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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.