Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing
Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing
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DOI：
10.1016/j.jpsychires.2017.11.011
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发表时间：
2018-02-01
影响因子：
4.8
通讯作者：
Malaspina, Dolores
中科院分区：
文献类型：
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作者：
Veras, Andre B.;Getz, Mara;Malaspina, Dolores
背景：催产素是一种影响社会认知与行为、情感调节整合的多肽激素。催产素也显着地指导神经元GABA神经传递在出生后从兴奋性到抑制性的转变。催产素受体(OXTR)与精神分裂症有关，精神分裂症是一种异质综合征。OXTR基因多态性与特定临床特征的关系有助于评估催产素在精神分裂症发病机制中的作用。方法：从症状、认知和早期生活创伤的特征良好的病例和对照组样本中鉴定出罕见编码OXTR单核苷酸变异(SNV)的精神分裂症患者。结果：48例患者中有5例存在罕见的OXTR单核苷酸变异。与其他病例相比，他们没有那么严重的消极症状(情绪表达和动力不足)，也没有那么严重的一般精神病理评分(抑郁和焦虑)。由于缺乏知觉组织和较慢的加工速度，他们表现出低于言语智力的非语言(表现)。他们还报告了更多的早期创伤暴露(身体和性虐待以及情感创伤)。结论：携带罕见OXTRSNV的病例与其他病例相比，负面和情感症状较少，但类似的精神症状，以及特定的认知缺陷。这些病例的临床特征与环境暴露于早期创伤，特别是性虐待有关，这可能影响了OXTR中具有特定SNV的受试者的精神分裂症的表达。
Background: Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific clinical features could aid in evaluating any role of oxytocin in the pathogenesis of schizophrenia.Method: Schizophrenia cases with rare missense coding OXTR single nucleotide variants (SNVs) were identified from a well-characterized sample of cases and controls who were assessed for symptoms, cognition and early life trauma.Results: Five of 48 cases showed rare OXTR variants. Compared to the other cases they had less severe negative symptoms (deficits in emotional expression and motivation) and less severe general psychopathology scores (depression and anxiety). They demonstrated lower nonverbal (performance) than verbal intelligence due to deficient perceptual organization and slow processing speed. They also reported greater early trauma exposure (physical and sexual abuse and emotional trauma).Conclusion: Cases carrying rare OXTR SNVs had less negative and affective symptoms than other cases, but similar psychotic symptoms, along with specific cognitive deficits. The clinical characterization of these cases occurred in association with environmental exposure to early trauma, especially sexual abuse, which may have influenced the expression of schizophrenia in subjects harboring specific SNVs in the OXTR.