Immaturity of brain as an endophenotype of neuropsychiatric disorders

Hideo Hagihara, Hirotaka Shoji, Keizo Takao, Noah M. Walton, Mitsuyuki Matsumoto, Tsuyoshi Miyakawa

研究成果: Review article査読

3 被引用数 (Scopus)

抄録

Schizophrenia and bipolar disorder are severe neuropsychiatric disorders, affecting about 1% of the population. Identifying endophenotypes in the brains of neuropsychiatric patients is now considered the way to understand the underlying mechanisms and to improve therapeutic outcomes. However, the endophenotypes and brain mechanisms of the disorders remain unknown. We have previously reported that a-CaMKII heterozygous knockout mice show abnormal behaviors related to neuropsychiatric disorders. In these mutant mice, almost all neurons in the hippocampal dentate gyrus stay at a pseudo-immature state, which we refer to as "immature dentate gyrus (iDG)." So far, the iDG phenotype and similar behavioral abnormalities have been found in Schnurri-2 knockout, SNAP-25 mutant, and forebrain-specific calcineurin knockout mice. In addition, we found that both chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the maturation state of the mature neurons, resulting in the iDG phenotype in wild-type mice. Such an iDG-like phenomenon was observed in the post-mortem brains from patients with schizophrenia/bipolar disorder. Recent studies suggest that cortex and amygdala of schizophrenia patients are also at a pseudo-immature state. Based on the findings, we proposed that immaturity of certain types of cells in the brain is a potential endophenotype of neuropsychiatric disorders.

本文言語English
ページ(範囲)67-79
ページ数13
ジャーナルJapanese Journal of Neuropsychopharmacology
34
3
出版ステータスPublished - 06-2014

All Science Journal Classification (ASJC) codes

  • 臨床心理学
  • 薬理学
  • 精神医学および精神衛生
  • 薬理学(医学)

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