Ellman Lauren M, Murphy Shannon K, Maxwell Seth D, Calvo Evan M, Cooper Thomas, Schaefer Catherine A, Bresnahan Michaeline A, Susser Ezra S, Brown Alan S
Department of Psychology, Temple University, Weiss Hall, 1701 N. 13(th) Street, Philadelphia, PA 19106, United States of America.
Analytic Psychopharmacology, Nathan S. Kline Institute, 140 Old Orangeburg Road Orangeburg, NY 10962, United States of America; New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States of America; Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, United States of America.
Schizophr Res. 2019 Nov;213:15-22. doi: 10.1016/j.schres.2019.07.002. Epub 2019 Jul 22.
Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype-decreased fetal growth-previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings.
Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review.
Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring.
Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.
孕期母亲压力与精神分裂症风险增加一直存在关联；然而，尚无研究探讨孕期母亲皮质醇水平与该疾病风险之间的关系。研究目的是确定产前皮质醇是否与精神分裂症风险以及一种中间表型——胎儿生长受限（此前已发现其与产前皮质醇和精神分裂症有关）的风险相关。鉴于先前的研究结果，还对暴露时间和胎儿性别进行了研究。
参与者来自一项前瞻性出生队列研究，包括64例被诊断为精神分裂症谱系障碍（SSD）的病例和117名对照。通过各孕期储存的血清测定母亲皮质醇水平，并使用半结构化访谈和病历审查对后代进行精神疾病诊断评估。
孕期母亲皮质醇水平与后代患精神分裂症的风险无关。孕晚期皮质醇水平与病例状态在胎儿生长方面存在显著交互作用。具体而言，与对照组相比，孕晚期母亲皮质醇水平较高的病例胎儿生长明显受限。此外，这些发现仅限于男性后代。
我们的结果表明，较高的产前皮质醇与一种与精神分裂症相关的中间表型——胎儿生长受限有关，但仅在患精神分裂症的男性后代中如此。这些发现与精神分裂症相关基因可能特异性地破坏男性胎儿胎盘功能的证据一致，也与男性在孕期更容易受到母亲皮质醇影响的研究结果相符。最后，结果表明，研究胎儿性别和中间表型对于理解产前因素导致精神分裂症的机制可能很重要。
