HIV-1 Infection, Injecting Drug Use, and Neuroendocrine Response to Psychological Stress.

BACKGROUND: Previous studies have suggested that HIV-1 infection is associated with neuroendocrine abnormalities including alterations in autonomic nervous system (ANS) activity. The norepinephrine (NE) response to cold pressor stress, an α-adrenergic challenge, is blunted in HIV-1 infection. Given the relation of ANS activity to the function of the hypothalamic-pituitary-adrenal (HPA) axis and its role in cognitive functioning, changes in response to stress may be a factor in HIV-related cognitive dysfunction. OBJECTIVE: In this study, we evaluated the NE and cortisol response of persons in three groups. DESIGN/PARTICIPANTS: We studied stress response in three groups: (1) those with HIV-1 infection and a history of injecting drug use (IDU), those with HIV-1 infection but no IDU, and a control group of uninfected individuals without a history of IDU. Stress was induced by administering a neuropsychological test known to induce an immediate increase in NE, the Stroop Color-Word Test. Blood samples were obtained immediately before and after participants completed the Stroop and then at two intervals over the next 20 minutes. Data were analyzed using mixed-effects repeated measures models. MAIN MEASURES: Serum norepinephrine, epinephrine, and cortisol. RESULTS: Analyses showed that those with both HIV-1 infection and history of IDU had a significantly greater NE response to stress that did not return to baseline over 20 minutes compared to those without infection or IDU history. Epinephrine and cortisol responses followed similar patterns, but between-group differences were not statistically significant. CONCLUSIONS: The combination of history of IDU and HIV infection may produce an exaggerated neuroendocrine response that does not quickly return to baseline levels. Given the potential impact of these on cognitive and physical function in affected these individuals, implementing stress management techniques with them may be important.

Evaluation of practice effect on neuropsychological measures among persons with and without HIV infection in northern India.

An evaluation of the effects of HIV infection on neurocognition over time is important for understanding disease progression. Changes in cognitive function can be evaluated longitudinally by using neuropsychological testing at repeated intervals. The assessment of change over time, however, is complicated by the potentially confounding influence of learning on repeated test administrations, often referred to as practice effect. In this study, we present data on testing of persons with or without HIV infection on a battery administered at study baseline and repeated 1 year later. Results suggest that practice effects may be diminished in persons with HIV infection compared to without it. This appears to be true even among those with relatively intact immune functioning as measured by CD4 count.

Childhood trauma and METH abuse among men who have sex with men: Implications for intervention.

Methamphetamine (METH) has become one of the most widely abused drugs in South Florida, particularly among MSM who may or may not be HIV seropositive. High rates of childhood trauma have been reported among HIV-infected MSM (Chartier et al., 2010), but, the association of childhood trauma, and mood disorders with methamphetamine use in HIV-infected men, has not been comprehensively explored. A better understanding of the association between these factors could improve existing substance abuse treatment intervention strategies and medical treatment programs (e.g., medication adherence; Carrico, 2010) to enhance positive health outcomes for male meth abusers living with the psychological consequences of childhood abuse. This study, as part of a larger study, examined the occurrence of childhood trauma and depression in a group of HIV seropositive METH abusing MSM. Significantly higher levels of depression symptom severity were found among METH users relative to non-METH users (p < .001). Irrespective of HIV status, METH users also reported higher frequencies of emotional, physical and sexual child abuse relative to non-METH users (p < .001). Among meth users, depression was predicted by childhood emotional neglect. These results suggest that childhood maltreatment may be implicated in the development of emotional distress (e.g., depression) and higher prevalence of methamphetamine/drug abuse in this population. These findings have important implications for substance abuse interventions, specifically targeting METH addiction among MSM. Addressing childhood trauma and depression may play a key role in enhancing the effectiveness of interventions for methamphetamine addiction.

Neuropsychological test performance among healthy persons in northern India: development of normative data.

Accurate identification of neurocognitive impairment associated with HIV infection (and other CNS-involved conditions) is dependent upon utilization of appropriate normative neuropsychological test performance data from healthy individuals with a similar background, culture, and characteristics of the target individual or group to be tested. In India, regional differences in language, culture, and availability of resources can significantly affect performance on neuropsychological testing. This study developed age- and education-adjusted normative data for commonly used neuropsychological test scores for use in northern India.

Marked reduction in serotonergic activity in a sexually aggressive adolescent male.

Serotonergic dysfunctions are implicated in conduct disorder, impulsivity, and aggression. Early adverse experiences increase the risk for these behaviors in adolescents. The authors investigated serotonergic activity in one adolescent male who experienced maternal abandonment and childhood abuse and exhibited severely aggressive sexual offenses. Platelet serotonin (5-HT) concentration, [14C]-5HT uptake kinetics, and plasma prolactin, cortisol response to D,L-fenfluramine (D,L-FEN) were measured. Results showed extremely low 5-HT concentration (2.9+/-0.7 ng/108 platelets), [14C]-5HT uptake rate (0.5+/-0.04 mM/min/107 platelets), undetectable Km and Vmax, and abnormally blunted prolactin, cortisol response to D,L-FEN. These abnormalities in this sexually aggressive adolescent may be a consequence of childhood abuse.

Human immunodeficiency virus infection in the CNS and decreased dopamine availability: relationship with neuropsychological performance.

Human immunodeficiency virus (HIV-1) infection in the central nervous system (CNS) is associated with a wide range of neurological, cognitive, and behavioral problems. HIV-1 enters the brain soon after the initial infection and is distributed in varying concentrations in different regions with specific affinity to the subcortical regions, particularly the basal ganglia, causing neurodegeneration of dopaminergic regions and resulting in the decreased availability of dopamine (DA) in the CNS. Although there are numerous reports on HIV-1-associated neuropsychological (NP) impairment, there is a paucity of studies showing a direct relationship between the decreased availability of dopamine in different regions of postmortem brains of HIV-1-infected individuals and the level of performance in different NP functions during life. Dopamine is the key neurotransmitter in the brain and plays a regulatory role for motor and limbic functions. The purpose of the present study was to investigate the relationship between the decreased availability of dopamine found in the postmortem brain regions (fronto-cortical regions, basal ganglia, caudate, putamen, globus pallidus, and substantia nigra) of individuals with HIV/AIDS and the antemortem level of performance (assessed as T scores) in different NP functions. The relationship between HIV-1 RNA levels in different brain regions and the level of performance in different NP domains was also investigated. We found that although DA concentrations were 2-53% lower in the brain regions of HIV-1-infected, HAART-treated individuals, compared with HIV-negative controls, a 45% decrease in DA levels in the substantia nigra (SN) of HIV-1-infected individuals was significantly correlated with the low level of performance (T scores) in the speed of information processing, learning, memory, verbal fluency, and average T scores across domains. In case of homovanillic acid (HVA), the variable changes in different regions, including the substantia nigra, basal ganglia, caudate, and putamen (compared to that in the HIV-negative individuals), were significantly correlated with the level of performance (T scores) in motor functions, speed of information processing, and attention/working memory. HIVRNA levels in the frontal cortex, caudate, and GP were significantly inversely correlated with abstract/executive function, motor, learning, verbal fluency, and attention/working memory. No significant correlations were found between HIVRNA in other brain regions and NP performance. These findings suggest that the decreased availability of dopamine in the SN (the main site of DA synthesis in the CNS), and changes in the levels of HVA in different brain regions are, in part, related with the lower level of performance in some of the NP functions in individuals with HIV/AIDS.

Education effects on the International HIV Dementia Scale.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) within the Indian subcontinent continues to spread. Although the primary clade of HIV in India differs from that of most Western countries, recent evidence suggests that the Indian clade (Clade C) also impacts neurocognitive functioning. India also has extremely high illiteracy rates that may confound detection of neurocognitive impairment, since many assessments to detect such impairment are heavily influenced by formal schooling. Among those with HIV/AIDS who have had limited educational opportunities and who are in the early stage of infection, the confounding effects of education on tests for neurocognitive impairment may be particularly salient. We therefore tested influence of HIV serostatus and education on a commonly used tool to screen for cognitive impairment, the International HIV Dementia Scale (IHDS), among Indian men and women in the catchment area of the Post Graduate Institute of Medical Education and Research (PGIMER) located in Chandigarh, India. Adjusted analyses showed that from a sample of 295 HIV-positive and HIV-negative individuals, only education was significantly associated with performance on the IHDS. HIV-negative and HIV-positive individuals, who were in the early stages of infection, performed similarly. Further development of this test to account for the effects of education on cut-off scores used to indicate possible dementia are needed, particularly for use in resource-limited settings such as India where low levels of education are widespread.

Mental health in HIV seronegative and seropositive IDUs in South Florida.

About one-third of HIV-infected people in the USA have a history of injection-drug use. Injecting drugs are a primary vector for HIV transmission. Drug and alcohol use are significant contributors to sexual transmission of the virus. In South Florida, urban injection-drug users (IDUs) represent a substantial population at risk for infection. Substance use management in this group is critical. As part of a larger study of at-risk populations in South Florida, we examined mental health differences among IDUs (n=117), HIV seropositive IDUs (n=130), and HIV seronegative non-IDUs (n=169). We explored factors associated with depression and anxiety between groups, and found HIV seronegative and seropositive IDUs not receiving antiretroviral (ARV) treatment to have poorer overall mental health than both HIV seropositive participants on ARVs and non-IDU participants. Our data support systems enhancement to meet the various psychosocial and health care needs among IDUs and highlight the need for resource allocation to target community-based integrated mental health services in urban populations. In addition, our data underscore the need for primary and secondary HIV prevention interventions to address the drug-use risk behaviors among IDUs to reduce the likelihood of HIV infection and transmission in this population.

HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: a two-year follow-up study.

BACKGROUND: It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other. While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B) infection on both immune and neuroendocrine systems, the consequence of HIV-1 clade C infection (with structural differences from HIV-1B virus) on these systems is not clearly understood. METHODS: We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS and their relationship with declining CD4+ cell counts in neurologically asymptomatic HIV-C infected individuals (N=84) in order to understand the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity. RESULTS: We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83+/-0.39 vs controls, 8.04+/-0.45; p<0.01), there was a significant decrease in DHEAS in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02+/-4.9 vs 185.1+/-12.03, p<0.001), and consequently a significant increase in cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19+/-0.002 vs control 0.058+/-0.006; p<0.001). Moreover, in HIV-1C infected individuals, there was a strong positive correlation between DHEAS and CD4 cells (r=0.2; p<0.05), and a strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and CD4 cells (r=-0.25; p<0.01; and r=-0.31; p<0.001, respectively). CONCLUSIONS: These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection, and that the evaluation of increase in plasma cortisol, a decrease in DHEAS, and an increase in cortisol:DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection. Furthermore, these findings may indicate the dysregulation of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity, the enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone-progesterone pathway, and that it may offer an opportunity for drug discovery targeting re-regulation of 3beta-HSD activity for potential therapeutic application in HIV-1C infection.

Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains.

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after infection and becomes localized in varying concentrations in different brain regions, the most vulnerable is the basal ganglia (BG). It is hypothesized that HIV-1-mediated neuropathogenesis involves degeneration of dopaminergic neurons in the substantia nigra and the loss of dopaminergic terminals in the BG, leading to deficits in the central dopaminergic activity, resulting in progressive impairment of neurocognitive and motor functions. In the era of highly active antiretroviral therapy (HAART), although the incidence of HIV-associated dementia (HAD) has decreased, the neurocognitive and neuropsychological deficits continue to persist after HAART. In this study, We investigated the impact of HIV-1 on dopaminergic activity with respect to concentrations of dopamine (DA) and homovanillic acid (HVA) in different regions of postmortem human brains of HIV-1-negative and HIV-1+ individuals and their relationship to neurocognitive impairment. We found that in HIV-1+ as well as HIV-negative cases, dopamine and HVA concentrations in ranged widely in different brain regions. In HIV-negative brain regions, the highest concentration of DA was found in putamen, caudate, substantia nigra, and the basal ganglia. In HIV-1+ cases, there was a significant decrease in DA levels in caudate nucleus, putamen, globus pallidus, and substantia nigra compared to that in HIV-negative cases. In HIV-1+ cases, a strong correlation was found between DA levels in substantia nigra and other brain regions. Concentration of HVA in HIV-negative cases was also highest in the regions containing high dopamine levels. However, no significant decrease in regional HVA levels was found in HIV-1+ cases. HIV-1 RNA load (nondetectable [ND] to log10 6.9 copies/g tissue) also ranged widely in the same brain regions of HIV-1+ cases. Interestingly, the brain regions having the highest HIV-1 RNA had the maximum decrease in DA levels. Age, gender, ethnicity, and postmortem interval were not correlated with decrease in DA levels. Profile of DA, HVA, and HIV-1 RNA levels in the brain regions of HIV-1+ individuals treated with HAART was similar to those not treated with HAART. A majority of HIV-1+ individuals had variable degrees of neurocognitive impairments, but no specific relationship was found between the regional DA content and severity of neurocognitive deficits. These findings suggest widespread deficits in dopamine in different brain regions of HIV-1-infected cases, and that these deficits may be the results of HIV-1-induced neurodegeneration in the subcortical regions of human brain.

Tumor necrosis factor-alpha levels in HIV-1 seropositive injecting drug users.

TNF-alpha is a highly pleiotropic cytokine and plays an important role in regulating HIV-1 replication. It may compromise the integrity of the blood-brain-barrier and, thus, may contribute to the neurotoxicity of HIV-1-infection. Both intravenous drug abuse (IDU) and HIV infection can increase TNF-alpha activity, but little information is available on the effects of a combination of these factors on TNF-alpha. We investigated plasma TNF-alpha levels and mRNA in the peripheral monocytes of 166 men and women in three groups: HIV-1-positive IDUs, HIV-1-negative IDUs, and HIV-negative non-IDU control participants. HIV-1-positive IDUs had higher TNF-alpha levels than HIV-1-negative IDUs who, in turn, had higher levels than controls. TNF-alpha mRNA expression in peripheral monocytes was significantly increased in both HIV-1-positive and negative IDUs compared to controls. These findings show that the effects of HIV infection and intravenous drug use may be additive in increasing TNF-alpha levels. Given the multiple effects of TNF-alpha in HIV infection, additional investigation of its role is needed.

Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

OBJECTIVE: To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. STUDY DESIGN: Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. RESULTS: Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. DISCUSSION: Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. CONCLUSION: Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls=119.1+10.5; p<0.05; AUC, HIV-1C =83.29+/-7.5 vs. controls=172.3+/-18.9; p<0.001), but no further change was observed in AUC of E in response to MSTCT at the two subsequent yearly visits. The basal plasma levels of ACTH in HIV-1C seropositives were not different than in the control subjects (pg/ml: HIV-1C=20.0+/-0.9 vs. controls=23.1+/-1.6; p=NS), but ACTH response to MSTCT in HIV-1C seropositive patients at the first visit was lower than in the controls (AUC, HIV-1C=23.57+/-1.5 vs. controls=30.94+/-3.5; p<0.05), and fluctuated between high and low at the second and third visits (AUC, 28.89+/-2.3 and 21.69+/-2.36, respectively). However, the baseline plasma levels of cortisol as well as the response of cortisol to MSTCT (AUC) in HIV-1C seropositive individuals were higher than in the control subjects at the first visit (mug/dl, HIV-1C=9.83+/-0.39 vs. controls=6.3+/-0.56; p<0.05; AUC, HIV-1C=12.31+/-0.7 vs. control=9.18+/-0.9; p<0.05), and remained high at the two subsequent yearly follow up visits of HIV-1C (AUC, 11.8+/-0.86 and 11.98+/-0.77, respectively). These findings demonstrate attenuated autonomic functions, a disconnection between response of ACTH and cortisol to the MSTCT challenge, and an inverse relationship between plasma levels of catecholamine(s) and cortisol. Since plasma catecholamines and cortisol are the peripheral mediators of the autonomic and HPA axis function, the findings of this study reflect the overall adverse effect of HIV-1C infection on autonomic as well as HPA axis functions. The findings, apart from being the first to demonstrate the progressive dysregulation of autonomic nervous system and HPA axis function among HIV-1C infected seropositive individuals much ahead of the onset of acquired immunodeficiency syndrome (AIDS), also suggest that MSTCT, involving visuoconstructive cognitive abilities, is an effective stressor for unraveling the underlying dysfunctions in the neuroendocrine functions in health and disease.

Human immunodeficiency virus type 1 RNA Levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction.

Human immunodeficiency virus type 1 (HIV-1) enters the central nervous system shortly after the infection and becomes localized in different regions of the brain, leading to various neurological abnormalities including motor disorders and neurocognitive deficits. Although HIV-1-associated functional abnormalities of the central nervous system (CNS) can be evaluated during life by using various test batteries, HIV-1 virus concentration in different brain regions can be measured only after death. The tissues obtained at autopsy provide a valuable source for determining the role of various factors, including that of HIV-1 viral load in the CNS, that may contribute to the regional CNS neuropathogenesis. For this study, we obtained from the National Institutes of Health-sponsored National NeuroAIDS Tissue Consortium (NNTC) the tissues from different brain regions collected at autopsy of HIV-1-positive (N = 38) and HIV-negative (N = 11) individuals, with postmortem intervals of 2 to 29 h, and measured HIV-1 RNA concentration in the frontal cortex, frontal cortex area 4, frontal cortex area 6, basal ganglia, caudate nucleus, putamen, globus pallidus, substantia nigra, and cerebrospinal fluid. Because HIV-1+ individuals were infected with the virus for up to 21 years and the majority of them had used highly active antiretroviral therapy (HAART), we used highly sensitive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay in order to detect a wide dynamic range of HIV-1 RNA with lower detection limit of a single copy. The primers and probes were from the long terminal repeat (LTR) region of HIV genome for achieving higher specificity and sensitivity of detection and amplification. Our results demonstrate a wide variation in the concentration of HIV-1 RNA in different brain regions (5.51 and 8,144,073; log(10) 0.74 and 6.91 copies/g tissue), and despite the high specificity and sensitivity of this method, viral RNA was not detected in 50% of all the samples, and in 30% to 64% of samples of each region of HIV-1+ individuals. However, the highest concentration of viral RNA was found in the caudate nucleus and the lowest concentration in the frontal cortex and cerebrospinal fluid. The viral RNA was undetectable in all samples of HIV-negative individuals.

A pilot study to test the effects of art-making classes for family caregivers of patients with cancer.

PURPOSE/OBJECTIVES: To test the effects of an art-making class (AMC) on reducing anxiety and stress among family caregivers of patients with cancer. DESIGN: A pretest and post-test quasi-experimental design. SETTING: A residential care facility near tertiary treatment centers in the southeastern United States. SAMPLE: The convenience sample of 69 family caregivers was aged 18-81 years (X = 48 years) and predominantly Catholic. Most had at least a high school education. Two-thirds were daughters, wives, or mothers of patients with cancer. METHODS: Participants completed a demographic data survey and a Beck Anxiety Inventory (BAI). Researchers collected a saliva sample from each participant to measure salivary cortisol, which indicates stress levels. Following pretesting, a two-hour AMC was delivered. Post-tests included a repeat BAI and a second saliva sample. MAIN RESEARCH VARIABLES: Anxiety and stress. FINDINGS: Anxiety was significantly reduced after AMC. Stress was reduced. CONCLUSIONS: The AMC appeared to reduce anxiety and stress. The addition of a control group and replication with larger numbers are suggested. The physiologic cortisol measure corroborated BAI findings but was difficult to obtain from some cultural groups and was expensive to analyze. IMPLICATIONS FOR NURSING: Family caregivers may benefit from participation in art-making interventions. Nurses should continue to investigate the use of creative approaches to promote holistic care.

HPA axis activity and neuropathogenesis in HIV-1 clade C infection.

A disturbance in the activity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported among individuals with HIV-1 infection. However, these studies have been carried out in the West where the infecting clade is clade B. HIV-1 infection is rapidly spreading in various parts of South East Asia, including India, where the HIV-1 infecting clade is largely clade C. An investigation of HPA axis activity in this type of infection is warranted since there are many structural differences between clades B and C. This study was carried out to investigate whether HIV-1 infection clade C interferes with the functions of the hippocampus and thereby affects the HPA axis. We tested the hypothesis that when hippocampus activity is disturbed, it leads to the development of neuropathogenesis in HIV-1 C-clade infected individuals. This study included asymptomatic HIV-1 seropositive individuals (n=117) and, age-matched, HIV-1 seronegative controls (n=29). Neuroendocrine function of the HPA axis was evaluated using plasma levels of cortisol, ACTH, and DHEA-S, both in the morning (0800-1000 hr) and evening (2000-2200 hr). A significant elevation of cortisol levels during A.M. and P.M. hours was observed in HIV-1 infected individuals when compared to the controls. Interestingly, no significant change in ACTH level was observed in HIV-1 seropositive subjects, either during A.M or P.M. Elevated levels of cortisol in HIV-1 seropositive subjects appear to be independent of ACTH and may be the result of a defective negative feedback mechanism. On the other hand, a significant decrease in the plasma levels of DHEA-S was observed during A.M. and P.M. hours in HIV-1 infected individuals, leading to an increased cortisol to DHEA-S ratio. Since increased levels of cortisol and decreased levels of DHEA-S are related to the development of neuropathogenesis, it is hypothesized that a study of the development of neurocognitive deficits among HIV-1 seropositive individuals in India is warranted.

Adrenocortical response to ovine corticotropin-releasing hormone in young men: cortisol measurement in matched samples of saliva and plasma.

BACKGROUND: Assessment of hypothalamic-pituitary-adrenal (HPA) axis function in stress-related health problems in humans is frequently carried out as a dynamic test by measuring the profile of increment in adrenocortical hormone (ACTH) and/or cortisol level in plasma in response to corticotropin-releasing hormone (CRH) administration. However, obtaining multiple blood samples for this type of test is not only an invasive procedure but also problematic to use in individuals with constricted or damaged veins which collapse during the blood draw such as the injecting drug users (IDUs) and HIV-1-infected individuals. Salivary cortisol measurement presents a non-invasive alternate approach to evaluate HPA axis activity in different situations. In order to validate the efficacy of salivary cortisol measurement for a dynamic test in IDUs and HIV-1-infected individuals, the present study was carried out to evaluate the cortisol profile in matched samples of plasma and saliva in healthy young men in response to ovine CRH (oCRH) administration. METHODS: Cortisol levels were measured in matched samples of plasma and saliva of healthy young men at baseline and over a 90-min period after administration of a single low dose of oCRH (1 microg/kg). RESULTS: Salivary cortisol levels were found to follow the profile similar to that of plasma, increasing significantly at each time point after oCRH administration from their respective baseline values (all Sign tests, p < 0.05). The peak level of cortisol occurred at 30 min in both fluids. Although salivary cortisol concentration was a fraction of the total plasma cortisol levels at all time points, there was a significant correlation in the values between the two fluids at baseline (r = 0.87, p < 0.02) as well as at 90 min (r = 0.70, p < 0.03). CONCLUSION: The findings support the earlier studies and substantiate the efficacy of using salivary free cortisol measurement for assessment of dynamic function of pituitary-adrenal axis in healthy young men and its application in individuals such as IDUs and HIV-infected individuals who may have difficulty in donating multiple blood samples.

Mood and hormone responses to psychological challenge in adolescent males with conduct problems.

BACKGROUND: Relations between stress hormones and antisocial behavior are understudied. METHODS: A subsample (n = 335) of at-risk males recruited in first grade for a longitudinal study were recruited at approximately 16 years of age for a laboratory study, including two psychological challenges: describing their worst experience on videotape, and a task in which a loud tone could be avoided. Measures of affect, urine, and saliva were collected multiple times before and after challenges. RESULTS: Negative affect increased following the worst-event challenge and decreased following the avoidance challenge. Mean conduct problems (CP) across ages 7-17 years were positively related to negative affect and inversely related to positive affect. CP were inversely related to post-challenge urinary epinephrine (E) levels when baseline E and potential confounds were controlled. Cortisol concentrations in saliva collected soon after the first challenge were positively related to CP in a post hoc subset of youths with extreme CP. CONCLUSIONS: Key findings A) associated persistent CP with more negative affectivity and less positive affectivity, B) replicated and extended prior findings of an inverse association of CP and urinary E, and C) suggested provocative hypotheses for future study relating CP, trauma history, trauma recall, and cortisol reactivity.

HIV-1 infection and its impact on the HPA axis, cytokines, and cognition.

Immediately after infection, Human immunodeficiency virus, type 1 (HIV-1) enters the central nervous system (CNS) and is localized in highest concentration in the hippocampus and basal ganglia. Since these areas are associated with HPA axis and autonomic activities as well as cognition, it has been hypothesized that these functions will be impacted adversely in HIV-1 infection. In the treatment of HIV infection, although the highly potent antiretroviral (HAART) drugs have been effective in reducing peripheral viral load and prolonging life expectancy, these drugs do not cross the blood-brain barrier in therapeutic concentrations. Therefore, it has been proposed that the beneficial effects of HAART on the CNS will be limited. Our investigations on seropositive individuals, showing hypo-reactivity of the autonomic system and HPA axis activity suggest that HIV-1 infection is a model of chronic stress. Furthermore, an elevated baseline TNF-alpha level as well as its increased reactivity to an alpha-adrenergic challenge among HIV-1+ individuals, may lead to additional neurodegeneration. It is proposed that the effects of HIV-1 infection on the brain will have implications for neurocognitive and mental health functioning in seropositive individuals even in patients undergoing HAART therapy. These outcomes may result in the need to develop facilities for long term "care-giving".