In a prospective study of 15 spouses of women with advanced breast carcinoma, lymphocyte stimulation responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were significantly suppressed during the first two months following the death of a spouse compared with prebereavement levels. A highly significant suppression was seen as early as one month after bereavement. No differences were found in total lymphocyte or B- or T-cell numbers. An intermediate level of mitogen responsivity was found during the four- to 14-month period after bereavement. Suppressed immunity following the death of a spouse may be related to the increased morbidity and mortality associated with bereavement. (JAMA1983;250:374-377)

Suppression of Lymphocyte Stimulation Following Bereavement

Interleukin-2 and interleukin-6 in schizophrenia and mania: Effects of neuroleptics and mood stabilizers

1 Parallel to the current rapid development of new immunological methods, immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system, neurotransmitters, psychological processes, and psychiatric disorders, especially in relation to cytokines, is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines, actively transported into the CNS, play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells, which in turn produce cytokines by a feedback mechanism Moreover, they strongly influence the dopaminergic, noradrenergic, and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor, sickness behavior and sleep are related to IL-1; disturbances of memory and cognitive impairment are to IL-2, in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia, and IL-6, on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders, a characteristic pattern of cytokine actions in the CNS, including influences of the cytokines on the blood-brain barrier, seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders.

The purpose of this study was to investigate immune-inflammatory markers in schizophrenia and the effects of chronic treatment with clozapine, an atypical antipsychotic agent, on these variables. Toward this end, we measured interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R in the blood of 26 normal controls and 14 schizophrenic patients before and after treatment with clozapine. The sIL-2R and IL-6 levels were significantly higher in younger (<35 years) schizophrenic subjects than in normal controls and older (≥ 35 years) schizophrenic subjects. The sIL-6R levels were significantly lower in schizophrenic subjects than in normal controls. Chronic treatment with clozapine significantly increased the blood concentration of sIL-2R; the increases in the latter were significantly related to the dose of clozapine but not to changes in severity of positive or negative symptoms. We conclude that: (a) schizophrenia in younger people is accompanied by increased IL-6 and sIL-2R secretion; and (b) subchronic treatment with clozapine increases sIL-2R levels. Increased plasma sIL-2R may be one mechanism by which neuroleptics exhibit their immunosuppressive effects.

Immune‐inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress-disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental health.

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J Blumenstein

Papers

Effect of psychotropic agents upon the blastogenic response of human t-lymphocytes.