BackgroundBipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear.MethodsWe aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains.ResultsEuthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008).LimitationsWe evaluated a modest sample size with concurrent pharmacological treatment.ConclusionsHigher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management.

Introduction Cognitive reserve (CR) refers to the ability of the brain to cope with damage or pathology. In bipolar disorder (BD), it has been seen that the effects of the disease may potentially reduce CR, thus compromising cognitive outcomes. This concept takes on special relevance in late life in BD, due to the increased risk of cognitive decline because of the accumulative effects of the disease and the potential effects of aging. Therefore, we believe that CR may be a protective factor against cognitive decline in older adults with bipolar disorder (OABD). Objectives The aim of this study was to study the CR in OABD compared with healthy controls (HC) and to analyze its association with psychosocial functioning and cognitive performance. Methods A sample of euthymic OABD, defined as patients over 50 years old, and HC were included. CR was assessed using the CRASH scale. Differences in demographic, clinical, and cognitive variables between patients and HC were analyzed by t-test or X2 as appropriated. Lineal simple and multiple regressions analyses were used to study the association of CR and several clinical variables with functional and cognitive performance. Results A total of 83 participants (42 OABD and 41 HC) were included. Compared to HC, OABD exhibited poorer cognitive performance (p<0.001), psychosocial functioning (p<0.001) and lower CR (p<0.001). Within the patient’s group, the linear simple regression analysis revealed that CR was associated with psychosocial functioning (β=-2.16; p=0.037), attention (β= 3.03; p=0.005) and working memory (β = 2.98; p=0.005) while no clinical factors were associated. Age and CR were associated with processing speed and verbal memory, but after applying multiple regression model, only the effect of age remained significant (β =-2.26; p= 0.030, and β =-2.23; p= 0.032 respectively). CR, age, and number of episodes were related to visual memory, but the multiple regression showed that only age (β = -2.37; p= 0.023) and CR (β = 3.99; p<0.001) were associated. Regarding executive functions only the number of manic episodes were significant. CR and age at onset were associated with visuospatial ability, but multiple regression only showed association of CR (β =2.23; p=0.032). Other clinical factors such as number of depressive or hypomanic episodes, illness duration, admissions, type of BD, and psychotic symptoms were not associated. Conclusions To the best of our knowledge, this is the first report that studies the CR in a sample of OABD. We demonstrated that OABD had lower CR than HC. Importantly, we observed that CR was associated with cognitive and psychosocial functioning in OABD, even more than disease-related factors. These results suggest the potential protector effect of CR against cognitive impairment, supporting that improving modifiable factors associated with the enhancement of CR can prevent cognitive decline. Disclosure of Interest L. Montejo: None Declared, C. Torrent Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00344) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER), S. Martín: None Declared, A. Ruiz: None Declared, M. Bort: None Declared, G. Fico Grant / Research support from: Fellowship from “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), V. Oliva: None Declared, M. De Prisco: None Declared, J. Sanchez-Moreno Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER),, E. Jimenez Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060)integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER),, A. Martinez-Aran: None Declared, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIIISubdireccio ́n General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151)., B. Sole: None Declared

Introduction In recent years, research has focused on the older adults with bipolar disorder (OABD), aged 50 years and over, a constantly growing population due to the increased of life expectancy. Actually, some authors suggest that these individuals constitute a distinct subtype with a specific and different needs such as seen in epidemiologic, clinical and cognitive features. Further research has revealed significant differences between females and males with BD in clinical and cognitive variables in middle-aged and young patients, but this topic among OABD population remains unclear. Objectives The aim of this study is to identify the distinctive profile in clinical, functional and neurocognitive variables between females and males in OABD. Methods A sample of OABD and Healthy Controls (HC) were included. Euthymic patients or in partial remission were included. Neurocognition was measured with a battery of tests that included premorbid intelligence quotient, working memory, verbal and visual memory, processing speed, language and executive functions. Independent t-test and Chi-squared test analysis were performed as appropriated. Results According to the analysis, statistically significant differences were seen between females and males. A more impaired cognitive profile is observed in women. They performed worse in the subscales of Arithmetic (F= 6.728, p = <0.001), forward digits (F= 0.936, p= 0.019) and Total Digits (F= 1.208, p= 0.019) of the WAIS-III, in the Stroop Color Word Test, color reading (F= 0.130, p= < 0.001), in the Continuous Performance Test, block change measure (F= 2.059, p= 0.037), in the Rey-Osterrieth Complex Figure-copy (F= 0.005, p= 0.029) and in the Boston Naming Test (F= 0.011, p= 0.024). Nor significant differences were found in clinical neither in psychosocial functioning variables. Conclusions In view of the following results, and since no differences were observed between women and men in terms of clinical and functional outcomes, it could be said that the differences observed in cognition cannot be explained by disease-related factors. Furthermore, these results highlight the need to develop a gender-specific cognitive interventions in OABD population. In this way, we could have an impact on the course of the illness to reach a better quality of life. Disclosure of Interest S. Martín-Parra: None Declared, C. Torrent Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00344) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIIISubdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), A. Ruiz: None Declared, M. Bort: None Declared, G. Fico Grant / Research support from: Fellowship from “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), V. Oliva: None Declared, M. Prisco: None Declared, J. Sanchez-Moreno Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), E. Jimenez Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), A. Martinez-Aran: None Declared, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151), B. Sole: None Declared, L. Montejo: None Declared

Objective: The aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD). Methods: One hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression. Results: Higher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over -report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = -0.27; t = -2.24: p = 0.029) and in the domain of attention/processing speed (Beta = -0.34; t = -2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints. Discussion: Our study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment.

Introduction Bipolar disorder (BD) is a chronic mental disorder characterized by mood instability1. BD is further related to neurocognitive and functional disruptions that remain remarkably stable even when patients are euthymic, leading to poor well-being and quality of life. Mindfulness means paying attention on purpose, in the present moment, and involves different facets such as observing, describing, acting with awareness, non-judging and non-reacting of inner experience. It remains unclear whether mindfulness and its specific facets are differentially associated with different aspects of attention and trait impulsivity in individuals with BD. Objectives To examine associations between different mindfulness facets, and different aspects of attention and trait impulsivity in BD. Methods This study was approved by the Hospital Clínic Ethics and Research Board (HCB/2017/0432). After informed consent, 94 outpatients, M age = 45.57, SD = 9.8, range 19-61 years, 41.5% Male, 63.8% BD-I according to DSM-5 criteria, in partial or total remission based on Young Mania Rating Scale (YMRS; M = 1.81, SD = 2.11) and Hamilton Depression Rating Scale (HDRS; M = 5.46, SD = 3.71) were enrolled in this study. Participants were evaluated using the Five Facet Mindfulness Questionnaire (FFMQ) to assess Mindfulness, the Trail Making Test (TMT-A) and the Conner’s Continuous Performance test (CPT-II) to assess Attention, and the Barratt Impulsiveness Scale (BIS-11) to assess Impulsivity. Pearson correlations were performed, and statistical significance was evaluated two-sided at the 5% threshold. Results Mindfulness-Describing was negatively associated with Cognitive and Non-Planning Impulsivity (r = -.43 and -.28, p < .001), Mindfulness-Acting with Awareness was negatively associated with Cognitive, Motor and Non-Planning Impulsivity (r = -.27 to -.45, p < .001), Mindfulness Non-Judging (r = -.33 and -.34, p < .001) and Non-Reacting (r = -.30 and -.46, p < .001) of inner experience were negatively associated with Cognitive and Motor Impulsivity. No associations were found between neither Mindfulness nor Impulsivity with any aspects of Attention. Conclusions Preliminary findings suggest that better performance in specific facets of mindfulness (describing, acting with awareness, non-judging or reacting of inner experience) may be related to a decrease in different aspects of trait impulsivity. Further longitudinal and interventional research is needed on underlying mechanisms. Nonetheless, our study suggests the need for including mindfulness-based approaches to improve behavioral and functional outcomes for those with BD. Funding This work was supported by the European Union Horizon 2020 research and innovation program (EU.3.1.3. Treating and managing disease: Grant 945151), CIBERSAM, FIS PI17/00941 ISCIII, European Regional Development Fund. References 1. Carvalho AF, Firth J, Vieta E. Bipolar Disorder. N Engl J Med. 2020;383(1):58-66. doi:10.1056/NEJMra1906193 Disclosure of InterestNone Declared

Background: Patients with bipolar disorder (BD) frequently suffer from neurocognitive deficits that can persist during periods of clinical stability. Specifically, impairments in executive functioning such as working memory and in self-processing have been identified as the main components of the neurocognitive profile observed in euthymic BD patients. The study of the neurobiological correlates of these state-independent alterations may be a prerequisite to develop reliable biomarkers in BD.Methods: A sample of 27 euthymic BD patients and 25 healthy participants (HC) completed working memory and self-referential functional Magnetic Resonance Imaging (fMRI) tasks. Activation maps obtained for each group and contrast images (i.e., 2-back > 1-back/self > control) were used for comparisons between patients and HC.Results: Euthymic BD patients, in comparison to HC, showed a higher ventromedial prefrontal cortex activation during working memory, a result driven by the lack of deactivation in BD patients. In addition, euthymic BD patients displayed a greater dorsomedial and dorsolateral prefrontal cortex activation during self-reference processing. Limitations: Pharmacotherapy was described but not included as a confounder in our models. Sample size was modest. Conclusion: Our findings revealed a lack of deactivation in the anterior default mode network (aDMN) during a working memory task, a finding consistent with prior research in BD patients, but also a higher activation in frontal regions within the central executive network (CEN) during self-processing. These results suggest that an imbalance of neural network dynamics underlying external/internal oriented cognition (the CEN and the aDMN, respectively) may be one of the first reliable biomarkers in euthymic bipolar patients.

Introduction Bipolar disorder (BD) is a chronic and recurrent mental condition characterized by mood fluctuations between hypomania or mania and depression, with high level of burden and mortality rates (Hayes et al., 2015). Subsyndromal mood symptoms, including residual depression, mania and/or anxiety, are major risk factors for episodic relapses after mood stabilisation (Samalin et al., 2016). A psychological protective mechanism against the occurrence of these maladaptative mood symptoms is dispositional mindfulness (DM). DM refers to paying purposeful attention to present moment experiences with a curious, non-judgmental and accepting attitude (Radford et al., 2014). DM has been barely assessed in BD and there is very little evidence on the relationship between DM, residual mood symptoms and quality of life Objectives To explore associations between DM, residual mood symptoms and quality of life in individuals with BD Methods After informed consent, a total of 94 adults (Mean age= 45.57 years, 41.50% Male) with diagnosis of BD according to DSM-5 criteria, in full or partial remission,were recruited from the Bipolar and Depressive Disorders Unit at the Hospital Clinic of Barcelona. The ethical committee approved this study. Dispositional mindfulness was assessed using the Mindfulness Attention Awareness Scale (MAAS).The presence of residual depressive symptoms was assessed with the Hamilton Depression Rating Scale (HDRS), residual mania symptoms were assessed with the Young Mania Rating Scale(YMRS), and anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale (HAM-A). The subjective quality of life was assessed with the Quality of Life in Bipolar Disorder Questionnaire (QoL-BD). Pearson correlations were carried out and the level of significance was set at p<0.05 Results DM was negatively related to residual depressive symptoms (r= -0.283; p=0.009) and to anxiety symptoms (r=-0.345; p<0.001), and positively related to quality of life (r=0.433; p<0.001), but not related to residual manic symptoms in BD Conclusions Our preliminary data suggest that BD patients with higher levels of DM may experience less depressive and anxiety subsyndromal symptoms and perceived higher quality of life. No associations were detected regarding mania symptoms. These findings support the use of mindfulness training as an adjunct therapy to pharmacotherapy to reduce residual mood symptoms and improve quality of life in patients with BD Disclosure of Interest None Declared