Electroencephalographic sleep of adolescents with major depression and normal controls.

Forty-nine, mostly outpatient (86%), nonbipolar adolescents, aged Tanner stage III to 18 years, with a current diagnosis of major depressive disorder and 40 adolescents without current presence or history of psychiatric disorder were studied polysomnographically for three consecutive nights. Sleep latency was significantly longer in the depressive groups. The nonendogenous depressive patients exhibited significantly more awake time and lower sleep efficiency during the sleep period. No significant group differences were found for first rapid eye movement (REM) period latency, REM density, or any other REM sleep measures. Age correlated significantly with REM latency and delta sleep time, especially among depressive patients. No significant correlations between sleep measures and severity of illness were found. It appears that the classic REM sleep findings associated with the adult depressive syndrome are not present among depressive adolescents, indicating a later ontogeny for these abnormalities.

Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. I. Overview of study design.

Although much is known about the virus believed by most experts to be the cause of the acquired immunodeficiency syndrome and about its pathogenic actions, major areas of ignorance remain. Among these are the reasons for the varying time between infection with human immunodeficiency virus and development of acquired immunodeficiency syndrome, the relationship between neurologic and medical aspects of the disease, the time course of neuropsychological findings, and the prevalence of psychiatric morbidity. We assessed 124 homosexual men who were positive for human immunodeficiency virus and 84 who were negative for the virus. In this article we describe the study design, method of recruitment, and medical and demographic characteristics of the cohort, which will be followed up for 5 years.

A comparison of sodium bicarbonate and sodium lactate infusion in the induction of panic attacks.

Infusion of sodium lactate has been shown by a number of investigators to induce panic in patients with panic disorder, but the pathophysiology underlying this phenomenon is unknown. One theory to explain lactate's anxiety-producing effects involves its ability to induce alkalosis because of metabolic conversion to bicarbonate. To test this hypothesis, we administered both sodium lactate and sodium bicarbonate infusions in counterbalanced order to patients with panic disorder. Thirteen of 22 subjects panicked in response to lactate and nine of 20 subjects panicked in response to bicarbonate. Although the rate of panic between the two infusion responses was not significantly different, several aspects of response to the two infusions indicated that lactate may be a more potent producer of anxiety than bicarbonate. An unexpected finding was that bicarbonate panickers had a reduction in arterial carbon dioxide pressure during the infusion, while bicarbonate nonpanickers had an increase in arterial carbon dioxide pressure during the infusion. Induction of hyperventilation and subsequent hypocapnia appears to be a common denominator between lactate- and bicarbonate-induced panic.

Personality disorders predict onset of Axis I disorders and impaired functioning among homosexual men with and at risk of HIV infection.

BACKGROUND: A longitudinal study was conducted to investigate whether personality disorders (PDs) increase risk for the development of future Axis I disorders and serious functional impairment among human immunodeficiency virus (HIV)-seropositive and HIV-seronegative homosexual men. METHOD: Baseline assessments of PDs, Axis I disorders and symptoms, and Global Assessments of Functioning were conducted with a community sample of 107 (66 HIV-positive and 41 HIV-negative) homosexual men participating in a longitudinal study with semiannual interviews over 3 years. RESULTS: Logistic regression analysis indicated that PDs predicted onset of subsequent Axis I disorders after controlling for both HIV status and lifetime Axis I history (adjusted odds ratio, 4.31; P=.01; 95% confidence interval, 1.39 to 13.32). Of the 21 participants with PDs, 16 (76%) were subsequently diagnosed with Axis I disorders on at least one occasion. By contrast, only 36 (42%) of the 86 participants without PDs were subsequently diagnosed with Axis I disorders. Further, 33% of the participants with PDs, in comparison with only 8% of those without PDs, were assigned Global Assessments of Functioning scores of 50 or lower, indicating serious impairment during the postbaseline study period (adjusted odds ratio, 5.70; P<.005; 95% confidence interval, 1.66 to 19.53). CONCLUSION: Personality disorders may contribute to increased risk for onset of Axis I disorders and serious impairment among homosexual men regardless of HIV serologic status.

Panic attacks during placebo procedures in the laboratory. Physiology and symptomatology.

Heart rate, respiratory measurements, and Acute Panic Inventory symptoms of 17 patients with panic disorder who experienced panic attacks during a placebo infusion (situationally provoked panic) were analyzed and compared with similar data from a group of 19 patients with panic disorder who panicked during lactate infusion. Previously, it was shown that the group with lactate-induced panic attacks exhibited increased minute ventilation compared with normal control subjects and nonpanicking patients with panic disorder during lactate infusion. The group with situationally provoked panic attacks exhibited significant increases in both heart rate and minute ventilation immediately preceding the onset of the panic attack. The increase in minute ventilation appeared to be caused more by increase in tidal volume than in respiratory frequency. The increase in heart rate in the group with situationally provoked panic attacks was very similar to that seen in the group with lactate-induced panic attacks, but the group with situationally provoked panic attacks appeared to have somewhat greater increase in minute ventilation than the group with lactate-induced panic attacks. This suggests that the metabolic alkalosis produced by lactate infusion might actually blunt the full expression of panic-associated respiratory stimulation. These data validate the belief that significant cardiorespiratory stimulation occurring during panic attacks in the laboratory is not simply secondary to the intrinsic physiologic effects of panic-inducing substances such as lactate, yohimbine, and carbon dioxide.

Clinical and laboratory correlates of human immunodeficiency virus infection in a cohort of intravenous drug users from New York, NY.

BACKGROUND: The human immunodeficiency virus (HIV) epidemic has increasingly involved intravenous drug users. Few studies have attempted to define its clinical and laboratory characteristics in this population. METHODS: We recruited 223 intravenous drug users from New York, NY, for a prospective study of the natural course of HIV infection. Medical history, physical examination, medical staging, and immunologic assessments were performed at 6-month intervals. We examined the baseline findings among this cohort. RESULTS: Of the total cohort, 65.9% were men and 34.1% were women, with 70.9% African American, 12.6% white, 11.7% white Latino, and 4.9% black Latino. At baseline, 44.4% were HIV negative and 55.6% were HIV positive. No significant association was noted between ethnicity, gender, and serologic status. Also no significant difference was noted for homelessness either across serologic status or gender. There was a trend toward an association between gender and use of drugs during the week before interview; the women showed higher drug use. A significant association was noted between HIV serologic status and reported history of pneumonia, oral candidiasis, cough, night sweats, fever, and lymphadenopathy on physical examination. In a regression model, white blood cell count, hematocrit, symptom/sign complex score, and CD4 cell number were significantly associated with HIV status. CONCLUSION: This study provided important historical, clinical, and immunologic characteristics that are useful in the identification and evaluation of the HIV-infected intravenous drug user.

Premorbid polysomnographic signs in depressed adolescents: a reanalysis of EEG sleep after longitudinal follow-up in adulthood.

BACKGROUND: This is a report of a clinical follow-up study (10-15 years later as young adults) of adolescent major depressives and normal control subjects. Polysomnographic data were obtained during the original study period when the subjects were adolescent (time 1). With clinical follow-up (time 2) assessments in hand, our objective was to ascertain whether there were any premorbid polysomnographic signs associated with depression during adolescence. METHODS: Based upon initial (during adolescence) and follow-up clinical assessments (as adults), new subject groupings were generated: depression-free normal subjects and original normal subjects who experienced a depressive episode during the follow-up period (latent depressives). Suicidality and recurrence of depression were also examined. Multivariate analysis of covariance was used to analyze group differences in sleep measures and logistic regression for predicting three outcomes: lifetime depression, lifetime suicidality, and recurrence. RESULTS: Comparison of the depression-free normal subjects, the latent depressives, and the original major depressives revealed significant differences for sleep latency and sleep period time. Comparing all lifetime depressives (original major depressives and the latent depressives) to depression-free normal subjects revealed significantly more stages 3 and 4 combined (ST34) sleep and greater sleep period times among the depressives. An analysis involving the presence or absence of suicidality revealed no overall significant differences between the groups. Comparison of the lifetime depressives grouped by nonrecurrent and recurrent depressive course to the depression-free normal subjects revealed significant difference for sleep period time. Using logistic regression, we found that a longer sleep latency and sleep period time significantly predicted lifetime depression. Gender, ST34 sleep, and an interaction term for ST34 sleep and REM latency significantly predicted lifetime suicidality. CONCLUSIONS: There was evidence of premorbid sleep abnormalities during adolescence. A general pattern of sleep disruption around sleep onset and during the first 100 min of the sleep period and overall sleep was evident among the major and lifetime depressives, involving sleep latency (initial insomnia), sleep period time (hypersomnia), REM latency, and slow-wave sleep. This adds to the body of literature that highlights the importance of the first 100 min of the sleep period in depression.

Stressful life events and EEG sleep in depressed and normal control adolescents.

EEG sleep measures in 35 depressed and 33 normal control adolescents were examined in relation to stressful life events occurring in the year before sleep studies. There was a significant interaction between stressful life events and diagnostic status for REM latency and total REM time. In the normal controls, the presence of stressful life events was significantly associated with reduced REM latency and increased total REM time. Among the depressed adolescents, there were no significant effects of stressful life events on REM latency or total REM time. The depressed adolescents with no stressful life events (n = 9) had significantly lower REM latency values compared to normal control adolescents with no stressful life events (n = 13)(61.7 +/- 50.0 vs. 132.1 +/- 79.0, p < or = .01). It appears that stressful life events influence at least some measures of adolescent sleep and should be considered in future controlled studies aimed at understanding sleep changes in adolescent depression.

High-dose carbon dioxide challenge test in anxiety disorder patients.

Many investigators have shown that panic disorder patients and possibly social phobics are hypersensitive to the anxiogenic effects of inhaled carbon dioxide (CO2). In this study we administered double-breath inhalation of 35% CO2 and 65% oxygen (O2) to panic disorder patients, social phobics, and normal controls. At baseline, panic disorder patients were characterized by higher pulse, anxiety score, and evidence of hyperventilation. Panic patients and social phobics panicked more often to 35% CO2 than to room air; normal controls did not have a higher rate of panic to CO2 than to room air. However, we did not find significant group differences in anxiety level, physiological measures, or biochemical measures in response to CO2 breathing compared with room air breathing. These results confirm earlier reports of baseline hyperventilation in panic disorder patients. However, 35% CO2 may be too high a dose to differentiate respiratory responses of patients compared with normals.

Effect of antipanic treatment on response to carbon dioxide.

BACKGROUND: Disordered breathing among patients with panic disorder, including hyperventilation during attacks and increased anxiogenic response to carbon dioxide (CO2) inhalation, is well established. We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy (CBT). METHODS: Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment (n = 21) or CBT (n = 8). After completing treatment, CO2 testing was repeated. A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests, separated by an average of 21.6 (SD = 8.8) weeks. RESULTS: Using a liberal standard, in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used, patients, but not controls, demonstrated a significant reduction in CO2 sensitivity between the first and second test. Using a more conservative .90 correlation standard reduced the sample size available and resulted in trend reduction in patients but no significant change in controls. There was a suggestion that the change was most pronounced in treatment responders, although the number of patient nonresponders is extremely small in this sample. CONCLUSIONS: These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder. We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems, both known to play a role in the control of respiration, may have a specific effect in reducing respiratory hyperactivity in panic disorder.

Nocturnal growth hormone secretion studies in adolescents with or without major depression re-examined: integration of adult clinical follow-up data.

BACKGROUND: Early sleep is associated with an increased secretion of human growth hormone (GH) through muscarinic inhibition of somatostatin, a GH suppressant. A clinical follow-up was performed approximately 1 decade after depressed and psychiatrically "normal" control adolescents, who were now young adults, had undergone baseline serial GH measurements over a 24-hour period on the third night of sleep polysomnography studies. METHODS: The study population consisted of 77 young adults who had received a diagnosis of adolescent major depressive disorder and had participated in the adolescent sleep and neuroendocrine studies. Alternatively, the young adult subjects were assessed as normal adolescent control subjects free of any psychiatric diagnosis. Blood samples had been collected for GH every 20 min during the 24-hour period coinciding with the third consecutive night of sleep electroencephalography. Subjects, now in young adulthood, were relocated and blindly reinterviewed using the Schedule for Affective Disorders and Schizophrenia (lifetime version). The original adolescent nocturnal GH data were analyzed in light of the information obtained regarding clinical course into adulthood. RESULTS: A substantial proportion of the nominally normal control group developed at least one episode of major depression or dysthymia during the follow-up period. "Latent" depressive subjects differed from depression-free control subjects by having exhibited a significantly more rapid increase of adolescent nocturnal GH secretion following sleep onset. Of the subjects who had experienced at least one lifetime major depressive episode during the follow-up, the subgroup who would go on to make suicide attempts secreted significantly greater amounts of GH during the first 4 hours of sleep. Adults with lifetime depression exhibited significantly reduced levels of GH in the 100 min preceding sleep onset during adolescence. CONCLUSIONS: Assignment of subjects based on longitudinal clinical follow-up into adulthood revealed that the sleep-related GH secretion paradigm has predictive value for future depressive episodes and future suicide attempts. Dysfunction of complex sleep-onset mechanisms may be a premorbid marker of depression and suicidal behavior.

Axis I psychiatric symptoms associated with HIV infection and personality disorder.

OBJECTIVE: The prevalences of personality disorders among HIV-positive and HIV-negative homosexual men were compared, and the presence of personality disorders was related to axis I psychiatric disorders, psychiatric distress, and impaired functioning. METHOD: The subjects were 162 homosexual men who either were HIV seronegative (N = 52) or were seropositive and had absent to moderate physical symptoms (N = 110). Lifetime and current histories of DSM-III-R axis I disorders, current diagnoses of DSM-III-R personality disorders, and levels of anxiety, depression, hopelessness, and adaptive functioning were assessed. RESULTS: In both the seropositive and seronegative groups, 19% of the study participants were diagnosed with personality disorders. The seropositive participants with personality disorders reported higher levels of psychiatric symptoms and poorer functioning than all participants without personality disorders, and they were over six times as likely as the seronegative participants without personality disorders to have current axis I disorders. CONCLUSIONS: These findings indicate that HIV infection and personality disorders may interactively increase the likelihood of clinically significant psychiatric symptoms.

The effect of zidovudine on neuropsychiatric measures in HIV-infected men.

The authors examined the effects of zidovudine on neuropsychiatric measures, at three assessment points separated by 6 months, in 25 HIV-positive men who took zidovudine for at least 6 months and a comparison group of 25 HIV-positive men with similar CD4+ T cell counts who had never taken zidovudine. Zidovudine had no statistically significant effect except for a slight improvement in Global Assessment of Functioning scale score. In this small group of subjects there was little benefit but also little evidence of CNS toxicity from zidovudine.

Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar disorder pedigrees.

OBJECTIVE: Schizophrenia following a traumatic brain injury could be a phenocopy of genetic schizophrenia or the consequence of a gene-environment interaction. Alternatively, traumatic brain injury and schizophrenia could be spuriously associated if those who are predisposed to develop schizophrenia have greater amounts of trauma for other reasons. The authors investigated the relationship between traumatic brain injury and psychiatric diagnoses in a large group of subjects from families with at least two biologically related first-degree relatives with schizophrenia, schizoaffective disorder, or bipolar disorder. METHOD: The Diagnostic Interview for Genetic Studies was used to determine history of traumatic brain injury and diagnosis for 1,275 members of multiplex bipolar disorder pedigrees and 565 members of multiplex schizophrenia pedigrees. RESULTS: Rates of traumatic brain injury were significantly higher for those with a diagnosis of schizophrenia, bipolar disorder, and depression than for those with no mental illness. However, multivariate analysis of within-pedigree data showed that mental illness was related to traumatic brain injury only in the schizophrenia pedigrees. Independent of diagnoses, family members of those with schizophrenia were more likely to have had traumatic brain injury than were members of the bipolar disorder pedigrees. The members of the schizophrenia pedigrees also failed to show the gender difference for traumatic brain injury (more common in men than in women) that was expected and was present in the bipolar disorder pedigrees. Subjects with a schizophrenia diagnosis who were members of the bipolar disorder pedigrees (and thus had less genetic vulnerability to schizophrenia) were less likely to have had traumatic brain injury (4.5%) than were subjects with schizophrenia who were members of the schizophrenia pedigrees (and who had greater genetic vulnerability to schizophrenia) (19.6%). CONCLUSIONS: Members of the schizophrenia pedigrees, even those without a schizophrenia diagnosis, had greater exposure to traumatic brain injury compared to members of the bipolar disorder pedigrees. Within the schizophrenia pedigrees, traumatic brain injury was associated with a greater risk of schizophrenia, consistent with synergistic effects between genetic vulnerability for schizophrenia and traumatic brain injury. Posttraumatic-brain-injury schizophrenia in multiplex schizophrenia pedigrees does not appear to be a phenocopy of the genetic disorder.

Glucocorticoid level and neuropsychiatric symptoms in homosexual men with HIV infection.

OBJECTIVE: There is a controversial literature suggesting that stress, anxiety, and depression are harmful to the immune system and therefore to health. Preclinical studies indicate that activation of the hypothalamic-pituitary-adrenal (HPA) axis by stress may be responsible for immunocompromise. The goal of this study was to assess this phenomenon in human immunodeficiency virus (HIV) infection. METHOD: Homosexual men in the community who did not meet modified Centers for Disease Control criteria for acquired immune deficiency syndrome (AIDS) were recruited for the study; 113 of the men were HIV positive and 77 were HIV negative. Very few of the men studied suffered from depression or anxiety disorder at the time of the first assessment. Twenty-four-hour urinary free cortisol levels were obtained from the 112 HIV-positive and 75 HIV-negative men whose 24-hour urine volumes were 500 ml or more. Cortisol levels were correlated with measures of medical, immunological, neurological, and psychiatric status. RESULTS: Small but significant correlations between 24-hour urinary free cortisol and medical status, level of depression, and level of anxiety were found in the HIV-positive group. There was no relationship between cortisol level and the number of CD4+ or CD8+ T lymphocytes or the CD4-CD8 ratio. CONCLUSIONS: Although HPA activation may be associated with stress in cases of HIV infection, it does not seem to be associated with further loss of CD4+ T lymphocytes. Subjects with HIV infection with the most evidence of medical complications may also be the most anxious and depressed.

Stability of mood despite HIV illness progression in a group of homosexual men.

OBJECTIVE: The authors investigated the association between mood status and progression of HIV illness. METHOD: In a research clinic at a university medical center, 112 HIV-positive and 52 HIV-negative homosexual men were enrolled in a 4-year prospective study with semi-annual assessments. The main study measures were psychiatric diagnoses according to the Structured Clinical Interview for DSM-III-R; level of functioning and psychiatric symptoms according to the Global Assessment of Functioning Scale (axis V, DSM-III-R), the Hamilton depression and anxiety scales, the Brief Symptom Inventory, and the Beck Hopelessness Scale; stage of HIV illness; and CD4 cell count. RESULTS: Among the HIV-positive men, there was no increase in rates of syndromal depression and anxiety over the 4 years despite substantial HIV illness progression. On all occasions, mean psychopathology symptom ratings were within the normal or not depressed range. However, compared to the HIV-negative men, the HIV-positive men had slightly more anxiety and somatic depressive symptoms throughout. The only measure that showed an increase in distress over time was orientation to the future; among the HIV-positive men, hopes for the future waned across assessments. Attrition in the group was largely attributable to the loss of men with lower CD4 cell counts and more advanced HIV illness. However, study dropouts did not differ on any psychiatric measure from subjects who remained during the first 3 years. CONCLUSIONS: In this group no significant increase in syndromal or symptomatic depression or anxiety over nine semiannual assessments was found, despite substantial HIV illness progression and some deaths. Psychopathology did not predict dropout or death.

Anxiogenic effects of CO2 and hyperventilation in patients with panic disorder.

OBJECTIVE: Previous studies have indicated that patients with panic disorder are more likely than normal subjects to have acute panic attacks during inhalation of CO2, but methodological objections have been raised. In this study the authors attempted to address three of these methodological problems by ensuring that raters who assessed whether panic attacks occurred were blind to subjects' diagnoses, by randomizing the order of administration of 5% CO2 and hyperventilation, and by challenging a greater number of subjects with 7% CO2. METHOD: Patients with panic disorder and normal subjects underwent 20-minute inhalations of 5% CO2 and 7% CO2 and 15 minutes of room-air hyperventilation. Ratings of panic/no panic during each condition were made separately by an assessor blind to diagnosis and by the subject. Scores on four panic rating scales were also recorded before and after each intervention. RESULTS: Room-air hyperventilation caused panic attacks in a small number of patients; the difference in panic rate between patients and comparison subjects was statistically significant by the subjects' but not by the raters' assessment. Panic rates during 5% CO2 and 7% CO2 were significantly greater among the patients by both assessments; the panic rate was greatest during 7% CO2. Order of administration did not significantly affect panic rates for hyperventilation and 5% CO2. CONCLUSIONS: Panic patients were clearly more sensitive to the anxiogenic effects of CO2 than comparison subjects, and CO2 was a more potent anxiogenic stimulus than room-air hyperventilation. Seven percent CO2 discriminated best between patients and comparison subjects and should be the focus of further research.

Relation of familial schizophrenia to negative symptoms but not to the deficit syndrome.

OBJECTIVE: Although a family history of schizophrenia has been associated with negative symptoms, family history is inconsistently related to the presence of the deficit syndrome. METHOD: The authors assessed family history and the deficit syndrome in 99 patients with DSM-III-R-diagnosed schizophrenia who were assessed during clinical treatment. Of these 99 patients, 45 were assessed both while antipsychotic free and during antipsychotic treatment to index their treatment response. RESULTS: Patients with (N=39) and without (N=60) a family history of schizophrenia had similar proportions of the deficit syndrome. Yet family history and deficit syndrome categorizations identified a group with greater negative symptoms on the Positive and Negative Syndrome Scale. Those with a family history had greater emotional withdrawal, poor rapport, and lack of spontaneity. Groups with and without the deficit syndrome similarly differed in these symptoms but also in affective blunting, motor retardation, and passive or apathetic social withdrawal. The study involving antipsychotic-free and antipsychotic treatment phases showed main medication effects explaining positive, psychopathology, depression, and activation symptoms but not negative symptoms. Only patients without a family history had improved negative symptoms with antipsychotic treatment. CONCLUSIONS: Patients with a family history of schizophrenia had greater and more treatment-resistant negative symptoms than those without a family history. They were not more likely to have the deficit syndrome. The group with a family history had more pathology only in negative symptoms related to psychosocial function. The stable negative symptoms specifically related to the genetic vulnerability to inherit schizophrenia might be those associated with psychosocial functioning.

Low levels of transthyretin in the CSF of depressed patients.

OBJECTIVE: Transthyretin plays an important role in the transport and distribution of thyroid hormone in the central nervous system (CNS). This study replicated and extended to patients with nonrefractory depressive illness a pilot study indicating that patients with refractory major depression have significantly lower levels of CSF transthyretin than do healthy comparison subjects. METHOD: Lumbar punctures were performed in drug-free subjects with DSM-III-R major depression (N = 18), DSM-III-R bipolar disorder, depressed phase (N = 1), and healthy comparison subjects (N = 24). CSF concentrations of transthyretin, determined by a quantitative dot-immunobinding assay, of the depressed patients and comparison subjects were compared by analysis of covariance (ANCOVA). The relationship between CSF transthyretin levels and Hamilton Depression Rating Scale scores was determined in a subset of the depressed patients. RESULTS: CSF concentrations of transthyretin were significantly lower in the depressed patients than in the comparison subjects by ANCOVA. Within the depressed group there was no significant overall correlation between CSF transthyretin levels and Hamilton depression scale scores, but there was a significant inverse correlation in male depressed patients (N = 8) between CSF transthyretin concentrations and Hamilton depression scores. CONCLUSIONS: Lower CSF transthyretin concentrations in depressed patients may reflect either a stable trait in this population or a state change secondary to depression or other factors. Lower CSF transthyretin concentrations may result in altered CNS thyroid hormone homeostasis. Such alteration could account for certain mood and neurovegetative symptoms of depression and might contribute to failure of standard antidepressant treatment.

Human immunodeficiency virus type-1 infection of homosexual men is accompanied by a decrease in circulating B cells.

As part of the multidisciplinary effort to characterize the natural history of human immunodeficiency virus type 1 (HIV-1) infection, the cell-surface phenotypes of lymphocytes from a cohort of homosexual men were analyzed in detail and related to clinical and laboratory parameters associated with HIV-1 infection. The present study represents a cross-sectional analysis of coded specimens from 153 homosexual men, of whom 74 were seronegative and 79 seropositive for HIV-1. Fewer circulating B lymphocytes (CD19+) were found in HIV-1-seropositive subjects relative to a seronegative reference group. HIV seropositivity was not associated with decreased numbers of CD8+ T cells or activated T cells, which suggests that the number of circulating B cells specifically decreased. In addition to CD19, B cells were measured by CD20 and CD21 in a subset of subjects, and decreases in circulating CD20+ and CD21+ B cells were also apparent in HIV-1-seropositive subjects. The decrease in B-cell numbers was present at the earliest stages of HIV-1 infection (asymptomatic, clinically silent) and became more pronounced at more advanced stages of HIV-1 infection. The absolute B-cell numbers correlated with absolute CD4+ cell numbers (r = 0.59, p less than 0.001). These data suggest that HIV-1 infection is associated with progressive, selective decreases in the numbers of circulating CD4+ T cells and B cells.