Stability of Cellular Immune Parameters over 12 Weeks in Patients with Major Depression or Somatoform Disorder and in Healthy Controls.

OBJECTIVE: Cellular immune status in major depression (MD) patients differs from that in somatoform disorder (SFD) patients and healthy controls (HC). It is still questionable whether the patterns of immune parameters remain stable over time. Therefore, we studied lymphocyte and monocyte cell counts and neopterin levels in peripheral blood of MD and SFD patients and HC over 12 weeks and tested for correlations between biochemical and psychometric parameters. METHODS: Thirty-nine patients with MD, 27 with SFD, and 51 HC were recruited. Peripheral blood was drawn at four visits, at 4-week intervals. We assessed the total cell count of B lymphocytes, natural killer (NK) cells, T lymphocyte subpopu-lations, and monocytes by flow cytometry, and neopterin serum levels by ELISA. Psychometric parameters were measured with questionnaires. RESULTS: Counts of lymphocytes, monocytes, and neopterin were stable in the SFD and HC groups. In the MD group, total CD3+, CD3+CD8+, NK cells, and CD3+CD25+ T cells showed inhomogeneous variances in Friedman tests, particularly in females. Neopterin correlated with depressed mood in MD patients, and with body mass index in HC. CONCLUSIONS: Cellular immune parameters are stable in HC and SFD. Our results may indicate influences of MD and gender on some cellular immune parameters. This may need to be considered in future immunological studies.

Values of Cytokines and Tryptophan Metabolites over a 12 Weeks Time Course in Patients with Depression and Somatoform Disorder.

OBJECTIVE: Previous studies have suggested alterations in the kynurenine pathway as a major link between cytokine and neurotransmitter abnormalities in psychiatric disorders. Most of these studies used a cross-sectional case-control study design. However, knowledge is still lacking regarding the stability over time of kynurenine pathway metabolites and the functionally related cytokines. Therefore, we studied the stability of cytokines and tryptophan (TRP) parameters over a period of 12 weeks. METHODS: A total of 117 participants-39 with major depression, 27 with somatoform disorder, and 51 healthy controls were enrolled. Four evaluations, including blood withdrawal and psychometric testing, were performed over a period of 12 weeks. We used ELISA to measure interleukin (IL)-6, IL-1 receptor antagonist (RA) and tumor necrosis factor α (TNF α). High-performance liquid chromatography was used to analyze neurotransmitter variables, i.e. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), 3-OH-kynurenine (3-HK), and kynurenic acid (KYNA). RESULTS: We found no significant fluctuations of TRP, its metabolites (5-HIAA, KYN, KYNA, and 3-HK), or the cytokines (IL-1RA, IL-6, and TNF α) in any of the groups over the 12 weeks. CONCLUSION: To our knowledge, this is the first longitudinal study performed in psychiatric patients to verify the stability and consequently the reliability of the biological parameters we investigated. Our data indicate that TRP metabolites and cytokines are reliable biological parameters in psychiatric research because they do not fluctuate significantly over time.

Blunted exercise-induced mobilization of monocytes in somatization syndromes and major depression.

BACKGROUND: Previous research indicates that physical activity may alter the number of immune cells. We examined whether increasing or decreasing the level of physical activity affects circulating lymphocyte and monocyte counts in patients with somatization syndromes and patients with major depression. METHODS: Thirty-eight participants with major depression, 26 participants with somatization syndromes and 47 healthy controls participated in the study. Using an experimental within-subject design, participants were involved in 1 week of increased physical activity (daily exercise sessions) and 1 week of reduced physical activity. Counts of total lymphocytes, lymphocyte subsets and monocytes were determined before and after each trial. Linear mixed models adjusted for sex, body mass index, age, fitness status and the order of trials were used for longitudinal data analysis. RESULTS: One week of exercise increases the number of monocytes in healthy controls (p<.05), but not in patients with somatization syndromes or patients with major depression. In addition, after 1 week of exercise, depressive symptoms were reduced in patients with major depression (p<.05) while somatoform symptoms were reduced (p<.05) in both clinical groups. Baseline comparisons and mixed models indicated reduced T helper cell counts in patients with somatization syndromes. LIMITATIONS: Relatively small sample size. The time of physical activity was relatively short and restricted to low-graded exercise. CONCLUSIONS: This study demonstrates a blunted mobilization of monocytes by exercise in both patients with somatization syndromes and patients with major depression. In addition, even one week of exercise reduces somatoform and depressive symptoms.

Exercise affects symptom severity but not biological measures in depression and somatization - results on IL-6, neopterin, tryptophan, kynurenine and 5-HIAA.

Exercise leads to symptom reduction in affective disorders and functional somatic syndromes. Biological hypotheses of underlying mechanisms include serotonergic and immunological pathways. We aimed to investigate biological features in persons with major depression and somatoform syndromes, and to analyze effects of short-term graded exercise on these parameters. Baseline values for depressive and somatoform symptoms, tryptophan, kynurenine, 5-hydroxyindoleacetic acid, neopterin and interleukin-6 were compared with those after one week of increased and one week of reduced physical activity. Thirty-eight persons with major depression, 27 persons with a minimum of 6-8 somatoform symptoms, and 48 healthy controls participated in the study. Depressive and somatoform symptoms were reduced after the active week, and an interaction pointed towards group-specific reduction of psychopathology. Participants with major depression had lower levels of kynurenine compared to controls, with intermediate concentrations in somatoform patients. There were no systematic associations of symptom improvement with biological changes. A possible limitation of the design is that a control condition with low physical activity, but no placebo condition was included. People with multiple somatoform symptoms and major depression benefit from a short and low-graded exercise intervention. These effects do not seem to be mediated by changes in serotonergic and inflammatory parameters.

The influence of physical activity on pain thresholds in patients with depression and multiple somatoform symptoms.

OBJECTIVES: Pain is a common symptom with high occurrence in somatoform syndromes and depressive disorders. Research in this area often focuses on experimental induction of pain and subsequent assessment of pain thresholds, ensuring repeatable stimuli of defined quality. Results on sensitivity to experimental pain in major depression are inconclusive, and data on pain thresholds in multiple somatoform symptoms are scarce. The goals of the present study were to differentiate between groups regarding the pressure pain thresholds, and to investigate the possible influence of physical activity on the pain thresholds in these groups. We postulate that physical fitness and physical activity influence pain thresholds in depression and persons with multiple somatoform symptoms. METHODS: Thirty-eight persons with major depression, 26 persons with a minimum of 6 to 8 somatoform symptoms (somatoform symptom index 8, SSI-8), and 47 healthy participants participated in the study. Baseline values of pressure pain thresholds assessed at different sites of the body were compared with those after 1 week of increased and 1 week of reduced physical activity. RESULTS: We used repeated measurement design (MANCOVA) and partial correlations for data analysis. Depressed participants reported lower pain thresholds compared with controls, and persons with SSI-8 showed intermediate thresholds. After 1 week of physical activity, participants reported higher pain thresholds. Men had higher pain thresholds following activity as compared with women. Participants who reported higher general fitness also showed higher pain thresholds. Sensitivity to pressure pain is associated with depression, but not with multiple somatoform symptoms. DISCUSSION: Short low-graded exercise can have reducing effects on perception of pressure pain. Physical activity level is a relevant covariate when using pressure pain assessment. Reduced general fitness can partially account for lower pain thresholds in depression.