MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Lancet Psychiatry. 2021 Dec;8(12):1045-1052. doi: 10.1016/S2215-0366(21)00253-4. Epub 2021 Oct 26.
For more than 150 years, controversy over the status of post-partum psychosis has hindered research and caused considerable confusion for clinicians and women, with potentially negative consequences. We aimed to explore the hypothesis that genetic vulnerability differs between women with first-onset post-partum psychosis and those with bipolar disorder more generally.
In this case-control study on first-onset post-partum psychosis and bipolar disorder in the UK, we included 203 women with first-onset post-partum psychosis (defined as a manic, mixed, or psychotic depression episode within 6 weeks of delivery without a psychiatric history) and 1225 parous women with a history of bipolar disorder. Information on women with bipolar disorder was obtained from the Bipolar Disorder Research Network database, and participants were recruited through screening community mental health teams across the UK and via the media and patient support organisations. All were assessed using a semistructured face-to-face psychiatric interview and psychiatric case note review. 2809 women from the general population were recruited via the national UK Blood Services and the 1958 Birth Cohort (UK National Child Development Study) as controls and matched to cases according to genetic ancestry. All self-reported their ethnicity as White and were recruited from across the UK. Polygenic risk scores (PRSs) were generated from discovery genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Logistic regression was used to model the effect of each PRS on diagnosis, and the RRs and ORs presented were adjusted for ten principal components of genetic variation to account for population stratification.
203 women with first-onset post-partum psychosis (median age at interview: 46 years [IQR 37-55]) and 1225 women with bipolar disorder (49 years [41-58]) were recruited between September, 1991, and May, 2013, as well as 2809 controls. Women with first-onset post-partum psychosis had similar bipolar disorder and schizophrenia PRSs to women with bipolar disorder, which were significantly higher than those of controls. When compared with controls, women with first-onset post-partum psychosis had an adjusted relative risk ratio (RR) for bipolar disorder PRSs of 1·71 (95% CI 1·56-1·86, p<0·0001) and for schizophrenia PRSs of 1·82 (1·66-1·97, p<0·0001). The effect sizes were similar when comparing women with bipolar disorder to controls (adjusted RR 1·77 [1·69-1·84], p<0·0001 for bipolar disorder PRSs; 2·00 (1·92-2·08), p<0·0001 for schizophrenia PRSs). Although women with bipolar disorder also had higher major depression PRSs than did controls (1·24 [1·17-1·31], p<0·0001), women with first-onset post-partum psychosis did not differ from controls in their polygenic liability to major depression (0·97 (0·82-1·11), p=0·63).
Our study supports the recognition of first-onset post-partum psychosis as a separate nosological entity within the bipolar disorder spectrum both in research and clinical settings.
Wellcome Trust and Medical Research Council.
150 多年来，产后精神病的地位一直存在争议，这阻碍了研究进展，并导致临床医生和女性感到困惑，可能会产生负面影响。我们旨在探讨这样一种假设，即初发产后精神病和一般双相情感障碍女性之间的遗传易感性存在差异。
在英国进行的这项关于初发产后精神病和双相情感障碍的病例对照研究中，我们纳入了 203 名初发产后精神病女性（定义为在分娩后 6 周内出现躁狂、混合或精神病性抑郁发作，且无精神病史）和 1225 名有双相情感障碍病史的经产妇。有双相情感障碍病史的女性信息来自双相情感障碍研究网络数据库，参与者通过英国各地社区心理健康团队以及媒体和患者支持组织招募。所有参与者均通过半结构式面对面精神病学访谈和精神病学病历回顾进行评估。通过全国英国血液服务中心和 1958 年出生队列（英国国家儿童发展研究）招募了 2809 名来自普通人群的女性作为对照，并根据遗传背景与病例相匹配。所有女性均自我报告为白人，并在英国各地招募。多基因风险评分（PRSs）是从精神分裂症、双相情感障碍和重度抑郁症的全基因组关联研究中产生的。使用逻辑回归模型来分析每个 PRS 对诊断的影响，呈现的相对风险比（RR）和比值比（OR）是在调整了 10 个主要遗传变异成分以考虑人群分层后得出的。
1991 年 9 月至 2013 年 5 月间，我们招募了 203 名初发产后精神病女性（访谈时的中位年龄：46 岁[IQR 37-55]）和 1225 名双相情感障碍女性（49 岁[41-58]），以及 2809 名对照。初发产后精神病女性的双相情感障碍和精神分裂症 PRS 与双相情感障碍女性相似，明显高于对照组。与对照组相比，初发产后精神病女性的双相情感障碍 PRS 的校正相对风险比（RR）为 1.71（95%CI 1.56-1.86，p<0.0001），精神分裂症 PRS 的 RR 为 1.82（1.66-1.97，p<0.0001）。与对照组相比，双相情感障碍女性的双相情感障碍 PRS 和精神分裂症 PRS 的校正 RR 也相似（双相情感障碍 PRS 为 1.77（1.69-1.84），p<0.0001；精神分裂症 PRS 为 2.00（1.92-2.08），p<0.0001）。尽管双相情感障碍女性的重度抑郁症 PRS 也高于对照组（1.24（1.17-1.31），p<0.0001），但初发产后精神病女性与对照组在重度抑郁症的多基因易感性方面没有差异（0.97（0.82-1.11），p=0.63）。
我们的研究支持在研究和临床环境中将初发产后精神病认定为双相情感障碍谱系内的一个独立疾病实体。
惠康信托基金会和医学研究理事会。
