Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and physiological predictors.

BACKGROUND: The primary aim of this study is to examine prospectively the association of stressful life events, social support, depressive symptoms, anger, serum cortisol and lymphocyte subsets with changes in multiple measures of human immunodeficiency virus (HIV) disease progression. METHODS: Ninety-six HIV-infected gay men without symptoms or anti-retroviral medication use at baseline were studied every 6 months for up to 9 years. Disease progression was defined in three ways using the Centers for Disease Control (CDC) classifications (e.g. AIDS, clinical AIDS condition and mortality). Cox regression models with time-dependent covariates were used, adjusting for control variables (e.g. race, age, baseline, CD4 T cells and viral load, number of anti-retroviral medications). RESULTS: Higher cumulative average stressful life events and lower cumulative average social support predicted faster progression to both the CDC AIDS classification and a clinical AIDS condition. Higher anger scores and CD8 T cells were associated with faster progression to AIDS, and depressive symptoms were associated with faster development of an AIDS clinical condition. Higher levels of serum cortisol predicted all three measures of disease progression. CONCLUSIONS: These results suggest that stressful life events, dysphoric mood and limited social support are associated with more rapid clinical progression in HIV infection, with serum cortisol also exerting an independent effect on disease progression.

Elevated substance P levels in HIV-infected men.

The neuropeptide, substance P, is a potent modulator of neuroimmunoregulation. Substance P and its receptor modulate HIV infection. HIV-seropositive men had significantly higher plasma substance P levels compared with uninfected controls, which were associated with decreased CD16 and CD56 natural killer (NK) cell populations. The changes in plasma substance P levels and decreases in NK subsets did not correlate with CD4 cell levels, but a diurnal pattern was suggested for substance P. The balance between substance P expression and functions of immune cells may be important in the immunopathogenesis of HIV infection.

Psychosocial-immune relationships in HIV disease.

Human immunodeficiency virus (HIV) is now commonly viewed as a chronic disease, which often consists of a wide array of recurrent and sometimes severe psychosocial stressors. An individual's response to these multiple challenges over time may impact their health. In this article, we review research examining the relationship of psychologic factors (eg, depression, stressful life events, coping, social support) with immune system function and disease course. We also explore some of the potential physiologic pathways that may underlie these types of psychosocial-immune relationships, as well as the effects of psychologic interventions, particularly cognitive-behavioral stress management (CBSM), on the psychosocial, neuroendocrine, and immune functioning of people living with HIV. We conclude by suggesting some areas for future research, particularly the study of HIV-positive women.

Managing the suicidal patient.

Suicide is a major public health problem. Worldwide, approximately 1% of deaths are due to suicide. In the United States, suicide is the eighth leading cause of death. More than 30,000 Americans commit suicide each year, and nearly 500,000 others make a serious suicide attempt warranting emergency medical attention. Suicide attempts account for 23% of psychiatric visits to emergency rooms.

Noradrenergic function and clinical outcome in antidepressant pharmacotherapy.

Controversy remains regarding the role of noradrenergic systems in determining clinical response to antidepressant pharmacotherapy. Pineal gland production of melatonin can serve as a physiologic index of noradrenergic function. The aim of this study was to examine the effects of antidepressant treatment on 24-hour urinary excretion of the principle metabolite of melatonin, 6-sulfatoxymelatonin in treatment responders and nonresponders. Twenty-four outpatients meeting DSM-III-R criteria for Major Depression received treatment with either fluvoxamine or imipramine for 6 weeks while participating in a placebo-controlled double-blind clinical trial. Twenty-four hour excretion of 6-sulfatoxymelatonin was measured at baseline and at the conclusion of the treatment trial. Changes in urinary excretion of 6-sulfatoxymelatonin distinguished antidepressant responders from nonresponders, with a significant increase observed in the former group and a significant decrease in the latter. The degree of clinical response was correlated with the change in 6-sulfatoxymelatonin excretion. These results suggest that enhanced noradrenergic function may play an important role in determining clinical response to antidepressant pharmacotherapy.

Ethnicity and seizure threshold.

1. Seizure threshold is an important variable in modern ECT treatment planning. To date, age, gender, and electrode placement have been used to predict seizure threshold, but the potential impact of ethnicity has received little attention. 2. In a retrospective pilot study of patients who received ECT, 20 pairs of first admission, right unilateral-treated, age- and sex-matched black and white patients were compared. 3. Black patients had higher seizure thresholds and were more likely to require restimulation, despite the finding that they were more likely to have been receiving concomitant medications which lower seizure threshold. However, ethnicity was confounded with variations in ECT dose titration, which were the strongest predictor of seizure threshold. 4. There were no differences in seizure length. Further study is necessary to confirm the impact of ethnicity on seizure threshold.

Antidepressant efficacy of venlafaxine.

Venlafaxine is a unique antidepressant medication with well documented efficacy and safety in the acute treatment of major depressive disorder. Reports suggest that it may also be effective in the treatment of dysthymic disorder and bipolar II depression, but the available data for these conditions are more limited compared to major depressive disorder. Several studies suggest that there may be a more rapid onset of action for venlafaxine in the treatment of major depression compared to other antidepressant pharmacotherapies, but this has not been fully established. Venlafaxine is also effective in the important long term continuation and maintenance phases of the treatment of depression.

Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS.

OBJECTIVE: This study examined prospectively the effects of stressful events, depressive symptoms, social support, coping methods, and cortisol levels on progression of HIV-1 infection. METHOD: Eighty-two homosexual men with HIV type-1 infection without AIDS or symptoms at baseline were studied every 6 months for up to 7. 5 years. Men were recruited from rural and urban areas in North Carolina, and none was using antiretroviral medications at entry. Disease progression was defined as CD4(+) lymphocyte count <200/microl or the presence of an AIDS indicator condition. RESULTS: Cox regression models with time-dependent covariates were used adjusting for race, baseline CD4(+) count and viral load, and cumulative average antiretroviral medications. Faster progression to AIDS was associated with higher cumulative average stressful life events, coping by means of denial, and higher serum cortisol as well as with lower cumulative average satisfaction with social support. Other background (e.g., age, education) and health habit variables (e.g., tobacco use, risky sexual behavior) did not significantly predict disease progression. The risk of AIDS was approximately doubled for every 1.5-unit decrease in cumulative average support satisfaction and for every cumulative average increase of one severe stressor, one unit of denial, and 5 mg/dl of cortisol. CONCLUSIONS: Further research is needed to determine if treatments based on these findings might alter the clinical course of HIV-1 infection.

High versus low basal cortisol secretion in asymptomatic, medication-free HIV-infected men: differential effects of severe life stress on parameters of immune status.

The authors hypothesized that HIV-infected men with high basal cortisol secretion would exhibit greater stress-related reductions in the ratio of Th1/Th2 cell-derived cytokines and numbers of CD8+ T and NK lymphocytes than low basal cortisol secretors. A semistructured interview was used to assess life stress during the preceding 6 months of 94 HIV-infected men classified as high and low cortisol secretors (n = 47/group). Increased levels of severe life stress were highly correlated with lower numbers of CD8+ T cells, CD16+ and CD56+ NK cells, CD57+ cells, and higher DHEA-S concentrations in the high cortisol group. Conversely, no significant correlations were found in the low cortisol group. No correlations were found between stress and CD4+ T helper/inducer cell counts, cytokine production, or testosterone levels in either participating group. These data suggest that severe stress in combination with high glucocorticoid activity may modify select parameters of immune status in HIV-infected men.

Magnetic detection to position human nasogastric tubes.

Placement of nasogastric tubes is one of the most commonly performed diagnostic and therapeutic medical procedures. Proper placement of the tube in the digestive tract below the diaphragm is crucial for efficacy and safety. This study evaluates a magnet detection system that allows percutaneous non-radiographic localization of the nasogastric tube tip. Each volunteer subject had the magnet detector placed over the abdomen, and was then intubated with a magnet-tagged nasogastric tube. Eighty-eight nasogastric tube placements were performed in 22 volunteers. The detection system located the nasogastric tube tip below the diaphragm in all 88 placements. Location in all attempts was confirmed by fluoroscopy. This method of correctly locating the tip of nasogastric tubes may obviate the need for radiographic imaging in most cases.

Progression to AIDS: the effects of stress, depressive symptoms, and social support.

OBJECTIVE: We examined the effects of stress, depressive symptoms, and social support on the progression of HIV infection. METHODS: Eighty-two HIV-infected gay men without symptoms or AIDS at baseline were followed up every 6 months for up to 5.5 years. Men were recruited from rural and urban areas in North Carolina as part of the Coping in Health and Illness Project. Disease progression was defined using criteria for AIDS (CD4+ lymphocyte count of <200/microl and/or an AIDS-indicator condition). RESULTS: We used Cox regression models with time-dependent covariates, adjusting for age, education, race, baseline CD4+ count, tobacco use, and number of antiretroviral medications. Faster progression to AIDS was associated with more cumulative stressful life events (p = .002), more cumulative depressive symptoms (p = .008), and less cumulative social support (p = .0002). When all three variables were analyzed together, stress and social support remained significant in the model. At 5.5 years, the probability of getting AIDS was about two to three times as high among those above the median on stress or below the median on social support compared with those below the median on stress or above the median on support, respectively. CONCLUSIONS: These data are among the first to demonstrate that more stress and less social support may accelerate the course of HIV disease progression. Additional study will be necessary to elucidate the mechanisms that underlie these relationships and to determine whether interventions that address stress and social support can alter the course of HIV infection.

Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients.

BACKGROUND: Dysthymic disorder is a relatively common illness that is often treated with antidepressants. Compared with the study of major depression, there has been little systematic study of potentiation strategies for antidepressant-refractory dysthymic disorder. METHOD: Following a patient's report of dramatic response to the addition of chromium supplementation to sertraline pharmacotherapy for dysthymic disorder (DSM-IV), the authors initiated a series of single-blind and open-label trials of chromium picolinate or chromium polynicotinate in the treatment of antidepressant-refractory dysthymic disorder. RESULTS: In a series of 5 patients, chromium supplementation led to remission of dysthymic symptoms. Single-blind substitution of other dietary supplements in each of the patients demonstrated specificity of response to chromium supplementation. CONCLUSION: Preliminary observations suggest that chromium may potentiate antidepressant pharmacotherapy for dysthymic disorder. Controlled studies are indicated to test the validity of these initial observations.

The effects of serotonin3 receptor blockade on the psychobiological response to intravenous clomipramine in healthy human subjects.

BACKGROUND: The purpose of this study was to determine the role that serotonin (5-HT)3 receptors play in the prolactin and nausea responses to clomipramine challenge. METHODS: Twenty healthy subjects were randomly assigned to pretreatment with either the selective 5-HT3 receptor antagonist ondansetron, or placebo, prior to intravenous infusion with clomipramine. RESULTS: Ondansetron pretreatment had no effect on the prolactin response to clomipramine challenge. There was a trend toward decreased nausea with ondansetron pre-treatment. CONCLUSIONS: These findings are consistent with other data suggesting that 5-HT3 receptors do not play a major role in the prolactin response to 5-HT challenge in human subjects, but may mediate nausea associated with enhanced 5-HT neurotransmission.

An overview of the principles of clinical psychopharmacotherapy.

The complexities of psychopharmacotherapy can be simplified through a careful consideration of certain fundamental guiding principles. While each patient is truly a unique individual, the general biological, psychosocial, and education issues reviewed above can provide a framework which can then be modified to meet the particular needs of a given patient.

Peripherally inserted central catheter placement in swine using magnet detection.

Positioning a PICC in the lower half of the superior vena cava is a crucial aspect of its safety and efficacy. A magnet detection system evaluated in this animal study presents a method that allows PICC placements to be performed without fluoroscopy. Forty-four localizations were studied in six pigs. The detection system located magnet-tagged PICCs with an average error of 0.40 cm and a standard deviation of 0.29 cm. The system provided real-time information about the path and orientation of the PICC tip during difficult insertions. This study demonstrates the accuracy of this magnet location system.

Psychoneuroendocrinology of depression. Prolactin.

Prolactin provides us with a window to the brain in our quest for understanding the psychobiology of depression, since the regulation of its release involves some of the monamine neurotransmitter systems that have been implicated in the pathophysiology of depression. Investigation examining basal prolactin plasma concentrations in depressed patients, including assessments of the rhythm of prolactin release, have not provided clear, consistent findings. Further exploration of the precise mechanisms involved in serotonin-stimulated prolactin release should shed light on the pathophysiology of abnormal prolactin responsivity in depression, and by extension, the psychobiologic basis of depression.

Heart rate variability at rest and during mental stress in patients with coronary artery disease: differences in patients with high and low depression scores.

This study tested the hypothesis that coronary artery disease (CAD) patients with high depressed mood scores differ in sympatho-vagal balance during mental stress compared to patients with low depressed mood scores. Using electrocardiographic monitoring, heart variability data from spectral analysis and hemodynamic parameters were obtained prior to and during mental stress from 34 men and 7 women. A public speaking task was used as the mental stressor. Patients were grouped by a median split of their Minnesota Multiphasic Personality Inventory-Depression score. During mental stress, patients with higher depression scores had greater changes in peak heart rate (p < .05) and low frequency to high frequency power ratio (p < 0.05) than patients with lower scores suggesting a shift toward more sympathetic activity during mental stress. These findings may be related to the reported relation between depression and survival risk in patients with CAD.

Heart rate variability in patients with coronary artery disease: differences in patients with higher and lower depression scores.

OBJECTIVE: This study tested the hypothesis that coronary artery disease patients with higher depression scores have lower heart rate variability during daily life. METHOD: Thirty-three men and nine women, ranging in age from 46 to 79, with coronary artery disease and exercise-induced ischemia were studied. The standard deviation of normal R-R intervals (SDNN) and average heart rate were obtained from 24-hour ambulatory electrocardiographic monitoring. Patients were grouped by a median split of the Minnesota Multiphasic Personality Inventory (MMPI-D) score. RESULTS: SDNN was lower (p = .009) and average heart rate was higher (p = .003) in patients with higher depression scores. These relationships remained substantially unaltered after statistically adjusting for the only demographic/clinical factor that varied between the groups: gender. CONCLUSIONS: In comparison to the lower depression score group, those with higher depression scores had lower heart rate variability during daily life. These findings may be related to the reported relationship between depression and survival risk in patients with coronary artery disease.

Severe life stress as a predictor of early disease progression in HIV infection.

OBJECTIVE: Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease. METHOD: Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression. RESULTS: The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis. CONCLUSIONS: This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.