To investigate the association of midlife and late-life undiagnosed mood symptoms, especially their comorbidity, with long-term dementia risk among multi-regional and ethnic adults.

The prospective study used data from the UK Biobank (N = 142,670; mean follow-up 11.0 years) and three Asian studies (N = 1,610; mean follow-up 4.4 years). Undiagnosed mood symptoms (manic symptoms, depressive symptoms and comorbidity of depressive and manic symptoms) and diagnosed mood disorders (depression, mania and bipolar disorders) were classified. Plasma levels of 168 metabolites were measured. The association between undiagnosed mood symptoms and 12-year dementia (including subtypes) risk and domain-specific cognitive function was examined. The contribution of metabolites in explaining the association between symptom comorbidity and dementia risk was estimated.

Undiagnosed mood symptoms were prevalent (11.4% in the UK cohort and 31.2% in Asian cohorts) among 1,462 (1.0%) and 74 (19.4%) participants who developed dementia. Comorbidity of undiagnosed mood symptoms was associated with higher dementia risk (sub-distribution hazard ratios = 9.46; 95% confidence interval = 4.07–21.97), especially Alzheimer’s disease, and with worse reasoning ability, poorer numeric memory and metabolic dysfunction. Glucose and total Esterified Cholesterol explained 9.1% of the association between symptom comorbidity and dementia, with most of the contribution being from glucose (6.8%).

Comorbidity of undiagnosed mood symptoms was associated with a higher cumulative risk of dementia in the long term. Glucose metabolism could be implicated in the development of mood disorders and dementia. The distinctive pathophysiological mechanism between psychiatric and neurodegenerative disorders warrants further exploration.

The nosology of mania has long been a conundrum. Prior studies have alternately concluded that it is an internalizing disorder, a thought disorder, or a unique condition. Unfortunately, nearly all existing studies assessed symptoms cross-sectionally. This is problematic for syndromes that follow a more episodic course, such as mania. Here, we test whether including a history of episodes, not simply current symptoms, can help resolve the placement of mania in the meta-structure of psychopathology.

First-admission patients with psychosis from the Suffolk County Mental Health Project (N = 337) were followed across 20 years. Internalizing, thought disorder, and mania symptoms were assessed at year 20, whereas corresponding episodes (i.e. depressive, psychotic, and manic) were assessed across three intervals spanning the previous 20 years. We tested five models to determine whether mania (current and past) loaded onto the internalizing factor, the thought disorder factor, or an independent factor. A final model was validated against established markers of bipolar disorder.

For depression and psychosis, current and past markers were congruent in loading onto internalizing and thought disorder factors, respectively. However, current and past markers of mania diverged: current mania was most strongly related to the thought disorder dimension, whereas past mania formed an independent factor. Classic correlates of mania – including family history, genetic risk, and neuropsychological function – were associated only with the history of mania dimension.

Including illness course in structural models of psychopathology suggests that mania is distinguished from internalizing and thought disorder factors, whereas assessments of current symptoms place it with psychosis. These findings require independent validation, but if replicated, they would support a separate spectrum of mania defined by the occurrence of episodes across the lifetime.

There are few economic evaluations of adjunctive psychosocial therapies for bipolar disorder.

Estimate the cost–utility of in-person psychosocial therapies for adults with bipolar disorder added to treatment as usual (TAU), from an Australian Government perspective.

We developed an economic model, estimating costs in 2021 Australian dollars (A$) and outcomes using quality-adjusted life-years (QALYs) gained and disability-adjusted life-years (DALYs) averted. The model compared psychoeducation, brief psychoeducation, carer psychoeducation, cognitive–behavioural therapy (CBT) and family therapy when added to TAU (i.e. pharmacotherapy) over a year for adults (18–65 years) with bipolar disorder. The relative risk of relapse was sourced from two network meta-analyses and applied to the depressive phase in the base case. Probabilistic sensitivity analysis and one-way sensitivity analyses were conducted, assessing robustness of results.

Carer psychoeducation was preferred in the base case when the willingness-to-pay (WTP) threshold is below A$1000 per QALY gained and A$1500 per DALY averted. Brief psychoeducation was preferred when WTP is between A$1000 and A$300 000 per QALY gained and A$1500 and A$450 000 per DALY averted. Family therapy was only preferred at WTP thresholds above A$300 000 per QALY gained or A$450 000 per DALY averted. In sensitivity analyses, brief psychoeducation was the preferred therapy. Psychoeducation and CBT were dominated (more costly and less effective) in base-case and sensitivity analyses.

Carer and brief psychoeducation were found to be the most cost-effective psychosocial therapies, supporting use as adjunctive treatments for adults with bipolar disorder and their families in Australia.

Findings from contemporary clinical trials suggest that psychedelics are generally safe and may be effective in the treatment of various psychiatric disorders. However, less is known about the risks associated with psychedelic use outside of medically supervised contexts, particularly in populations that are typically excluded from participation in clinical trials.

Using a preregistered longitudinal observational research design with a purposive sample of US residents between 18 and 50 years old (N=21,990), we investigated associations between self-reported naturalistic psychedelic use and psychotic and manic symptoms, with emphasis on those with psychiatric histories of schizophrenia or bipolar I disorder.

The follow-up survey was completed by 12,345 participants (56% retention), with 505 participants reporting psychedelic use during the 2-month study period. In covariate-adjusted regression models, psychedelic use during the study period was associated with increases in the severity of psychotic and manic symptoms. However, such increases were only observed for those who reported psychedelic use in an illegal context. While increases in the severity of psychotic symptoms appeared to depend on the frequency of use and the intensity of challenging psychedelic experiences, increases in the severity of manic symptoms appeared to be moderated by a personal history of schizophrenia or bipolar I disorder and the subjective experience of insight during a psychedelic experience.

The findings suggest that naturalistic psychedelic use specifically in illegal contexts may lead to increases in the severity of psychotic and manic symptoms. Such increases may depend on the frequency of use, the acute subjective psychedelic experience, and psychiatric history.

Time distortions characterise severe mental disorders, exhibiting different clinical and neurobiological manifestations. This systematic review aims to explore the existing literature encompassing experimental studies on time perception in patients with bipolar disorder (BD), considering psychopathological and cognitive correlates.

Studies using an experimental paradigm to objectively measure the capacity to judge time have been searched for. Selected studies have been described based on whether i) explicit or implicit time perception was investigated, ii) the temporal intervals involved were sub-second or supra-second, and iii) a perceptual or motor timing paradigm was used.

Only 11 met the criteria for inclusion in the review. The available literature shows that the performance of BD patients mostly aligns with controls within sub-second timeframes (six articles), while a different pattern emerges within supra-second intervals based on the clinical phase of the disease (seven articles). Specifically, for longer temporal spans, BD patients tend to overestimate the duration during manic states and underestimate it during depressive states. Notably, no studies have directly investigated the neurobiological mechanisms associated with time perception.

This review indicates that BD patients exhibit time perception similar to controls within sub-second intervals, but tend to overestimate time and underestimate it based on the clinical phase within supra-second intervals. Expanding the understanding of time perception in BD, particularly in relation to clinical phases and cognitive function, is of great importance. Such insights could deepen our understanding of the disorder, refine diagnostic processes, and guide the development of innovative therapeutic interventions.

Several psychological models of bipolar disorder propose that certain types of appraisals can lead to increases in manic symptoms.

We tested whether the belief that being ‘high’ is a natural part of one’s personality and correlates with manic symptoms 4 months later when controlling for manic symptoms at baseline.

This was a prospective 4-month follow-up design using self-report measures. Forty people with a diagnosis of bipolar disorder completed a measure of manic symptoms, a measure of appraisals associated with bipolar disorder, and a single-item measure, ‘To what extent do you feel like being “high” is a natural part of your personality?’, at baseline and follow-up.

The single-item measure showed modest stability over time and construct validity in its correlation with a standardised measure of appraisals in bipolar disorder. As predicted, the single-item measure correlated with manic symptoms at follow-up when controlling for manic symptoms at baseline.

The belief that being ‘high’ is a natural part of one’s personality is a potential predictor of manic symptoms. Further research needs to study the potential mediating mechanisms such as activating behaviours, and control for indicators of the bipolar endophenotype.

Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions.

The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder.

We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients.

Recruitment is ongoing.

This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder.

We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder.

The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates.

We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = −3.19, 95% CI: −5.30 to −1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = −1.57, 95% CI: −2.88 to −0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables.

Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.