A systematic review and meta-analysis was conducted to investigate the prevalence and antecedents/outcomes of loneliness and social isolation among individuals with severe mental disorders (SMD), such as schizophrenia, schizoaffective disorder, bipolar disorder or major depressive disorder.

Five well-known electronic databases (PubMed, PsycINFO, CINAHL, Web of Science and Scopus) were searched (plus a hand search). Observational studies that report the prevalence and, if available, antecedents and consequences of loneliness/isolation among individuals with SMD were included. Key characteristics were extracted, and a meta-analysis was performed. Our systematic review was preregistered on PROSPERO (ID: CRD42024559043). The PRISMA guidelines were followed. The Joanna Briggs Institute (JBI) standardized critical appraisal tool developed for prevalence studies was applied to assess the quality of the included studies.

The initial search yielded 4506 records, and after duplicate removal and screening, a total of 10 studies were finally included. The studies included used data from Europe, Asia, North America, and Oceania. Two studies employed a longitudinal design, while all other studies had a cross-sectional design. Most of the studies included between 100 and 500 individuals with SMD. All studies involved both male and female participants, with women typically comprising about 40% of the sample. The average age of participants often ranged from approximately 30 to 40 years. The estimated prevalence of loneliness was 59.1% (95% CI: 39.6% to 78.6%, I2 = 99.3, P < .001) among individuals with any diagnosis of SMD. Furthermore, the estimated prevalence of objective social isolation was 63.0% (95% CI: 58.6% to 67.4%) among individuals with schizophrenia or schizophrenia spectrum disorder. The quality of the studies was moderate to good. Subjective well-being and depressive symptoms in particular were found to contribute to loneliness in the included studies.

The present systematic review with meta-analysis identified high levels of loneliness and objective social isolation among those with SMD. These findings stress the importance of monitoring and addressing social needs in this vulnerable group, which may have a positive effect on the life quality of individuals with SMD. Future research in neglected regions (e.g. South America and Africa) is recommended. Different diagnoses within severe mental disorders should be distinguished in future studies. Furthermore, additional longitudinal studies are required to explore the antecedents and consequences of loneliness and social isolation among individuals with SMD.

It is widely known that people with a severe and persistent mental illness (SPMI) are more at risk of poor physical health outcomes because of disparities in healthcare access and provision. Less is known about the quality of end-of-life (EoL) care in people with SPMI who have a life-limiting disease.

A comprehensive and systematic literature search in PubMed, Embase, Web of Science, Scopus, and CINAHL electronic databases (from inception to November 2023) was conducted, without language restriction, for reviews on EoL care and/or palliative sedation for people with SPMI and a life-limiting disease. A critical appraisal of the selected reviews was performed. Data were analyzed according to the four principles of biomedical ethics.

Ten reviews were included. These show that people with SPMI are at risk of suboptimal EoL care. Stigma among healthcare professionals, lack of integrated care policies, absence of advanced care planning, and insufficient expertise and training in palliative care of psychiatrists have been identified as key challenges to the provision of adequate EoL care for people with SPMI. No data were found about palliative sedation.

To optimize palliative and EoL care for SPMI patients with a life-limiting disease, a policy of coordinated and integrated mental and physical healthcare is needed. Moreover, education and training initiatives to reduce stigma and discrimination among all healthcare workers and to enhance palliative care skills in psychiatrists should be offered. Finally, more research is needed on EoL particularly on palliative sedation for people with SPMI and a life-limiting disease.

Impairment in both psychosocial functioning and neurocognition (NC) performance is present in bipolar disorder (BD) yet the role of sex differences in these deficits remains unclear. The present systematic review and meta-analysis examined whether males and females with BD demonstrate differences in psychosocial functioning and NC performance.

The Cochrane Library, EMBASE, PsycINFO, PubMed, Scopus, and Web of Science databases were systematically searched from inception until November 20, 2023.

Twenty studies published between 2005 and 2023 with a total sample size of 2286 patients with BD were included. A random effects meta-analysis revealed a statistically significant result with a small effect (SMD = 0.313) for sex differences in verbal learning and memory as well as visual learning and memory (SMD = 0.263). Females outperformed males in both domains. No significant sex differences were observed for any other NC outcome or psychosocial functioning. High heterogeneity and differences in assessment scales used should be considered when interpreting these findings, given their potential impact on results.

Future research should adopt a more homogenous, standardized approach using longitudinal designs to gain a clearer insight into sex differences in this population. This approach so may increase the use of preventative therapeutic options to address the difficult clinical challenge of reaching cognitive and functional recovery.

Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.

Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviours, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviours in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1’s analogues interact with alcohol-related behaviours may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.

A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviours were assessed.

Preclinical studies (n = 19) indicate that GLP-1RAs attenuate alcohol-related behaviours, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (n = 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations.

Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioural modifications in individuals living with alcohol use disorder.

Impaired emotion regulation has been proposed as a putative endophenotype in bipolar disorder (BD). Functional magnetic resonance imaging (fMRI) studies investigating this in unaffected first-degree relatives (UR) have thus far yielded incongruent findings. Hence, the current paper examines neural subgroups among UR during emotion regulation.

71 UR of patients with BD and 66 healthy controls (HC) underwent fMRI scanning while performing an emotion regulation task. Hierarchical cluster analysis was performed on extracted signal change during emotion down-regulation in pre-defined regions of interest (ROIs). Identified subgroups were compared on neural activation, demographic, clinical, and cognitive variables.

Two subgroups of UR were identified: subgroup 1 (39 UR; 55%) was characterized by hypo-activity in the dorsolateral, dorsomedial, and ventrolateral prefrontal cortex and the bilateral amygdalae, but comparable activation to HC in the other ROIs; subgroup 2 (32 UR; 45%) was characterized by hyperactivity in all ROIs. Subgroup 1 had lower success in emotion regulation compared to HC and reported more childhood trauma compared to subgroup 2 and HC. Subgroup 2 reported more anxiety, lower functioning, and greater attentional vigilance toward fearful faces compared to HC. Relatives from both subgroups were poorer in recognizing positive faces compared to HC.

These findings may explain the discrepancy in earlier fMRI studies on emotion regulation in UR, showing two different subgroups of UR that both exhibited aberrant neural activity during emotion regulation, but in opposite directions. Furthermore, the results suggest that impaired recognition of positive facial expressions is a broad endophenotype of BD.

Accelerated ageing indexed by telomere attrition is suggested in schizophrenia spectrum- (SCZ) and bipolar disorders (BD). While inflammation may promote telomere shortening, few studies have investigated the association between telomere length (TL) and markers of immune activation and inflammation in severe mental disorders.

Leucocyte TL defined as telomere template/amount of single-copy gene template (T/S ratio), was determined in participants with SCZ (N = 301) or BD (N = 211) and a healthy control group (HC, N = 378). TL was analysed with linear regressions for associations with levels of 12 immune markers linked to SCZ or BD. Adjustments were made for a broad range of potential confounding variables. TL was measured by quantitative polymerase chain reaction (qPCR) and the immune markers were measured by enzyme immunoassays.

A positive association between levels of soluble tumour necrosis factor receptor 1A (sTNF-R1) and TL in SCZ (β = 0.191, p = 0.012) was observed. Plasma levels of the other immune markers were not significantly associated with TL in the BD, SCZ or HC groups.

There was limited evidence of association between immune markers and TL in SCZ and BD. The results provide little support for involvement of immune dysregulation, as reflected by current systemic markers, in telomere attrition-related accelerated ageing in severe mental disorders.

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.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Estimating the risk of developing bipolar disorder (BD) in children and adolescents (C&A) with depressive disorders is important to optimize prevention and early intervention efforts. We aimed to quantitatively examine the risk of developing BD from depressive disorders and identify factors which moderate this development.

In this systematic review and meta-analysis (PROSPERO:CRD42023431301), PubMed and Web-of-Science databases were searched for longitudinal studies reporting the percentage of C&A with ICD/DSM-defined depressive disorders who developed BD during follow-up. Data extraction, random-effects meta-analysis, between-study heterogeneity analysis, quality assessment, sub-group analyses, and meta-regressions were conducted.

Thirty-nine studies were included, including 72,371 individuals (mean age=13.9 years, 57.1% females); 14.7% of C&A with a depressive disorder developed BD after 20.4–288 months: 9.5% developed BD-I (95% CI=4.7 to 18.1); 7.7% developed BD-II (95% CI=3.2% to 17.3%); 19.8% (95% CI=9.9% to 35.6%) of C&A admitted into the hospital with a depressive disorder developed BD. Studies using the DSM (21.6%, 95% CI=20.2% to 23.1%) and studies evaluating C&A with a major depressive disorder only (19.8%, 95% CI=16.8% to 23.1%) found higher rates of development of BD. Younger age at baseline, a history of hospitalization and recruitment from specialized clinics were associated with an increased risk of developing BD at follow-up. Quality of included studies was good in 76.9% of studies.

There is a substantial risk of developing BD in C&A with depressive disorders. This is particularly the case for C&A with MDD, DSM-diagnosed depressive disorders, and C&A admitted into the hospital. Research exploring additional predictors and preventive interventions is crucial.

To examine if the COVID-19 pandemic had a differential impact longitudinally over four years on psychological and functional impact in individuals with a pre-existing anxiety, bipolar or emotionally unstable personality Disorder (EUPD).

Semi-structured interviews were conducted with 52 patients attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases (ICD)-10 diagnosis of an anxiety disorder (n = 21), bipolar disorder (n = 18), or EUPD (n = 13) at four time points over a four-year period. Patients’ impression of the impact of the COVID-19 pandemic was assessed in relation to anxiety and mood symptoms, social and occupational functioning and quality of life utilising psychometric instruments and Likert scale data, with qualitative data assessing participants’ subjective experiences.

Individuals with EUPD exhibited higher anxiety (BAI) symptoms compared to individuals with bipolar disorders and anxiety disorders (F = 9.63, p = 0.001), with a more deleterious impact on social functioning and quality of life also noted at all time points. Themes attained from qualitative data included isolation resulting from COVID-19 mandated restrictions (N = 22), and these same restrictions allowing greater appreciation of family (n = 19) and hobbies/nature (n = 13).

Individuals with EUPD reported increased symptomatology and reduced functioning and quality of life as a consequence of the COVID-19 pandemic over a four-year period compared to individuals with either an anxiety or bipolar disorder. This could be related to the differing interaction of the COVID-19 pandemic’s restrictions on the symptoms and support requirements of this cohort.

There is a lack of large-scale studies exploring labor market marginalization (LMM) among individuals diagnosed with bipolar disorder (BD). We aimed to investigate the association of BD with subsequent LMM in Sweden, and the effect of sex on LMM in BD.

Individuals aged 19–60 years living in Sweden with a first-time BD diagnosis between 2007 and 2016 (n = 25 231) were followed from the date of diagnosis for a maximum of 14 years. Risk of disability pension (DP), long-term sickness absence (SA) (>90 days), and long-term unemployment (>180 days) was compared to a matched comparison group from the general population, matched 1:5 on sex and birth year (n = 126 155), and unaffected full siblings (n = 24 098), using sex-stratified Cox regression analysis, yielding hazard ratios (HRs) with 95% confidence intervals (CIs).

After adjusting for socioeconomic factors, baseline labor market status, and comorbid disorders, individuals with BD had a significantly higher risk of DP compared to the general population (HR = 16.67, 95% CI 15.33–18.13) and their unaffected siblings (HR = 5.54, 95% CI 4.96–6.18). Individuals with BD were also more likely to experience long-term SA compared to the general population (HR = 3.19, 95% CI 3.09–3.30) and their unaffected siblings (HR = 2.83, 95% CI 2.70–2.97). Moreover, individuals diagnosed with BD had an elevated risk of long-term unemployment relative to both comparison groups (HR range: 1.75–1.78). Men with BD had a higher relative risk of SA and unemployment than women. No difference was found in DP.

Individuals with BD face elevated risks of LMM compared to both the general population and unaffected siblings.

Bipolar disorder (BD) has a significant impact on functioning in the absence of acute mood episodes. This has been associated with subsyndromal symptoms, co-morbidities, and emotional dysregulation. The present study aims to evaluate the acceptability and preliminary efficacy of imagery-based cognitive therapy (ImCT) in a French community setting. We were particularly interested in the link between mental imagery and emotional dysregulation as this may clarify the mechanisms involved in the potential efficacy of the therapy and ultimately improve its relevance.

Ten participants underwent ImCT, with weekly assessments of mood fluctuations, anxiety, and emotional dysregulation conducted over 1 month (i.e. pre-therapy, post-therapy and 1-month follow-up). Recovery, post-traumatic stress symptoms and self-compassion were measured at baseline and post-therapy. Attrition rates and satisfaction were measured.

All participants who completed therapy (n=8) reported high levels of satisfaction. Five of them showed reliable individual improvement on emotion dysregulation scores. At the group level, a significant decrease in mood fluctuation with a large effect size was found post-therapy.

ImCT showed good acceptability among participants who completed the study. Importantly, our study is the first to provide an indication that ImCT may alleviate subsyndromal mood symptoms but also emotional dysregulation in individuals with BD. This latter finding is particularly relevant given the scarcity of validated psychosocial interventions targeting emotional dysregulation in BD.