MRNA expression patterns and distribution of white matter neurons in dorsolateral prefrontal cortex of depressed patients differ from those in schizophrenia patients

Abstract

Background Schizophrenia, bipolar illness, and major depressive disorder have distinct presentations, but share some common symptoms. Hence, some common cellular and molecular abnormalities may be identifiable in these disorders. Methods We examined cell-specific markers in the dorsolateral prefrontal cortex of brains from 18 patients with bipolar or major depressive disorder, and 18 matched controls, using in situ hybridization histochemistry and staining for nicotinamide-dinucleotide phophate-diaphorase (NADPH). The distribution of NADPH-positive interstitial cells of the white matter and the expression of the mRNA for the 67 KD form of glutamic acid decarboxylase (GAD 67) had previously been shown to be altered in prefrontal cortex of schizophrenics. Other markers identifying glutamatergic neuronal populations were α-type II calcium/calmodulin dependent protein kinase (CAMKII-α), brain derived neurotrophic factor, (BDNF) and the putative transcription factor, T-brain–1 (TBR1). Results Expression of GAD 67 and the distribution of NADPH-positive cells in the white matter were not significantly altered in the dorsolateral prefrontal cortex of depressed subjects. Expression of CAMKII-α and TBR1 mRNAs was significantly increased in bipolar patients but not in major depressed patients, and there was a trend toward reduced BDNF expression in both groups. Abnormal patterns of gene expression and neuronal distribution in schizophrenics are markedly different from those in depressed patients. Conclusions The findings that TBR1 and CAMKII-α expression is increased only in bipolar patients suggests abnormalities of specific genes related to a major cortical cell type and its connectivity.