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