Diurnal Alterations in Gene Expression Across Striatal Subregions in Psychosis.
Diurnal Alterations in Gene Expression Across Striatal Subregions in Psychosis.
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DOI：
10.1016/j.biopsych.2022.08.013
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发表时间：
2023-01-15
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
精神病是精神分裂症的一个特征，在双相情感障碍中非常普遍。值得注意的是，患有这些疾病的个体也会严重扰乱睡眠和昼夜节律，而睡眠和昼夜节律的紊乱会加重或加剧精神病症状。精神病与纹状体有关，尽管迄今为止还没有研究直接测量分子节律并确定它们在精神病患者的纹状体中是如何改变的。在这里，我们进行RNA测序和差异表达和节律性分析，以研究昼夜变化的基因表达在人类死后纹状体亚区（NAc，尾状核和壳核）在精神病受试者（n = 36）相对于未受影响的比较受试者（n = 36）。跨区域，我们发现差异表达的免疫相关的转录和大量的损失的核心生物钟基因的节奏与精神病。在脑桥核（NAc）中，精神病受试者中与神经元相关的转录物表达减少，但仅在夜间死亡的受试者中。此外，我们发现了小核仁RNA的节律性损失和精神病受试者的NAc中的多巴胺能信号的节律性增加。区域之间的比较表明，在尾状核和壳核的节律性是更相似的精神病患者比匹配的比较科目。总之，这些发现揭示了纹状体中差异和节律性基因表达差异，这可能有助于精神病患者的纹状体功能障碍和精神病。
Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals suffering with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances to sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis. Here, we perform RNA-sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (NAc, caudate, and putamen) in subjects with psychosis (n=36) relative to unaffected comparison subjects (n=36). Across regions, we find differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens (NAc), mitochondrial-related transcripts have decreased expression in psychosis subjects, but only in those who died at night. Additionally, we find a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the NAc of psychosis subjects. Between region comparisons indicate that rhythmicity in the caudate and putamen is far more similar in subjects with psychosis than in matched comparison subjects. Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.
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影响因子：
15.9
作者：
Der-Avakian A;Markou A
通讯作者：
Markou A
DOI：
10.1176/appi.ajp.2020.19111210
发表时间：
2020-12-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Glausier JR;Enwright JF 3rd;Lewis DA
通讯作者：
Lewis DA
影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
DOI：
10.1002/ajmg.b.30151
发表时间：
2005-04-05
影响因子：
2.8
作者：
Castensson, A;Åberg, K;Jazin, E
通讯作者：
Jazin, E
影响因子：
--
作者：
Howes, Oliver D.;Montgomery, Andrew J.;Grasby, Paul M.
通讯作者：
Grasby, Paul M.