Recent benzodiazepine use in depressed patients: a confound of psychoimmunologic studies?

UNLABELLED: Several studies have indicated that benzodiazepines influence immunity in both animals and humans. As these medications are commonly utilized by and for psychiatric patients, investigation of psycho-immunologic relationships in human psychiatric disorders may be confounded by use of these medications. METHOD: We undertook an investigation for possible effects of recent benzodiazepine use on depression-immune relationships by comparing 43 patients with current major depressive disorder (MDD) who used benzodiazepines in the week prior to study to 27 patients with current MDD but no use of benzodiazepines in the past month. Both functional and ennumerative measures were investigated. RESULTS: We found no differences in absolute numbers of lymphocytes or the lymphocyte and NK functional measures. We did find differences between these two groups in the percentage of lymphocytes and of NK cells. Upon further analysis, controlling for symptom severity, these differences were shown to not be independently predicted by benzodiazepine use. CONCLUSION: Immune measures in subjects with current MDD and recent benzodiazepine use did not differ from those without such recent use. Therefore, such recent use is unlikely to confound PNI results.

Psychosocial and immune effects of self-hypnosis training for stress management throughout the first semester of medical school.

This study was a 19-week prospective conducted to determine the effectiveness of a self-hypnosis/relaxation intervention to relieve symptoms of psychological distress and moderate immune system reactivity to examination stress in 35 first-year medical students. Twenty-one subjects were randomly selected for training in the use of self-hypnosis as a coping skill and were encouraged to practice regularly and to maintain daily diary records related to mood, sleep, physical symptoms, and frequency of relaxation practice. An additional 14 subjects received no explicit training in stress-reduction strategies, but completed similar daily diaries. Self-report psychosocial and symptom measures, as well as blood draws, were obtained at four time points: orientation, late semester, examination period, and postsemester recovery. It was found that significant increases in stress and fatigue occurred during the examination period, paralleled by increases in counts of B lymphocytes and activated T lymphocytes, PHA-induced and PWM-induced blastogenesis, and natural killer cell (NK) cytotoxicity. No immune decreases were observed. Subjects in the self-hypnosis condition reported significantly less distress and anxiety than their nonintervention counterparts, but the two groups did not differ with respect to immune function. Nevertheless, within the self-hypnosis group, the quality of the exercises (ie, relaxation ratings) predicted both the number of NK cells and NK activity. It was concluded that stress associated with academic demands affects immune function, but immune suppression is not inevitable. Practice of self-hypnosis reduces distress, without differential immune effects. However, individual responses to the self-hypnosis intervention appear to predict immune outcomes.

Analysis of partial variance (APV) as a statistical approach to control day to day variation in immune assays.

The considerable day to day variability in some immunologic assays can obscure relationships among measures of interest and thereby complicate interpretation of findings when effect sizes are modest. Analysis of partial variance (APV) is a technique that utilizes data obtained from controls run in the laboratory on the day of each assay to control for day to day variance statistically. The application of this technique to permit detection of otherwise obscured effects for both larger and smaller samples is exemplified utilizing data from two studies in which subjects were assessed on multiple different dates. These included a study of the association of depression with in vitro immune measures in 296 adolescents and a longitudinal study of 20 spouses of patients admitted to a cardiac intensive care unit studied together with 20 matched controls. APV was most useful in analyses of mitogen-induced lymphocyte proliferation assays, which had considerable day to day variability. In general, multivariate studies with functional immune measures may benefit most from application of this technique.

Immunity, major depression, and panic disorder comorbidity.

Because recent research reports indicated clinical and biological differences in major depression with and without comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) panic disorder, and as altered immune measures were reported in selected subgroups of depressive patients, we investigated 51 pairs of major depressive episode (MDE) subjects, and gender- and age-matched healthy controls in order to determine if T lymphocytes number and function abnormalities were associated with Panic Disorder comorbidty. We found that those MDE subjects with DSM-III-R panic disorder (PD) had greater numbers of T cells (p less than 0.05) and PHA mitogen (p less than 0.05) responses than depressive patients without PD, as well as increased phytohemagglutinin (PHA) (p less than 0.05) concanavalin A (ConA) (p less than 0.02) mitogen responses compared to their controls. These data suggest that panic disorder comorbidity significantly contributes to the variance of immunologic parameters in major depression and has to be carefully assessed within psychoimmunological studies of psychiatric patients with affective disorders.

Facial pain, distress, and immune function.

Chronic facial pain syndromes are associated with high levels of distress and depression. Immune system measures were investigated in otherwise healthy patients suffering from chronic temporomandibular pain and dysfunction syndrome (TMPDS) and in matched controls. No mean differences were found between TMPDS patients and the controls on any of the immune measures; however, both ConA and PWM responses in TMPDS patients were decreased in relation to the level of demoralization (P less than 0.05). Cognitive symptoms such as low self-esteem and perceptions of helplessness/hopelessness were implicated in these effects. In addition, among patients pain severity was independently associated with decreased ConA response (P less than 0.05). The data suggest possible correlates of stress-induced changes in the immune system.

Psychoneuroimmunology: potential relevance to chronic orofacial pain.

Studies undertaken over the past ten years have demonstrated that stress and depression can induce immune alterations, including decreased numbers of immunocompetent cells and impaired lymphocyte and natural killer cell activity. Factors such as age and severity of symptomatology influence these effects. The substantial stress and depression associated with chronic pain syndromes and the evidence for opioid involvement in immunomodulation suggest that immune system changes may occur in some patients with chronic facial pain.