MRNA expression patterns and distribution of white matter neurons in dorsolateral prefrontal cortex of depressed patients differ from those in schizophrenia patients.
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 phosphate-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 alpha-type II calcium/calmodulin dependent protein kinase (CAMKII-alpha), brain derived neurotrophic factor, (BDNF) and the putative transcription factor, T-brain-1 (TBR1).


RESULTS
Expression of GAD67 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-alpha 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-alpha expression is increased only in bipolar patients suggests abnormalities of specific genes related to a major cortical cell type and its connectivity.
Molnar
Margherita
M
Center for Neuroscience, University of California, Davis, California 95616, USA.
Potkin
Steven G
SG
Bunney
William E
WE
Jones
Edward G
EG
D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D046508:Culture Techniques; D003865:Major Depressive Disorder / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D007527:Isoenzymes; D012333:RNA, Messenger; D009249:NADP; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1