HIV-1 neurocognitive disorders and chemokine receptors.
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AIDS Dementia Complex↗
Biomedical subjects
J H Atkinson
Publications and source records attributed to J H Atkinson.
Social and psychological characteristics of HIV-infected women and gay men. HIV Neurobehavioral Research Center (HNRC) Group.
In this paper, we examine social and psychological characteristics of 60 HIV+ women and gay men, matched on age and stage of HIV infection. A discriminant function analysis was performed using measures of life adversity, psychological distress, and psychosocial resources. The best combination of predictors for distinguishing between HIV+ women and gay men was comprised of satisfaction with emotional support, network size, use of avoidant coping, Hamilton depression, and loneliness scores [chi 2(7) = 14.8, p < .05]. Women reported more satisfaction with emotional support, although gay men had larger social networks. Gay men used more avoidant coping and had higher lonelines scores as compared to women, although women reported more depressive symptoms. Utilizing this set of psychosocial variables, we correctly classified 73% of the HIV+ women and 67% of the HIV+ men. These findings suggest the importance of considering subgroup differences in the design of counseling programs for HIV+ individuals.
Adaptation, Psychological↗
Neurological Symptoms, Not Signs, Are Common in Early HIV Infection.
UNLABELLED: Objective. To examine the cross-sectional prevalence of neurological symptoms and signs in a large cohort of human immunodeficiency virus (HIV)-seropositive men, and determine the relationship of the symptoms to disease stage, immunologic markers, and independent variables from neuropsychological (NP) testing and psychiatric interview. METHODS: One hundred-nine controls and 386 HIV-infected volunteers enrolled in the HIV Neurobehavioral Research Center (HNRC) longitudinal study. The majority, without acquired immune deficiency syndrome (AIDS), were screened for alcohol/substance abuse; previous diagnosis of HIV-associated dementia; and HIV-unrelated developmental, neurological, medical, and neurobehavioral conditions which potentially impair cognition; and underwent a structured neurological interview and examination, standardized NP testing, and psychiatric interview as part of a more extensive battery. A large subset (N = 377) underwent lumbar puncture for cerebrospinal fluid (CFS) examination. We examined the relationship of sixteen select but independent variables, using stepwise multiple regressions, from demographic/staging, immunological, NP, and psychiatric domains to neurological symptoms in an effort to identify possible predictors of subclinical nervous systems involvement. Results. All categories of neurological symptoms were significantly more prevalent among medically asymptomatic (CDC stage A) subjects than controls, with a further rise in prevalence in those with more advanced stages of infection. The most marked rise was seen in cognitive and sensorimotor complaints. In contrast, significant findings on neurological examination were evident in only the sicker (stage C) subjects. Stage of illness, serum β2-microglobulin, psychiatric indices of depressed mood or anxiety, and NP "motor" performance were the most significant independent variables associated with the presence of neurological symptoms. CSF pleocytosis was seen early (CDC stage A), and may reflect the presence of HIV in the central nervous system (CNS) at the least stages of infection. We also confirmed the value of CSF β2m and neopterin as important markers of advancing disease stage. Whether they predict subclinical CNS involvement is to be determined by longitudinal observations. Conclusion. Neurological complains are common in medically asymptomatic HIV subjects whereas signs are not. The symptoms correlate with commonly determined independent measures of depression, anxiety, NP tests of fine motor speed and strength, as well as indices of disease worsening (CDC stage, serum β2m).
AIDS Dementia Complex↗
Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.
We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.
Adult↗
Is gender dysphoria dysphoric? Elevated depression and anxiety in gender dysphoric and nondysphoric homosexual and bisexual men in an HIV sample. HNRC Group.
Few if any studies before the AIDS epidemic suggested that male homosexuals may on average have higher levels of depression than male heterosexuals. However, several samples of homosexual and bisexual men in HIV studies suggest that depression and anxiety are high in these populations, and that this psychiatric morbidity began before the AIDS epidemic. We tested the hypothesis that high childhood gender nonconformity (CGN) is associated with depression and anxiety, and so might account for differences in these variables among samples of homosexuals. A total of 254 homosexual or bisexual male subjects were assessed for depression, anxiety, and associated symptoms using various self-report and interview measures, as well as for CGN (using the Freund Feminine Gender Identity scale, FGI). For comparison purposes only, we also evaluated the subjects for the DSM-III diagnosis of Ego-Dystonic Homosexuality. Highly gender nonconforming men (high FGI scores) were more likely to have current symptoms of anxiety and depression by self-report, and to have had a lifetime history of depression by clinical interview. This association was more often due to FGI items dealing with childhood than adulthood. When the FGI was broken into subscales by a prior factor analysis, stepwise regression suggested that the subscale measuring core gender identity nonconformity (so-called "gender dysphoria") was more reliably associated with depression and anxiety than were the factors measuring nonconformity in the areas of masculine and feminine gender roles, or genitoerotic (sexual) roles. This subscale was also the only FGI measure correlating with Ego-Dystonic Homosexuality. AIDS (CDC stage and HIV serostatus) and age did not account for these findings. We conclude that the often-reported higher levels of depression, anxiety, and associated symptoms among homosexual and bisexual men in AIDS studies are more common in the subgroup of such men who are gender dysphoric. Theoretical and clinical implications of these data are discussed.
Adult↗
Decline in working memory associated with HIV infection. HNRC Group.
HIV infection has been associated with decline in a number of cognitive functions that are components of 'working memory'. Thus, tests of working memory that require the interaction of these components may be particularly sensitive to cognitive dysfunction that arises from HIV infection. To assess this possibility, working memory was examined in 147 HIV-seropositive (HIV+) and 38 HIV-seronegative (HIV-) males using the Reading Span Test and the Digit Span subtest from the Wechsler Memory Scale-Revised (WMS-R). Speed of information processing, a component of some working memory tasks, was assessed with a version of the Sternberg Memory Scanning task. Results indicated that symptomatic HIV+ subjects were impaired relative to HIV- control subjects on the Reading Span and Digit Span tests. Asymptomatic and mildly symptomatic HIV+ groups exhibited a trend toward impairment on these tests, and on the whole, a greater proportion of HIV+ subjects than HIV- subjects were impaired. The groups did not differ significantly in information processing speed. These results indicate that deficits in working memory are apparent in at least a subset of HIV-infected individuals. These deficits are most apparent in symptomatic HIV+ individuals, but the decline may begin during the asymptomatic phase of infection.
Adult↗
The HNRC 500--neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center.
The present study examined neuropsychological (NP) functioning and associated medical, neurological, brain magnetic resonance imaging (MRI), and psychiatric findings in 389 nondemented males infected with Human Immunodeficiency Virus-Type 1 (HIV-1), and in 111 uninfected controls. Using a comprehensive NP test battery, we found increased rates of impairment at each successive stage of HIV infection. HIV-related NP impairment was generally mild, especially in the medically asymptomatic stage of infection, and most often affected attention, speed of information processing, and learning efficiency; this pattern is consistent with earliest involvement of subcortical or frontostriatal brain systems. NP impairment could not be explained on the bases of mood disturbance, recreational drug or alcohol use, or constitutional symptoms; by contrast, impairment in HIV-infected subjects was related to central brain atrophy on MRI, as well as to evidence of cellular immune activation and neurological abnormalities linked to the central nervous system.
AIDS Dementia Complex↗
Stress and depressive symptoms prospectively predict immune change among HIV-seropositive men. HIV Neurobehavioral Research Center Group.
LIFE stress, mood, and other psychosocial factors may help to explain variability in HIV (human immunodeficiency virus) disease progression. Attempts to support this notion empirically have produced mixed findings; several studies report a positive relationship between psychosocial factors and various indicators of disease progression or immune function (e.g., Evans et al. 1992; Goodkin et. al. 1992), whereas others have failed to detect any association (e.g., Perry et. al. 1992).
Adaptation, Psychological↗
Psychiatric morbidity associated with acquired immune deficiency syndrome-related grief resolution.
This study examined acquired immune deficiency syndrome (AIDS)-related grief resolution and psychiatric morbidity in 286 human immunodeficiency virus (HIV)-positive and HIV-negative gay men examined between 1989 and 1993 in San Diego, CA. Psychiatric morbidity, mood ratings, and bereavement assessments were obtained using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scales for Depression and Anxiety, and Texas Revised Inventory of Grief. Sixty percent of the men (N = 171) reported a loss within the previous 12 months. Eighteen percent of the bereaved met criteria for unresolved grief. No differences were evident in lifetime psychiatric disorders, yet men with unresolved grief demonstrated an elevated prevalence of current major depression and panic disorder when compared with resolved grievers. Clinician sensitivity to the grief process and its relationship to psychiatric complications is an important component of comprehensive psychiatric and medical care of men at high risk for HIV during this era of AIDS.
Acquired Immunodeficiency Syndrome↗
Neurocognitive disorders in HIV-1 infection. HNRC Group. HIV Neurobehavioral Research Center.
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AIDS Dementia Complex↗
Neuroleptic treatment of HIV-associated psychosis. HNRC group.
The aim of this rater-blinded randomized study was to evaluate the efficacy and side effects of haloperidol and thioridazine in the treatment of new-onset psychosis in HIV-positive individuals. Participants were 13 men who had no history of psychosis prior to infection with HIV, and whose psychosis was not attributable to delirium or to non-HIV-related organic factors. Participants were evaluated at baseline after at least one month without neuroleptic treatment and then weekly for six weeks of the experimental treatment using several rating scales. The mean daily dose in chlorpromazine equivalents was 124 mg. Both neuroleptics produced modest but significant reduction in overall level of psychosis and in positive symptoms, but not in negative symptoms. All the haloperidol-treated patients developed extrapyramidal side effects and required treatment with anticholinergic medication, whereas three of the five thioridazine-treated patients had noticeable side effects. We make recommendations for the treatment of HIV-associated psychosis with neuroleptics.
AIDS Dementia Complex↗
HIV-associated psychosis: a study of 20 cases. San Diego HIV Neurobehavioral Research Center Group.
OBJECTIVE: Psychosis is an uncommon but serious complication of infection with HIV. This article presents the results of a study of HIV-infected individuals with psychosis. METHOD: The authors evaluated 20 HIV-infected men who had noniatrogenic new-onset psychosis without delirium, current substance abuse, or previous psychotic episodes. Clinical, neuropsychological, CSF, magnetic resonance imaging, and neuropathologic assessments were made. A comparison group consisting of 20 nonpsychotic HIV-infected men matched to the psychotic subjects with respect to age, race, years of education, and Centers for Disease Control HIV stage was also evaluated. RESULTS: The psychotic patients differed from the nonpsychotic comparison subjects in having significantly higher rates of past stimulant and sedative/hypnotic abuse or dependence and, at follow-up, a significantly higher rate of mortality. They also showed a trend toward greater global neuropsychological impairment. CONCLUSIONS: New-onset psychosis may be, at least in part, a manifestation of an HIV-associated encephalopathy.
AIDS Dementia Complex↗
Natural history of neuropsychiatric manifestations of HIV disease.
The neuropsychiatric manifestations of HIV disease include neurobiologic and psychobiologic phenomena. The former consist of primary CNS complications caused directly by HIV, and include cognitive disorders (mild neurocognitive disorder and HIV-associated dementia) and other CNS diseases such as myelopathy and the demyelinating neuropathies; and secondary disorders (principally deliria) occasioned by opportunistic infections, neoplasms, cerebrovascular events, and the effects of metabolic derangements and medications. The latter (psychobiologic) phenomena reflect efforts to cope with various nodal, or transition points, in HIV disease; such points of transition include time of serostatus determination, adaptation to asymptomatic seropositivity, response to early medical symptomatology, and later transition to frank AIDS. Anxiety symptoms and various efforts to cope with anxiety (e.g., denial, anger, withdrawal, hypochondriacal preoccupation) all can punctuate these transition points. Additionally, there may be reactivation of long-standing psychopathology (e.g., depression) in seropositive individuals who tend to belong to a group that has an elevated prevalence of pre-infection psychiatric disorder. These interacting neurobiologic and psychobiologic phenomena pose challenges to the psychiatrist who must develop a good understanding of the medical aspects of HIV infection, as well as the neuropsychiatry of AIDS. In this way psychiatric physicians can play an important role in early identification of neuropsychiatric complications, assist the medical team to anticipate emotional and behavioral disturbances, and develop treatment plans that maximize our ability to help those with HIV infection achieve the best possible quality of life.
AIDS Dementia Complex↗
Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group.
Magnetic resonance imaging was used to compare male subjects seropositive for antibody to human immunodeficiency virus type 1 (HIV positive), with and without medical symptoms, with two groups of men who were seronegative (HIV negative). The control subjects included men at high risk for exposure to HIV-1 and those at low risk. None of the HIV-positive subjects met criteria for HIV-associated dementia or had detectable opportunistic brain disease. Quantitative image-analytic techniques were used to estimate volumes of ventricular and cortical cerebrospinal fluid, cerebral white matter, and cortical and subcortical gray matter structures. Relative to low-risk group control subjects and asymptomatic HIV-positive subjects, nondemented but medically symptomatic HIV-positive subjects showed significant increases in cerebrospinal fluid, reduced volume of cerebral white matter, and reduced cerebral gray matter volumes. Unexpectedly, however, some cerebrospinal fluid increases and gray matter volume decreases were present in the seronegative high-risk control subjects as well.
Adult↗
Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid. The HIV Neurobehavioral Research Center Group.
As part of a longitudinal study, 265 cerebrospinal fluid (CSF) specimens from 204 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects and 43 seronegative controls were evaluated. Of the 204 seropositive persons, 78 (38%) had > or = 1 CSF culture positive for HIV-1; the probability of being culture positive increased as the number of CSF samples obtained increased (P = .0018). Significantly correlated with culture positivity were elevations in CSF protein level (P = .014) and CSF white blood cell count (P = .001). Virus was more readily cultured from clarified CSF (89%, 42/47) than from the cellular fraction (30%, 14/47; P < .00001). Amplification of HIV-1 DNA by polymerase chain reaction (PCR) from 25 seropositive persons was positive in 9 (82%) of 11 culture-positive and in 4 (29%) of 14 culture-negative specimens, while amplification of viral RNA detected all 11 culture-positive and 9 (64%) of the 14 culture-negative CSF specimens. These data support the hypothesis that the development of HIV-1-associated neurocognitive disorders are not dependent solely on the presence of HIV-1 within the central nervous system.
Adult↗
Mild neurocognitive disorder: needed addition to the nosology of cognitive impairment (organic mental) disorders.
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Cognition Disorders↗
Functional status and well-being in a placebo-controlled trial of zidovudine in early symptomatic HIV infection.
To determine the effect of zidovudine on functional status and well-being in patients with early symptomatic human immunodeficiency virus (HIV) infection, 70 subjects in a randomized, placebo-controlled trial (ACTG Protocol 016) were observed for 1 year using a brief quality-of-life questionnaire. Thirty-four subjects were assigned to placebo and 36 subjects to zidovudine, 200 mg orally every 4 h (1,200 mg daily). Functional status and well-being were measured every 3 months using a 30-item self-administered questionnaire derived from health ratings from the Medical Outcomes Study. The mean changes from baseline for zidovudine versus placebo groups were compared using paired and two-sample t tests. Subjects receiving a placebo reported better quality of life compared to baseline than subjects receiving zidovudine at 24 weeks for all dimensions of well-being, including overall health, energy, mental health, health distress, pain, and quality of life. The difference between the two groups' changes from baseline for overall health was 11.5 points on a 100-point scale (p = 0.02), and 11.1 points for energy (0.002). There were no differences between changes from baseline along various dimensions of functional status (physical, social, role, and cognitive function). At 52 weeks both groups reported worse overall health than at baseline, and changes in scores were more similar for the two groups. Although zidovudine has previously been demonstrated to delay progression of disease for patients with mildly symptomatic HIV infection, early in treatment the net effect of a 1,200 mg daily dose of zidovudine may diminish patients' subjective well-being.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
HIV-1 associated neurocognitive disorder. The HNRC Group.
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Adult↗