Elsevier

Biological Psychiatry

Volume 59, Issue 8, 15 April 2006, Pages 689-695
Biological Psychiatry

Original article
Reduced Glucocorticoid Receptor α Expression in Mood Disorder Patients and First-Degree Relatives

https://doi.org/10.1016/j.biopsych.2005.09.026Get rights and content

Background

Individuals with mood disorders exhibit altered function of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. The glucocorticoid receptor (GR) plays an important role in the negative feedback regulation of the HPA axis. There are two protein isoforms of GR, GRα and GRβ, which have distinct biological activity. It has not been examined whether GRα messenger RNA (mRNA) and GRβ mRNA expressions are altered in peripheral blood cells of mood disorder patients.

Methods

Using quantitative reverse transcription polymerase chain reaction (RT-PCR), GRα mRNA and GRβ mRNA were measured in peripheral blood cells of major depressive disorder patients (depressive n = 18; remissive n = 38), bipolar disorder patients (depressive n = 13; remissive n = 35), normal control subjects (n = 31), and first-degree relatives of major depressive (n = 17) and bipolar (n = 15) disorder patients.

Results

Reduced expression of GRα mRNA was shown in both bipolar and major depressive disorder patients in a current depressive state as well as in remission. First-degree relatives of bipolar disorder patients also showed GRα mRNA reduction. Altered GRβ mRNA expression was not found in mood disorder patients.

Conclusions

Our results suggest that reduced GRα mRNA expression might be trait-dependent and associated with the pathophysiology of mood disorders.

Section snippets

Subjects

Major depressive and bipolar disorder patients were diagnosed according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American Psychiatric Association 1994). These included both outpatients and inpatients of the Division of Neuropsychiatry of the Yamaguchi University Hospital. The extent of depressive state was assessed by a 21-item Hamilton Depression Rating Scale (HDRS). Subjects were regarded as under a current depressive state when

Results

The mean ages were not significantly different between major depressive disorder patients, bipolar disorder patients, and normal control subjects (F = 1.95, df = 4,131, p = .106) (Table 2). Regarding the gender distribution, bipolar disorder patients showed a larger ratio of female to male (Χ2 = 12.7, df = 4, p = .013). Levels of plasma cortisol did not differ between major depressive disorder patients, bipolar disorder patients, and normal control subjects (F = .92, df = 4,58, p = .456).

Discussion

In this study, we demonstrated that GRα mRNA level reduction occurs in peripheral blood cells of individuals with major depressive disorder and bipolar disorder, in both a depressive state as well as in remission. Reduced GRα mRNA expression was also shown in first-degree relatives of bipolar disorder patients but not in those of major depressive disorder patients. Based on these and previous findings that GRα mRNA reduction occurred in the cerebral cortex, hippocampus, and amygdala of mood

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