Decreased expression of mineralocorticoid receptor mRNA in the prefrontal cortex in schizophrenia and bipolar disorder.

Abstract

Abnormal prefrontal cortical activity, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and deficits in slow-wave sleep (SWS) have been extensively reported in patients with affective disorders and schizophrenia, yet the underlying pathophysiological mechanisms have not been completely elucidated. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are two nuclear hormone receptors of primary importance in the control of stress-related and circadian HPA activity. A recent study showed that blocking brain MR activity not only enhances CRF-induced ACTH and cortisol release, but also significantly reduces SWS in humans. We hypothesized that the expression of MR would be deficient in the prefrontal cortex of patients with schizophrenia and affective disorders. The MR mRNA expression in the post-mortem prefrontal cortex of patients with major depression (MD), bipolar (BP), and schizophrenic (SZ) disorders and non-psychiatric controls (n=15 for each patient group, and n=14 for controls) was determined by in-situ hybridization. In the dorsolateral prefrontal cortex Brodmann's area 9 (BA 9), MR mRNA was significantly lower (p<0.05) in all laminae (I-VI) in BP, and in laminae I, III, IV and VI in SZ than in the controls. MR mRNA in BA 9 was negatively correlated with the duration of psychiatric illnesses. In BA 46, MR mRNA was not significantly different among groups, but was positively correlated with brain pH. These results provide the first evidence of deficient prefrontal MR mRNA expression in BP and SZ. Whether these findings may be linked to the abnormal prefrontal function, HPA axis activation, or the deficits in SWS found in these major psychiatric illnesses remains to be further explored.