Search

Objectives: In healthy populations, caffeine appears to have beneficial effects on health; however, patients with bipolar disorder (BD) are routinely advised to limit caffeine use in psychoeducation programmes. We aimed to examine all literature reporting whether caffeine intake/withdrawal impacts the natural course of BD, in terms of clinical outcomes. Methods: PubMed, Embase and PsycINFO were searched (up to 17/07/2020) and all studies reporting data on individuals with BD comparing a measure of caffeine use with illness severity (symptoms of mania, depression, psychosis, anxiety, sleep or suicidality) were included. Results: Of the 1678 records reviewed, 17 studies met inclusion criteria (10 case reports, 1 retrospective cohort study, 5 cross‐sectional studies, 1 interventional study). Most case reports described people with BD switching to manic, hypomanic or mixed states after consuming caffeine in variable amounts and/or whose serum lithium concentrations increased after reducing caffeine consumption. The interventional study found that caffeine may suppress lithium concentrations, while the retrospective cohort study reported that participants who drank coffee had more suicidality than non‐drinkers. Conclusions: The literature examining clinical effects of caffeine in patients with BD is not conclusive. Acute increases in caffeine consumption may precede the occurrence of manic symptoms in patients with BD, potentially through a direct stimulant effect, affecting sleep patterns and/or the metabolism of lithium or other medications, although increases in caffeine intake could also be a consequence of an ongoing manic relapse or a prodromal sign. Further research is needed to determine whether caffeine use impacts the long‐term prognosis of BD. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive remediation therapy (CRT) may benefit people with bipolar disorder type I and II for whom cognitive impairment is a major contributor to disability. Extensive research has demonstrated CRT to improve cognition and psychosocial functioning in people with different diagnoses, but randomised trials of evidenced therapy programmes are lacking for bipolar disorders. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. Methods: This proof‐of‐concept, single‐blind randomised trial recruited participants aged 18‐65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment‐as‐usual (TAU) with or without individual CRT for 12 weeks. The partly computerised CRT programme ("CIRCuiTS") was therapist‐led and is evidence‐based from trials in those with psychotic illnesses. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention‐to‐treat analyses. Trial registration: ISRCTN ID32290525. Results: Sixty participants were recruited (02/2016‐06/2018) and randomised to CRT (n = 29) or TAU (n = 31). Trial withdrawals were equivalent (CRT n = 2/29; TAU n = 5/31). CRT satisfaction indicated high acceptability. Intention‐to‐treat analyses (N = 60) demonstrated greater improvements for CRT‐ than TAU‐randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in the following domains (week 25 effect sizes reported here): IQ (SES = 0.71, 95% CI [0.29,1.13]), working memory (SES = 0.70, 95% CI [0.31,1.10]), executive function (SES = 0.93, 95% CI [0.33,1.54]), psychosocial functioning (SES = 0.49, 95% CI [0.18,0.80]) and goal attainment (SES = 2.02, 95% CI [0.89,3.14]). No serious adverse events were reported. Conclusions: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof‐of‐concept trial encourage further investigation in a definitive trial. [ABSTRACT FROM AUTHOR]

Background: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.Method: Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions.Results: Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25-1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23-1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81-1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.80-1.30) and psychological (ES = 1.43, 95% CI 0.50-2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66-0.91) and psychological control (ES = 0.94, 95% CI 0.36-1.52).Conclusions: Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with long-term physical deterioration after COVID-19. Mental health recovery has been less well investigated. Early studies have shown minimal effect from the virus, although studies have not focused on whether people living with frailty may have different psychiatric outcomes. We aimed to examine the effect of living with frailty on mental health outcomes one year after hospital with COVID-19.Methods: We undertook a multicentre cross-sectional study of people admitted with COVID-19. We assessed quality of life (ICECAP-O and MRC), psychiatric symptoms including: generalised anxiety (GAD-7), depression (Patient Health Questionnaire-9), and trauma (Trauma Screening Questionnaire). Frailty was measured using the Clinical Frailty Scale (CFS). We used a multivariable mixed-effects logistic and linear regression to examine the adjusted odds ratio (aOR) and adjusted mean difference (aMD).Results: From eight hospitals 224 participants consented. Median follow-up time from admission 358 days (IQR 153-418), mean age 63.8 (SD = 13.7), 34.8% female (n = 78), and 43.7% living with frailty (n = 98 CFS 4-8). People living with frailty were significantly more likely to have symptoms of anxiety aOR = 5.72 (95% CI 1.71-19.13), depression aOR = 2.52 (95% CI 1.59-14.91), post-traumatic stress disorder aMD = 1.16 (95% CI 0.47, 1.85), and worse quality of life aMD = 1.06 (95% CI 0.76-1.36).Limitations: Patient-rated symptoms were captured rather than formal mental health diagnoses. CFS has not been validated in under 65-year-olds.Conclusions: Living with frailty is associated with significant psychiatric morbidity and reduced wellbeing one year after COVID-19 hospital admission. We recommend clinical follow-up after COVID-19 for people living with frailty should include a psychiatric assessment. [ABSTRACT FROM AUTHOR]

Background: Many patients with depressive disorders demonstrate resistance to psychological therapy. A frequent finding is hypothalamic-pituitary-adrenal (HPA) axis alterations. As cortisol is known to modulate cognitive processes, those patients may be less likely to profit from psychological therapy.Aims: To conduct a systematic review and meta-analysis on cortisol as a predictor of psychological therapy response.Method: The Cochrane Library, EMBASE, MEDLINE and PsycINFO databases were searched. Records were included if they looked at patients with any depressive disorder engaging in psychological therapy, with a pre-treatment cortisol and a post-treatment symptom measure.Results: Eight articles satisfied our selection criteria. The higher the cortisol levels before starting psychological therapy, the more symptoms patients with depression experienced at the end of treatment and/or the smaller their symptom change.Conclusions: Our findings suggest that patients with depression with elevated HPA functioning are less responsive to psychological therapy. [ABSTRACT FROM AUTHOR]

Biological factors are known to be important in understanding the pathogenesis of Major Depressive Disorder (MDD). Oxidative stress and neuroinflammation pathways are likely to play a critical role here. We undertook a study to investigate two novel biomarkers - serum NADPH oxidase 1 (NOX1) and Raftlin levels - in treatment-naive, smoking-free first episode patients with MDD compared to healthy controls (HCs) matched for age, sex and body mass index. We found increased NOX1 and Raftlin levels in MDD patients compared to HCs. Both parameters showed very good diagnostic performance in the MDD group. In addition, we found a significant positive correlation between depression severity (HAM D) scores and both biomarker levels in the patient group. To the best of our knowledge, this is the first human study to evaluate serum NOX1 and Raftlin levels in depression. NOX1, an important source of reactive oxygen species (ROS), and Raftlin, which may play a role in the inflammatory process, represent novel potential biomarkers of MDD. These findings support the implication of oxidative stress and inflammatory processes in patients with MDD, and indicate that the deteriorated ROS-antioxidant balance can be regulated via NOX1 in patients with depression. • We investigated the levels of NOX1 and Raftlin in patients with major depressive disorder. • We found that patients had increased serum NOX1 and raftlin levels compared to healthy controls. • Both parameters showed very good diagnostic performance in patients with major depressive disorder. • We concluded that the deteriorated ROS-antioxidant balance can be regulated via NOX1 in patients with depression. [ABSTRACT FROM AUTHOR]

• This is the first systematic review to assess longer term psychiatric symptoms experienced by COVID-19 survivors • 33 studies were included assessing 6,743 participants, with outcomes assessed between one and six months after diagnosis. • From the included studies there was no clear evidence of survivors experiencing worse anxiety or depression as compared to general population levels. Acute effects of COVID-19 can be life-threatening. Alterations in mental health during the active infection have been documented, but the long-term consequences are less clear. A systematic review was undertaken to investigate the effect of COVID-19 infection on long-term mental health outcomes. Three databases [PubMed, Medline (Ovid) and Cochrane library] were searched between 1st October 2019 and 29th August 2021 with additional hand searching to identify all published studies reporting symptoms of generalised anxiety, depression, post-traumatic stress disorder (PTSD), or sleep disturbance in participants at least one month after COVID-19 infection. The prevalence and mean symptom score of each were assessed. Eight hundred and eighty five studies were found, of which 33 were included in the review involving a total of 6743 participants. The studies' risk of bias were typically fair quality. The median study age of participants was 57.8 years (IQR 49.3–60.7), with 63.0% male (IQR 57.0%–73.0%). Participants typically experienced no or mild symptoms of long-term anxiety (GAD-7, STAI-S, HADS) and depression (PHQ-9, BDI, PHQ-2, HADS). Prevalence varied depending on the measurement tool. Sleep disturbances (primarily insomnia) were most commonly reported as mild. PTSD prevalence was similar to anxiety and depression. The overall effect of the pandemic has been linked with worsening psychiatric symptoms. However, the long-term effect from direct COVID-19 infection has been associated with no or mild symptoms. Studies exhibited the long-term prevalence of anxiety, depression, PTSD, and sleep disturbances to be comparable to general population levels. [ABSTRACT FROM AUTHOR]

Objectives: The early pathogenesis and precursors of Bipolar Disorder (BD) are poorly understood. There is some cross-sectional and retrospective evidence of affective lability as a predictor of BD, but this is subject to recall biases. The present review synthesises the prospective evidence examining affective lability and the subsequent development of BD at follow-up. Methods: The authors performed a systematic search of PubMed, PsycInfo and Embase (1960–June 2020) and conducted hand searches to identify studies assessing affective lability (according to a conceptually-inclusive definition) at baseline assessment in individuals without a BD diagnosis, and a longitudinal follow-up assessment of bipolar (spectrum) disorders. Results are reported according to the PRISMA guidelines, and the synthesis without meta-analysis (SWiM) reporting guidelines were used to strengthen the narrative synthesis. The Newcastle–Ottawa Scale was used to assess risk of bias (ROB). Results: 11 articles describing 10 studies were included. Being identified as having affective lability at baseline was associated with an increased rate of bipolar diagnoses at follow-up; this association was statistically significant in six of eight studies assessing BD type I/II at follow-up and in all four studies assessing for bipolar spectrum disorder (BSD) criteria. Most studies received a 'fair' or 'poor' ROB grade. Conclusions: Despite a paucity of studies, an overall association between prospectively-identified affective lability and a later diagnosis of BD or BSD is apparent with relative consistency between studies. This association and further longitudinal studies could inform future clinical screening of those who may be at risk of BD, with the potential to improve diagnostic accuracy and facilitate early intervention. [ABSTRACT FROM AUTHOR]

Background: Treatment resistant depression (TRD) poses a significant clinical challenge, despite a range of efficacious specialist treatments. Accurately predicting response a priori may help to alleviate the burden of TRD. This study sought to determine whether outcome prediction can be achieved in a specialist inpatient setting.Methods: Patients at the Affective Disorders Unit of the Bethlam Royal Hospital, with current depression and established TRD were included (N = 174). Patients were treated with an individualised combination of pharmacotherapy and specialist psychological therapies. Predictors included clinical and sociodemographic characteristics, and polygenic risk scores for depression and related traits. Logistic regression models examined associations with outcome, and predictive potential was assessed using elastic net regularised logistic regressions with 10-fold nested cross-validation.Results: 47% of patients responded (50% reduction in HAMD-21 score at discharge). Age at onset and number of depressive episodes were positively associated with response, while degree of resistance was negatively associated. All elastic net models had poor performance (AUC<0.6). Illness history characteristics were commonly retained, and the addition of genetic risk scores did not improve performance.Limitations: The patient sample was heterogeneous and received a variety of treatments. Some variable associations may be non-linear and therefore not captured.Conclusions: This treatment may be most effective for recurrent patients and those with a later age of onset, while patients more severely treatment resistant at admission remain amongst the most difficult to treat. Individual level prediction remains elusive for this complex group. The assessment of homogenous subgroups should be one focus of future investigations. [ABSTRACT FROM AUTHOR]

Background: England's primary care service for psychological therapy (Improving Access to Psychological Therapies [IAPT]) treats anxiety and depression, with a target recovery rate of 50%. Identifying the characteristics of patients who achieve recovery may assist in optimizing future treatment. This naturalistic cohort study investigated pre-therapy characteristics as predictors of recovery and improvement after IAPT therapy., Methods: In a cohort of patients attending an IAPT service in South London, we recruited 263 participants and conducted a baseline interview to gather extensive pre-therapy characteristics. Bayesian prediction models and variable selection were used to identify baseline variables prognostic of good clinical outcomes. Recovery (primary outcome) was defined using (IAPT) service-defined score thresholds for both depression (Patient Health Questionnaire [PHQ-9]) and anxiety (Generalized Anxiety Disorder [GAD-7]). Depression and anxiety outcomes were also evaluated as standalone (PHQ-9/GAD-7) scores after therapy. Prediction model performance metrics were estimated using cross-validation., Results: Predictor variables explained 26% (recovery), 37% (depression), and 31% (anxiety) of the variance in outcomes, respectively. Variables prognostic of recovery were lower pre-treatment depression severity and not meeting criteria for obsessive compulsive disorder. Post-therapy depression and anxiety severity scores were predicted by lower symptom severity and higher ratings of health-related quality of life (EuroQol questionnaire [EQ5D]) at baseline., Conclusion: Almost a third of the variance in clinical outcomes was explained by pre-treatment symptom severity scores. These constructs benefit from being rapidly accessible in healthcare services. If replicated in external samples, the early identification of patients who are less likely to recover may facilitate earlier triage to alternative interventions.

Background: Immune dysregulation appears involved in affective disorder pathophysiology. Inflammatory biomarkers have been linked with the cognitive impairment observed in people with bipolar disorders and as such are candidate markers that may improve with, and/or predict outcomes to, cognitive remediation therapies (CRT)., Aims: Nine candidate biomarkers were examined as putative mediators and/or moderators to improvements following CRT compared with treatment as usual (TAU) from a randomised controlled trial., Method: Euthymic adults with bipolar disorders who had been randomised to CRT ( n = 23) or TAU ( n = 21) underwent blood testing before and after a 12 week intervention period. Five cytokines and four growth factor proteins, selected a priori , were examined in association with global cognition and psychosocial functioning outcomes., Results: CRT attenuated a reduction in the brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor and vascular endothelial growth factor-C compared to TAU. For the BDNF, lower baseline levels predicted better functional outcomes across the sample but was more pronounced in TAU versus CRT participants and indicated larger CRT effects in those with a higher BDNF. A moderation effect was also apparent for tumour necrosis factor-β and interleukin-16, with greater CRT versus TAU effects on functioning for participants with lower baseline levels., Conclusions: Although preliminary, results suggest that CRT may exert some protective biological effects, and that people with lower levels of neurotrophins or cytokines may benefit more from CRT. We note an absence of associations with cognitive (versus functional) outcomes. These findings require further examination in large well-controlled studies.

Background: Existing self-rated depression measurement tools possess a range of psychometric drawbacks, spanning a range of validity and reliability constructs. The gold standard self-rated depression scales contain several variable items that are often non-specific, require respondents to have a certain level of language understanding and limited scoring options resulting in low sensitivity. The Maudsley three-item visual analogue scale (M3VAS) was developed to address these challenges., Aims: This study aimed to translate the M3VAS into Chinese and test its reliability and validity., Method: First, both M3VAS scales (assessing current severity and change in severity) were translated according to a standardised protocol to finalise the Chinese version. Reliability and validity were then examined among 550 young people with moderate to severe depression (patient health questionnaire-9 (PHQ-9) score ≥15) in a cross-sectional opportunistic questionnaire survey., Results: The content validity of each item (six items, across both scales) ranged from 0.83 to 1.00. Exploratory factor analysis denoted a total of two common factors, with a variance contribution rate of 64.34%. The total score correlated positively with the PHQ-9 total score ( r = 0.241, P < 0.01). The Chinese version of the M3VAS had good reliability and validity values, and the confirmatory factor model fit well., Conclusions: The psychometric properties of the Chinese version of the M3VAS suggest that this scale can feasibly evaluate depression among young people in China.

Background: Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging ( 7 Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose., Methods: Lithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2-7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7 Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout., Results: 7 Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7 Li-signal intensities (approximately 2-4×) compared to other study participants., Limitations: Lithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7 Li exhibits imperfect spatial separation of signal from adjacent pixels., Conclusions: 7 Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10-60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field., Competing Interests: Declaration of competing interest RS declares honoraria from Janssen (unrelated to this work). All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects., Methods: CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30-40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models., Discussion: This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action., Trial Registration: Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting., (© 2023. The Author(s).)

Background: Lithium is widely evidenced for its neuropsychiatric benefits. Advantages of 'sub-therapeutic' doses are increasingly being reported, which is apposite given enduring concerns around adverse effects of 'therapeutic' doses. We aimed to synthesise all available evidence from interventional studies investigating low-dose lithium (LDL) across neuropsychiatric outcomes., Methods: Electronic databases were systematically searched to include studies where a group of adult humans were treated with LDL (∼serum level ≤0.6 mmol/L), where data describing a neuropsychiatric outcome were reported either before and after treatment, and/or between lithium and a comparator., Results: 18 articles were examined and grouped according to outcome domain (cognition, depression, mania, and related constructs e.g., suicidality). Significant benefits (versus placebo) were identified for attenuating cognitive decline, and potentially as an adjunctive therapy for people with depression/mania. Across studies, LDL was reported to be safe., Conclusions: Despite the paucity and heterogeneity of studies, LDL's apparent pro-cognitive effects and positive safety profile open promising avenues in the fields of neurodegeneration, and augmentation in affective disorders. We urge future examinations of LDL's potential to prevent cognitive/affective syndromes., Competing Interests: Competing interests In the last 36 months: RS declares an honorarium from Janssen. AHY declares honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. JK owns shares in AstraZeneca and GSK plc. MFJ declares honoraria for speaking from Janssen, Lundbeck, EMS and Daiichi Sankyo; honoraria for consulting from Janssen and Lundbeck; and research grant support from Lundbeck and Heptares Therapeutics. Other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD., Methods: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors., Results: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning., Conclusions: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: Cognitive remediation (CR) can reduce cognitive and functional difficulties in people with bipolar disorder (BD). To date, there is limited evidence on the contribution of session attendance and therapy components to treatment outcomes. This study explores whether attendance and core CR components contribute to treatment outcomes., Methods: This is a secondary analysis using data from a randomized controlled trial comparing CR plus treatment-as-usual (TAU; n = 40) to TAU only (n = 40) in euthymic people with BD. Session attendance was measured by number of sessions and by achieving therapy completion, pre-defined as attending ≥20 sessions. We used instrumental variable analysis to examine the effect of attendance on treatment outcomes. We then considered the association between core therapy components (i.e., massed practice, errorless learning, strategy use, therapist contact) and post-treatment outcome changes using correlation., Results: The CR group improved significantly in measure of global cognition, psychosocial functioning, and goal attainment. Therapy recipients attended 27.1 sessions on average, with 32 (80%) completing the minimum number of 20 sessions. Attending more sessions and achieving therapy completion were associated with improved treatment outcomes, but this relationship was not significant within the subgroup of CR completers. Improvement in psychosocial functioning was associated with therapist contact and goal attainment with selecting useful strategies during therapy., Conclusions: Our findings highlight the relevance of session attendance, specifically the importance of achieving a minimum threshold of CR sessions, for outcome improvement. Strategy use and therapist contact might facilitate improvements in psychosocial functioning and personal recovery goals., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Recent evidence suggests that cognitive remediation (CR) may reduce cognitive and functional difficulties in people with bipolar disorder (BD). However, there is a limited understanding of whether, and which, pre-treatment factors influence who will benefit from CR and this information could help to develop optimal therapy delivery. We aim to identify and examine baseline factors moderating post-treatment improvement., Methods: This is a secondary analysis of data from a randomized controlled trial comparing CR (n = 40) to treatment-as-usual (TAU; n = 40) in euthymic people with BD. Elastic net regression was used to identify patient characteristics and baseline measures associated with post-treatment improvement in cognition, psychosocial functioning, and goal attainment. We then tested the moderating effect of retained variables on each outcome using multivariable linear regression., Results: Despite lower baseline cognitive performance being associated with greater post-treatment changes in cognition and psychosocial functioning, there was no evidence of treatment response moderation. CR effect on goal attainment was larger for participants with better baseline cognitive performance, but this moderating effect did not reach significance (p = 0.09). Those with more severe baseline subjective cognitive complaints (p = 0.03) and more previously completed psychological therapies (p = 0.02) had also larger gains in goal attainment., Conclusions: Treatment benefits in cognition and psychosocial functioning might not be affected by pre-treatment factors and patient characteristics. However, baseline cognition and perceived deficits may influence the effect of CR on achieving recovery goals. Therapy adaptations may be required to exert greater benefits for less responsive patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives Although cognitive dysfunction is a prominent feature of bipolar disorder (BD), previous research presents limitations in estimating the proportion of euthymic patients experiencing clinically relevant deficits and identifying predictors of cognitive difficulties. We explored the relevance of recommended definitions of clinically significant cognitive impairment for functional outcomes, estimated its prevalence, and identified patient characteristics associated with cognition. Methods We assessed cognitive performance across four domains in 80 euthymic participants with BD. Participants were categorized based on two criteria for clinically significant cognitive impairment and we assessed the ability of these criteria to differentiate participant performance on established functional outcomes. Variable selection with elastic net regression was used to identify sociodemographic and clinical factors associated with cognitive performance. Selected variables were examined as predictors of clinically significant cognitive impairment with logistic regression. Results According to the selected criterion, 34% presented with clinically significant cognitive impairment. Poorer current cognitive performance was associated with older age, lower estimated premorbid IQ, more currently prescribed psychotropic medications, fewer previous psychological therapies, and current use of antipsychotics. A model with premorbid IQ, psychotropic medications and previous psychological therapies as predictors of cognitive impairment correctly classified 75% of the participants. Conclusions This is one of the first studies to use a model selection approach to identify factors associated with cognitive difficulties in BD. Our findings offer the initial steps towards a predictive model for cognitive impairment. This could improve treatment decisions and prioritization for euthymic patients with BD, particularly the implementation of cognitive interventions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Functional impairment is a major target in the treatment of bipolar disorder (BD), but the magnitude and type of functional difficulties differ across patients. Findings on predictors of overall functioning and specific functional areas are inconsistent. We aimed to characterize functional difficulties and identify factors associated with global functioning and individual domains in euthymic patients., Methods: The Functional Assessment Short Test (FAST) was used to assess overall psychosocial functioning and specific functional domains in 80 euthymic participants with BD. Participants also completed a clinical interview and a cognitive assessment. Model selection with elastic net regression was performed to identify predictors of global functioning. We then examined the association of these predictors with individual functional domains using correlation., Results: FAST scores indicated moderate or severe impairment for 54% of the sample, with occupational functioning showing the highest impairment rate. Elastic net regression selected a model with three variables (higher residual depressive symptoms, lower executive functioning, more perceived cognitive deficits) as predictors of overall functioning. No significant associations were found between these predictors. Depressive symptoms were associated with interpersonal relationships and leisure time, executive skills with occupational functioning, and perceived deficits with cognitive functioning., Conclusions: Residual depressive symptoms were the strongest predictor of overall functioning which highlights the importance of assessing and targeting subthreshold symptoms for recovery. Executive difficulties were associated with functioning, particularly occupational skills, independently of depressive symptoms. Interventions targeting these difficulties, such as cognitive and functional remediation, may be key treatment options towards facilitating functional recovery., (Copyright © 2021 Elsevier Ltd. All rights reserved.)