Abstract:
:Mitochondria have been linked to the etiology of schizophrenia (SZ). However, studies of mitochondria in SZ might be confounded by the effects of pharmacological treatment with antipsychotic drugs (APDs) and other common medications. This review summarizes findings on relevant mitochondria mechanisms underlying SZ, and the potential impact of psychoactive drugs including primarily APDs, but also antidepressants and anxiolytics. The summarized data suggest that APDs impair mitochondria function by decreasing Complex I activity and ATP production and dissipation of the mitochondria membrane potential. At the same time, in the brains of patients with SZ, antipsychotic drug treatment normalizes gene expression modules enriched in mitochondrial genes that are decreased in SZ. This indicates that APDs may have both positive and negative effects on mitochondria. The available evidence suggests three conclusions i) alterations in mitochondria functions in SZ exist prior to APD treatment, ii) mitochondria alterations in SZ can be reversed by APD treatment, and iii) APDs directly cause impairment of mitochondria function. Overall, the mechanisms of action of psychiatric drugs on mitochondria are both direct and indirect; we conclude the effects of APDs on mitochondria may contribute to both their therapeutic and metabolic side effects. These studies support the hypothesis that neuronal mitochondria are an etiological factor in SZ. Moreover, APDs and other drugs must be considered in the evaluation of this pathophysiological role of mitochondria in SZ. Considering these effects, pharmacological actions on mitochondria may be a worthwhile target for further APD development.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Chan ST,McCarthy MJ,Vawter MPdoi
10.1016/j.schres.2019.09.007subject
Has Abstractpub_date
2020-03-01 00:00:00pages
136-147eissn
0920-9964issn
1573-2509pii
S0920-9964(19)30416-5journal_volume
217pub_type
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pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
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pub_type: 信件
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更新日期:2008-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2008-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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更新日期:2015-04-01 00:00:00
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更新日期:2018-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.schres.2015.03.010
更新日期:2015-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-04-01 00:00:00
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更新日期:2020-02-01 00:00:00
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pub_type: 杂志文章
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