The impact of environmental factors in severe psychiatric disorders.
The impact of environmental factors in severe psychiatric disorders.
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DOI：
10.3389/fnins.2014.00019
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发表时间：
2014
影响因子：
4.3
通讯作者：
Falkai P
中科院分区：
文献类型：
--
作者：
Schmitt A;Malchow B;Hasan A;Falkai P
在过去的几十年里，精神分裂症一直被认为是一种发育障碍。神经发育假说认为精神分裂症与遗传和环境因素导致出生前或出生后大脑发育异常有关。第一个疾病症状出现在成年早期的突触修剪和髓鞘形成过程中。结构 MRI 研究的荟萃分析揭示了首发患者和纵向病程中海马体积的缺陷，证实了这一假设。除了严重精神疾病中危险基因的影响外，环境因素也可能影响围产期的大脑发育。一些环境因素，如产前母体病毒感染、产科并发症（常见因素为缺氧）或神经发育过程中的压力，已被确定在精神分裂症和双相情感障碍中发挥作用，可能导致海马体积变小。在重度抑郁症中，围产期或成年期的心理社会压力是一个重要的触发因素。在动物研究中，慢性应激或重复施用糖皮质激素已被证明会诱导糖皮质激素敏感的海马神经元变性，并可能导致情感障碍的病理生理学。改变染色质结构的表观遗传机制（例如组蛋白乙酰化和 DNA 甲基化）可能介导环境因素对特定基因转录调控的影响，并成为基因与环境相互作用的重要因素。在动物模型中，应该更深入地研究基因与环境的相互作用，以揭示病理生理机制。这些发现可能会带来影响严重精神疾病表观遗传靶点的新治疗策略。
During the last decades, schizophrenia has been regarded as a developmental disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related to genetic and environmental factors leading to abnormal brain development during the pre- or postnatal period. First disease symptoms appear in early adulthood during the synaptic pruning and myelination process. Meta-analyses of structural MRI studies revealing hippocampal volume deficits in first-episode patients and in the longitudinal disease course confirm this hypothesis. Apart from the influence of risk genes in severe psychiatric disorders, environmental factors may also impact brain development during the perinatal period. Several environmental factors such as antenatal maternal virus infections, obstetric complications entailing hypoxia as common factor or stress during neurodevelopment have been identified to play a role in schizophrenia and bipolar disorder, possibly contributing to smaller hippocampal volumes. In major depression, psychosocial stress during the perinatal period or in adulthood is an important trigger. In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons and may contribute to the pathophysiology of affective disorders. Epigenetic mechanisms altering the chromatin structure such as histone acetylation and DNA methylation may mediate effects of environmental factors to transcriptional regulation of specific genes and be a prominent factor in gene-environmental interaction. In animal models, gene-environmental interaction should be investigated more intensely to unravel pathophysiological mechanisms. These findings may lead to new therapeutic strategies influencing epigenetic targets in severe psychiatric disorders.
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影响因子：
4.3
作者：
Brown, Alan S
通讯作者：
Brown, Alan S
影响因子：
17.7
作者：
Brown, AS;van Os, J;Susser, ES
通讯作者：
Susser, ES
DOI：
10.1007/s00406-002-0391-4
发表时间：
2002-12-01
影响因子：
4.7
作者：
Albus, M;Hubmann, W;Mohr, F
通讯作者：
Mohr, F
影响因子：
6.7
作者：
Brown AS
通讯作者：
Brown AS
DOI：
10.1007/7854_2010_38
发表时间：
2010-01-01
期刊：
BEHAVIORAL NEUROBIOLOGY OF SCHIZOPHRENIA AND ITS TREATMENT
影响因子：
--
作者：
Akbarian, Schahram
通讯作者：
Akbarian, Schahram