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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012792-05
Application #
6655136
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (01))
Program Officer
Khalsa, Jagjitsingh H
Project Start
1999-09-01
Project End
2006-03-31
Budget Start
2003-09-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2003
Total Cost
$447,014
Indirect Cost
Name
University of Miami School of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
052780918
City
Miami
State
FL
Country
United States
Zip Code
33146
Jones, Deborah L; Waldrop-Valverde, Drenna; Gonzalez, Peggy et al. (2010) Mental health in HIV seronegative and seropositive IDUs in South Florida. AIDS Care 22:152-8
Ownby, Raymond L; Kumar, Adarsh M; Benny Fernandez, J et al. (2009) Tumor necrosis factor-alpha levels in HIV-1 seropositive injecting drug users. J Neuroimmune Pharmacol 4:350-8
Kumar, Adarsh M; Borodowsky, Irina; Fernandez, Benny et al. (2007) Human immunodeficiency virus type 1 RNA Levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction. J Neurovirol 13:210-24
Waldrop-Valverde, Drenna; Ownby, Raymond L; Wilkie, Frances L et al. (2006) Neurocognitive aspects of medication adherence in HIV-positive injecting drug users. AIDS Behav 10:287-97
Waldrop-Valverde, Drenna; Ownby, Raymond L; Kumar, Mahendra (2005) Influence of depression and HIV serostatus on the neuropsychological performance of injecting drug users. Psychiatry Clin Neurosci 59:372-8
Kumar, Adarsh M; Solano, Maria P; Fernandez, Jesus B et al. (2005) Adrenocortical response to ovine corticotropin-releasing hormone in young men: cortisol measurement in matched samples of saliva and plasma. Horm Res 64:55-60
Waldrop-Valverde, Drenna; Valverde, Eduardo (2005) Homelessness and psychological distress as contributors to antiretroviral nonadherence in HIV-positive injecting drug users. AIDS Patient Care STDS 19:326-34
Waldrop, Drenna; Ownby, Raymond L; Kumar, Mahendra (2004) Serial position effects in HIV-infected injecting drug users. Int J Neurosci 114:493-516
Kumar, Mahendra; Kumar, Adarsh M; Waldrop, Drenna et al. (2003) HIV-1 infection and its impact on the HPA axis, cytokines, and cognition. Stress 6:167-72
Miguez-Burbano, Maria Jose; Pineda-Medina, Luisamaria; Lecusay, Robert et al. (2002) Continued high risk behaviors in HIV infected drug abusers. J Addict Dis 21:67-80

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