Activation of indices of cell-mediated immunity in bipolar mania

doi:10.1016/S0006-3223(98)00159-0

Biological Psychiatry

Volume 45, Issue 8, 15 April 1999, Pages 989-994

https://doi.org/10.1016/S0006-3223(98)00159-0 Get rights and content

Abstract

Background: Evidence supports that marcophages as well as lymphocytes and their products may be involved in the pathophysiology of psychiatric disorders. Whether patients with bipolar disorder have activation or reduction of immunity during a manic episode remains unclear.

Methods: The purpose of this case–control study was to investigate the lymphocyte proliferation to phytohemagglutinin (PHA), concanavalin A, and pokeweed mitogen, and plasma levels of soluble interleukin-2 receptor (sIL-2R) and sIL-6R in patients with bipolar mania (DSM-III-R). The subjects were 23 physically healthy patients with Young Mania Rating Scale (YMRS) scores ≥26 as well as aged ≤45 years and 23 age- and gender-matched normal control subjects. The above immune variables were measured in acute mania and consequent remission (YMRS scores ≤12) among bipolar patients.

Results: The lymphocyte proliferation to PHA and the plasma sIL-2R levels, but not sIL-6R, of bipolar patients were significantly higher in acute mania than in consequent remission. These elevations were not due to differences in medication status. Only in acute mania were the plasma sIL-2R levels of patients significantly higher than control subjects. A positive correlation between the changes of manic severity and plasma sIL-2R levels was observed. Remitted bipolar patients and normal control subjects did not differ in any of these measures.

Conclusions: Cell-mediated immunity activation in bipolar mania was demonstrated and may be through a specifically state-dependent immune response.

Introduction

Several lines of evidence support that macrophages and their products (cytokines) play an integral role in the pathophysiology of certain psychiatric disorders, including depressive disorder and schizophrenia Maes et al 1991, Smith 1992. An acute phase (AP) protein response has been reported in major depression, schizophrenia, and mania (Maes et al 1997). Bipolar disorder is a mood disorder that may manifest psychosis in manic episode. Additionally, an increased prevalence of thyroid autoantibodies (Haggerty et al 1990) and immune-related diseases (Tsai et al 1997b) were reported in bipolar disorder patients; however, reports on the assessment of immunity in mania are limited and remain controversial.

Kronfol and House (1988) reported that an impairment in cell-mediated immunity (CMI) was found in a small group of manic patients as reflected by a reduced in vitro lymphocyte response to mitogen stimulation. Reduced cellular immune function in manic patients was also supported by lower antibody-dependent cellular cytotoxicity (Barsi et al 1989), whereas the soluble interleukin-2 receptor (sIL-2R) is released from activated T cells into the blood (Caruso et al 1993). As plasma concentrations of sIL-2R and sIL-6R were significantly higher in manic patients than in normal control subjects, activation of CMI in mania was suggested (Maes et al 1995a). Furthermore, based on no evidence of immune system activation in euthymic bipolar disorder, Rapaport (1994) implied that the immune differences in symptomatic bipolar patients probably represent a state-dependent effect. Since age, gender, and symptomatic severity have effects on immunity in patients with mood disorder Rapaport 1994, Schleifer et al 1989, Schleifer et al 1996, it is probable neither evaluating the immune parameters after a well-defined remission period nor comparing them with age- and gender-matched controls led to the inconsistent results Barsi et al 1989, Kronfol and House 1988, Maes et al 1995a.

To the best of our knowledge, comparisons of the immune status between healthy control subjects and bipolar patients in acute mania as well as consequent remission have not been done yet. It is hypothesized that the alternation in immunity of bipolar patients should be found during various affective states. In an attempt to clarify the immunological pathophysiology of bipolar disorder, we evaluated the lymphocyte proliferation to different mitogens and the plasma levels of sIL-2R and sIL-6R among bipolar patients in acute mania and remission. The questions to be addressed are: 1) does immune activation occur in a manic episode? and 2) is there any immune modulator(s) related to the severity of mania in bipolar disorder?

Section snippets

Subjects

Acute in-patients of Taipei City Psychiatric Center, Taiwan meeting DSM-III-R (American Psychiatric Association 1987) diagnostic criteria for bipolar disorder, manic were invited to participate. They were clinically diagnosed by authors (S.-Y. Tsai and K.-P. Chen) with a well-validated semistructural schedule, Psychiatrist Diagnosis Assessment, which had been described extensively elsewhere (Tsai et al 1997a). The severity of manic symptoms was rated on the Young Mania Rating Scale (YMRS, Young

Results

The plasma sIL-2R levels of bipolar patients in acute mania were significantly higher than in consequent remission (p < .025) and those of control subjects (p < .001) (Table 1); however, in neither acute mania nor remission was there a significant difference in plasma sIL-6R concentrations between bipolar patients and control subjects. In bipolar patients, there was a significantly positive correlation between change in plasma sIL-2R levels (Δ sIL-2R, Δ = mania minus remission values) and

Discussion

Based on comparison between acute mania and consequent remission of bipolar individuals, a major finding of this study is that manic episode is accompanied by significantly higher PHA-induced lymphocyte proliferation as well as elevated plasma sIL-2R levels. Stimulation of lymphocytes by Con A tended to be increased in acute mania, although this result did not reach significance. PHA and Con A are known to stimulate mostly T cells. PWM is a B-cell mitogen, although T-cell dependent. Most

Acknowledgements

This study is supported in part by the National Scientific Council of Taiwan, grants NSC 87-2815-C-038-005-B and 86-2314-B-038-016.

The authors thank Miss Pei-Yun Chen for the statistical analysis and Miss Tzu-Ling Liu for technical assistance.

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Original ArticlesActivation of indices of cell-mediated immunity in bipolar mania

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Acknowledgements

Psychiatry Res

Biol Psychiatry

Biol Psychiatry

Schizophr Res

Toxicol Lett

Biol Psychiatry

Biol Psychiatry

J Psychiatr Res

J Affect Disord

Schizophr Res

Psychiatry Res

J Affect Disord

Biol Psychiatry

Biol Psychiatry

Psychiatry Res

Med Hypotheses

J Affect Disord

Original Articles
Activation of indices of cell-mediated immunity in bipolar mania