Schizophrenia (SCZ) and bipolar disorder (BD) share substantial clinical and neuroanatomical features, yet the neurogenetic basis underlying their shared gray matter volume (GMV) deficits remains poorly understood.

We conducted meta-analyses to identify convergent GMV alterations across the two disorders. Genome-wide association studies (GWAS) were performed to uncover genetic variants associated with the shared GMV deficits region in UK Biobank participants. Polygenic risk score (PRS)-GMV associations were analyzed to examine the cumulative influence of genetic risk on GMV in regions with shared deficits. Furthermore, pleiotropic SNPs jointly associated with SCZ, BD, and shared GMV deficits were identified. Spatiotemporal gene expression profiling was utilized to characterize the developmental trajectories, and molecular docking was performed to explore potential drugs.

Meta-analysis revealed consistent overlapping GMV reductions in frontal, temporal, and insular regions across SCZ and BD, based on 6,620 patients and 7,762 controls. GWAS identified 14 SNPs associated with the shared GMV deficits. PRS analyses showed that modestly higher SCZ polygenic risk correlated with decreased GMV of shared regions. Two pleiotropic SNPs – rs11191368 and rs79668541 – were linked to both disorders and the shared GMV deficits. Spatiotemporal expression analyses demonstrated distinct developmental trajectories, and molecular docking highlighted 168 drugs with binding interactions for shared genes.

This study delineates shared neurogenetic mechanisms linking GMV abnormalities to genetic risk across SCZ and BD. Given the cross-sectional design, future longitudinal studies in independent cohorts are warranted to validate these findings and clarify the temporal relationships.

While there have been reports on the relationship between cancer and depression, reports on the association between cancer and manic states, a reciprocal state of depression, have been relatively few. Therefore, we conducted a systematic review on the relationships between cancer and manic states, focusing on their etiology, clinical course, and impact on cancer treatments.

A systematic review was conducted using four electronic databases, following the PRISMA guidelines. The scope of the study included research on manic or hypomanic states associated with cancer in patients with no prior history of mental illness, published from 1950 to August, 2021. The study protocol was registered with PROSPERO (CRD42020182372).

Fifty-six studies, including 67 cases, were identified. The etiology of manic states in cancer patients was classified into organic, drug-induced, and psychogenic, with steroids being the most predominant causative agent. Approximately half of the patients discontinued cancer treatment following the onset of manic states. This was associated with a low rate of pharmacological treatment during the acute and maintenance phase of mania. The onset of manic states was most frequent during cancer treatment; however, about 15% of the cases exhibit manic symptoms before cancer diagnosis.

This systematic review illustrated the clinical characteristics of manic state regarding differences in the etiology, timing of onset, pharmacological treatments, duration to remission, recurrence, and impact on cancer treatment. Manic states, which are comorbid with cancer, have significant clinical impacts on cancer prognosis. Therefore, appropriate pharmacological treatment for manic states is critical to consolidate appropriate cancer treatment. A substantial proportion of patients exhibit manic symptoms prior to the diagnosis of cancer, warranting further investigation into the possibility of the concept of “premonitory mania.”

Subcortical nuclei – including the thalamus, basal ganglia, and hippocampus-amygdala complex – are key regions in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). While cortical–subcortical connectivity is well studied, fine intra- and inter-subcortical patterns are less known. This study aimed to identify shared and distinct functional connectivity alterations across SZ, BD, and MDD using a high-resolution subcortical atlas.

Resting-state functional magnetic resonance imaging data from 800 participants (200 per group: SZ, BD, MDD, and healthy controls) in a single-site cohort were analyzed. Subcortical structures were parcellated into 27 regions per hemisphere – thalamus (8 regions), hippocampus (5 regions), amygdala (2 regions), and striatum (12 regions) – based on the a priori atlas. Pairwise functional connectivity among the 54 regions was computed for each participant, and group differences were assessed using general linear models.

Patients with SZ exhibited significantly reduced intra-thalamic connectivity and increased intra-striatal connectivity, as well as enhanced connectivity between the thalamus, striatum, and limbic regions. Patients with BD showed reduced intra-thalamic and intra-striatal connectivity, along with decreased thalamus–amygdala and thalamus–striatum connectivity. In MDD, the predominant finding was reduced intra-limbic connectivity, accompanied by mild reductions in intra-thalamic and striatum–limbic connectivity.

The results suggest that intra-thalamic hypoconnectivity appears common to SZ, BD, and MDD, with graded degrees of severity. In contrast, distinct alterations in intra-striatal and striatum–limbic connectivity may differentiate mood disorders from SZ. These shared and disorder-specific subcortical connectivity patterns enhance the understanding of psychiatric neurobiology and may guide the development of targeted, disorder-tailored interventions.

Although lithium has been used effectively as a medication to treat bipolar and major depressive disorders, there are limited data defining lithium use patterns during pregnancy.

To investigate trends and patterns of lithium prescribing in the perinatal period (before, during and after pregnancy) among pregnancies in the UK.

We conducted a population-based study using primary healthcare records from the Clinical Practice Research Datalink GOLD, analysing 752 112 pregnancies during the period 1995–2018. We assessed the prevalence and patterns of lithium prescriptions, including discontinuation, continuation and dosage. Maternal characteristics were defined for lithium non-users and users, and between those who continued and discontinued use.

From 1995 to 2018, the prevalence of lithium prescribing per 10 000 pregnancies was 3.02 (95% CI: 2.64, 3.44) before pregnancy, 1.89 (95% CI: 1.59, 2.23) during pregnancy and 2.81 (95% CI: 2.44, 3.21) postpartum. Prescribing during pregnancy was low across the study period, with the most recent prevalence in 2018 of 1.03 (95% CI: 0.26, 4.11) per 10 000 pregnancies. Among 337 pregnancies with perinatal lithium prescribing, 48.4% involved a diagnosis of bipolar disorder. Of 227 pregnancies where lithium was prescribed preconception, 15.4% continued treatment throughout pregnancy; discontinuation occurred before pregnancy in 20.7%, and during second or third trimester in 30.8%; 33.0% followed other prescribing patterns. Women who discontinued lithium were more likely to be younger, have a body mass index ≥30 kg/m2, a diagnosis of bipolar disorder, a history of smoking and >10 primary care consultations in the 12 months preconception, compared with those who continued treatment.

Lithium prescribing during pregnancy in the UK is uncommon and discontinuation is frequent, particularly in the later stages of pregnancy. These findings highlight the need for proactive perinatal mental healthcare strategies and close clinical monitoring, to reduce unintentional first-trimester exposure while ensuring continuity of care for maternal mental health.

C-reactive protein (CRP) has been studied in relation to bipolar disorder (BD) and suicidality independently. Although suicide risk is elevated in youth with BD, little is known about the association of CRP with suicidality in this population.

211 youth participated, including 23 BD with lifetime suicide attempts (BDSA), 45 BD with lifetime non-suicidal self-injury (NSSI; BDNSSI), 39 BD without lifetime suicide attempt or NSSI (BDNo-SA/NSSI), and 104 healthy controls (HC). Suicide attempts and NSSI were assessed systematically. Fasting blood samples yielded CRP levels. Primary analyses controlled for age, sex, and body mass index percentile.

CRP levels differed across groups (F3,204 = 3.40, p = 0.02, ηp2 = 0.05). In post hoc analyses, CRP levels were significantly higher among BDSA (3.44 ± 6.42 mg/L) vs HC (0.81 ± 0.90 mg/L; p < 0.01) and BDNo-SA/NSSI (1.42 ± 3.31 mg/L; p = 0.01) groups; however, no difference was seen with the BDNSSI group (1.83 ± 2.22 mg/L; p = 0.12). Between-group differences in CRP levels persisted in independent sensitivity analyses controlling for current mood symptoms, lifetime mania score, lifetime smoking, and medications, but not with lifetime depression score.

Suicide attempts among youth with BD are associated with elevated CRP. Given accessibility of CRP testing, the present findings have potential clinical implications. Larger, longitudinal studies with repeated measures are needed to examine time-varying associations between CRP and suicide risk among youth with BD.

The individual effects of genetic factors and adverse childhood experiences (ACEs) on risk of psychosis, including schizophrenia (SCZ) and bipolar disorder (BIP), have been widely acknowledged, but their interaction effects on individual psychopathological symptoms remain unclear.

Based on data from 163,704 individuals in the UK Biobank, we investigated the joint effects of polygenic risk scores (PRSs) of SCZ and BIP and ACEs on psychopathology. ACEs status and 55 psychopathological symptoms from seven domains were measured retrospectively using an online mental health questionnaire in 2016. Recent genome-wide association studies for SCZ and BIP were combined with genotype data to generate PRSs. Logistic regression analyses were then conducted to explore univariate and joint main effects of PRSs and ACEs on psychopathological symptoms, as well as their additive and multiplicative interaction effects.

The interaction mechanisms for PRSs and ACEs varied across symptom domains: additive interactions were observed on the depression (RERIBIP-ACEs = 0.20–0.25), anxiety (RERISCZ-ACEs = 0.20; RERIBIP-ACEs = 0.22–0.26), help-seeking (RERISCZ-ACEs = 0.24; RERIBIP-ACEs = 0.23), and cognition domains (RERISCZ-ACEs = −0.23 to -0.17), whereas multiplicative interactions were only detected on the psychotic (betaSCZ-ACEs = −0.543; betaBIP-ACEs = −0.181), mania (betaBIP-ACEs = −0.195), self-harm or suicide (betaSCZ-ACEs = −0.118), and cognitive domains (betaSCZ-ACEs = −0.204 to −0.157).

The interplay mechanisms for genetic liability to SCZ and BIP and ACEs vary across symptom domains. This study reveals heterogeneity in gene–ACEs interaction mechanisms underlying psychosis and may provide personalized guidance for psychological care after ACEs.

Early economic evaluations (EEE) can evaluate the economic potential of new innovative healthcare solutions. We present a methodological framework for EEE in bipolar disorder and use eLi12 as an illustrative case, a new method to estimate 12-h lithium blood levels when blood sampling deviates from the 12-h timing, enabling more flexibility for patients and better data on 12-h lithium levels.

A decision-analytic model evaluated the costs and consequences of eLi12 for the treatment of bipolar disorder from a Danish national healthcare payer perspective, assessing the minimum efficacy threshold where eLi12 would be considered cost-effective compared with standard of care. The primary outcome was net monetary benefit (NMB), and we estimated quality-adjusted life-years (QALYs) assuming a willingness-to-pay threshold of €67,000/QALY gained. Costs associated with bipolar disorder and lithium treatment (e.g. hospitalisations, suicides, lost productivity, implementation costs) were estimated from literature, Danish registries, and expert opinion.

Assuming 28,000 patients with bipolar disorder whereof 10,000 are treated with lithium, a 2.5% reduction in number of hospitalisations and suicides are sufficient for eLi12 to be considered cost-effective within one year of implementation. When using a longer time horizon, allowing more savings to be included and thus considering a smaller improvement to be sufficient, less than 1% improvement by using eLi12 would be sufficient within a three-year time horizon.

EEE can evaluate the health economic potential of new innovative methods, supporting early investment decisions and guiding research. eLi12 can have significant healthcare savings, emphasising the relevance of studying clinical implementation.

Stigma towards individuals with mental, neurodevelopmental, and neurological conditions is associated with problems accessing healthcare (e.g. schizophrenia) and gaining employment (e.g. epilepsy). In Ireland, stigma differs towards different conditions, with previous research showing that schizophrenia is viewed more negatively than bipolar disorder or autism. More detailed understanding of stigma in Ireland requires replication of these findings in a larger, population-representative sample.

1,232 participants around Ireland completed a survey examining knowledge, attitudes, and behaviours towards schizophrenia, bipolar disorder, autism, and epilepsy as a comparator. Knowledge, attitudes, and behaviours towards these groups were compared using cumulative link mixed models.

Perception of others’ stigma and participants’ own self-reported behaviour were more negative towards schizophrenia compared to any of the other groups. Familiarity with mental health issues was associated with more positive self-reported behaviour towards those with schizophrenia. This improvement in behaviour was mediated by reduced perception of danger of this group. In contrast, greater mental health knowledge had no such impact on behaviour. Bipolar disorder was the second-most negatively perceived condition, followed by autism and epilepsy.

These findings support our recent pilot study and provide further evidence that stigma differs towards different conditions in Ireland, with Irish people perceiving more negative societal attitudes, and self-reporting more negative behaviour, towards schizophrenia. The finding that familiarity with schizophrenia predicted more positive behaviour and that this was mediated by reduced perception of danger suggests targets for future anti-stigma interventions.

Increasing evidences show that inflammation might be involved in bipolar disorder (BD), but the association between abnormal brain function and inflammation in BD is still unclear. In this study, we tried to explore the disrupted brain functional network topology, peripheral inflammatory cytokine levels, and their correlations in unmedicated bipolar II depression (BDII-D).

In this study, 65 individuals with unmedicated BDII-D and 50 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of the whole-brain functional connectome at both global and nodal levels. Besides, serum levels of 17 inflammatory cytokines were measured in both BDII-D and HCs. Correlations between topological properties, clinical variables, and peripheral inflammatory cytokine levels in BDII-D were calculated.

Compared with HCs, at the global level, BDII-D showed significantly higher $ \lambda $, decreased $ \gamma $, $ \sigma $, Eglo, and Eloc; at the nodal level, BDII-D showed decreased Enodal in the right olfactory cortex, left pallidum, and vermis. Besides, BDII-D showed higher levels of interleukin-8 (IL-8), interleukin-10 (IL-10), and granulocyte colony-stimulating factor (G-CSF) compared with the HCs. In BDII-D, $ \gamma $ and $ \sigma $ were significantly negatively correlated with the Hamilton Depression Rating Scale (HDRS) scores and number of episodes. Also, IL-8 level showed significant negative correlation with $ \gamma $, $ \sigma $, and Enodal of the left pallidum in BDII-D.

Reduced information segregation and integration, and lower nodal efficiency in the left pallidum were associated with proinflammatory cytokine IL-8 level and might contribute to severe depressive symptoms in unmedicated BDII-D.

Bipolar disorder is a recurrent and disabling condition, with a critical clinical need to prevent transitions from euthymia or depression (normal or low activation states) to mania (a high activation state). This study investigates how disruptions in sleep–wake and circadian rhythms may trigger these high activation states, to inform more effective relapse prevention strategies.

We developed a computational agent-based model integrating empirical evidence, clinical expertise, and lived experience to simulate how 24-hour sleep–wake behaviors (SWBs) influence manic episodes. Individual characteristics were drawn from the Brain and Mind Youth Cohort (N = 2,330), and multiple scenarios were simulated to assess how SWB dynamics affect the emergence and course of mania.

In the absence of all irregularities, no individuals experienced a manic episode. Removing behavioral feedback loops resulted in a substantial reduction in manic episodes and delayed onset. In contrast, eliminating light–dark entrainment slightly increased the frequency of manic episodes, suggesting that seasonal adaptation plays a stabilizing role. When examining components of SWB separately, removing sleep irregularities alone had only a modest effect on mania rates, whereas reducing activity irregularities led to the largest benefit: a significant drop in mean manic episodes, a delay in onset, and preventing mania in 65% of the simulated agent population.

Our findings highlight the value of computational modeling for uncovering causal dynamics in mental health. These specific findings demonstrate how daily irregularities in sleep–wake behavior may be a necessary condition for mania. Targeting behavioral regularity may offer a powerful pathway for prevention and early intervention.

DNA methylation influences gene–environment interactions and brain development in bipolar disorder (BD). We aimed to identify BD-associated epigenetic loci and examine their associations with brain structural variation.

We conducted an epigenome-wide association study (BD group, n = 90; healthy controls group, n = 161) to identify BD-associated DNA methylation loci, and we additionally performed copy number alteration and functional enrichment analyses. The correlations between epigenetic loci and cortical thickness (CT) were assessed using Pearson’s partial correlation analysis, and the co-methylation effect of the epigenetic loci identified in the neuroimaging–epigenetic analysis was investigated.

A total of 156 differentially methylated positions (DMPs) and 7 differentially methylated regions were identified, and the genes associated with them were observed to be enriched in biological processes related to muscle hypertrophy and neuronal activity. Significant correlations between the methylation levels of 13 DMPs associated with three genes (miR886, PLEC1, and ICAM5) and the CT of the right postcentral gyrus and inferior frontal gyrus were identified. Specifically, 10 DMPs associated with the CpG island in the upstream region of the miR886 gene showed negative correlations with the right postcentral gyrus CT, implicating miR886-associated CpG-island methylation in regional cortical thinning.

Epigenetic changes might play an important role in brain structural changes in BD. These multimodal findings nominate miR886-related methylation as a candidate molecular correlate of cortical thinning and warrant replication and mechanistic follow-up in larger, state-diverse cohorts.

Poverty is associated with the severity of common mental health disorders and increased physical comorbidities. However, its effects on severe mental illness (SMI), beyond increasing their incidence, are less understood, especially in low- and middle-income countries. We here examined the relationship between baseline household income and subsequent mental and physical health outcomes in a large cohort of individuals diagnosed with schizophrenia or bipolar disorder in Colombia.

Retrospective cohort and case–control study using electronic health records from over 5 million Colombians. We identified individuals diagnosed with schizophrenia or bipolar disorder and their baseline household income. Mental health outcomes included third-line antipsychotic treatments (clozapine or antipsychotic polypharmacy) and psychiatric hospitalizations. Physical outcomes included diagnoses of hypertension, type 2 diabetes, and HbA1c levels, compared with rates in individuals without SMI.

We included 12,216 (6,485 women) participants newly diagnosed with bipolar disorder or schizophrenia between 2019 and 2023. Compared to middle-income participants (between $700–1,750USD/month), patients on a low income (less than $700USD/month) were more likely to require third-line antipsychotic treatment (OR 1.84 [1.64, 2.08]) and psychiatric hospitalization (incidence rate ratio 1.30 [1.21, 1.41]). Low-income participants with SMI had hypertension and diabetes rates like middle-income participants without SMI who were 20 years older. However, the combined effect of SMI and low income together posed a less-than-additive risk. Lower income was associated with higher HbA1c levels in diabetes, while a diagnosis of SMI was associated with lower levels.

Low income at SMI onset is associated with worse mental and physical health outcomes.

Bipolar disorder (BD) involves immune-inflammatory dysregulation. This systematic review and meta-analysis assessed complete blood count-based inflammatory indices – neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios – in BD versus healthy controls (HCs), major depressive disorder (MDD), and across BD mood states.

Databases were searched through June 2025 for observational studies reporting at least one ratio in adults with BD and including as comparators either HCs, MDD, or within-BD mood-state contrasts (mania, bipolar depression, euthymia). Quality was appraised using BIOCROSS. Random-effects meta-analyses, sensitivity analyses, and meta-regressions were performed. GRADE was adapted to rate evidence certainty.

Fifty-one studies (38,309 participants) met the inclusion criteria. Compared to HCs, BD showed higher NLR (SMD = 0.44, p < 0.001) and MLR (SMD = 0.28, p < 0.001). In mania, NLR (SMD = 0.62, p < 0.001), MLR (SMD = 0.51, p < 0.001), and PLR (SMD = 0.18, p = 0.014) were all elevated versus HCs. Depression showed lower PLR (SMD = –0.14, p < 0.001) and euthymia higher NLR (SMD = 0.37, p = 0.002). Compared to MDD, BD had higher NLR (SMD = 0.21, p < 0.001) and MLR (SMD = 0.18, p < 0.001). Similarly, mania showed higher NLR (SMD = 0.53, p < 0.001) and MLR (SMD = 0.41, p < 0.001), while bipolar depression lower PLR (SMD = –0.15, p < 0.001). Mania had higher NLR (SMD = 0.32, p < 0.001), MLR (SMD = 0.32, p < 0.001), and PLR (SMD = 0.14, p = 0.028) than depression and higher MLR than euthymia (SMD = 0.44, p = 0.027), while depression had lower NLR (SMD = –0.28, p = 0.012) and PLR (SMD = –0.22, p < 0.001). Evidence certainty was mixed.

NLR, MLR, and PLR emerge as non-specific, group-level correlates of immune-inflammatory dysregulation in BD, however offering limited discrimination between bipolar and unipolar depression. Notwithstanding their potential role as trait- and state-related markers in BD, further studies are needed to support translation into clinically useful biomarkers.

Seeking to clarify the parent-offspring transmission of Major Depression (MD) and type I Bipolar Disorder (BD), we examined offspring MD and BD risk in five informative parental pairs: Unaffected x MD, Unaffected x BD, MDxMD, MDxBD and BDxBD.

We identified 289,637 individuals born in Sweden 1970-1990, followed through 2018, from parents with MD and/or BD identified from Swedish medical registers. We quantified the MD→MD, BD→BD, MD→BD and BD→MD parent-offspring transmission and explored effects of parental illness on MD→BD conversions.

The risk for MD was modestly and similarly increased in offspring of Unaffected x MD (HR=1.64) and Unaffected x BD parents (HR=1.53), higher in MDxMD and MDxBD pairings (HRs=2.39 and 2.47) and slightly lower in BDxBD matings (HR=2.29). By contrast, risk for BD was much higher in Unaffected x BD versus Unaffected x MD matings (HRs = 5.59 vs. 1.70), further elevated modestly in MDxBD matings (HR=6.26) and very high in BDxBD matings (HR=13.61). The rate of offspring MD→BD conversions was substantially increased by parental BD but not parental MD. Offspring BD was equally predicted by paternal and maternal affective illness while offspring MD was more strongly predicted by maternal than paternal affective illness.

Examining risk for MD and BD in offspring of different parental mating types of MD and BD is an informative strategy for further clarifying the cross-generational transmission of these two partially related and partially distinct mood disorders.

Bipolar disorder (BD) is associated with impairments in facial emotion recognition (FER), affecting social functioning and quality of life. Understanding FER deficits in BD is crucial for tailoring interventions and improving treatment outcomes. This systematic review and meta-analysis aims to evaluate FER differences among individuals with BD, unaffected first-degree relatives (FDRs), and healthy controls (HCs), exploring predictors related to patient and study characteristics.

We systematically searched PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO databases from inception to March 28, 2024. Random-effects meta-analyses were conducted to explore differences in accuracy and reaction time during FER identification and discrimination tasks.

A total of 100 studies were included, comprising 4920 individuals with BD (females = 56%, mean age = 34.1 ± 9.1), 676 FDRs (females = 55%, mean age = 36.1 ± 12), and 4909 HCs (females = 53.2%, mean age = 32.5 ± 9.5). Compared to HCs, adults with BD exhibited significantly lower accuracy (SMD = −0.47; 95% CIs = −0.56, −0.38) and higher reaction time (SMD = 0.57; 95%CIs = 0.33, 0.81) during facial emotion identification tasks. During facial emotion discrimination tasks, adults with BD had significantly lower accuracy than HCs (SMD = −0.59; 95%CIs = −0.78, −0.4), but similar speed. No significant differences were observed between BD and FDRs. Meta-regressions identified several predictors of FER performance, including manic symptom severity, stimulus duration, and presence of practice before task.

FER deficits appear to be a core feature of BD and require specialized, systematic assessment. Identifying these deficits may help guide interventions aimed at improving affective cognition and social outcomes in individuals with BD.