The risk of offspring mood and anxiety disorders in the context of prenatal maternal somatic diseases: a systematic review and meta-analysis

Aims The importance of prenatal maternal somatic diseases for offspring mood and anxiety disorders may be overlooked or undervalued. We conducted the first systematic review and meta-analysis assessing the risk of offspring mood and anxiety disorders in the context of prenatal maternal somatic diseases. Methods We screened articles indexed in Embase (including Embase, MEDLINE, PubMed-not-MEDLINE), PsycARTICLES and PsycINFO databases up to August 2021. 21 studies were included. We examined the overall associations between prenatal maternal somatic diseases and offspring mood/anxiety disorders. Analyses were stratified according to maternal somatic diseases and follow-up duration. Results We observed an increased risk of mood and anxiety disorders in the context of prenatal maternal somatic diseases [relative risk (RR) = 1.26; 95% confidence interval (CI) 1.15–1.37, RR = 1.31; 95% CI 1.24–1.38]; maternal obesity(RR = 1.92; 95% CI 1.72–2.11), hypertensive disorders (RR = 1.49; 95% CI 1.11–1.86) and infertility (RR = 1.26, 95% CI 1.14–1.39) were risk factors for mood disorders; maternal polycystic ovary syndrome (RR = 1.61; 95% CI 1.42–1.80), severe obesity (RR = 1.56; 95% CI 1.44–1.68) and moderate obesity (RR = 1.36; 95% CI 1.28–1.44) were risk factors for anxiety disorders. Prenatal maternal somatic diseases increased the risk of mood disorders in childhood and adulthood (RR = 1.71; 95% CI 1.34–2.09/RR = 1.19; 95% CI 1.09–1.30), as well as the risk of anxiety disorders in adulthood (RR = 1.33; 95% CI 1.26–1.41). Conclusion The results indicate that prenatal maternal somatic diseases are associated with offspring mood and anxiety disorders, and that the associations may be long-lasting.

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS.