Bipolar disorder (BD) is a multifaceted illness encompassing mood, energy, cognitive and biorhythms alterations. Sleep disturbances are common in prodromic, acute and inter-episodic phases of BD. Suicidality presents a known association with sleep disturbances. However, their interplay in BD remains intricate and not fully elucidated.

The aim of the present systematic review (SR) and meta-analysis (MA) is to summarise the available evidence and to provide an estimate of the association between sleep disturbances and suicidality, defined as presence of suicide ideation, behaviour and suicide attempts, in patients with BD.

We conducted a comprehensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, PsycINFO, and SCOPUS databases. We included all studies reporting an association between sleep problems and suicidal behaviour in BD patients. No language restriction was imposed. Effect sizes were calculated as odds ratio (OR) for dichotomic variables, standard mean difference (SMD) for continuous outcomes, and Spearman’s coefficient (r) for correlations. Heterogeneity was assessed using the I2 statistic. Global inconsistency was evaluated using the Q statistics with the corresponding p-value.

The initial search yielded 911 unique abstracts, of which 62 underwent full-text screening. Fourteen publications were included, comprising twelve cross-sectional and two longitudinal studies. The total sample consisted of 19,601 subjects diagnosed with BD, of which 51.76% were females and 69.52% had a diagnosis of BD type 1. We found that people with BD and sleep disturbances tend to have higher suicidality, both current (SMD=0.79, 95%CI=0.53, 1.05) and lifetime (OR=1.8; 95%CI=1.41, 2.55), when compared with people with BD and no sleep disturbances. Additionally, patients with BD and a history of suicide attempts tend to have more sleep problems (OR=1.37, 95%CI=1.21, 1.55). Moreover, a positive correlation exists between suicidality and poor sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) (r= 0.24, 95%CI=0.10, 0.36). No heterogeneity was found, except in the subanalysis of correlation (I2=66.67%, Q p-value=0.01).

Our SRMA outlines a positive relation between sleep disturbances and suicidality in patients with BD. The small number of included studies and the scarcity of longitudinal studies, preventing the inference of a causal relationship, represent the major limitations of this study. Also, studies with objective measures of sleep alterations are currently lacking. The prompt recognition, objective measurement, and treatment of sleep alterations could be crucial in averting or reducing suicidal attempts in BD.

C. Possidente: None Declared, M. Bort: None Declared, M. De Prisco: None Declared, V. Oliva: None Declared, G. Fico Grant / Research support from: Fellowship from “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), L. Bracco: None Declared, C. Sommerhoff: None Declared, L. Montejo: None Declared, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672, PI22/00840) 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. 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-Subdireccio ́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).

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).

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.

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.

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.

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.

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

Predicting acute affective episodes in individuals with Bipolar Disorder (BD) remains a clinical challenge. Specific environmental stressors, including air pollution, noise, and temperature variations might worsen affective symptoms or sleep in the general population, but their role in BD relapses is often overlooked. Indeed, they might exacerbate BD by perturbing circadian rhythms – fundamental aspects of BD.

We thereby present the protocol of this pilot study and future preliminary data. We aim to longitudinally assess sleep alterations, mood fluctuations, and environmental exposure to several factors (air pollutants, climate, noise, artificial light-at-night, green space access) in patients with BD and to check the association of these variables with BD relapses.

In this pilot study, we will recruit 40 patients with BD in a 6-month prospective study. Patients were assessed during baseline, at 3 and 6 months. Data recollected will consist of a subjective (questionnaires) and objective (through meteorological stations) evaluation of physical environmental factors around the home residence; clinical assessment of mood and circadian rhythms, and continuous tracking of sleep-wake patterns, energy, and movement using actigraphy.

Expected results will show that exposure to a worse environment (higher pollution, noise, light exposure, climate) will be associated with worse BD outcomes (i.e., relapse, mood symptoms, sleep alterations).

We will be sharing preliminary data from our ongoing study, offering insights into early patterns and findings that shed light on our objectives.

None Declared

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.

The aim of this study is to identify the distinctive profile in clinical, functional and neurocognitive variables between females and males in OABD.

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.

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.

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.

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

Bipolar disorder (BD) is a chronic and recurrent disease characterized by acute mood episodes alternated with periods of euthymia. The available literature postulates that a biphasic dysregulation of mitochondrial bioenergetics might be observed in BD.

We aimed to explore differences in in vivo mitochondrial respiration (1) intra-individually: longitudinally within patients during an acute mood episode of BD and after clinical remission, and (2) inter-individually: between patients with BD on depressive or manic episodes and healthy controls (HC).

Patients admitted to our acute psychiatric ward with a manic episode or bipolar depression were recruited. Different mitochondrial oxygen consumption rates (OCRs) were assessed during the acute episode (T0) and after clinical remission (T1) in one million of peripheral blood mononuclear cells (PBMC): Routine, Leak, ETC and Rox. They were measured as picomoles of oxygen per million cells (pmol O2/million). This experiment was also conducted in HC. High-resolution respirometry was performed at 37°C by polarographic oxygen sensors in a two-chamber Oxygraph-2k system. Manic and depressive symptoms were assessed using standardized psychometric scales. Oxygen consumption capacity was compared (1) intra-individually, during acute episodes and after clinical remission, and (2) inter-individually, during acute manic and depressive episodes, and in HC. Statistical analyses were performed with SPSS, GraphPad and R Statistics.

20 patients with BD (15 manic, 5 depressed) and 10 HC were included. A significant increase in the maximal oxygen consumption capacity (ETC) was observed in clinical remission (27.4 ± 17.4) compared to the acute episodes (21.1 ± 11.7, p = 0.001), which remained significant after subtracting Rox from the other rates (p = 0.001). At T1, patients admitted with a manic episode tended to show higher mean ETC (31.2 ± 18.7) compared with T0 (24.1 ± 12.0, p = 0.074); the tendency persisted after Rox subtraction (p = 0.076). Patients admitted with a depressive episode also showed higher ETC means in T1 (16.3 ± 3.8) compared to T0 (12.1 ± 3.4), but there were not significant differences (p = 0.231). When HC, manic and depressive patients at T0 were compared between them, significant differences were observed in ETC (H =8.5; p =0.014) and Rox (H =13.8; p = 0.001). After Rox deduction, differences in ETC remained (H =11.7; p = 0.003). Individuals with bipolar depression showed lower ETC rates (12.1 ± 3.4) than those with a manic episode (24.1 ± 12.0; t = -3.5, p = 0.003), which was also found after Rox deduction (p = 0.001).

In both manic and depressive episodes in BD, mitochondrial respiration might be reduced and increase after clinical remission. Further studies with larger samples will allow to confirm these results and also to identify potential mitochondrial state-dependent biomarkers.

A. Giménez-Palomo Grant / Research support from: AGP is supported by a Rio Hortega 2021 grant (CM21/00094) from the Spanish Ministry of Health financed by ISCIII and cofinanced by Fondo Social Europeo Plus (FSE+)., M. Guitart-Mampel: None Declared, A. Meseguer: None Declared, M. Valentí: None Declared, L. Bracco: None Declared, H. Andreu: None Declared, E. Vieta: None Declared, G. Garrabou: None Declared, I. Pacchiarotti: None Declared

Psychotic patients often require pharmacological treatment, which may prove ineffective, leading to treatment-resistant psychosis necessitating the use of clozapine. However, the emergence of side effects can result in discontinuation, potentially triggering a relapse of psychotic symptoms. One significant side effect is antipsychotic-induced weight gain which, over time, can lead to adverse metabolic events. Recent translational research is evaluating the impact of prenatal factors on the metabolic outcomes of psychotic patients, using a surrogate marker of the intrauterine milieu such as birth weight (BW).

We aim to evaluate the changes in leptin, adiponectin, and insulin levels in patients with treatment-resistant psychosis who initiate clozapine treatment due to persistent psychotic symptoms.

Subjects older than 18 years with a diagnostic of a major mental disorder and initiating clozapine were enrolled in this 18-months longitudinal study. Neurohormones levels, including leptin, adiponeptin, and insulin were measured at baseline, 8 and 18 months during follow-up. Statistical analysis were conducted by using a fixed-effects model.

A total of 23 subjects initiating clozapine were evaluated during the initial mandatory 18-week period. Neurohormones, specifically leptin and adiponectin, were measured at three time points: baseline, 8 weeks, and 18 weeks. The changes in leptin levels were significantly associated with birth BW with sex differences, being inversely correlated only in females. Adiponectin was significantly associated with BW, being inversely correlated in males. Conversely, there was no observed association between insulin levels and BW.

Our findings highlight the significance of prenatal factors in influencing the subsequent evolution of neurohormones in individuals initiating clozapine treatment. This suggests that subjects with lower BW tend to exhibit elevated neurohormone values, emphasizing the role of prenatal events in this context.

None Declared

Early detection and intervention are critical for improved outcomes in mental disorders, and this is particularly true for bipolar disorders. Understanding the risk factors involved in the onset of the disease and the subsequent relapses and recurrences may lead to better results as regards to functional outcomes, which are the most relevant for patients and their significant others. This presentation will review those factors and discuss which ones can be used as targets for early intervention. It has been argued that, most often, early intervention comes late, and it is therefore paramount to build on strategies aimed at effective detection of people at risk and situations that may lead to recurring episodes of illness. Treatments not only aimed at treating symptoms, but at improving illness trajectories are necessary, and pharmacological formulations and interventions improving treatment adherence are particularly relevant to avoid interruptions of effective therapies.

E. Vieta Grant / Research support from: Boehringer-ingelheim, Compass, Janssen, Lundbeck, Novartis, Consultant of: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris

The kynurenine pathway has been suggested to be involved in the pathophysiology of psychiatric disorders, including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD).

To conduct a systematic review and meta-analysis of the kynurenine pathway metabolites from cerebrospinal fluid samples in SZ, BD, and MDD.

PubMed and Scopus databases were searched from inception to April 2022 to identify case-control studies assessing kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK)] in SZ, BD, and MDD vs. healthy controls (HC). PRISMA guidelines were followed in the literature review. The random effects model parameter was selected when comparing the standardized mean differences (SMD) between groups.

A total of 23 articles met inclusion criteria (number of articles k=8, 8, 11 for SZ, BD, and MDD, respectively). For SZ, KA levels were increased in SZ compared to HC (SMD=2.64, CI=1.16-4.13, p=0.0005, I2=96%, k=6, n=384). KYN levels were not significantly different between SZ and HC (SMD=4.19, CI=-0.70 to 9.09, p=0.0933, I2=99%, k=4, n=188). For BD, TRP levels (k=7) did not differ significantly between BD and HC. There was a limited number of studies to conclude increased levels of KA in BD (k=2). For MDD, although some studies tended toward increased levels of KYN in those with remission vs. decreased levels in those with current depression, there were no significant differences in any of the kynurenine metabolite levels. There was a limited number of studies to conclude increased levels of QA in MDD (k=2).

KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There may be alterations in this pathway based on population characteristics and mood states.

E. Salagre: None Declared, B. Fernandes: None Declared, M. Inam: None Declared, I. Grande Grant / Research support from: Spanish Ministry of Science and Innovation (MCIN) (PI19/00954) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdireccion General de Evaluacion y el Fondos Europeos de la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia_PRTR); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); and the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), CERCA Programme / Generalitat de Catalunya as well as the Fundació Clínic per la Recerca Biomèdica (Pons Bartran 2022-FRCB_PB1_2022), Paid Instructor of: ADAMED, Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare , E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed 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, Paid Instructor of: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Novartis, Orion Corporation, Organon, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda, J. Quevedo: None Declared, Z. Zhao: None Declared

Antidepressants (AD) are one of the most prescribed pharmacological treatments in developed countries. AD efficacy is well-proven in anxiety, depressive and other mental disorders, but their use is also common in individuals without psychiatric health conditions. Indeed, recent evidence reported an increase in AD prescription over the latest years. Concern has been raised on the overuse of AD in several countries, and societal policies and national guidelines have been developed to regulate their use in the general population.

Several factor might be used to explain this increase, including the more safety profile of new AD classes (i.e. SSRI, or vortioxetine) compared to old AD, a possible overall increase in the incidence of depressive and anxiety disorders, or their inappropriate prescription in mild conditions which could be managed without pharmacological treatment as first-step option in primary care (PC).

Explore AD prescription patterns in relation to mental health diagnoses and identify the most relevant factors involved in PC health systems. Understanding the variables influencing AD prescription would allow designing strategies and guidelines to make appropriate use of this pharmacological group in PC. As part of the PRESTO project (www.prestoclinic.cat), here we investigated the changes in frequency and the variables associated with AD prescription in a population-representative sample of people attending PC between 2010 –2019 in Catalonia, Spain.

We retrieved AD prescription, sociodemographic, and health-related data using individual electronic health records from a population-representative sample (N=947.698) attending PC between 2010-2019. Prescription of AD was calculated using DHD (Defined Daily Doses per 1,000 inhabitants/day). We compared cumulative changes in DHD with cumulative changes in diagnoses with an indication for AD during the study period. We used Poisson regression to examine sociodemographic and health-related variables associated with AD prescription.

Both AD prescription and mental health diagnoses with an indication for AD gradually increased. At the end of the study period, DHD of AD prescriptions and mental health diagnoses with an indication for AD reached cumulative increases of 404% and 49% respectively. Female sex (incidence rate ratio (IRR)= 2.83), older age (IRR = 25.43), and lower socio-economic status (IRR= 1.35) were significantly associated with increased risk of being prescribed an AD.

Our results from a large and representative cohort of patients confirm a steady increase of AD prescriptions that is not explained by a parallel increase in mental health diagnoses with an indication for AD. A trend on AD off-label and over-prescriptions in the PC system in Catalonia can be inferred from this dissociation.

M. Gonzalez: None Declared, G. anmella Grant / Research support from: received CME-related honoraria, or consulting fees from Janssen-Cilag, Lundbeck, Lundbeck/Otsuka, and Angelini, with no financial or other relationship relevant to the subject of this article, E. vieta Grant / Research support from: received research support from or served as consultant, adviser or speaker for AB-Biotics, Abbott, Abbvie, Adamed, Angelini, Biogen, Celon, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo SmithKline, Janssen, Lundbeck, Organon, Otsuka, Rovi, Sage pharmaceuticals, Sanofi-Aventis, Shire, Sunovion, Takeda, and Viatris, out of the submitted work, M. Primé-Tous: None Declared, X. Segú: None Declared, A. Mas: None Declared, D. Hidalgo Grant / Research support from: received CME-related honoraria or adviser from Abbott, Angelini, Janssen-Cilag and Ethypharm with no financial or other relationship relevant to the subject of this article.

Many studies have investigated whether there exist predictors of good response to antimanic drugs in bipolar disorder (BD). However, these factors predict response or only indicate benign illness course.

To shed some light on the topic, we tested whether the response to antimanic drugs showed any variability beyond that expected by the effects of illness course and placebo.

We included all double-blind, placebo-controlled RCTs of oral pharmacotherapies targeting adult patients with acute bipolar mania from 1991 to 2020. The primary outcome was the variance of the improvement in manic symptoms in treated individuals compared to placebo. The effect size was the log variability ratio (logVR). We performed a random-effects meta-analysis, including assessments of heterogeneity, sensitivity/cumulative/subgroup analyses, and meta-regression.

42 RCTs (46 comparisons) from a total of 8,438 BD patients with acute mania (53.7% male, mean age=39.3; 5,563 treatment/2,875 control groups) were included in the analysis. Individuals in active treatment groups did not show variability in the response beyond that observed in individuals under placebo (VR=1; 95% C.I.=0.97,1.03; p-value=0.97). No heterogeneity was detected between the studies (I2=0%; tau2=0%; Q=29.21; df=45; p-value=0.97). Results were similar in the leave-one-out/cumulative/subgroup analyses. Meta-regression did not show influences by age, sample size, sex, severity of manic symptoms at baseline, or clinical features (rapid cycling, mixed or psychotic features).

This meta-analysis shows no evidence of differences in the individual response to treatments. These findings suggest that the average treatment effect is a reasonable assumption for the individual BD patient with acute mania. The presented article adds evidence to the equivalent results in schizophrenia-spectrum disorders, clinical high-risk state for psychosis, and major depressive disorder, not supporting classification in responders vs. non-responders. However, these findings should be balanced with results from other fields supporting such classification.

None Declared

Emotion dysregulation (ED) is a multidimensional construct involving the lack of awareness, understanding and acceptance of emotions, a reduced access to adaptive and appropriate strategies to modulate the intensity or duration of emotional responses, and the inability to control behaviors in accordance with desired goals when experiencing negative emotions. ED is outlined in the general population and several psychiatric disorders, including bipolar disorder (BD), and influences its clinical course and management, quality of life, and daily social functioning.

The objective of this systematic review was to examine the correlations between maladaptive (i.e., positive and negative rumination, negative focus, risk taking behaviors, suppression, and dampening) and adaptive (i.e., cognitive reframing, adaptive coping, and acceptance) strategies of emotion regulation (ER) and depressive and manic symptoms of BD.

We searched the literature from inception to April 12, 2022, and included studies focusing on ER/ED assessed with a validated scale. We conducted multiple pairwise meta-analyses for correlations between ED dimension (or overall ED) and the measures of depressive and manic symptoms of BD, and separate Bayesian network meta-analyses to examine which aspects of emotion regulation were most closely associated with depressive and manic symptoms of BD. The Pearson’s r coefficients were adjusted using sample-size weights and Fisher’s r-to-z transformed was conducted.

A total of 13,826 records was identified and, after duplicate removal and title/abstract evaluation, 442 were explored at the full text. Sixteen studies were finally included. Results from pairwise meta-analyses are shown in Figure 1, results from network meta-analyses in Figure 2 and 3. Both depressive and manic BD symptomatology were found to be related to maladaptive ER strategies, with the only difference of positive rumination, associated only to manic symptoms. Negative rumination and risk-taking behaviors were the strategies more correlated to both manic and depressive symptoms, as confirmed by both pairwise metanalyses and network metanalyses. On the other hand, depressive symptomatology appeared more correlated with decreased adaptive strategies than manic symptomatology.

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ED has a significant correlation with BD symptomatology, therefore it should be explicitly considered during clinical assessment, diagnosis, and intervention on BD, and specific treatments should be implemented. More studies, and with longitudinal design, are needed to better explore these associations and their causal direction. In addition, future studies should mainly focus on the complex interactions between cognitive, social, and cultural aspects, and biological correlates to improve knowledge on a topic that is still poorly investigated.

V. Oliva: None Declared, M. De Prisco: None Declared, G. Fico Grant / Research support from: “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), Consultant of: Angelini, Janssen-Cilag and Lundbeck, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Consultant of: Angelini, Idorsia, Lundbeck, Pfizer, Takeda, M. Fornaro: None Declared, A. Serretti Consultant of: Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier, and Taliaz, J. Radua Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00394, CPII19/00009) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and the Instituto de Salud Carlos III, 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 co-financed 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. Thanks the support of 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), Consultant of: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris

Emotion regulation (ER) is the ability to assess, monitor, or modify emotional reactions to achieve a goal (Gross. Psychological inquiry 2015; 26 1-26). When ER strategies are rigidly or maladaptively applied, emotional dysregulation (ED) can occur (Thompson. Development and psychopathology 2019; 31 805-815). ED is common in people diagnosed with bipolar disorder (BD), but it can also be described in other clinical populations given its transdiagnostic nature. Numerous aspects of ED have been described in BD (De Prisco et al. Neuroscience & Biobehavioral Reviews 2022; 104914), but it is unclear whether these manifest similarly in other conditions such as major depressive disorder (MDD) or borderline personality disorder (BPD), or whether they are specific to BD.

The objective of this systematic review and meta-analysis is to examine the literature comparing BD with other psychiatric disorders in terms of ED, focusing on those studies using validated clinical tools.

A systematic search from inception to April 28th, 2022, was conducted exploring the PubMed/MEDLINE,EMBASE, Scopus, and PsycINFO databases. Those studies providing quantitative data on ED in people diagnosed with BD and compared with clinical groups were eligible for inclusion. No restriction about age, sample size, or language were applied. Random effect meta-analyses were conducted, and effect sizes were calculated as standardized mean differences (SMD).

A total of 3,239 records was identified and, after duplicate removal and title/abstract evaluation, 112 were explored at the full text. Twenty-nine studies were finally included, and it was possible to perform a meta-analysis with twenty-two (145 comparisons) of them. Only studies comparing BD with MDD, and BPD provided sufficient data to perform a meta-analysis. People with BD did not differ from people with MDD in most of the comparisons considered. However, BD patients presented higher positive rumination (two comparisons: SMD=0.46; CI=0.27, 0.64; p=8.5e-07; I2=0%; and SMD=0.34; CI=0.15, 0.52; p=2.7e-04; I2=0%) and risk-taking behaviors (SMD=0.48; CI=0.27, 0.69; p=8.11e-06; I2=0%). In contrast, people with BPD displayed an overall higher degree of ED (SMD=-1.22; CI=-1.94, -0.5; p=9.1e-04; I2= 90.7) and used fewer adaptive ER strategies. Additionally, higher levels of self-blaming (SMD=-0.80; CI=-1.11, -0.50; p=2.68e-07; I2=0) and impulsive behavior (SMD=-0.76; CI=-0.89, -0.63; p=5.4e-29; I2=0) were observed.

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ED is a trans-diagnostic construct that spans a continuum of different psychiatric disorders. Outlining the specific clinical features of one disorder versus another may help future research to increase our knowledge of these issues and develop new treatment strategies to reduce the clinical burden of these patients.

M. De Prisco: None Declared, V. Oliva: None Declared, G. Fico Grant / Research support from: “La Caixa” Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), Consultant of: Angelini, Janssen-Cilag and Lundbeck, J. Radua Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00394, CPII19/00009) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) and the Instituto de Salud Carlos III, I. Grande Grant / Research support from: Spanish Ministry of Science and Innovation (MCIN) (PI19/00954) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdirección General de Evaluación y el Fondos Europeos de la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia_PRTR ); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); and the the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), CERCA Programme / Generalitat de Catalunya as well as the Fundació Clínic per la Recerca Biomèdica (Pons Bartran 2022-FRCB_PB1_2022), Consultant of: ADAMED, Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare, N. Roberto: None Declared, G. Anmella Grant / Research support from: Rio Hortega 2021 grant (CM21/00017) from the Spanish Ministry of Health financed by the Instituto de Salud Carlos III (ISCIII) and co-financed by the Fondo Social Europeo Plus (FSE+), Consultant of: Janssen-Cilag, Lundbeck, Lundbeck/Otsuka, and Angelini, D. Hidalgo-Mazzei Grant / Research support from: Juan Rodés JR18/00021 granted by the Instituto de Salud Carlos III (ISCIII), M. Fornaro: None Declared, A. de Bartolomeis Consultant of: Janssen, Lundbeck, and Otsuka and lecture fees for educational meeting from Chiesi, Lundbeck, Roche, Sunovion, Vitria, Recordati, Angelini and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, and Takeda, Chiesi, Recordati, Angelini, Vitria, A. Serretti Consultant of: Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier, and Taliaz, 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 co-financed 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. Thanks the support of 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), Consultant of: AB-Biotics, AbbVie, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), Consultant of: Angelini, Idorsia, Lundbeck, Pfizer, Takeda

A significant proportion of people attending Primary Care (PC) have anxiety-depressive symptoms and work-related burnout and there is a lack of resources to attend them. The COVID-19 pandemic has worsened this problem, particularly affecting healthcare workers, and digital tools have been proposed as a workaround.

We present the development, feasibility and effectiveness studies of chatbot (Vickybot) aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout in PC patients and healthcare workers.

User-centered development strategies were adopted. Main functions included self-assessments, psychological modules, and emergency alerts. (1) Simulation: HCs used Vickybot for 2 weeks to simulate different possible clinical situations and evaluated their experience. (3) Feasibility and effectiveness study: People consulting PC or healthcare workers with mental health problems were offered to use Vickybot for one month. Self-assessments for anxiety (GAD-7) and depression (PHQ-9) symptoms, and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every two weeks. Feasibility was determined based on the combination of both subjective and objective user-engagement Indicators (UEIs). Effectiveness was measured using paired t-tests as the change in self-assessment scores.

(1) Simulation: 17 HCs (73% female; mean age=36.5±9.7) simulated different clinical situations. 98.8% of the expected modules were recommended according to each simulation. Suicidal alerts were correctly activated and received by the research team. (2) Feasibility and effectiveness study: 34 patients (15 from PC and 19 healthcare workers; 77% female; mean age=35.3±10.1) completed the first self-assessments, with 34 (100%) presenting anxiety symptoms, 32 (94%) depressive symptoms, and 22 (64.7%) work-related burnout. Nine (26.5%) patients completed the second self-assessments after 2-weeks of use. No significant differences were found for anxiety [t(8) = 1.000, p = 0.347] or depressive [t(8) = 0.400, p = 0.700] symptoms, but work-related burnout was significantly reduced [t(8) = 2.874, p = 0.021] between the means of the first and second self-assessments. Vickybot showed high subjective-UEIs, but low objective-UEIs (completion, adherence, compliance, and engagement).

The chatbot proved to be useful in screening the presence and severity of anxiety and depressive symptoms, in reducing work-related burnout, and in detecting suicidal risk. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising, but suggest the need to adapt and enhance the smartphone-based solution in order to improve engagement. Consensus on how to report UEIs and validate digital solutions, especially for chatbots, are required.

None Declared

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.

To examine associations between different mindfulness facets, and different aspects of attention and trait impulsivity in BD.

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.

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.

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.

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.

1. Carvalho AF, Firth J, Vieta E. Bipolar Disorder. N Engl J Med. 2020;383(1):58-66. doi:10.1056/NEJMra1906193

None Declared

Current evidence has hypothesized the involvement of mitochondrial dysfunction during the acute episodes of BD compared to symptomatic remission. So far, no studies have compared mitochondrial and bioenergetic functions both in-vivo (respiratory parameters) and ex-vivo (cellular respiration) in different phases of the disease in the same individuals.

This multidisciplinary pilot study aims at assessing bioenergetic and mitochondrial intra-individual differences between manic and euthymic states.

Four patients with a manic episode admitted to our acute psychiatric ward were recruited. Bioenergetic parameters were measured at admission (T0) and after symptomatic remission (T1).

At admission (T0) and before discharge (T1), HAMD and YMRS total scores were obtained. For the assessment of cellular respiration, polymorphonuclear cells were obtained by a Ficoll density gradient centrifugation procedure. To determine oxygen consumption (at T0 and T1), a million of living peripheral blood mononuclear cells (PBMC) were used. High-resolution respirometry was performed at 37°C by polarographic oxygen sensors in a two-chamber Oxygraph-2k system.

Specific oxygen uptakes (Routine: basal oxygen consumption; Proton Leak: oxygen consumption not coupled to ATP synthesis; and ETC: maximal capacity of the electron transport chain) rates were obtained using mitochondrial chain inhibitors and uncouplers. Oxygen consumption was normalized for protein concentration. Results are expressed as picomoles of oxygen per millilitre (pmol O2/s*μg prot).

Also, a constant work rate exercise test was performed on a cycle ergometer and basal and effort respiratory variables were measured.

Statistical analysis was performed with the SPSS v. 25.0 and GraphPad. Results were expressed as means and SD. Nonparametric tests (Mann–Whitney, Pearson) were used to determine differences (significant at p value <0.05).

One patient was a man and three patients were women, with a mean age of 28 years old. HAMD initial and final mean scores were 11.0 and 7.0, and mean YMRS scores were 21.5 and 7.0 respectively.

Results from mitochondrial oxygen consumption revealed that mean basal oxygen consumption tended to be higher in T1 (0.98±0.45) than in T0, and maximal respiratory capacity was significantly increased in T1 (2.26±0.33; p=0.028) compared to T0.

Mean lactate levels and pH levels were similar in T0 and T1. Scales scores were not correlated to different pH or lactate changes after the effort task. Higher initial oxygen consumption was significantly correlated to higher maximal capacity (p<0.05) in T0 and T1.

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Our preliminary results suggest that mania could imply lower oxygen consumption capacity, which should be confirmed in future studies. A bigger study is planned to determine changes in bioenergetic patterns and capacity for aerobic response in manic and depressive episodes.

None Declared

When completing the medical record of a patient with bipolar disoder (BD), hardly anything is more impacting than a family history of completed suicide (FHS). In fact, FHS is a main risk factor for personal suicide attempts and death in this population. There are few modifiable protective factors against suicide in BD, such as lithium treatment and absence of substance abuse.

We aimed to explore the relationship between a FHS and clinical characteristics in patients with BD. Given the impact that FHS has on the individual and on healthcare professionals, we hypothesized that it would modify behaviors towards a higher prevalence of the modifiable protective factors against suicide, namely more treatment with lithium and less drug addiction.

This is a cross-sectional study that included all patients with BD that were followed up in a specialised unit between 1998 and 2020. Only subjects with complete information on FHS were retained for the analysis. We assessed sociodemographic and clinical data and described it with measures of frequency, central tendency and dispersion. Differences between subjects with and without FHS were calculated with χ², Fisher’s exact test and Student’s t-test as appropriate. We set the significance level at p≤0.05. All tests were two-tailed.

The sample consisted of 480 subjects with a mean age of 45.9 years (standard deviation 14.4, range 18-88), of which 54.4% (n=261) were women. 69.2% (n=332) had a diagnosis of BD type I and 30.8% (n=148) of BD type II. 77 subjects (16%) had a FHS. Regarding differences between groups, those with relatives who had committed suicide did not show statistically significant differences in terms of sociodemographic variables (age, gender, civil status, employment) or key clinical features (type of BD, illness duration, psychotic features, predominant polarity, rapid cycling, number of lifetime manic and depressive episodes, comorbid personality disorder), neither did they have a higher use of lithium (55.8% vs 59.3%, p=0.572) nor lower substance use disorder (10.9% vs 15.5%, p=0.34). Predictably, people with FHS had a higher prevalence of family history of mental and affective disorders (96.1% vs 70.9%, p<0.001; 86.3% vs 56.3%, p<0.001) and of stressful life events (71.6% vs 58.9%, p=0.05). Personal lifetime suicide attempts also tended to be higher (36.4% vs 26.7%, p=0.088).

Contrary to our hypothesis, in our sample of subjects with BD a FHS was not associated with a higher prevalence of the modifiable protective factors against suicide. Therefore, although suicide has a major impact both in families and healthcare professionals, our results suggest it does not modify attitudes towards prevention in a real-life scenario. The main limitation of our study is its cross-sectional design, which does not allow for causal inference. In conclusion, there is room for improvement in the fight against suicide.

None Declared

Cognitive impairment has been commonly found in patients with bipolar disorder (BD).(1) Recent evidence supports the view that global and cognitive functioning decrease as a function of number of prior mood episodes, but the relationship is still not clear. (2)

We conducted a cross-sectional study to explore the associations between the lifetime number of affective episodes and functioning, in particular, cognitive functioning in a cohort of patients with BD.

Adult patients with BD were recruited if euthymic for at least 3 months. Socio-demographic and clinical variables were recollected at the baseline evaluation. Functioning was evaluated at baseline with the functioning assessment short test (FAST). The strength of the association between the lifetime number of affective episodes and FAST subscores was explored with Spearman’s correlation test. Linear regression was computed using cognitive functioning as the dependent variable and a set of clinically relevant variables including the lifetime number of affective episodes as independent variables after controlling for illness duration.

261 BD patients were recruited. Patients with a higher number of lifetime affective episodes showed a significant positive correlation with higher FAST global score (r=0.334, p<0.001) and FAST cognitive functioning subscore (r=0.331, p<0.001). At the linear regression, a higher number of affective episodes was associated to worse cognitive functioning (b=0.037, 95%CI [0.011-0.064], p=0.005).

Poor cognitive functioning in BD could be the result of multiple affective relapses. A timely diagnosis with subsequent effective prophylactic treatment may prevent poor functional outcomes in real-world patients with BD.

None Declared

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.