Takeshi Okuda, Sohei Kimoto, Rika Kawabata, Yufan Bian, Makoto Tsubomoto, Kazuya Okamura, John F Enwright, Mitsuru Kikuchi, David A Lewis, Takanori Hashimoto
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引用次数: 0
Abstract
Background: In schizophrenia (SZ), impairments in cognitive functions, such as working memory, have been associated with alterations in certain types of inhibitory neurons that utilize the neurotransmitter γ-aminobutyric acid (GABA) in the dorsolateral prefrontal cortex (DLPFC). For example, GABA neurons that express parvalbumin (PV) or somatostatin (SST) have more prominent gene expression alterations than those that express vasoactive intestinal peptide (VIP). In bipolar disorder (BD) and major depression (MD), which exhibit similar, but less severe, cognitive impairments than SZ, alterations of transcript levels in GABA neurons have also been reported. However, the extent to which GABA neuron subtype-selective transcripts in the DLPFC are affected, and the relative magnitudes of the diagnosis-associated effects, have not been directly compared across SZ, BD, and MD in the same study.
Methods: We used quantitative polymerase chain reaction to examine levels of GABA neuron subtype-selective transcripts (PV, potassium voltage-gated channel modifier subfamily-S member-3, SST, VIP, and calretinin mRNAs), as well as the pan-GABA neuron marker 67 kDa glutamate decarboxylase mRNA, in DLPFC total gray matter of 160 individuals, including those with SZ, BD, or MD and unaffected comparison (UC) individuals.
Results: Relative to UC individuals, individuals with SZ exhibited large deficits in levels of all transcripts except for calretinin mRNA, whereas individuals with BD or MD showed a marked deficit only for PV or SST mRNAs, respectively.
Conclusions: These findings suggest that broader and more severe alterations in DLPFC GABA neurons might contribute to the greater cognitive impairments in SZ relative to BD and MD.
期刊介绍:
Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.