BACKGROUND: Schizophrenia and bipolar disorder frequently face significant delay in diagnosis, leading to being missed or misdiagnosed in early stages. Both disorders have also been associated with trait and state immune abnormalities. Recent machine learning-based studies have shown encouraging results using diagnostic biomarkers in predictive models, but few have focused on immune-based markers. Our main objective was to develop supervised machine learning models to predict diagnosis and illness state in schizophrenia and bipolar disorder using only a panel of peripheral kynurenine metabolites and cytokines.
METHODS: The cross-sectional I-GIVE cohort included hospitalized acute bipolar patients (n = 205), stable bipolar outpatients (n = 116), hospitalized acute schizophrenia patients (n = 111), stable schizophrenia outpatients (n = 75) and healthy controls (n = 185). Serum kynurenine metabolites, namely tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinaldic acid (QUINA), xanthurenic acid (XA), quinolinic acid (QUINO) and picolinic acid (PICO) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), while V-plex Human Cytokine Assays were used to measure cytokines (interleukin-6 (IL-6), IL-8, IL-17, IL-12/IL23-P40, tumor necrosis factor-alpha (TNF-ɑ), interferon-gamma (IFN-γ)). Supervised machine learning models were performed using JMP Pro 17.0.0. We compared a primary analysis using nested cross-validation to a split set as sensitivity analysis. Post-hoc, we re-ran the models using only the significant features to obtain the key markers.
RESULTS: The models yielded a good Area Under the Curve (AUC) (0.804, Positive Prediction Value (PPV) = 86.95; Negative Prediction Value (NPV) = 54.61) for distinguishing all patients from controls. This implies that a positive test is highly accurate in identifying the patients, but a negative test is inconclusive. Both schizophrenia patients and bipolar patients could each be separated from controls with a good accuracy (SCZ AUC 0.824; BD AUC 0.802). Overall, increased levels of IL-6, TNF-ɑ and PICO and decreased levels of IFN-γ and QUINO were predictive for an individual being classified as a patient. Classification of acute versus stable patients reached a fair AUC of 0.713. The differentiation between schizophrenia and bipolar disorder yielded a poor AUC of 0.627.
CONCLUSIONS: This study highlights the potential of using immune-based measures to build predictive classification models in schizophrenia and bipolar disorder, with IL-6, TNF-ɑ, IFN-γ, QUINO and PICO as key candidates. While machine learning models successfully distinguished schizophrenia and bipolar disorder from controls, the challenges in differentiating schizophrenic from bipolar patients likely reflect shared immunological pathways by the both disorders and confounding by a larger state-specific effect. Larger multi-centric studies and multi-domain models are needed to enhance reliability and translation into clinic.

BACKGROUND: Little is known about rates of COVID-19 vaccine uptake among youth with bipolar spectrum disorders (BSD). As such, the aim of this study is to assess rates and predictors of COVID-19 vaccine uptake among youth with BSD and their caregivers in the United States.
METHODS: Youth and their main caregiver were recruited from a large pragmatic study cohort Youth who were aged 8-22 at the time of this data collection, had a bipolar-spectrum disorder diagnosis, had overweight or obesity, and were treated with a second-generation antipsychotic were invited to participate in an online survey and interview assessing the impact of the COVID-19 pandemic.
RESULTS: A total of 453 surveys and 341 interviews were completed 07/2021-05/2022 by youth and their caregivers. Sixty-seven percent of caregivers and 63 % of youth reported receiving the COVID-19 vaccine. Vaccine uptake rates among youth and caregivers were highly correlated. Predictors of vaccine uptake among youth were older age and living in the Northeast Region of the United States. Predictors of caregiver vaccine uptake were male sex, higher annual household income and not having to quarantine due to COVID-19.
CONCLUSIONS: The sample was small and not a full representation of a population with bipolar-spectrum disorders therefore, the results may not be generalizable. The study design and statistical method do not allow for causal inferences to be made.
CONCLUSIONS: These findings may aid in targeting interventions to maximize COVID-19 and other vaccine uptake in youth with bipolar disorders and their families.

BACKGROUND: Chronotype is associated with circadian rhythmicity, a core etiological factor underlying bipolar disorder (BD). Given converging evidence linking late chronotype with poor mental health, the goal of the present study was to examine chronotype (in)stability and its relation to mood symptoms over time.
METHODS: Participants with BD I (n = 271), BD II (n = 88), and healthy controls (n = 217) were included (follow-upM=10 years, Range=5-15) from the Prechter Longitudinal Study. Chronotype category and midpoint of sleep, corrected for weekend sleep-debt (MSFsc), were measured with the Munich Chronotype Questionnaire administered every 12 months alongside clinician-rated mood and medication usage. Self-reported mood was measured bi-monthly. Mixed effects models tested whether mood was associated with (in)stability of chronotype category and MSFsc covarying for age, sex, age, and medication.
RESULTS: Compared to HC, individuals with BD self-reported having a later chronotype that significantly fluctuated over time. Individuals with BDI showed significantly less stability in MSFsc than HC. Anticonvulsant use was associated with more stability in MSFsc whereas antidepressant use was associated with less stability in MSFsc.
CONCLUSIONS: In a large longitudinal cohort, individuals with BD displayed significant instability in circadian typology. Psychopharmacology in BD may have differential impacts on circadian timing that is important to monitor.

UNASSIGNED: The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic category \"Psychotic disorder not otherwise specified\" (PNOS) is seldom investigated, and we lack knowledge about long-term outcomes. We examined long-term symptom severity, global functioning, remission/recovery rates, and diagnostic stability after the first treatment for PNOS.
UNASSIGNED: Participants with first-treatment PNOS (n = 32) were reassessed with structured interviews after 7 to 10 years. The sample also included narrow schizophrenia spectrum disorders (SSD, n = 94) and psychotic bipolar disorders (PBD, n = 54). Symptomatic remission was defined based on the Remission in Schizophrenia Working Group criteria. Clinical recovery was defined as meeting the criteria for symptomatic remission and having adequate functioning for the last 12 months.
UNASSIGNED: Participants with baseline PNOS or PBD had lower symptom severity and better global functioning at follow-up than those with SSD. More participants with PNOS and PBD were in symptomatic remission and clinical recovery compared to participants with SSD. Seventeen (53%) PNOS participants retained the diagnosis, while 15 participants were diagnosed with either SSD (22%), affective disorders (19%), or substance-induced psychotic disorders (6%). Those rediagnosed with SSD did not differ from the other PNOS participants regarding baseline clinical characteristics.
UNASSIGNED: Long-term outcomes are more favorable in PNOS and PBD than in SSD. Our findings confirm diagnostic instability but also stability for a subgroup of participants with PNOS. However, it is challenging to predict diagnostic outcomes of PNOS based on clinical characteristics at first treatment.

OBJECTIVE: To investigate: (i) whether mood states associated with bipolar disorder are associated with poorer quality of life in older adults, and (ii) what are some of the predictors of quality of life in older adults with mood states associated with bipolar disorder.
METHODS: The authors completed a cross-sectional multilevel analysis of panel data from seven waves of The English Longitudinal Study of Ageing dataset. The main analysis included 567 participants who reported experiencing mood states associated with bipolar disorder. Some participants reported this in more than one wave, resulting in 835 observations of mood states associated with bipolar disorder across the seven waves. Quality of life was assessed using the Control, Autonomy, Self-realization, and Pleasure-19 (CASP-19) measure.
RESULTS: The presence of mood states associated with bipolar disorder was significantly associated with poorer quality of life, even after controlling for multiple covariates (age, sex, social isolation, loneliness, alcohol use, education level, and economic status). Loneliness significantly predicted poorer quality of life in older adults with mood states associated with bipolar disorder. In contrast, higher educational attainment and being female predicted better quality of life in this group.
CONCLUSIONS: Older adults with mood states associated with bipolar disorder have potentially worse quality of life compared to the general population, which may be partly driven by loneliness. This has ramifications for the support offered to this population and suggests that treatments should focus on reducing loneliness to improve outcomes.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% (n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% (n = 11), initiated lithium prior to pregnancy, 11% (n = 2) initiated during pregnancy and 27% (n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

UNASSIGNED: Clinical observations suggest that individuals with a diagnosis of bipolar face difficulties regulating emotions and impairments to their cognitive processing, which can contribute to high-risk behaviours. However, there are few studies which explore the types of risk-taking behaviour that manifest in reality and evidence suggests that there is currently not enough support for the management of these behaviours. This study examined the types of risk-taking behaviours described by people who live with bipolar and their access to support for these behaviours.
UNASSIGNED: Semi-structured interviews were conducted with n = 18 participants with a lived experience of bipolar and n = 5 healthcare professionals. The interviews comprised open-ended questions and a Likert-item questionnaire. The responses to the interview questions were analysed using content analysis and corpus linguistic methods to develop a classification system of risk-taking behaviours. The Likert-item questionnaire was analysed statistically and insights from the questionnaire were incorporated into the classification system.
UNASSIGNED: Our classification system includes 39 reported risk-taking behaviours which we manually inferred into six domains of risk-taking. Corpus linguistic and qualitative analysis of the interview data demonstrate that people need more support for risk-taking behaviours and that aside from suicide, self-harm and excessive spending, many behaviours are not routinely monitored.
UNASSIGNED: This study shows that people living with bipolar report the need for improved access to psychologically informed care, and that a standardised classification system or risk-taking questionnaire could act as a useful elicitation tool for guiding conversations around risk-taking to ensure that opportunities for intervention are not missed. We have also presented a novel methodological framework which demonstrates the utility of computational linguistic methods for the analysis of health research data.

BACKGROUND: Bipolar disorders (BD) are among the most significantly impairing of childhood and adolescent psychiatric disorders. Although BD symptoms may begin in adolescence, they are frequently not diagnosed until adulthood, and accordingly BD scales could aid diagnostic assessment in paediatric populations. This review aims to synthesis the evidence for the accuracy of BD symptom index tests for discriminating BD from non-BD (other diagnoses or healthy controls) in paediatric population. Additionally, several theoretically relevant moderators of diagnostic accuracy were evaluated.
METHODS: A systematic search across three databases were conducted from 1980 to 2022, augmented by grey literature database searches, citation chaining and contacting authors. Data from eligible studies were synthesized using meta-analysis. A multilevel model was fitted to account for nested effect sizes, with 31 potential moderators examined in univariate and multivariate models.
RESULTS: Twenty-Eight studies were eligible, yielding 115 effect sizes for analysis. Meta-analytic modelling indicated BD symptom index tests have a high diagnostic accuracy (g = 1.300; 95% CI: 0.982 - 1.619; p < .001) in paediatric population. Accuracy was relative to the type of comparison group, index test content, index test informant and index test\'s scale or subscale.
CONCLUSIONS: Screening tests based on mania content, caregiver report and non-healthy comparison groups have clinical utility in identifying paediatric BD. Other informant-and-content combination may not accurately identify paediatric BD. Unlike healthy controls, tests derived from studies using non-healthy comparison groups, represent BD symptom non-specificity and BD symptom overlap with other disorders, providing external validity and clinical utility.

The challenges faced by caregivers of people living with serious mental illness in Canada are well documented in the literature including emotional distress, financial strain, social isolation, and concerns about their physical health following the impact of caregiving. Peer support programs (including peer support groups) emerged as a promising method to attempt to address these challenges. While there is evidence on the positive impacts of peer support groups in providing support for caregivers, the mechanisms by which peer support groups operate and influence support for caregivers of people living with serious mental illness are less understood. This qualitative study took on a co-designed participatory research approach. Fifteen adult caregivers of people living with serious mental illness across Canada were engaged through key informant interviews that lasted for 45 - 60 min each. A thematic analysis was carried out to help understand the operational mechanisms of peer support groups in influencing support for caregivers. The key informant interviews allowed for the identification and description of the following operational mechanisms that influenced the support caregivers received from peer support groups: (1) Group dynamics; (2) Messaging/content; (3) Equity and inclusion, (4) Group philosophy; and (5) Privacy concerns. Findings from this study showed that caregivers identified a number of operational mechanisms of peer support groups that explained how they felt supported when they participated in peer support groups. Among other operational mechanisms, group dynamics in terms of the gathering of caregivers of different age brackets and varying caregiving experience negatively influenced the peer support experience of caregivers. This pointed to the need for group dynamics that consider close age ranges and similar caregiving experience during group meetings to enhance support for caregivers. Caregivers also identified a gap in equity and inclusion in peer support groups that could have otherwise enriched their experience and enhanced the support they looked to receive from the group. Practical examples to enhance equity and inclusion include promoting active listening, using inclusive language, encouraging diverse representation and asking for feedback from peer support group members. While peer support groups in Canada exist independently of one another, it may help to consolidate evidence-based recommendations in the operational mechanisms of these groups, for the benefit of caregivers who turn to these groups for support, having been left on their own by an otherwise fractured mental health system.

A minority of premature ventricular contractions (PVC) and ventricular tachycardias (VT) have an intramural origin, which represents a challenge for conventional radiofrequency ablation. Bipolar ablation has the potential ability to create deeper and more transmural lesions and has been demonstrated to be optimal treatment in these cases. Bipolar ablation carries a relatively low risk of complications and is effective in eliminating or reducing the burden of ventricular arrhythmias. Despite its utility and efficacy, the clinical use of bipolar ablation is limited, and B-RF technology is still investigational and not widely available. This article reviews the technique of bipolar ablation and all its advantages when applied to specific scenarios.