Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis.

It has been hypothesized that the immune system plays a pathogenetic role in psychiatric disorders, in particular in major depression and schizophrenia. This hypothesis is supported by a number of reports on altered circulating levels and in vitro production of cytokines in these disorders. However, the respective evidence is not consistent. This may be in part due to an incomplete control for numerous confounding influences in earlier studies. We investigated the plasma levels of cytokines and soluble cytokine receptors in psychiatric patients (N = 361) upon hospital admission and compared the results to those obtained in healthy controls (N = 64). By multiple regression analysis we found that circulating levels of interleukin-1 receptor antagonist (IL-1Ra), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors (sTNF-R p55, sTNF-R p75) and IL-6 were significantly affected by age, the body mass index (BMI), gender, smoking habits, ongoing or recent infectious diseases, or prior medication. Cytokine or cytokine receptor levels were significantly increased in patients treated with clozapine (sIL-2R, sTNF-R p75), lithium (TNF-alpha, sTNF-R p75, IL-6) or benzodiazepines (TNF-alpha, sTNF-R p75). Taking all these confounding factors into account, we found no evidence for disease-related alterations in the levels of IL-1Ra, sIL-2R, sTNF-R p75 and IL-6, whereas levels of TNF-alpha and sTNF-R p55 in major depression and sTNF-R p55 in schizophrenia were slightly decreased compared to healthy controls. We conclude that, if confounding factors are carefully taken into account, plasma levels of the above mentioned cytokines and cytokine receptors yield little, if any, evidence for immunopathology in schizophrenia or major depression.

Effects of granulocyte colony-stimulating factor on night sleep in humans.

Numerous animal studies suggest that cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mediate increased sleep amount and intensity observed during infection and are, moreover, involved in physiological sleep regulation. In humans the role of cytokines in sleep-wake regulation is largely unknown. In a single-blind, placebo-controlled study, we investigated the effects of granulocyte colony-stimulating factor (G-CSF, 300 microgram sc) on the plasma levels of cytokines, soluble cytokine receptors, and hormones as well as on night sleep. G-CSF did not affect rectal temperature or the plasma levels of cortisol and growth hormone but did induce increases in the plasma levels of IL-1 receptor antagonist and both soluble TNF receptors within 2 h after injection. In parallel, the amount of slow-wave sleep and electroencephalographic delta power were reduced, indicating a lowered sleep intensity. We conclude that G-CSF suppresses sleep intensity via increased circulating amounts of endogenous antagonists of IL-1beta and TNF-alpha activity, suggesting that these cytokines are involved in human sleep regulation.

Plasma levels of cytokines and soluble cytokine receptors during treatment with haloperidol.

OBJECTIVE: Clozapine increases the levels of cytokines and soluble cytokine receptors. The authors investigated whether haloperidol has similar effects. METHOD: Rectal temperature, white blood cell counts, and plasma levels of cytokines and soluble cytokine receptors were assessed before and during 6 weeks of haloperidol treatment in 10 psychiatric patients. RESULTS: Haloperidol at mean doses of 7.0 mg/day (SD = 3.4), 6.9 mg/day (SD = 3.4), and 5.0 mg/day (SD = 3.1) at the end of the 1st, 2nd, and 6th weeks of treatment, respectively, did not affect rectal temperature, white blood cell counts, or plasma level of interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor p55 or p75, or soluble interleukin-2 receptor. CONCLUSIONS: Haloperidol is unlikely to confound the results of studies investigating disease-related alterations in the levels of a broad range of cytokines and soluble cytokine receptors in schizophrenia.

The influence of clozapine treatment on plasma granulocyte colony-stimulating (G-CSF) levels.

The antipsychotic drug clozapine frequently induces transient increases in white blood cell counts that have been found to be sensitive, but non-specific, predictors of subsequent life-threatening agranulocytosis. Granulocyte colony-stimulating factor (G-CSF) is an endogenous hematopoietic growth factor that plays a pivotal role in granulopoiesis. In addition, G-CSF has successfully been used to treat clozapine-induced agranulocytosis. We performed a longitudinal investigation of the plasma levels of G-CSF in 20 schizophrenic patients during six weeks of clozapine treatment. Clozapine transiently increased plasma G-CSF levels in 55% of the subjects studied. This effect was most prominent at the end of the second week of treatment. Increased G-CSF levels were accompanied by increased granulocyte and monocyte counts, increased rectal temperature and increased plasma levels of other cytokines and cytokine receptors. The results presented suggest that G-CSF is involved in clozapine-induced increases in granulocyte counts seen early during treatment. Like granulocytosis, granulocytopenia is known to occur in conjunction with increased systemic G-CSF levels. Therefore, we hypothesize that a persistent increase along with a decline in white cell counts following an early spike during clozapine treatment might predict the occurrence of agranulocytosis.

[Structured day care therapy program for eating disorders]. / Strukturiertes tagklinisches Therapie-Programm für Essstörungen.

A day hospital group treatment program is detailed which could offer effective treatment to many patients with anorexia nervosa and bulimia nervosa who would otherwise require inpatient treatment. Important clinical advantages over an inpatient program are described. The psychotherapy is cognitive-behavioral oriented and is done in groups. A multi-disciplinary team approach is used. The day hospital treatment program includes psychological, social and eating-related interventions. Main characteristics are the motivation-phase, the contact between patients of different therapy-phases, the involvement of families in therapy and the support of self-help. First empirical outcome results are presented.