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Introduction Bipolar disorder (BD) is a source of marked disability, morbidity, and premature death. There is a paucity of research on personalized psychosocial interventions for BD, especially in lowresource settings. A previously published pilot randomized controlled trial (RCT) of a Culturally adapted PsychoEducation (CaPE) intervention for BD in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes towards BD, and improvement in mood symptom scores and health-related quality of life measures compared to treatment-as-usual (TAU). Objectives This protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Methods A multicentre individual, parallel arm, RCT of CaPE in 300Pakistani adults with BD. Participants over the age of 18, with adiagnosis of bipolar I and II and who are currently euthymic, will berecruited from seven sites including Karachi, Lahore, Multan, Rawalpindi,Peshawar, Hyderabad and Quetta. Time to recurrence will be the primaryoutcome assessed using Longitudinal Interval Follow-up Evaluation(LIFE). Secondary measures will include mood symptomatology, qualityof life and functioning, adherence to psychotropic medications, andknowledge and attitudes towards BD. Results Full ethics approval has been received from National Bioethics Committee (NBC) of Pakistan and Centre for Addiction and Mental Health (CAMH), Toronto, Canada. The study has completed sixty-five screening across the seven centres, of which forty-eight participants have been randomised. Conclusions A successful trial will lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority patients with BD. Disclosure of Interest None Declared

Introduction Low and middle-income countries (LMICs) hold the majority of disease burden attributed to major depressive disorder (MDD). Despite this, there remains a substantial gap for access to evidence-based treatments for MDD in LMICs like Pakistan. Measurement-based care (MBC) incorporates systematic administration of validated outcome measures to guide treatment decision making and is considered a low-cost approach to optimise better clinical outcomes for individuals with MDD but there is a paucity of evidence on the efficacy of MBC in LMICs. Objectives This protocol highlights a randomized trial which will include Pakistani outpatients with moderate to severe major depression. Methods Participants will be randomised to either MBC (guided by schedule), or standard treatment (guided by clinicians’ judgement), and will be prescribed with paroxetine (10–60mg/day) or mirtazapine (7.5–45mg/day) for 24 weeks. Outcomes will be evaluated by raters blind to study protocol and treatment. Results National Bioethics Committee (NBC) of Pakistan has given full ethics approval. The trial is being conducted and reported as per recommendation of the CONSORT statement for RCTs. Conclusions With increasing evidence from high-income settings supporting the effectiveness of MBC for MDD, it is now necessary to explore its feasibility, utility. and efficacy in low-resource settings. The results of the proposed trial could inform the development of a low-cost and scalable approach to efficiently optimise outcomes for individuals with MDD in Pakistan. Disclosure of Interest None Declared

Introduction Neuropsychiatric symptoms (NPS) are common during the course of neurocognitive disorders. NPS have been previously reported in early and late stages of Alzheimer’s Disease. However, our understanding of NPS in high-risk states for dementia such as mild cognitive impairment (MCI) and major depressive disorder (MDD) is poor. Objectives To compare the frequency and factor structure of neuropsychiatric symptoms among individuals with Mild Cognitive Impairment (MCI), Major Depressive Disorder (MDD) in remission, and comorbid MCI and MDD (in remission) (MCI-D). Methods We used baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study, a multicenter trial across five academic sites in Toronto, Canada (clinical trial No. NCT0238667). We used ANOVA or χ2-test to compare frequency of NPS across groups. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items in the three groups. Results We included 374 participants with a mean age of 72.0 years (SD = 6.3). In the overall sample, at least one NPS was present in 64.2% participants, and 36.1 % had at least moderate severity NPS (36.1%). Depression (54%, χ2 < 0.001) and apathy (28.7%, χ2=0.002) were more prevalent in the MCI-D group as compared to MCI and MDD groups. In factor analysis, NPS grouped differently in MCI, MDD, and MCI-D groups. A “psychotic” subgroup emerged among MCI and MCI-D, but not in MDD. Night-time behaviors and disinhibition grouped differently across all three groups. Conclusions Prevalence of NPS seems higher in persons with MCI-D as compared to those with only MCI or MDD. The factor structure of NPS differed between MCI, MDD, and MCI-D groups. Future studies should investigate the association of NPS factors with cognition, function, and illness biomarkers. Disclosure of Interest None Declared

Introduction Bipolar disorder (BD) is associated with premature death and ischemic heart disease is the main cause of excess mortality. The predictive power of heart rate variability (HRV) for mortality has been confirmed in patients with or without cardiovascular disease. While several studies have analyzed the association between HRV and BD, their results are incongruent; and none has analyzed the effect of the clinical factors characterizing illness burden on HRV. Objectives To assess the association between HRV and the following factors characterizing illness burden: illness duration, number and type of previous episode(s), duration of the most severe depressive or hypomanic/manic episode, severity of episodes, co-morbid psychiatric disorders, family history of BD or suicide, and duration and polarity of current episode in participants experiencing one. Methods We used a wearable device in 53 BD participants to assess the association between HRV using 4 measures (RMSSD, SDANN, SDNN and RR Triangular Index) and the abovementioned clinical factors characterizing illness burden. For each of the 4 HRV measures we ran 11 models, one for each burden of illness clinical factor as an independent variable. Results Longer illness duration, higher number of depressive episodes, and family history of suicide were negatively correlated with HRV; in the 14 participants experiencing a depressive episode, the MADRS score was negatively correlated with HRV Conclusions Our study analyzed the association between burden of illness and HRV in BD, while controlling for functional cardiovascular status, age, sex, BMI, education, and treatment. Our results showed that high illness burden is associated with reduced HRV. Disclosure No significant relationships.

N-acetyl-aspartate (NAA) and myo-inositol (mI) are neurometabolites reflecting neuronal viability and astrocyte activity, respectively. These are quantified using proton magnetic resonance spectroscopy (1H-MRS) and may be biomarkers for Alzheimer's disease dementia (AD). Our objectives were: 1) Compare dorsolateral prefrontal cortex (DLPFC) NAA and mI levels between AD and cognitively healthy control participants (HC) 2) assess if NAA/mI ratio can distinguish groups, and 3) explore the relationship between metabolites and cognition. The study included 64 participants over 55, 41 with AD. Bilateral DLPFC NAA and mI levels were quantified using 3 T 1H-MRS and normalized to H2O. NAA and NAA/mI ratio were lower in AD vs. HC. mI was unchanged. The NAA/mI ratio at a cut-off value of 1.69 showed 59% sensitivity and 87% specificity at distinguishing AD from HC. NAA was associated positively with cognition. In conclusion, DLPFC metabolite changes suggest altered mitochondrial function in AD. NAA/mI ratio shows good specificity in distinguishing AD from HC, suggesting its role in complementing other biomarkers. Future studies should evaluate NAA/mI ratio with other disease specific biomarkers., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset., Design/methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601)., Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning., Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Major depressive disorder (MDD) is a heterogeneous condition; multiple underlying neurobiological and behavioral substrates are associated with treatment response variability. Understanding the sources of this variability and predicting outcomes has been elusive. Machine learning (ML) shows promise in predicting treatment response in MDD, but its application is limited by challenges to the clinical interpretability of ML models, and clinicians often lack confidence in model results. In order to improve the interpretability of ML models in clinical practice, our goal was to demonstrate the derivation of treatment-relevant patient profiles comprised of clinical and demographic information using a novel ML approach., Methods: We analyzed data from six clinical trials of pharmacological treatment for depression (total n = 5438) using the Differential Prototypes Neural Network (DPNN), a ML model that derives patient prototypes which can be used to derive treatment-relevant patient clusters while learning to generate probabilities for differential treatment response. A model classifying remission and outputting individual remission probabilities for five first-line monotherapies and three combination treatments was trained using clinical and demographic data. Prototypes were evaluated for interpretability by assessing differences in feature distributions (e.g. age, sex, symptom severity) and treatment-specific outcomes., Results: A 3-prototype model achieved an area under the receiver operating curve of 0.66 and an expected absolute improvement in remission rate for those receiving the best predicted treatment of 6.5% (relative improvement of 15.6%) compared to the population remission rate. We identified three treatment-relevant patient clusters. Cluster A patients tended to be younger, to have increased levels of fatigue, and more severe symptoms. Cluster B patients tended to be older, female, have less severe symptoms, and the highest remission rates. Cluster C patients had more severe symptoms, lower remission rates, more psychomotor agitation, more intense suicidal ideation, and more somatic genital symptoms., Conclusion: It is possible to produce novel treatment-relevant patient profiles using ML models; doing so may improve interpretability of ML models and the quality of precision medicine treatments for MDD., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objects: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups., Methods: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies., Results: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59)., Conclusions: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients., Methods: We developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n ≥ 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health., Results: We identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables., Conclusion: The essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: The Canadian population has poor and inequitable access to psychiatric care despite a steady per-capita supply of psychiatrists in most provinces. There is some quantitative evidence that practice style and characteristics vary substantially among psychiatrists. However, how this compares across jurisdictions and implications for workforce planning require further study. A qualitative exploration of psychiatrists' preferences for practice style and the practice choices that result is also lacking. The goal of this study is to inform psychiatrist workforce planning to improve access to psychiatric care by: (1) developing and evaluating comparable indicators of supply of psychiatric care across provinces, (2) analysing variations and changes in the characteristics of the psychiatrist workforce, including demographics and practice style and (3) studying psychiatrist practice choices and intentions, and the factors that lead to these choices., Methods and Analysis: A cross-provincial mixed-methods study will be conducted in the Canadian provinces of British Columbia, Manitoba, Ontario and Nova Scotia. We will analyse linked-health administrative data within three of the four provinces to develop comparable indicators of supply and characterise psychiatric services at the regional level within provinces. We will use latent profile analysis to estimate the probability that a psychiatrist is in a particular practice style and map the geographical distribution of psychiatrist practices overlayed with measures of need for psychiatric care. We will also conduct in-depth, semistructured qualitative interviews with psychiatrists in each province to explore their preferences and practice choices and to inform workforce planning., Ethics and Dissemination: This study was approved by Ontario Tech University Research Ethics Board (16637 and 16795) and institutions affiliated with the study team. We built a team comprising experienced researchers, psychiatrists, medical educators and policymakers in mental health services and workforce planning to disseminate knowledge that will support effective human resource policies to improve access to psychiatric care in Canada., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic disrupted the delivery of diabetes care and worsened mental health among many patients with type 2 diabetes (T2D). This disruption puts patients with T2D at risk for poor diabetes outcomes, especially those who experience social disadvantage due to socioeconomic class, rurality, or ethnicity. The appropriate use of communication technology could reduce these gaps in diabetes care created by the pandemic and also provide support for psychological distress., Objective: The purpose of this study is to test the feasibility of an innovative co-designed Technology-Enabled Collaborative Care (TECC) model for diabetes management and mental health support among adults with T2D., Methods: We will recruit 30 adults with T2D residing in Ontario, Canada, to participate in our sequential explanatory mixed methods study. They will participate in 8 weekly web-based health coaching sessions with a registered nurse, who is a certified diabetes educator, who will be supported by a digital care team (ie, a peer mentor, an addictions specialist, a dietitian, a psychiatrist, and a psychotherapist). Assessments will be completed at baseline, 4 weeks, and 8 weeks, with a 12-week follow-up. Our primary outcome is the feasibility and acceptability of the intervention, as evident by the participant recruitment and retention rates. Key secondary outcomes include assessment completion and delivery of the intervention. Exploratory outcomes consist of changes in mental health, substance use, and physical health behaviors. Stakeholder experience and satisfaction will be explored through a qualitative descriptive study using one-on-one interviews., Results: This paper describes the protocol of the study. The recruitment commenced in June 2021. This study was registered on October 29, 2020, on ClinicalTrials.gov (Registry ID: NCT04607915). As of June 2022, all participants have been recruited. It is anticipated that data analysis will be complete by the end of 2022, with study findings available by the end of 2023., Conclusions: The development of an innovative, technology-enabled model will provide necessary support for individuals living with T2D and mental health challenges. This TECC program will determine the feasibility of TECC for patients with T2D and mental health issues., Trial Registration: ClinicalTrials.gov NCT04607915; https://clinicaltrials.gov/ct2/show/NCT04607915., International Registered Report Identifier (irrid): DERR1-10.2196/39724., (©Lenka Vojtila, Diana Sherifali, Rosa Dragonetti, Iqra Ashfaq, Scott Veldhuizen, Farooq Naeem, Sri Mahavir Agarwal, Osnat C Melamed, Allison Crawford, Philip Gerretsen, Margaret Hahn, Sean Hill, Sean Kidd, Benoit Mulsant, Eva Serhal, Leah Tackaberry-Giddens, Carly Whitmore, Jennifer Marttila, Frank Tang, Seeta Ramdass, Gloria Lourido, Sanjeev Sockalingam, Peter Selby. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 17.01.2023.)

Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE-BD)., Experimental Procedures: Cross-sectional analysis of the GAGE-BD dataset to determine differences and similarities between lithium users and non-users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non-lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site., Results: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non-users among those with evidence of rapid cycling and non-bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non-users., Conclusion: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross-sectional approach and data harmonisation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT)., Methods: This is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12., Results: At 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (β = - 0.03 (95% C.I.; - 0.0662, - 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH., Conclusion: In lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes., (© 2022. The Author(s).)

Objectives: To compare the prevalence of physical morbidities among men and women with older adult bipolar disorder (OABD), and men with and without OABD., Methods: Cross-sectional analysis of the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) database and non-OABD data from the Health in Men Study. OABD defined as bipolar disorder among adults aged greater than or equal to 50 years. Outcomes of interest were diseases affecting the cardiovascular, respiratory, gastrointestinal, renal, musculoskeletal and endocrinological systems., Results: We examined 1407 participants with OABD aged 50-95 years, of whom 787 were women. More women than men showed evidence of morbidities affecting the respiratory, gastrointestinal, musculoskeletal and endocrinological systems. More men with than without OABD showed evidence of cardiovascular, renal and endocrinological diseases., Conclusion: GAGE-BD data showed that physical morbidities affect more women than men with OABD, and more men with than without OABD. The underlying reasons for these differences require clarification., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study., Design: Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed., Setting: Community-based multi-centered study based in Toronto across 5 academic sites., Participants: Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls., Measurements: We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores., Results: A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD., Conclusions: This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.

Objectives: Antipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS., Experimental Design: The observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models., Principal Observations: 46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012)., Conclusions: APS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships., (Copyright © 1964–2022 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Objective: Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning., Methods: This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF)., Results: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals., Conclusions: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The rapid rise of cases of coronavirus disease 2019 (COVID-19) has led to the implementation of public health measures on an unprecedented scale. These measures have significantly affected the training environment and the mental health of health care providers and learners. Design thinking offers creative and innovative solutions to emergent complex problems, including those related to training and patient care that have arisen as a result of the COVID-19 pandemic. Design thinking can accelerate the development and implementation of solution prototypes through a process of inspiration, ideation, and implementation. Digital technology can be leveraged as part of this process to provide care and education in new or enhanced ways. Online knowledge hubs, videoconference-based interactive sessions, virtual simulations, and technology-enhanced coaching for health care providers are potential solutions to address identified issues. Limitations of this model include inherent bias toward utilitarian instead of egalitarian principles and the subsequent threat to diversity, equity, and inclusion in solutions. Although medical educators have embraced digital transformation during the COVID-19 pandemic, there is a need to ensure that these changes are sustained., (Copyright © 2020 by the Association of American Medical Colleges.)

Background: Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified., Objective: Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms., Methods: We examined the distribution of NPS using the Neuropsychiatric Inventory (NPI) scores in three cohorts from the Prevention of Alzheimer's Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study: older patients with a lifetime history of major depressive disorder (MDD) in remission, patients with mild cognitive impairment (MCI), and patients with combined MCI and MDD. We also examined the link between individual NPS and CVRFs, Framingham risk score, and Hachinski ischemic score in a combined sample., Results: Analyses were based on a sample of 140 subjects, 70 with MCI, 38 with MCI plus MDD, and 32 with MDD. There was no effect of age, gender, education, cognition, or CVRFs on the presence (NPI >1) or absence (NPI = 0) of NPS. Depression was the most prevalent affective NPS domain followed by night-time behaviors and appetite changes across all three diagnostic groups. Agitation and aggression correlated negatively while anxiety, disinhibition, night-time behaviors, and irritability correlated positively with CVRFs (all p-values <0.05). Other NPS domains showed no significant association with CVRFs., Conclusion: CVRFs are significantly associated with individual NPI sub-scores but not with total NPI scores, suggesting that different pathologies may contribute to different NPS domains.

Objective: Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long-term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D 2/3 receptor (D 2/3 R) blockade by antipsychotics., Methods: Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D 2/3 R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate., Results: Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: β = -.38, t = -2.48, P = .01; left: β = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (β = -.43, t = -0.26, P = .03)., Conclusion: We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D 2/3 R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Obstructive sleep apnea (OSA) is frequently comorbid with late-life depression. The purpose of this project was to determine, using a sample of older adults with major depressive disorder, whether patient-reported diagnosis of OSA was associated with rate of response to venlafaxine., Methods: Participants from this multisite study were adults ≥60 years old (n = 468) with major depressive disorder and a Montgomery Asberg Depression Rating Scale (MADRS) score of ≥15. Depression response was the outcome variable, defined as a MADRS score of ≤10 for two consecutive assessments at the end of 12 weeks of open-label treatment with venlafaxine 300 mg/day. To assess OSA, participants were asked if they had been diagnosed with OSA using polysomnography., Results: Eighty participants (17.1%) reported a diagnosis of OSA prior to baseline. Participants with OSA were more likely to be male, report greater impairment on measures of health, experience a longer duration of the index episode, and receive an adequate antidepressant trial prior to entering the study. During the 12 weeks of treatment, 40.8% responded to treatment with venlafaxine (43.6%, n = 169/388 of the no OSA group, and 27.5%, n = 22/80 of the OSA group). Participants without OSA were 1.79 times more likely to respond to treatment (HR: 1.79 [95%CI: 1.13-2.86], P < .05) compared to those with OSA., Conclusions: OSA may impair response to antidepressant pharmacotherapy in depressed older adults. Future studies of antidepressant response rates among depressed older adults with OSA should both prospectively diagnose OSA and monitor adherence to treatments such as continuous positive airway pressure., (© 2016 Wiley Periodicals, Inc.)

Objective: This study explored whether older black and white adults with major depressive disorder differed in rates of remission or attrition during open-label treatment with venlafaxine and supportive care., Methods: A total of 47 black (10%) and 412 white (90%) adults age ≥60 were treated with open-label venlafaxine extended-release (≤300 mg per day) for 12-14 weeks during the initial phase of an multisite, randomized, placebo-controlled augmentation trial. Participants were help-seeking older adults with nonpsychotic major depressive disorder (single or recurrent episode) referred from specialty clinics, primary care practices, advertisements, and research programs. Remission was defined as a Montgomery-Asberg Depression Rating Scale score of ≤10 for two consecutive assessments at the end of 12 weeks. Kaplan-Meier curves displayed time to dropout and time to initial remission. Cox proportional hazards models assessed differences in attrition and remission rates., Results: Black participants had greater baseline general medical comorbidity, worse physical health-related quality of life, and poorer cognitive function than white participants. White participants were more likely to have received an adequate trial of antidepressant and psychotherapy before study entry. Baseline depression severity, depression duration, age at onset, and recurrence history did not differ between groups. The groups had similar final doses of venlafaxine and similar rates of attrition and remission. Side-effect profiles were comparable between the groups., Conclusions: Despite greater medical comorbidity, lower cognitive function, and less adequate prior exposure to antidepressant treatment and psychotherapy, black participants were no more likely to discontinue antidepressant pharmacotherapy and experienced a rate of remission comparable to white participants.