Postpartum psychosis is a severe psychiatric condition marked by the abrupt onset of psychosis, mania, or psychotic depression following childbirth. Despite evidence for a strong genetic basis, the roles of common and rare genetic variation remain poorly understood. Leveraging data from Swedish national registers and genomic data from the All of Us Research Program, we estimated family-based heritability at 55% and whole-genome sequencing-based heritability at 46%. Rare coding variant analysis identified HMGCR as a gene in which rare damaging variants confer risk for postpartum psychosis (FDR < 0.05). Analyses of 240,009 participants from the All of Us Research Program and 58,990 participants from the Mount Sinai BioMe Biobank identified significant associations linking deleterious rare variants in HMGCR to vascular dementia and mental disorder, not otherwise specified, supporting the gene's broader psychiatric relevance. Additionally, among the top 200 genes ranked by association statistics, 17% of bipolar disorder, 21% of schizophrenia, and 16-25% of multiple autoimmune disorders exhibit a possible association with postpartum psychosis. These findings reveal unique genetic contributions and shared pathways, providing a foundation for understanding pathophysiology and advancing therapeutic strategies.

Objective: Parental prenatal mood and anxiety disorders (PMAD) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors. Method: A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to January 2024. Of 2,170 articles screened, 64 met the inclusion criteria. Meta-analyses were conducted on 20 studies, and 44 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I^2) and publication bias (Egger's test). The review followed PRISMA and MOOSE guidelines. Results: Maternal PMADs were associated with a significantly increased risk of ADHD (OR 1.91, 95% CI 1.45-2.52) and ASD (OR 1.57, 95% CI 1.37-1.81) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR 1.24, 95% CI 1.15-1.34). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior. Conclusions and Relevance: Parental PMADs are significantly associated with an increased risk of NDDs in children. These associations may be influenced by both genetic predispositions and environmental factors. Understanding these pathways is important for informing interventions aimed at mitigating mental health risks in families and supporting child development.

OBJECTIVE:Postpartum psychosis is one of the most severe psychiatric conditions, with high risks of suicide and infanticide if untreated. Although genetic factors contribute to the risk of postpartum psychosis, the extent of familial risk remains to be determined. The authors compared relative recurrence risk across different family relationship types, hypothesizing that relative recurrence risk for postpartum psychosis varies by degree of genetic relatedness and is higher in female full siblings than in cousins. METHODS:This cohort study consisted of 1,648,759 women from the Swedish nationwide registers, of whom 2,514 (0.15%) experienced postpartum psychosis within 3 months of their first-ever childbirth. The authors estimated the relative recurrence risk of postpartum psychosis for female full siblings and cousins as a measure of familial risk. RESULTS:The relative recurrence risk of postpartum psychosis in full siblings was 10.69 (95% CI=6.60, 16.26) when adjusted for year of and age at childbirth. Although cousins showed an elevated relative recurrence risk, these results did not reach statistical significance (1.78, 95% CI=0.70, 3.62). Despite the higher familial risk of postpartum psychosis among full siblings, the absolute risk for women with an affected sibling was relatively low, estimated at 1.60% within the entire population. CONCLUSIONS:The observed increased risk of postpartum psychosis in full siblings suggests both genetic and shared environmental influences. However, the lack of significant results in cousins hampers a more accurate distinction between these factors. Furthermore, despite increased relative recurrence risk in siblings, their overall likelihood of developing postpartum psychosis remains low. This study underscores the need for further research to better understand the intricate interplay of genetics and shared environment in the development of postpartum psychosis.

Medication management in women with bipolar disorder (BD) in the perinatal period is challenging, given that many patients taper or stop medication during pregnancy, and the postpartum period is an extremely high-risk period for relapse. The objective of this narrative review was to investigate the perinatal efficacy as well as potential adverse effects on the child of common treatments for bipolar disorder. These treatments include lithium, lamotrigine, other antiepileptics, quetiapine, olanzapine, aripiprazole, other antipsychotics, antidepressants, benzodiazepines, Z-drugs, and other sleep medication. Despite the worldwide decline in lithium use, it remains the gold standard for acute and maintenance treatment of BD, and we continue to advise its use in women of reproductive age. In contrast, medications with a high risk for teratogenicity such as valproate and carbamazepine should be avoided in women of childbearing potential. Women with bipolar disorder are at very high risk of relapse after delivery, but this risk is more than twofold lower with adequate pharmacological prophylaxis. We advise to make a written perinatal bipolar relapse prevention plan in collaboration with the patient, family, and healthcare professionals, which includes a description of: (1) maintenance treatment during pregnancy, (2) preferred mode of delivery, (3) medication immediately after delivery and the first months postpartum for relapse prevention, (4) preferred plan for feeding (breast-feeding versus bottle-feeding), (5) strategies to assist women in ensuring adequate sleep and stable circadian rhythm in the first weeks after delivery, and (6) how to recognize the first symptoms of relapse and which intervention strategies to take.

BACKGROUND: As people live longer, maintaining brain health becomes essential for extending health span and preserving independence. Brain degeneration and cognitive decline are major contributors to disability. In this study, we investigated how metabolic health influences the brain age gap estimate (brainAGE), which measures the difference between neuroimaging-predicted brain age and chronological age. METHODS: K-means clustering was applied to fasting metabolic markers including insulin, glucose, leptin, cortisol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, steady-state plasma glucose, and body mass index of 114 physically and cognitively healthy adults. The homeostatic model assessment for insulin resistance served as a reference. T1-weighted brain magnetic resonance imaging was used to calculate voxel-level and global brainAGE. Longitudinal data were available for 53 participants over a 3-year interval. RESULTS: K-means clustering divided the sample into 2 groups, those with favorable (n = 58) and those with suboptimal (n = 56) metabolic health. The suboptimal group showed signs of insulin resistance and dyslipidemia (false discovery rate-corrected p < .05) and had older global brainAGE and local brainAGE, with deviations most prominent in cerebellar, ventromedial prefrontal, and medial temporal regions (familywise error-corrected p < .05). Longitudinal analysis revealed group differences but no significant time or interaction effects on brainAGE measures. CONCLUSIONS: Suboptimal metabolic status is linked to accelerated brain aging, particularly in brain regions rich in insulin receptors. These findings highlight the importance of metabolic health in maintaining brain function and suggest that promoting metabolic well-being may help extend health span.

Background: Postpartum psychosis affects 1-2 per 1,000 women following childbirth and constitutes a psychiatric emergency with significant risks for maternal and infant outcomes. While a personal history of bipolar disorder is the most established risk factor, nearly half of affected women have no prior psychiatric diagnosis, underscoring the need for improved risk stratification strategies. Methods: In this nationwide Swedish register-based cohort study, we analyzed 676,293 women with at least one sister who delivered their first liveborn child between 1980 and 2017. A secondary analysis included 100,652 women with at least one brother. Postpartum psychosis was defined as psychiatric hospitalization for mania, psychosis, or depression with psychotic features within 90 days postpartum. Associations between sibling psychiatric diagnoses and postpartum psychosis were estimated using logistic regression, adjusting for maternal age and birth year. Hierarchical clustering was applied to identify familial subtypes based on sibling psychiatric profiles. Results: Among 885 women (3.7 per 1,000) diagnosed with postpartum psychosis, we observed strong associations with sister diagnoses of schizoaffective disorder (OR, 14.50; 95% CI, 4.44-34.30) and postpartum psychosis (OR, 10.69; 95% CI, 6.60-16.26). Significant associations were also found for sister diagnoses of schizophrenia (OR, 7.10; 95% CI, 1.76-18.60) and bipolar disorder (OR, 6.26; 95% CI, 4.00-9.29). In brother-sister pairs, the strongest association was with bipolar disorder (OR, 6.23; 95% CI, 2.21-13.67). Cluster analysis revealed four familial subtypes, with 6.3% of cases showing distinct patterns of familial psychiatric burden: predominantly internalizing (anxiety/bipolar/personality disorders), predominantly externalizing (substance use disorders), and a broad affective-psychotic pattern with multiple comorbidities. Conclusions: Familial psychiatric disorders, particularly those with psychotic or affective features, are strong risk markers for postpartum psychosis. These findings support the conceptualization of postpartum psychosis as a disorder with heterogeneous familial liability and highlight the potential utility of incorporating sibling psychiatric history into perinatal mental health screening, especially for women without prior psychiatric diagnoses. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by a grant from the Beatrice and Samuel A. Seaver Foundation (BM, SS); the National Institute of Mental Health (NIMH), R21MH131933 (BM), R01 HD111117 (TKR), and R01MH122869 (VB). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Swedish Ethical Review Authority approved the study and waived the requirement for informed consent owing to the use of de-identified registry data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data may be obtained from a third party and are not publicly available. Data cannot be shared publicly owing to restrictions by law. Data are available from the National Medical Registries in Sweden after approval by the Swedish Ethical Review Authority.

Postpartum psychosis (PP) is an acute and severe psychiatric illness with onset within weeks after delivery and a high risk of suicide and infanticide. Most women with PP experience severe mood symptoms, including mania, mixed episodes, or depression with psychotic features. Impaired cognition, irritability, and agitation are also common. The specific timing of PP strongly suggests a biological basis, because the postpartum time period is characterized by profound endocrine, immune, neuroanatomical, and physiological changes in the brain. Genetic studies show a unique risk architecture, partly shared with bipolar disorder. PP stands out as one of the most distinct clinical phenotypes in psychiatry due to its characteristic rapid onset, severity, phenomenology, treatment response, and prognosis. Despite this, as of August 2025, PP does not have a distinct diagnostic classification in the DSM. This expert consensus panel, in close collaboration with patient organizations and key interested partners, recommends classifying PP as a distinct category within DSM-5 and ICD-11. We recommend classification within the bipolar disorders chapter of the DSM because 1) most women with PP have prominent affective symptoms; 2) treatment response to lithium and electroconvulsive therapy is excellent; 3) in half of the cases, first-onset PP is also the first onset of bipolar disorder; 4) pregnant women with bipolar disorder are at very high risk of PP; and 5) the genetic risk architecture for PP is distinct but overlapping with bipolar disorder. This consensus statement summarizes scientific evidence that PP is a distinct mental illness within the bipolar spectrum; correct classification will improve detection and treatment.

OBJECTIVE:Antipsychotic medications are widely prescribed, including during pregnancy, and pregnant individuals worry about the potential sequelae for the child. Although antipsychotics do not seem to be teratogenic, the long-term neurodevelopmental impact of prenatal exposure remains unclear. A systematic review was conducted to determine if intrauterine antipsychotic exposure increases the risk of adverse neurodevelopmental outcomes. METHOD:A systematic search was performed in MEDLINE, Cochrane, Embase, and PsycINFO for studies published before September 7, 2024. We included original studies assessing cognitive, motor, behavioral, social, and psychiatric outcomes in children prenatally exposed to antipsychotics, excluding case reports, reviews, preclinical studies, and studies without a control group. Quality and risk of bias were assessed using the Newcastle-Ottawa Scale. RESULTS:Of 1,349 studies identified, full text of 56 was screened, and 16 were included in the review. The number of exposed participants ranged from 11 to >15,000. In the 8 studies assessing motor development, early motor delays were observed but did not persist into later childhood. Neurodevelopmental disorders were assessed in 7 studies. Crude estimates showed greater risk in exposed children, but after adjusting for confounders, most studies found no significant risk. The mean NOS score was 7.1. CONCLUSION:Transient motor delays may be associated with antipsychotic use during pregnancy, although future studies adjusting for confounding factors should clarify this risk. After adjustment for confounders, the risk of neurodevelopmental disorders in school-age children does not seem to be increased. Studies with longer follow-up time are required to further investigate the risk of neurodevelopmental disorders. PLAIN LANGUAGE SUMMARY:This systematic review of research examines the mental, behavioral, and cognitive health outcomes of children whose mothers took antipsychotics during pregnancy. Sixteen articles were included in the review; the number of exposed participants in each study ranged from 11 to >15,000. The authors found that the majority of studies, especially those with longer-term follow-up and larger samples, did not identify increased neurodevelopmental problems in children who were exposed to antipsychotics during pregnancy. Some studies noted transient motor delays in exposed infants, but the authors found that they did not sufficiently account for the potential influence of severe maternal mental illness on this association. CLINICAL GUIDANCE:• Antipsychotic use during pregnancy may be indicated for effective treatment of severe mental illness in pregnant women. • A discussion that involves the risks of untreated maternal mental illness alongside existing data on antipsychotic exposure in pregnancy and its potential neurodevelopmental impact on children is an important step in supporting informed decision making. STUDY REGISTRATION INFORMATION:Neurodevelopmental Consequences of Antenatal Exposure to Antipsychotic Medication: A Systematic Review and Meta-Analysis; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024499352.

Background Depression and anxiety are common in the perinatal period. While most of those affected respond well to treatment, a subpopulation is more resistant. Understanding more about individuals who do not respond well to available treatments may improve care for this group. Methods We administered entry and exit self-report measures to 178 women who participated in a specialized partial hospitalization program for perinatal individuals. Baseline measures of anxiety, obsessive symptoms, sleep quality, early life adversity, and adult attachment security were examined as potential predictors of response to treatment. Results While no individual baseline survey predicted treatment response, clustering patients on the basis of a combination of self-report adult attachment styles and early life adversity yielded four distinct groups. A cluster with high attachment anxiety, high attachment avoidance, and childhood history of verbal and emotional abuse was less responsive to treatment than the other groups. Conclusions Combining detailed information about self-report adult attachment style and early life adversity may improve prediction of treatment response in individuals with perinatal mood and anxiety disorders.

Background Personal and family history of psychiatric disorders are key risk factors for postpartum depression (PPD), yet their combined contribution has been understudied.Objective To examine personal and family psychiatric history, alone and combined, and their effect on absolute risk and relative risk (RR) of mild/moderate or severe PPD.Methods In this cohort study, we used data from 142 064 childbirths with PPD screenings from 2015 to 2021 merged with population registers. Exposures were personal and family psychiatric history defined as a psychiatric hospital contact or psychotropic prescription fills by index mothers and their parents prior to delivery. Outcomes were mild/moderate PPD (Edinburgh Postnatal Depression Scale, cut-off: ≥11 within 12 weeks post partum) and severe PPD (antidepressant fill or depression diagnosis within 6 months post partum). We calculated absolute risks and RRs using Poisson regression models adjusted for parity, education, maternal age, and calendar year.Findings Of the 142 064 participants, 23.4% had no psychiatric history, 47.4% had only family history, 6.0% had only personal history, and 23.2% had both. The latter group had the highest risk of PPD: absolute risk of mild/moderate PPD was 11.7% (95% CI 11.5%; 11.8%), and adjusted RR: 2.35 (95% CI 2.22; 2.49). Alone, personal psychiatric history was the most potent risk factor. Dose–response relationship based on severity of personal and family psychiatric history was found.Discussion Our study documents a substantial association between personal and family psychiatric history and PPD risk.Clinical implications Evaluating combinations of risk factors is important to improve risk assessment.

Objectives:Recommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes.Methods:In this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available.Results:There were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient -0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes.Conclusion:Based on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.Appeared originally in Bipolar Disord 2021; 23:49-54.