Subjective Arousal and Perceived Control Clarify Heterogeneity in Inflammatory and Affective Outcomes

Overactivation of proinflammatory pathways in response to stress may play an important role in the pathophysiology of psychiatric disorders such as major depressive disorder. Autonomic arousal in response to chronic stress has been mechanistically linked to the activation of proinflammatory pathways. However, not all individuals who experience chronic stress or increased inflammation develop pathological elevations in symptoms of mood and anxiety disorders. This heterogeneity poses a challenge in using inflammation as a marker of individual risk or vulnerability for related psychiatric conditions. Rodent models of pathological stress suggest that the outcomes of chronic stress may largely depend on individual differences in perceived control. In the current study, we used this theoretical framework to disambiguate the influence of autonomic arousal and perceived control on inflammatory and psychological outcomes in a large sample of adults from the Midlife in the United States dataset (wave 2; MIDUS-2) (Final N=1030), and further replicated our approach in a second (MIDUS-Refresher) cohort (Final N=728). Using k-means clustering we created subgroups systematically differing in subjective arousal (high/low) and perceived control (low/high) and compared these subgroups on inflammatory markers and psychological outcomes. Overall results showed that high subjective arousal uniquely and reliably predicted higher levels of Interleukin-6, C-Reactive Protein, and Fibrinogen. However, domain specific heterogeneity in pathological and adaptive affective outcomes, depended on both subjective arousal and perceived control. These results further extend and expand upon basic work in rodent models of stressor controllability and illustrate a useful way to probe mechanistic phenotypes in humans

ANXIOUS SYMPTOMS INFLUENCE DELAYED-TYPE HYPERSENSITIVITY SKIN-TEST IN SUBJECTS DEVOID OF ANY PSYCHIATRIC MORBIDITY RID B-1297-2011

The present study aimed to evaluate the relationship between anxious/depressive symptoms and cell-mediated immunity (Delayed-type Hypersensitivity skin test, DTH) in subjects devoid of any psychiatric morbidity. Forty-eight females and twenty-four males were studied, ages ranging 21-60. These subjects completed the Beck Depression Inventory (BDI) for evaluation of depressive symptoms and the State-Trait Anxiety Inventory (STAIX1, STAIX2) for evaluation of anxious symptoms; subsequently on the same day they were tested for DTH using the Multitest CMI system (Merieux Institute, France). Subjects were split into three groups using the 33rd and 66th percentiles of DTH response (cumulative induration diameter). In females, subjects with larger DTH response (DTH > 8 mm) had significantly lower levels of ''state'' anxiety (scores at STAIX1; Kruskall-Wallis test, P=.04). On the contrary, no differences were observed between groups considering scores obtained by males at self-evaluation rating scales. Our data seem to support the hypothesis that activity of immune system as measured by DTH skin test may be influenced by affective status in the context of everyday life

Lack of correlation between defective cell-mediated-immunity and levels of secreted or circulating cytokines in a study of 90 cancer-patients.

In this study we examined the levels of IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha and sIL-2R in the sera and culture supernatants of PHA-stimulated lymphocytes from a series of 90 cancer patients. The expression of the IL-2R p55 chain (alpha subunit) on PHA-stimulated lymphocytes was also evaluated together with the blastogenic response of peripheral blood mononuclear cells (PBMC) to PHA, PHA plus rIL-2 and rIL-2 alone. Ninety cancer patients (70 men and 20 women; mean age 57.8 years, range 27-80) with advanced solid malignancies at different sites were studied. The lymphocyte blastogenic response to PHA was significantly lower in cancer patients than in normal individuals. The proliferative response to rIL-2 alone was also significantly depressed in cancer patients. The frequency of CD25(+) PHA-stimulated lymphocytes from cancer patients was not significantly different from that of the control group. The serum values for IL-1 alpha, IL-1 beta, IL-6 and sIL-2R were significantly higher in cancer patients than in controls, while the serum level of IL-2 was within the normal range. The levels of sIL-2R released in the supernatant of PHA-stimulated PBMC of cancer patients were significantly lower than those of the control group. However, the levels of IL-1 alpha, IL-1 beta, IL-2, IL-6 and TNF-alpha, in the supernatants of PHA-stimulated PBMC of cancer patients were in the same range as those of the control group. These results suggest that the observed immune-deficiency in cancer patients cannot be explained on the basis of a defective production of key immunoregulatory cytokines since the lymphocytes from cancer patients produced physiological amounts of cytokines. We suggest that the observed defective cell-mediated immunity may be due to a defect in transmembrane signalling by the cytokines

Chronic caregiving stress alters peripheral blood immune parameters: The role of age and severity of stress RID B-1297-2011

Background: To examine the impact of chronic psychological stress on the immune system, a series of cellular and humoral immunological parameters was compared in 18 female caregivers of handicapped people and 18 age- and sexmatched controls. Methods: The immunological parameters included assessment of T cell number (T cells, T helper, and T suppressor/cytotoxic) and function (delayed-type cutaneous hypersensitivity), antibody titers for latent herpesviruses (cytomegalovirus and herpes simplex virus 1 and 2), and markers of inflammation (complement C3 and C4 factors and c-reactive protein). Serum immunoglobulins (IgG, IgM, IgA, IgE) and titers for the nonlatent virus roseola were used to control for nonspecific elevations in serum proteins. Results were associated with the age of the investigated subjects, the severity of stress (family burden) and the degree of disability of the handicapped people. Results: Caregivers had a significantly lower percentage of T cells, a significantly higher percentage of T suppressor/cytotoxic cells and a significantly lower T helper:suppressor ratio. Subjects were also analyzed after division into two groups according to the median age (45 years). Compared to their matched controls, older caregivers (mean age = 50.3) also had lower numbers of T cells and T helper cells and higher antibody titers for cytomegalovirus. In addition, in the caregiver population severity of stress was significantly positively correlated with T suppressor/cytotoxic cells and negatively correlated with T helper:suppressor ratio. No other differences in the immune parameters were found between caregivers and controls. Conclusions: The results indicate that psychological stress differentially affects various aspects of the immune system and confirm the relevant role of age and severity of stress in modulating these influences