RARE DISEASE
Postpartum psychosis
Postpartum psychosis
Postpartum psychosis
Synonyms: Puerperal psychosis
Synonyms: Puerperal psychosis
Synonyms: Puerperal psychosis
Drug discovery
0
drugs
With orphan designations
Overview
Postpartum psychosis is a psychiatric emergency characterized by acute onset of psychotic symptoms (delusions, hallucinations), manic or depressive features, and cognitive disturbances within days to weeks postpartum. It affects 1-2 per 1,000 births, with rapid progression and significant risks of self-harm or infant harm. Immediate hospitalization and multidisciplinary care are critical, combining antipsychotics (e.g., haloperidol), mood stabilizers (e.g., lithium), benzodiazepines, and electroconvulsive therapy (ECT) for refractory cases [1][3][6][11].
Burden
Mortality: 5% suicide risk; 4.5% infanticide risk in depressive subtypes [11][12].
Long-term morbidity: 50–80% develop bipolar disorder; 56% experience recurrent non-postpartum psychiatric episodes [13][15].
Healthcare costs: Prolonged hospitalization (median 40 days) and need for long-term mental health monitoring [8][15].
Therapies
Pharmacotherapy: First-line use of antipsychotics (e.g., risperidone) and mood stabilizers (e.g., lithium); benzodiazepines for agitation [3][8][15].
ECT: Reserved for severe, refractory cases or catatonia [6][8].
Inpatient care: Mother-baby units preferred to support bonding; crisis intervention and safety planning [1][6][15].
Categories: rare gynecological and obstetric diseases, rare neurological diseases
Research Papers
376 drug discovery papers about Postpartum psychosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
376 drug discovery papers about Postpartum psychosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-01 | Therapeutic potential of aripiprazole in the treatment of postpartum psychopathological conditions - clinical and hormonal aspects
Introduction The research was conducted on a sample of 12 patients in the postpartum period, of whom 8 had postpartum depression, and 4 had postpartum psychosis. The influence of aripiprazole on prolactin level and therapeutic outcome was analyzed. In patients with postpartum depression, those who received aripiprazole had a more pronounced decrease in prolactin and a shorter hospitalization. Similar findings were recorded in patients with psychosis. The findings indicate a potential benefit of aripiprazole in the treatment of postpartum disorders. Objectives The connection between hormonal changes and psychological disorders in the postpartum period is complex and is the subject of numerous studies. Prolactin, a hormone that increases after childbirth, can be associated with the development of depressive and psychotic symptoms. The aim of this study was to examine the association of prolactin level with the intensity of symptoms and the effect of aripiprazole. Methods The sample included 12 patients hospitalized for postpartum psychological disorders. Eight patients were diagnosed with postpartum depression, and four with postpartum psychosis. In patients with postpartum depression, two groups were formed: group A (n=4) received an antidepressant and aripiprazole (5 mg), while group B (n=4) received only antidepressants. For postpartum psychosis, two patients received aripiprazole in addition to olanzapine, and two only olanzapine. Initial and control measurement of prolactin level was performed in both groups. Results In patients with postpartum depression, the maximum prolactin level was 785 mIU/L. In Group A there was a 38% drop in prolactin, while in Group B the drop was 17%. The average duration of hospitalization was 18 days for Group A and 26 days for Group B. In patients with postpartum psychosis, the maximum prolactin level was 1478 mIU/L. A greater therapeutic response and decrease in prolactin was observed in patients who received aripiprazole compared to those who received olanzapine. During hospitalization, a control measurement of prolactin was carried out, which confirmed a more pronounced drop in the groups that received aripiprazole. Conclusions The control measurement of prolactin showed a more pronounced reduction in the group of patients receiving aripiprazole. At the same time, a shorter stay in the hospital and a better therapeutic response were recorded. These findings support the hypothesis that aripiprazole, as a partial agonist of the D2 receptor, can have a beneficial effect in the regulation of postpartum mental disorders along with hormonal stabilization. Aripiprazole in low doses can have a beneficial therapeutic effect not only on symptoms but also on prolactin regulation. Research limitations are: - A small sample of respondents - No randomization Disclosure of Interest None Declared
2026-06-01 | Neuropsychiatric Insights into Postpartum Psychosis: A Four-Case Series with CSF, EEG, and Neuroimaging Correlates
Introduction Postpartum psychosis (PP) is a rare but severe psychiatric emergency, affecting 1–2 per 1000 births and associated with high risks of maternal suicide and infanticide (Munk-Olsen et al., NEJM, 2011). Traditionally considered within the affective spectrum, atypical features such as catatonia, cognitive impairment, and suicidality suggest broader neurobiological mechanisms. Emerging evidence links PP with neuroimmune dysregulation and metabolic vulnerability, yet systematic integration of cerebrospinal fluid (CSF), electroencephalogram (EEG), and neuroimaging remains scarce (Bergink et al., Am J Psychiatry, 2016). Objectives We present four PP cases with multimodal biological evaluation to explore neurobiological contributors and treatment implications. Methods Four women with acute-onset PP within two weeks postpartum were retrospectively analyzed. All underwent psychiatric evaluation, Bush–Francis Catatonia Rating Scale when relevant, EEG, brain MRI, and CSF analysis (cell count, protein, glucose, autoimmune panel including anti-NMDAR). Two also had FDG-PET scans. Treatments and six-month outcomes were recorded. Results Case 1 (30y): Confabulation, visual hallucinations, memory deficits, catatonia (BFCRS=14). Catatonia improved with lorazepam. MRI/CSF/EEG unremarkable. Olanzapine 5 mg/day plus high-dose thiamine produced full remission of cognitive and perceptual symptoms. Case 2 (28y): Suicide attempt, resistant hallucinations and persecutory delusions. EEG slowing; PET showed patchy parietal hypometabolism; CSF revealed increased immunoglobulins. Symptoms improved after IV methylprednisolone. Case 3 (31y): Irritable mania with referential delusions. EEG slowing; PET revealed bilateral frontal and posterior cingulate hypometabolism; CSF non-specific. Remission achieved after eight ECT sessions plus quetiapine 300 mg/day. Case 4 (39y): Bipolar history, persecutory delusions, aggression. CSF showed type 2 oligoclonal bands; EEG and PET were non-specific. Symptoms improved with eight ECT sessions plus lithium 600 mg/day and risperidone 4 mg/day. EEG slowing was observed in three of four cases. All patients remained relapse-free at six months. Conclusions This case series demonstrates the heterogeneity of PP, from catatonia and hallucinations to suicidality and mania. Multimodal evaluation revealed clinically meaningful abnormalities, including CSF immunoglobulin elevation, oligoclonal bands, and FDG-PET hypometabolism. Personalized interventions, including thiamine, corticosteroids, antipsychotics and ECT, proved decisive. To our knowledge, this is among the first PP series systematically integrating CSF, EEG, and PET findings with treatment outcomes. These results support neuroimmune and metabolic contributions and emphasize the need for prospective biomarker-driven studies to guide individualized management. Disclosure of Interest None Declared
2026-05-27 | Postpartum Depression as Multi-Domain Ground State Transition Failure: Hormonal Collapse, Identity Displacement, and the Wrong Attractor of Maternal Anhedonia
We apply the Displacement Framework to postpartum depression (PPD), formalizing it as the predictable product of five simultaneous ground-state displacements occurring at childbirth: hormonal S° (estrogen/progesterone crash at the steepest hormonal gradient in human biology, with allopregnanolone collapse disrupting GABAergic tone), circadian S° (sleep fragmentation preventing nocturnal Φ-clearing), identity S° (matrescence — the structural transition from old self to maternal identity), relational S° (partner relationship restructured, new dependency bond), and somatic S°. Ten formal propositions are derived covering: multi-domain displacement as the PPD landscape, maximal-rate hormonal crash as primary displacement trigger, the three-structure differentiation (baby blues = acute displacement with self-organized return; PPD = failed return entering W_PPD; postpartum psychosis = catastrophic displacement), maternal anhedonia wrong attractor deepened by shame-concealment positive feedback loop, matrescence as structural identity transition failure, sleep deprivation as displacement amplifier and return-path blocker, social isolation as basin-deepening mechanism (modern nuclear family stripping alloparenting infrastructure), brexanolone as displacement-mechanism reversal (synthetic ALLO targeting GABAergic collapse directly), multi-domain return path necessity, and paternal PPD as shared perinatal landscape displacement. The framework shows PPD is not depression with a timing modifier but a structurally distinct wrong attractor with a unique shame-concealment deepening mechanism.
2026-05-22 | Estradiol surges as dual-purpose mechanisms in evolutionary psychiatry: Neuroendocrine stabilization, stress regulation, and psychosis vulnerability.
Estradiol exerts protective effects against psychosis, yet its functional role across the reproductive cycle remains incompletely defined. Prior work demonstrates that estrogen modulates dopaminergic, serotonergic, and immune signaling pathways that influence cognition and psychiatric vulnerability. We propose that peri-ovulatory estradiol surges may reflect a selection-shaped neuroendocrine mechanism serving dual functions: enhancing mate-selection-relevant cognition while transiently buffering, defined here as transient stabilization of neural network activity in response to hormonal fluctuations, against psychosis vulnerability during peak fertility. In this framework, "evolutionary" refers to regulatory systems shaped by selection pressures across generations, rather than to reproduction itself. This model extends the estrogen protection hypothesis by situating cyclic estradiol signaling within an evolutionary psychiatry framework. We further propose a dual-hormone buffering system in which estradiol's excitatory and plasticity-enhancing effects are balanced by progesterone and its metabolite allopregnanolone, which regulate inhibitory tone and stress responsivity via GABA_A receptor signaling. Dysregulation or rapid withdrawal of either hormone may unmask latent vulnerabilities, contributing to psychiatric instability across reproductive transitions, including perimenstrual, postpartum, and perimenopausal states. This coordinated hormonal system may have conferred adaptive advantages by stabilizing cognition and affect during critical reproductive phases. Disruption of this balance in modern contexts may increase vulnerability to psychiatric disorders. This model generates testable predictions and supports receptor-specific therapeutic strategies, including selective estrogen receptor modulators and neurosteroid-based interventions.
2026-05-05 | Cariprazine in Human Milk: Cautionary Implications for Use During Lactation.
Cariprazine is a dopamine D2/D3 partial agonist approved for treatment-resistant depression, bipolar disorder (BD) and schizophrenia. Women with bipolar disorder face an increased risk of postpartum mania and psychosis, as childbirth often triggers episodes. While continuing cariprazine can be crucial for maternal well-being, limited data exist on its peripartum safety. The objective of this research is to assess the risk of infant exposure to maternal cariprazine via breast milk. Breast milk samples were released from the InfantRisk Human Milk Biorepository from 5 lactating women who were taking cariprazine 1.5 to 4.5 mg daily, 4 of whom continued the drug since pregnancy. Timed samples were collected and analyzed using liquid chromatography-tandem mass spectrometry for cariprazine and its active metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR). Infant risk was assessed by determining relative infant dose (RID%) and maternal reports of infant outcomes. Cariprazine and its metabolites were detectable in all participants' milk samples. Mean RID% was 1.23% for cariprazine, 0.09% for DCAR, and 1.22% for DDCAR, yielding a cumulative exposure of 2.54% RID; the highest individual dose-standardized RID was 3.99% (cumulative). Two mothers self-reported infant lethargy, one of which resolved after maternal dose reduction. Estimated infant exposure to cariprazine and its active metabolites falls below standard safety thresholds. However, reported infant adverse effects and the potential for metabolite accumulation due to DDCAR's long half-life necessitate further research to examine potential long-term adverse effects while breastfeeding, particularly in infants exposed to higher maternal doses. These findings represent the first empirical data on cariprazine during lactation and highlight the need for further studies, including pharmacokinetic modeling, to inform clinical guidance.
proteins
2026-05-30 | Economic and Social Burden of Untreated Maternal Mental Health Problems
Maternal mental health is a critical component of public health and family well-being. Mental health disorders during pregnancy and the postpartum period are among the most common complications of childbirth, yet they remain underdiagnosed and undertreated worldwide. Untreated maternal mental health problems not only affect the mother but also create profound economic, social, developmental, and healthcare burdens on families, communities, and nations. Conditions such as postpartum depression, anxiety disorders, post-traumatic stress disorder (PTSD), bipolar disorder, and psychosis can impair maternal functioning, negatively influence infant growth and development, disrupt family relationships, reduce workforce productivity, and increase healthcare expenditure.
2026-02-22 | ‘The Words were Like a Charnel House’: Towards a Body of Postpartum Psychosis Life Writing
Postpartum psychosis (PP) is a psychiatric emergency developing shortly after childbirth. Its symptoms oscillate between insomnia, mania, delusions, and audiovisual hallucinations. Among other intrusive cognitions, PP can produce distressing beliefs that one’s baby has died, or that the person experiencing PP is dead themselves. Despite a low risk of infanticide, owing to certain historical thought-worlds, PP retains a stigmatising association with death. Its very nature challenges autobiographical frameworks of articulation, so life writing about PP spans a wide gamut—from less formalised online narratives like Naomi Knoles’s, to Catherine Cho’s memoir Inferno (2020), and Elizabeth Sankey’s documentary Witches (2024). These texts speak to both the limitations and indispensability of life writing which brings birth/birthing into contact with death across three different registers—actual, delusional, and metaphorical—in the context of maternal mental health. For Alice Flaherty, writing illuminated the shadowy recesses between birth and death, body and thought after her twin sons died at birth, creating a textual ‘charnel house’ to their memory (2015). This essay reaches for the edges of life in PP autobiography to curate the beginnings of a ‘charnel house’ to similar strands in this life writing, which may otherwise elude critical literary attention.
2026-01-09 | Maternal psychiatric disorders before, during, and after pregnancy: a national cohort study in Sweden.
Maternal mental health is a critical public health issue, yet the evidence on rates of incident psychiatric disorders before, during, and after pregnancy is limited. This study aimed to describe the calendar time trends and characterize and compare the risk of maternal psychiatric disorders before, during, and after pregnancy. Leveraging the national and regional registers in Sweden, we conducted a cohort study of all women who gave birth 2003-2019 in Sweden (1,799,010 pregnancies from 1,052,977 women). We identified any incident diagnosis of psychiatric disorders recorded during three periods: the preconceptional year, pregnancy, and the postpartum year. We calculated age and calendar year standardized incidence rate (SIR) of psychiatric disorders annually, and by week across three periods. We further estimated the incidence rate ratio (IRR) using the rate during corresponding preconceptional weeks as the reference. The SIR of maternal psychiatric disorder overall increased from 2003-2019, especially for preconceptional disorders. During the preconceptional year the weekly SIR of any psychiatric disorder was stable at around 25 per 1000 person-years. The SIR gradually decreased during pregnancy to a minimum of 4 per 1000 person-years and bounced back to the preconceptional levels during the postpartum year. This trend was similar in all subtypes of psychiatric disorders, except for depression and psychosis for which an increase was noted at 5-15 and 0-20 postpartum weeks, respectively. An increased incidence rate of maternal psychiatric disorder diagnosed before, during, and after pregnancy was found over time. Our findings suggest an increased risk of depression and psychosis shortly after delivery, although a lowered risk of other psychiatric disorders during and after pregnancy, compared to before pregnancy.
2025-11-01 | Urgency in the Fourth Trimester: Postpartum Psychosis as a Psychiatric Crisis
Postpartum psychosis (PPP) is a rare but severe psychiatric emergency, affecting 1–2 out of every 1,000 new mothers (1). Unlike postpartum depression, which is currently more widely recognized and characterized by persistent sadness, loss of interest, sleep disturbances, guilt or feelings of worthlessness, difficulty concentrating, changes in appetite, psychomotor changes, and thoughts of death or suicide while remaining in contact with reality, PPP involves a loss of reality and may include dangerous behaviours driven by delusional beliefs. Its urgency lies in the significantly elevated risks of suicide and infanticide, estimated at around 5% and 4%, respectively (2). Immediate recognition and treatment are critical, as most affected women require psychiatric hospitalization to prevent tragic outcomes for both mother and child.
2025-02-10 | Childbirth in Primiparous Adolescents: Prevalence, Pregnancy Profile, Maternal and Perinatal Prognosis
Introduction: Adolescent childbirth is a public health and social problem worldwide. It is associated with both maternal and perinatal morbidity and mortality. The general objective of our study is to determine the prevalence and profile of pregnant women, and to assess the maternal and perinatal prognosis of adolescent childbirth in Kisangani. Methods: This was a prospective, multicenter, case-control observational study conducted over a seven-month period, from February 1 to August 31, 2024, in primiparous adolescent gestational carriers (cases) and primiparous gestational carriers aged 20 to 34 years (controls) who delivered in five health facilities in the city of Kisangani, Democratic Republic of Congo. Results: The prevalence of teenage childbirth was 13.8%. Adolescents were more likely than controls to be in secondary education and to be unemployed. Compared with controls, pregnant adolescents were more likely to have poor ANC attendance. There was a statistical difference between the two groups in relation to pelvic anomaly, rupture of membranes on admission, hypertensive disorders, vicious presentation, caesarean section, episiotomy, postpartum anaemia and puerperal psychosis. In fact, these morbidities were more common in adolescent girls than in controls. Compared with controls, neonatal depression, prematurity, low birth weight and perinatal death were more prevalent in the newborns of teenage mothers. Conclusion: The prevalence of teenage childbirth is high in Kisangani; there is an association between unmarried status, lack of employment, low socio-economic status, poor ANC follow-up and teenage childbirth in Kisangani. The latter is also associated with high maternal and perinatal morbidity and mortality.
cell therapies
2026-06-20 | What are the recovery rates for women with postpartum psychosis treated in a Mother and Baby Unit compared to a general adult psychiatric ward?
Preliminary data from the ESMI study protocol suggests that women with postpartum psychosis treated in Mother and Baby Units experience significantly lower readmission rates compared to those treated in general psychiatric wards.
2025-04-01 | Late-Onset Puerperal Psychosis: A Case Report and Challenges in Treatment Decisions
Introduction The perinatal period is a vulnerable time for women, with specific risk factors for mental health issues. Puerperal psychosis typically presents within the first month postpartum, although the perinatal period extends through the first year after delivery. This condition is understudied, and its nature and pathophysiology remain subjects of debate. Objectives To describe a case of late-onset puerperal psychosis, highlighting the challenges in decision-making regarding medical approach. Methods A clinical case report and a non-systematic review of the literature. Results A 39-year-old woman was brought to the Emergency Unit by her relatives due to paranoid delusions that her partner and in-laws were attempting to poison her. She had previously sought mental health care only once, as an adolescent, for anxiety symptoms following her parents’ divorce. She is the mother of a 5-year-old child and a 10-month-old infant, with no reported complications during pregnancy or delivery. The patient reported experiencing strange occurrences over the preceding 10 days, beginning during a family vacation when she became suspicious of the food and the organization of meals. She believed her in-laws were poisoning her and expressed concern about transmitting poison to her infant through breast milk. Upon returning home, these fears intensified, extending to suspicions that her husband, mother, and sister were involved. She had drastically reduced her food intake the prior days before consulting, her appearance was malnourished and disheveled. Further psychopathological exploration revealed delusional beliefs centered on being poisoned and potentially poisoning her baby through breastfeeding. These delusions were accompanied by confusion, perplexity, and heightened anxiety. She denied experiencing hallucinations and had no thoughts of harm toward herself or others. Low-dose olanzapine treatment was initiated and outpatient management was initially chosen to minimize disruption to her role as a mother, in accordance with the patient’s preference and the presence of family support. However, hospitalization ultimately became necessary, resulting in complete resolution of psychotic symptoms after 14 days, with olanzapine titrated to a higher dose (20 mg per day). Conclusions Puerperal psychosis is a complex condition with potentially severe consequences for both maternal and infant health, including disruptions in mother-child bonding. This case underscores the need for further research and resource allocation in this area. Specifically, the development of more psychiatric mother-baby units could help prevent unnecessary separations, promote bonding, and provide opportunities for early parenting interventions. Disclosure of Interest None Declared
2019-04-25 | Do Defective Immune System-Mediated Myelination Processes Increase Postpartum Psychosis Risk?
Postpartum (or puerperal) psychosis (PP) is a rare, severe psychiatric disorder that affects women shortly after childbirth; risk is particularly high in individuals with a history of bipolar disorder or PP, but the underlying pathophysiology remains poorly understood. Emerging evidence suggests that immune system (dys)function plays an important role in disorder onset. On the basis of new findings from clinical and animal model studies, we hypothesise that the abundance and/or activity of regulatory T cells, and the efficacy of consequent (re)myelination processes in the brain mediated by CCN proteins, is perturbed in PP; this pathway may be modulated by risk and protective/treatment factors for the disorder, and identifying abnormalities within it could signpost novel predictive biomarkers and therapeutic targets.
2017-01-31 | A qualitative investigation in the role of the baby in recovery from postpartum psychosis
Psychosis after childbirth is a rare but severe type of mental health difficulty experienced by perinatal women. Research has explored mothers' experiences of onset and recovery from psychosis after childbirth. This study explored the role of the baby in 12 mothers' experiences of recovery. A thematic analysis of the data identified three core themes that described the role of the baby in the mothers' recovery from psychosis after childbirth. Findings revealed that the baby was central to recovery, experienced by mothers as both helpful and unhelpful. The baby interacted with the mother, increasing self‐efficacy, and reducing emotional distress. Findings also showed that the baby could act as a barrier to recovery by increasing the women's emotional distress and hindering access to help and self‐care. The findings of the study add to the existing evidence based on recovery from psychosis after childbirth. The research and clinical implications of these findings are discussed with reference to the existing literature. Key Practitioner Message The baby has an important role in recovery from psychosis after childbirth. The baby can be perceived by mothers to both hinder and help their recovery. Interacting with the baby can be helpful for the mothers' recovery by improving their self‐efficacy and reducing emotional distress. Specialist interventions offered by a mother and baby unit can provide practical support that facilitates mother–baby interactions, which helps move women forward in the recovery process.
2013-11-07 | Evaluating the clinical effectiveness of a specialized perinatal psychiatry inpatient unit
Women experiencing severe perinatal mental illness during pregnancy or postpartum have unique needs when psychiatric hospitalization is indicated. Although many countries have established mother-baby psychiatric units, similar facilities have not been available in the US. In 2011, the University of North Carolina at Chapel Hill inaugurated the first Perinatal Psychiatry Inpatient Unit in the US. We describe the unique characteristics of the patient population and report clinical outcomes guiding development and refinement of treatment protocols. Ninety-two perinatal patients were admitted between September 2011 and September 2012, and 91 completed self-report measures at admission and discharge. Perinatal unipolar mood disorder was the most frequent primary diagnosis (60.43 %), and 11 patients (12 %) were admitted with psychosis. The data document clinically and statistically significant improvements in symptoms of depression, anxiety, and active suicidal ideation between admission and discharge (p < 0.0001), as assessed by the Edinburgh Postnatal Depression Scale, Patient Health Questionnaire, and Generalized Anxiety Disorder Scale. Overall functioning was also improved, demonstrated by a significant mean difference of -10.96 in total scores of the Work and Social Adjustment Scale (p < 0.0001). Data suggest that delivering specialized and targeted interventions for severe maternal mental illness in a safe and supportive setting produces positive patient outcomes.
gene therapies
2026-02-06 | Postpartum Psychosis: could genetic vulnerability to insomnia or short sleep duration be protective?
Postpartum Psychosis (PP) is a severe and understudied perinatal mental illness which disproportionately affects women with bipolar disorder (BD). A relationship between sleep disturbance and PP is often assumed, but is poorly understood. From a cohort of 2099 individuals with BD, 343 parous women were identified and screened for perinatal psychiatric complications. We compared 117 women who developed PP with 226 who did not. Polygenic Risk Scores (PRS) for BD, schizophrenia, insomnia, short sleep, long sleep, sleep efficiency and sleep duration were computed using PRS-CS. Logistic regression was used to model the effect of each PRS on PP. Higher PRS for insomnia and short sleep were associated with reduced risk of PP. Individuals in the lowest decile for insomnia PRS (RR 1.96, 95% CI 1.25-3.07, p = 3.50 × 10⁻³) and short sleep PRS (RR 2.23, 95% CI 1.40-3.54, p = 7.94 × 10⁻⁴) had approximately double the risk of PP than individuals in the highest decile. The other PRS were not associated with PP. Mendelian Randomisation analyses did not support a causal relationship between sleep traits and PP. However, we demonstrate that the integration of PRS with bipolar subtype can improve prediction accuracy. Individuals with genetic vulnerability to insomnia or short sleep may develop a heightened tolerance to sleep disruption earlier in life, mitigating the impact of childbirth on mood. These findings suggest that genetic susceptibility to sleep disturbance may be important in the aetiology of PP, offering a new potential avenue for risk stratification and targeted prevention.
2025-08-12 | Searching for the Puerperal Trigger: Molecular Genetic Studies of Bipolar Affective Puerperal Psychosis
The available evidence suggests that the puerperium is a period of increased risk for acute episodes of illness in bipolar (BP) women and points to genetic factors as influencing vulnerability to postpartum triggering of such episodes. We have previously reported compelling evidence of familiarity of vulnerability to puerperal episodes in female sibs with BP disorder and find similar familial clustering for episodes of narrowly defined postpartum episodes in siblings with major depression. Molecular genetic approaches hold out the promise of uncovering the nature of the puerperal trigger leading to important improvements in the prevention and treatment of postpartum affective episodes. A research strategy focusing on positional and candidate gene approaches may prove fruitful in the search for susceptibility genes for both postpartum triggering in particular and for the affective disorder diathesis in general. We have identified the subset of families in the Wellcome Trust UK-Irish BP sib-pair molecular genetic linkage genome screen that include at least one female who has suffered an episode of puerperal psychosis. Analysis of this more homogeneous subgroup of families resulted in a genome-wide significant linkage signal (LOD = 4.07) on chromosome 16p13 and genome wide suggestive linkage on chromosome 8q24. We are undertaking association studies in women with postpartum psychosis at a number of candidate genes of interest in BP disorder with an emphasis on those for which the expression is influenced by steroid hormones.
2024-12-14 | Postpartum Psychosis: could chronic insomnia or short sleep be protective?
Postpartum Psychosis (PP) is a severe and understudied perinatal mental illness which disproportionately affects women with bipolar disorder (BD). A relationship between sleep disturbance and PP is often assumed, but is poorly understood. Data from 2099 BD subjects were screened to identify parous women. Individuals who developed PP and those who had not were compared in our analyses. Polygenic Risk Scores (PRS) for BD, schizophrenia, insomnia, short sleep, long sleep and sleep efficiency were computed using PRS-CS. Logistic regression was used to model the effect of each PRS on PP. Higher PRS for insomnia and short sleep were protective against PP. Individuals in the lowest decile for insomnia PRS (RR 1.96, 95% CI 1.25-3.07, p = 3.50 x 10 -3) and short sleep PRS (RR 2.23, 95% CI 1.40-3.54, p = 7.94 x 10 -4) had approximately double the risk of PP than individuals in the highest decile. BD, schizophrenia, long sleep and sleep efficiency PRS were not associated with PP. Mendelian Randomisation analyses did not support a causal relationship between sleep traits and PP. However, we demonstrate that the integration of PRS with clinical variables can improve prediction accuracy. Individuals with genetic vulnerability to insomnia or short sleep may develop a heightened tolerance to sleep disruption earlier in life, mitigating the impact of childbirth on mood. These findings suggest that genetic susceptibility to sleep disturbance may play a crucial role in the aetiology of PP, offering a new potential avenue for risk stratification and targeted prevention.
small molecules
2026-06-01 | Therapeutic potential of aripiprazole in the treatment of postpartum psychopathological conditions - clinical and hormonal aspects
Introduction The research was conducted on a sample of 12 patients in the postpartum period, of whom 8 had postpartum depression, and 4 had postpartum psychosis. The influence of aripiprazole on prolactin level and therapeutic outcome was analyzed. In patients with postpartum depression, those who received aripiprazole had a more pronounced decrease in prolactin and a shorter hospitalization. Similar findings were recorded in patients with psychosis. The findings indicate a potential benefit of aripiprazole in the treatment of postpartum disorders. Objectives The connection between hormonal changes and psychological disorders in the postpartum period is complex and is the subject of numerous studies. Prolactin, a hormone that increases after childbirth, can be associated with the development of depressive and psychotic symptoms. The aim of this study was to examine the association of prolactin level with the intensity of symptoms and the effect of aripiprazole. Methods The sample included 12 patients hospitalized for postpartum psychological disorders. Eight patients were diagnosed with postpartum depression, and four with postpartum psychosis. In patients with postpartum depression, two groups were formed: group A (n=4) received an antidepressant and aripiprazole (5 mg), while group B (n=4) received only antidepressants. For postpartum psychosis, two patients received aripiprazole in addition to olanzapine, and two only olanzapine. Initial and control measurement of prolactin level was performed in both groups. Results In patients with postpartum depression, the maximum prolactin level was 785 mIU/L. In Group A there was a 38% drop in prolactin, while in Group B the drop was 17%. The average duration of hospitalization was 18 days for Group A and 26 days for Group B. In patients with postpartum psychosis, the maximum prolactin level was 1478 mIU/L. A greater therapeutic response and decrease in prolactin was observed in patients who received aripiprazole compared to those who received olanzapine. During hospitalization, a control measurement of prolactin was carried out, which confirmed a more pronounced drop in the groups that received aripiprazole. Conclusions The control measurement of prolactin showed a more pronounced reduction in the group of patients receiving aripiprazole. At the same time, a shorter stay in the hospital and a better therapeutic response were recorded. These findings support the hypothesis that aripiprazole, as a partial agonist of the D2 receptor, can have a beneficial effect in the regulation of postpartum mental disorders along with hormonal stabilization. Aripiprazole in low doses can have a beneficial therapeutic effect not only on symptoms but also on prolactin regulation. Research limitations are: - A small sample of respondents - No randomization Disclosure of Interest None Declared
2026-06-01 | Neuropsychiatric Insights into Postpartum Psychosis: A Four-Case Series with CSF, EEG, and Neuroimaging Correlates
Introduction Postpartum psychosis (PP) is a rare but severe psychiatric emergency, affecting 1–2 per 1000 births and associated with high risks of maternal suicide and infanticide (Munk-Olsen et al., NEJM, 2011). Traditionally considered within the affective spectrum, atypical features such as catatonia, cognitive impairment, and suicidality suggest broader neurobiological mechanisms. Emerging evidence links PP with neuroimmune dysregulation and metabolic vulnerability, yet systematic integration of cerebrospinal fluid (CSF), electroencephalogram (EEG), and neuroimaging remains scarce (Bergink et al., Am J Psychiatry, 2016). Objectives We present four PP cases with multimodal biological evaluation to explore neurobiological contributors and treatment implications. Methods Four women with acute-onset PP within two weeks postpartum were retrospectively analyzed. All underwent psychiatric evaluation, Bush–Francis Catatonia Rating Scale when relevant, EEG, brain MRI, and CSF analysis (cell count, protein, glucose, autoimmune panel including anti-NMDAR). Two also had FDG-PET scans. Treatments and six-month outcomes were recorded. Results Case 1 (30y): Confabulation, visual hallucinations, memory deficits, catatonia (BFCRS=14). Catatonia improved with lorazepam. MRI/CSF/EEG unremarkable. Olanzapine 5 mg/day plus high-dose thiamine produced full remission of cognitive and perceptual symptoms. Case 2 (28y): Suicide attempt, resistant hallucinations and persecutory delusions. EEG slowing; PET showed patchy parietal hypometabolism; CSF revealed increased immunoglobulins. Symptoms improved after IV methylprednisolone. Case 3 (31y): Irritable mania with referential delusions. EEG slowing; PET revealed bilateral frontal and posterior cingulate hypometabolism; CSF non-specific. Remission achieved after eight ECT sessions plus quetiapine 300 mg/day. Case 4 (39y): Bipolar history, persecutory delusions, aggression. CSF showed type 2 oligoclonal bands; EEG and PET were non-specific. Symptoms improved with eight ECT sessions plus lithium 600 mg/day and risperidone 4 mg/day. EEG slowing was observed in three of four cases. All patients remained relapse-free at six months. Conclusions This case series demonstrates the heterogeneity of PP, from catatonia and hallucinations to suicidality and mania. Multimodal evaluation revealed clinically meaningful abnormalities, including CSF immunoglobulin elevation, oligoclonal bands, and FDG-PET hypometabolism. Personalized interventions, including thiamine, corticosteroids, antipsychotics and ECT, proved decisive. To our knowledge, this is among the first PP series systematically integrating CSF, EEG, and PET findings with treatment outcomes. These results support neuroimmune and metabolic contributions and emphasize the need for prospective biomarker-driven studies to guide individualized management. Disclosure of Interest None Declared
2026-05-27 | Postpartum Depression as Multi-Domain Ground State Transition Failure: Hormonal Collapse, Identity Displacement, and the Wrong Attractor of Maternal Anhedonia
We apply the Displacement Framework to postpartum depression (PPD), formalizing it as the predictable product of five simultaneous ground-state displacements occurring at childbirth: hormonal S° (estrogen/progesterone crash at the steepest hormonal gradient in human biology, with allopregnanolone collapse disrupting GABAergic tone), circadian S° (sleep fragmentation preventing nocturnal Φ-clearing), identity S° (matrescence — the structural transition from old self to maternal identity), relational S° (partner relationship restructured, new dependency bond), and somatic S°. Ten formal propositions are derived covering: multi-domain displacement as the PPD landscape, maximal-rate hormonal crash as primary displacement trigger, the three-structure differentiation (baby blues = acute displacement with self-organized return; PPD = failed return entering W_PPD; postpartum psychosis = catastrophic displacement), maternal anhedonia wrong attractor deepened by shame-concealment positive feedback loop, matrescence as structural identity transition failure, sleep deprivation as displacement amplifier and return-path blocker, social isolation as basin-deepening mechanism (modern nuclear family stripping alloparenting infrastructure), brexanolone as displacement-mechanism reversal (synthetic ALLO targeting GABAergic collapse directly), multi-domain return path necessity, and paternal PPD as shared perinatal landscape displacement. The framework shows PPD is not depression with a timing modifier but a structurally distinct wrong attractor with a unique shame-concealment deepening mechanism.
2026-05-22 | Estradiol surges as dual-purpose mechanisms in evolutionary psychiatry: Neuroendocrine stabilization, stress regulation, and psychosis vulnerability.
Estradiol exerts protective effects against psychosis, yet its functional role across the reproductive cycle remains incompletely defined. Prior work demonstrates that estrogen modulates dopaminergic, serotonergic, and immune signaling pathways that influence cognition and psychiatric vulnerability. We propose that peri-ovulatory estradiol surges may reflect a selection-shaped neuroendocrine mechanism serving dual functions: enhancing mate-selection-relevant cognition while transiently buffering, defined here as transient stabilization of neural network activity in response to hormonal fluctuations, against psychosis vulnerability during peak fertility. In this framework, "evolutionary" refers to regulatory systems shaped by selection pressures across generations, rather than to reproduction itself. This model extends the estrogen protection hypothesis by situating cyclic estradiol signaling within an evolutionary psychiatry framework. We further propose a dual-hormone buffering system in which estradiol's excitatory and plasticity-enhancing effects are balanced by progesterone and its metabolite allopregnanolone, which regulate inhibitory tone and stress responsivity via GABA_A receptor signaling. Dysregulation or rapid withdrawal of either hormone may unmask latent vulnerabilities, contributing to psychiatric instability across reproductive transitions, including perimenstrual, postpartum, and perimenopausal states. This coordinated hormonal system may have conferred adaptive advantages by stabilizing cognition and affect during critical reproductive phases. Disruption of this balance in modern contexts may increase vulnerability to psychiatric disorders. This model generates testable predictions and supports receptor-specific therapeutic strategies, including selective estrogen receptor modulators and neurosteroid-based interventions.
2026-05-05 | Cariprazine in Human Milk: Cautionary Implications for Use During Lactation.
Cariprazine is a dopamine D2/D3 partial agonist approved for treatment-resistant depression, bipolar disorder (BD) and schizophrenia. Women with bipolar disorder face an increased risk of postpartum mania and psychosis, as childbirth often triggers episodes. While continuing cariprazine can be crucial for maternal well-being, limited data exist on its peripartum safety. The objective of this research is to assess the risk of infant exposure to maternal cariprazine via breast milk. Breast milk samples were released from the InfantRisk Human Milk Biorepository from 5 lactating women who were taking cariprazine 1.5 to 4.5 mg daily, 4 of whom continued the drug since pregnancy. Timed samples were collected and analyzed using liquid chromatography-tandem mass spectrometry for cariprazine and its active metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR). Infant risk was assessed by determining relative infant dose (RID%) and maternal reports of infant outcomes. Cariprazine and its metabolites were detectable in all participants' milk samples. Mean RID% was 1.23% for cariprazine, 0.09% for DCAR, and 1.22% for DDCAR, yielding a cumulative exposure of 2.54% RID; the highest individual dose-standardized RID was 3.99% (cumulative). Two mothers self-reported infant lethargy, one of which resolved after maternal dose reduction. Estimated infant exposure to cariprazine and its active metabolites falls below standard safety thresholds. However, reported infant adverse effects and the potential for metabolite accumulation due to DDCAR's long half-life necessitate further research to examine potential long-term adverse effects while breastfeeding, particularly in infants exposed to higher maternal doses. These findings represent the first empirical data on cariprazine during lactation and highlight the need for further studies, including pharmacokinetic modeling, to inform clinical guidance.
proteins
2026-05-30 | Economic and Social Burden of Untreated Maternal Mental Health Problems
Maternal mental health is a critical component of public health and family well-being. Mental health disorders during pregnancy and the postpartum period are among the most common complications of childbirth, yet they remain underdiagnosed and undertreated worldwide. Untreated maternal mental health problems not only affect the mother but also create profound economic, social, developmental, and healthcare burdens on families, communities, and nations. Conditions such as postpartum depression, anxiety disorders, post-traumatic stress disorder (PTSD), bipolar disorder, and psychosis can impair maternal functioning, negatively influence infant growth and development, disrupt family relationships, reduce workforce productivity, and increase healthcare expenditure.
2026-02-22 | ‘The Words were Like a Charnel House’: Towards a Body of Postpartum Psychosis Life Writing
Postpartum psychosis (PP) is a psychiatric emergency developing shortly after childbirth. Its symptoms oscillate between insomnia, mania, delusions, and audiovisual hallucinations. Among other intrusive cognitions, PP can produce distressing beliefs that one’s baby has died, or that the person experiencing PP is dead themselves. Despite a low risk of infanticide, owing to certain historical thought-worlds, PP retains a stigmatising association with death. Its very nature challenges autobiographical frameworks of articulation, so life writing about PP spans a wide gamut—from less formalised online narratives like Naomi Knoles’s, to Catherine Cho’s memoir Inferno (2020), and Elizabeth Sankey’s documentary Witches (2024). These texts speak to both the limitations and indispensability of life writing which brings birth/birthing into contact with death across three different registers—actual, delusional, and metaphorical—in the context of maternal mental health. For Alice Flaherty, writing illuminated the shadowy recesses between birth and death, body and thought after her twin sons died at birth, creating a textual ‘charnel house’ to their memory (2015). This essay reaches for the edges of life in PP autobiography to curate the beginnings of a ‘charnel house’ to similar strands in this life writing, which may otherwise elude critical literary attention.
2026-01-09 | Maternal psychiatric disorders before, during, and after pregnancy: a national cohort study in Sweden.
Maternal mental health is a critical public health issue, yet the evidence on rates of incident psychiatric disorders before, during, and after pregnancy is limited. This study aimed to describe the calendar time trends and characterize and compare the risk of maternal psychiatric disorders before, during, and after pregnancy. Leveraging the national and regional registers in Sweden, we conducted a cohort study of all women who gave birth 2003-2019 in Sweden (1,799,010 pregnancies from 1,052,977 women). We identified any incident diagnosis of psychiatric disorders recorded during three periods: the preconceptional year, pregnancy, and the postpartum year. We calculated age and calendar year standardized incidence rate (SIR) of psychiatric disorders annually, and by week across three periods. We further estimated the incidence rate ratio (IRR) using the rate during corresponding preconceptional weeks as the reference. The SIR of maternal psychiatric disorder overall increased from 2003-2019, especially for preconceptional disorders. During the preconceptional year the weekly SIR of any psychiatric disorder was stable at around 25 per 1000 person-years. The SIR gradually decreased during pregnancy to a minimum of 4 per 1000 person-years and bounced back to the preconceptional levels during the postpartum year. This trend was similar in all subtypes of psychiatric disorders, except for depression and psychosis for which an increase was noted at 5-15 and 0-20 postpartum weeks, respectively. An increased incidence rate of maternal psychiatric disorder diagnosed before, during, and after pregnancy was found over time. Our findings suggest an increased risk of depression and psychosis shortly after delivery, although a lowered risk of other psychiatric disorders during and after pregnancy, compared to before pregnancy.
2025-11-01 | Urgency in the Fourth Trimester: Postpartum Psychosis as a Psychiatric Crisis
Postpartum psychosis (PPP) is a rare but severe psychiatric emergency, affecting 1–2 out of every 1,000 new mothers (1). Unlike postpartum depression, which is currently more widely recognized and characterized by persistent sadness, loss of interest, sleep disturbances, guilt or feelings of worthlessness, difficulty concentrating, changes in appetite, psychomotor changes, and thoughts of death or suicide while remaining in contact with reality, PPP involves a loss of reality and may include dangerous behaviours driven by delusional beliefs. Its urgency lies in the significantly elevated risks of suicide and infanticide, estimated at around 5% and 4%, respectively (2). Immediate recognition and treatment are critical, as most affected women require psychiatric hospitalization to prevent tragic outcomes for both mother and child.
2025-02-10 | Childbirth in Primiparous Adolescents: Prevalence, Pregnancy Profile, Maternal and Perinatal Prognosis
Introduction: Adolescent childbirth is a public health and social problem worldwide. It is associated with both maternal and perinatal morbidity and mortality. The general objective of our study is to determine the prevalence and profile of pregnant women, and to assess the maternal and perinatal prognosis of adolescent childbirth in Kisangani. Methods: This was a prospective, multicenter, case-control observational study conducted over a seven-month period, from February 1 to August 31, 2024, in primiparous adolescent gestational carriers (cases) and primiparous gestational carriers aged 20 to 34 years (controls) who delivered in five health facilities in the city of Kisangani, Democratic Republic of Congo. Results: The prevalence of teenage childbirth was 13.8%. Adolescents were more likely than controls to be in secondary education and to be unemployed. Compared with controls, pregnant adolescents were more likely to have poor ANC attendance. There was a statistical difference between the two groups in relation to pelvic anomaly, rupture of membranes on admission, hypertensive disorders, vicious presentation, caesarean section, episiotomy, postpartum anaemia and puerperal psychosis. In fact, these morbidities were more common in adolescent girls than in controls. Compared with controls, neonatal depression, prematurity, low birth weight and perinatal death were more prevalent in the newborns of teenage mothers. Conclusion: The prevalence of teenage childbirth is high in Kisangani; there is an association between unmarried status, lack of employment, low socio-economic status, poor ANC follow-up and teenage childbirth in Kisangani. The latter is also associated with high maternal and perinatal morbidity and mortality.
cell therapies
2026-06-20 | What are the recovery rates for women with postpartum psychosis treated in a Mother and Baby Unit compared to a general adult psychiatric ward?
Preliminary data from the ESMI study protocol suggests that women with postpartum psychosis treated in Mother and Baby Units experience significantly lower readmission rates compared to those treated in general psychiatric wards.
2025-04-01 | Late-Onset Puerperal Psychosis: A Case Report and Challenges in Treatment Decisions
Introduction The perinatal period is a vulnerable time for women, with specific risk factors for mental health issues. Puerperal psychosis typically presents within the first month postpartum, although the perinatal period extends through the first year after delivery. This condition is understudied, and its nature and pathophysiology remain subjects of debate. Objectives To describe a case of late-onset puerperal psychosis, highlighting the challenges in decision-making regarding medical approach. Methods A clinical case report and a non-systematic review of the literature. Results A 39-year-old woman was brought to the Emergency Unit by her relatives due to paranoid delusions that her partner and in-laws were attempting to poison her. She had previously sought mental health care only once, as an adolescent, for anxiety symptoms following her parents’ divorce. She is the mother of a 5-year-old child and a 10-month-old infant, with no reported complications during pregnancy or delivery. The patient reported experiencing strange occurrences over the preceding 10 days, beginning during a family vacation when she became suspicious of the food and the organization of meals. She believed her in-laws were poisoning her and expressed concern about transmitting poison to her infant through breast milk. Upon returning home, these fears intensified, extending to suspicions that her husband, mother, and sister were involved. She had drastically reduced her food intake the prior days before consulting, her appearance was malnourished and disheveled. Further psychopathological exploration revealed delusional beliefs centered on being poisoned and potentially poisoning her baby through breastfeeding. These delusions were accompanied by confusion, perplexity, and heightened anxiety. She denied experiencing hallucinations and had no thoughts of harm toward herself or others. Low-dose olanzapine treatment was initiated and outpatient management was initially chosen to minimize disruption to her role as a mother, in accordance with the patient’s preference and the presence of family support. However, hospitalization ultimately became necessary, resulting in complete resolution of psychotic symptoms after 14 days, with olanzapine titrated to a higher dose (20 mg per day). Conclusions Puerperal psychosis is a complex condition with potentially severe consequences for both maternal and infant health, including disruptions in mother-child bonding. This case underscores the need for further research and resource allocation in this area. Specifically, the development of more psychiatric mother-baby units could help prevent unnecessary separations, promote bonding, and provide opportunities for early parenting interventions. Disclosure of Interest None Declared
2019-04-25 | Do Defective Immune System-Mediated Myelination Processes Increase Postpartum Psychosis Risk?
Postpartum (or puerperal) psychosis (PP) is a rare, severe psychiatric disorder that affects women shortly after childbirth; risk is particularly high in individuals with a history of bipolar disorder or PP, but the underlying pathophysiology remains poorly understood. Emerging evidence suggests that immune system (dys)function plays an important role in disorder onset. On the basis of new findings from clinical and animal model studies, we hypothesise that the abundance and/or activity of regulatory T cells, and the efficacy of consequent (re)myelination processes in the brain mediated by CCN proteins, is perturbed in PP; this pathway may be modulated by risk and protective/treatment factors for the disorder, and identifying abnormalities within it could signpost novel predictive biomarkers and therapeutic targets.
2017-01-31 | A qualitative investigation in the role of the baby in recovery from postpartum psychosis
Psychosis after childbirth is a rare but severe type of mental health difficulty experienced by perinatal women. Research has explored mothers' experiences of onset and recovery from psychosis after childbirth. This study explored the role of the baby in 12 mothers' experiences of recovery. A thematic analysis of the data identified three core themes that described the role of the baby in the mothers' recovery from psychosis after childbirth. Findings revealed that the baby was central to recovery, experienced by mothers as both helpful and unhelpful. The baby interacted with the mother, increasing self‐efficacy, and reducing emotional distress. Findings also showed that the baby could act as a barrier to recovery by increasing the women's emotional distress and hindering access to help and self‐care. The findings of the study add to the existing evidence based on recovery from psychosis after childbirth. The research and clinical implications of these findings are discussed with reference to the existing literature. Key Practitioner Message The baby has an important role in recovery from psychosis after childbirth. The baby can be perceived by mothers to both hinder and help their recovery. Interacting with the baby can be helpful for the mothers' recovery by improving their self‐efficacy and reducing emotional distress. Specialist interventions offered by a mother and baby unit can provide practical support that facilitates mother–baby interactions, which helps move women forward in the recovery process.
2013-11-07 | Evaluating the clinical effectiveness of a specialized perinatal psychiatry inpatient unit
Women experiencing severe perinatal mental illness during pregnancy or postpartum have unique needs when psychiatric hospitalization is indicated. Although many countries have established mother-baby psychiatric units, similar facilities have not been available in the US. In 2011, the University of North Carolina at Chapel Hill inaugurated the first Perinatal Psychiatry Inpatient Unit in the US. We describe the unique characteristics of the patient population and report clinical outcomes guiding development and refinement of treatment protocols. Ninety-two perinatal patients were admitted between September 2011 and September 2012, and 91 completed self-report measures at admission and discharge. Perinatal unipolar mood disorder was the most frequent primary diagnosis (60.43 %), and 11 patients (12 %) were admitted with psychosis. The data document clinically and statistically significant improvements in symptoms of depression, anxiety, and active suicidal ideation between admission and discharge (p < 0.0001), as assessed by the Edinburgh Postnatal Depression Scale, Patient Health Questionnaire, and Generalized Anxiety Disorder Scale. Overall functioning was also improved, demonstrated by a significant mean difference of -10.96 in total scores of the Work and Social Adjustment Scale (p < 0.0001). Data suggest that delivering specialized and targeted interventions for severe maternal mental illness in a safe and supportive setting produces positive patient outcomes.
gene therapies
2026-02-06 | Postpartum Psychosis: could genetic vulnerability to insomnia or short sleep duration be protective?
Postpartum Psychosis (PP) is a severe and understudied perinatal mental illness which disproportionately affects women with bipolar disorder (BD). A relationship between sleep disturbance and PP is often assumed, but is poorly understood. From a cohort of 2099 individuals with BD, 343 parous women were identified and screened for perinatal psychiatric complications. We compared 117 women who developed PP with 226 who did not. Polygenic Risk Scores (PRS) for BD, schizophrenia, insomnia, short sleep, long sleep, sleep efficiency and sleep duration were computed using PRS-CS. Logistic regression was used to model the effect of each PRS on PP. Higher PRS for insomnia and short sleep were associated with reduced risk of PP. Individuals in the lowest decile for insomnia PRS (RR 1.96, 95% CI 1.25-3.07, p = 3.50 × 10⁻³) and short sleep PRS (RR 2.23, 95% CI 1.40-3.54, p = 7.94 × 10⁻⁴) had approximately double the risk of PP than individuals in the highest decile. The other PRS were not associated with PP. Mendelian Randomisation analyses did not support a causal relationship between sleep traits and PP. However, we demonstrate that the integration of PRS with bipolar subtype can improve prediction accuracy. Individuals with genetic vulnerability to insomnia or short sleep may develop a heightened tolerance to sleep disruption earlier in life, mitigating the impact of childbirth on mood. These findings suggest that genetic susceptibility to sleep disturbance may be important in the aetiology of PP, offering a new potential avenue for risk stratification and targeted prevention.
2025-08-12 | Searching for the Puerperal Trigger: Molecular Genetic Studies of Bipolar Affective Puerperal Psychosis
The available evidence suggests that the puerperium is a period of increased risk for acute episodes of illness in bipolar (BP) women and points to genetic factors as influencing vulnerability to postpartum triggering of such episodes. We have previously reported compelling evidence of familiarity of vulnerability to puerperal episodes in female sibs with BP disorder and find similar familial clustering for episodes of narrowly defined postpartum episodes in siblings with major depression. Molecular genetic approaches hold out the promise of uncovering the nature of the puerperal trigger leading to important improvements in the prevention and treatment of postpartum affective episodes. A research strategy focusing on positional and candidate gene approaches may prove fruitful in the search for susceptibility genes for both postpartum triggering in particular and for the affective disorder diathesis in general. We have identified the subset of families in the Wellcome Trust UK-Irish BP sib-pair molecular genetic linkage genome screen that include at least one female who has suffered an episode of puerperal psychosis. Analysis of this more homogeneous subgroup of families resulted in a genome-wide significant linkage signal (LOD = 4.07) on chromosome 16p13 and genome wide suggestive linkage on chromosome 8q24. We are undertaking association studies in women with postpartum psychosis at a number of candidate genes of interest in BP disorder with an emphasis on those for which the expression is influenced by steroid hormones.
2024-12-14 | Postpartum Psychosis: could chronic insomnia or short sleep be protective?
Postpartum Psychosis (PP) is a severe and understudied perinatal mental illness which disproportionately affects women with bipolar disorder (BD). A relationship between sleep disturbance and PP is often assumed, but is poorly understood. Data from 2099 BD subjects were screened to identify parous women. Individuals who developed PP and those who had not were compared in our analyses. Polygenic Risk Scores (PRS) for BD, schizophrenia, insomnia, short sleep, long sleep and sleep efficiency were computed using PRS-CS. Logistic regression was used to model the effect of each PRS on PP. Higher PRS for insomnia and short sleep were protective against PP. Individuals in the lowest decile for insomnia PRS (RR 1.96, 95% CI 1.25-3.07, p = 3.50 x 10 -3) and short sleep PRS (RR 2.23, 95% CI 1.40-3.54, p = 7.94 x 10 -4) had approximately double the risk of PP than individuals in the highest decile. BD, schizophrenia, long sleep and sleep efficiency PRS were not associated with PP. Mendelian Randomisation analyses did not support a causal relationship between sleep traits and PP. However, we demonstrate that the integration of PRS with clinical variables can improve prediction accuracy. Individuals with genetic vulnerability to insomnia or short sleep may develop a heightened tolerance to sleep disruption earlier in life, mitigating the impact of childbirth on mood. These findings suggest that genetic susceptibility to sleep disturbance may play a crucial role in the aetiology of PP, offering a new potential avenue for risk stratification and targeted prevention.
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