pathogenesis of mental
disorders occurring in HIV-1+ IDUs as well as in HIV-1- IDUs. Attempts will
also be made to examine the role of plasma HIV-mRNA load (as well as blood CD4
cell counts) and that of HAART (highly active antiretroviral therapy) in HIV-1+
subjects since these drugs do not readily cross the blood-brain-barrier.
StatusFinished
Effective start/end date9/1/993/31/06

Funding

  • National Institute on Drug Abuse: $447,014.00
  • National Institute on Drug Abuse: $426,129.00
  • National Institute on Drug Abuse: $416,142.00
  • National Institute on Drug Abuse: $436,418.00
  • National Institute on Drug Abuse

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