- Email: [email protected]
P.2.d.043 A naturalistic study of antipsychotic-induced weight gain in bipolar disorder
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P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)
(Sibling–control: time × group F 7,476 = 2.2, p = 0.111) and alphaamylase (Sibling vs. control: time × group interaction F 7,469 = 1.6, p = 0.170) levels as healthy controls, suggesting that genetic predisposition for BD1 did not have a large effect on stress system functionality. In summary, in the current study euthymic BD1 patients had a substantially blunted endocrine stress response and exaggerated autonomic stress response. Antipsychotic use has a profound blunting effect on the cortisol response of BD1 patients, suggesting that the blunted cortisol response may be the result of antipsychotic use rather than constitute a specific BD1 phenotype. References [1] Bender, R.E., Alloy, L.B., 2011. Life stress and kindling in bipolar disorder: review of the evidence and integration with emerging biopsychosocial theories. Clin Psychol Rev 31, 383–398. [2] Cervantes, P., Gelber, S., Kin, F.N., Nair, V.N., Schwartz, G., 2001. Circadian secretion of cortisol in bipolar disorder. J Psychiatry Neurosci. 26, 411–416. [3] Lake, C.R., Pickar, D., Ziegler, M.G., Lipper, S., Slater, S., Murphy, D.L., 1982. High plasma norepinephrine levels in patients with major affective disorder. Am J Psychiatry. 139, 1315–1318.
P.2.d.042 Identification and semi-quantification of potential biomarkers for bipolar disorder with a novel mass spectrometric methodology
controls. The results are based on four different technical replicates of LC-MS runs. Among these 37 proteins, there are several proteins involved in CNS processes as e.g. neurite outgrowth, synaptic plasticity and neurotransmitter release, and some of them have previously been implicated in neuropsychiatric disorders. A few examples [fold change (FC) is reported as the ratio between the BP1 patients and the controls] are: Cadherin 13 (p = 0.005, FC = 0.82), Neuronal pentraxin receptor (p = 0.015, FC = 0.81), Voltage-dependent calcium channel subunit alpha-2/delta-1 (p = 0.015, FC = 0.88), SLIT- and NTRK-like protein 1 (p = 0.015, FC = 0.87), Ly-6/neurotoxin-like protein (p = 0.023, FC = 0.89) and Chromogranin A (p = 0.029, FC = 0.84). Patients with type 1 BP disorder have decreased CSF levels of these proteins as compared to controls. The findings in this study will be followed up and validated in larger patient cohorts by additional TMT semiquantitative studies but also with immunoassays and a targeted MS method called selected reaction monitoring (SRM). Conclusions: The results from this study clearly demonstrate that this approach is promising in order to find relevant biomarkers for BD. A panel of biological markers would be very helpful in the diagnostic assessment of patients and to predict and evaluate treatment responses.
P.2.d.043 A naturalistic study of antipsychotic-induced weight gain in bipolar disorder
J. Holm´en Larsson1 ° , J. Gobom1 , J. Jakobsson1 , M. H¨oltt¨a1 , K. Blennow1 , H. Zetterberg1 , M. Land´en1 1 University of Gothenburg, Institute of Neurosence and Physiology, G¨oteborg, Sweden
H. Najar1 ° , E. Palsson1 , M. Land´en1 1 University of Gothenburg, Psychiatry and neurochemistry, G¨oteborg, Sweden
Aims and purpose: There is a great need for expanding our knowledge on molecular mechanisms that underlie common neuropsychiatric disorders as Bipolar disorder (BD) and to find new biological markers, biomarkers, for disease diagnosis and for monitoring the effects of therapies. One valuable source for biomarkers is cerebrospinal fluid (CSF), as it is in close contact with the CNS and contains large numbers of endogenous proteins with great potential value as biomarkers. In the search for new potential biomarkers in CSF from BD patients, we have developed a new sensitive exploratory proteome-wide approach (proteomics) based on high-resolution liquid chromatography-mass spectrometry (LCMS) combined with Tandem Mass Tag (TMT) labeling, enabling a multiplexed semi-quantification approach. No previous semiquantitative proteome-wide studies on CSF have been performed in BD, giving this study a unique scope. Methodology: LC-MS analysis was performed on a Q-Exactive instrument with Orbitrap detection and the combination with stable isotope labeling of proteins has greatly improved the ability to perform quantitative proteomic analyses of hundreds of endogenous proteins in small quantities of biological samples (50 ul CSF) in a single experiment. Six different isobaric TMT reagents (TMT 6-plex), each with a unique reporter mass, are utilized and this makes it possible to multiplex the analysis. A pool of all samples in the study is used as a comparative control in every sample set (5 samples + 1 pool) for the semi-quantification. To prepare the protein samples, we use tryptic digestion to cleave the proteins into shorter peptides and this methodology has now been employed on a CSF patient material from 15 bipolar type 1 (BP1) patients and 15 controls (Ctrls). Results: In this exploratory proteome-wide study we identified 37 proteins that show significantly (Mann–Whitney test, p < 0.05) different CSF protein levels in the BD patients as compared to
Purpose: Mood stabilizers such as lithium or valproic acid are the first line of treatment in bipolar disorder. However, a significant proportion of patients are also treated with atypical antipsychotics. Both mood stabilizer and atypical antipsychotics can induce weight gain as a side effect [1]. This contributes to poor health in the afflicted individuals and jeopardizes adherence to treatment. However not all patients experience adverse metabolic side effects when treated with antipsychotic medication. Further, little is known about the interactive effects of mood stabilizers and atypical antipsychotics on weight gain in clinical practice. Our aim was to investigate how weight gain is affected by atypical antipsychotics, when used as an add-on treatment to a mood stabilizer, in everyday clinical practice. Methods: We collected patient data from the national quality register for bipolar disorder in Sweden. Patients in the register who began add-on treatment with atypical antipsychotics between two yearly follow-up visits were included. We excluded cases with a diagnosis of schizoaffective disorder, age <18 years, treatment with typical antipsychotics or missing BMI data. Further, we added a reference group matched for age and sex and only treated with a mood stabilizer. The final analysis included 1180 patients with 575 patients in the group receiving treatment with atypical antipsychotics and 605 patients in the reference group. The primary outcome measure was change in body weight measured either as absolute weight or BMI (body mass index) between the two yearly visits. As a secondary outcome measure the prevalence of clinically significant weight gain, defined as 7% gain in body weight [2], was also analyzed. We also evaluated the effect of different confounders including age, sex, starting BMI, total number of mood episodes, subdiagnosis, global assessment of functioning (GAF) score, treatment with antidepressants and previous treatment with antipsychotics on weight gain in the two groups.
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical) Results: There was no difference in weight gain measured either as absolute weight (p = 0.69) or BMI (p = 0.53) between the group treated with atypical antipsychotics and the reference group. 18.1% of patients receiving atypical antipsychotics as an add on treatment had a clinically significant weight gain compared to 11.4% in the reference group. This difference was statistically significant (p = 0.001) with an odds ratio of 1.7. The effect remained statistically significant when controlling for potential confounders (p = 0.020, odds ratio 1.5). Furthermore, patients with a clinically significant weight gain were younger [2], had lower baseline BMI [2], had more mood episodes and were more likely to also self-report an increase in body weight as a side effect (5.6% compared to 2.1%). Conclusions: Our findings suggest that add-on treatment with atypical antipsychotics in patients with bipolar disorder is not associated with weight gain. Add-on treatment was associated with a modest increase in the risk of gaining clinically significant weight. Although no general effect of antipsychotics was found further studies are needed to identify risk factors such as genetic variation that could help identify vulnerable patients to avoid treatment with antipsychotics or to allocate more resources to prevent weight gain. References [1] Torrent C, Amann B, Sanchez-Moreno J, Colom F, Reinares M, Comes M, Rosa AR., Scott J, Vieta E. Weight gain in bipolar disorder: pharmacological treatment as a contributing factor. Acta Psychiatr Scand 2008: 118: 4−18. [2] Kinon BJ, Kaiser CJ, Ahmed S, Rotelli MD, Kollack-Walker S. Association between early and rapid weight gain and change in weight over one year of olanzapine therapy in patients with schizophrenia and related disorders. J Clin Psychopharmacol 2005; 25: 255–258.
P.2.d.044 Functional remediation in bipolar disorder: results of the one-year follow-up C. Torrent1 ° , C.M. Bonnin2 , A. Martinez-Aran2 , C. Arango3 , B.L. Amann4 , B. Sol´e2 , A. Gonz´alez-Pinto5 , J.M. Crespo6 , R. Tabar´es-Seisdedos7 , M. Reinares8 , J. Valle9 , P. GarciaPortilla10 , A. Iba˜nez11 , E. Vieta8 1 Clinical Institute of Neuroscience, IDIBAPS CIBERSAM. ENBREC Bipolar Disorders Program, Barcelona, Spain; 2 Clinical Institute of Neuroscience, IDIBAPS, Bipolar Disorders Program, Barcelona, Spain; 3 Gregorio Mara˜ no´ n University General Hospital, Health Research Institute (IISGM) CIBERSAM, Madrid, Spain; 4 FIDMAG Hermanas Hospitalarias Research Foundation ´ CIBERSAM Barcelona Spain, Barcelona, Spain; 5 Alava University Hospital CIBERSAM, University of the Basque Country Kronikgune, Vitoria, Spain; 6 Department of Psychiatry University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL) CIBERSAM, Barcelona, Spain; 7 University of Valencia CIBERSAM, Deaptment of medicine, Valencia, Spain; 8 Clinical Institute of Neuroscience, IDIBAPS, CIBERSAM, Bipolar Disorders Program, Barcelona, Spain; 9 Autonomous University of Madrid Research Institute of the Hospital de la Princesa CIBERSAM, Department of psychiatry, Madrid, Spain; 10 University of Oviedo. CIBERSAM, Department of psychiatry, Oviedo, Spain; 11 Ramon y Cajal Hospital Ramon y Cajal Institute of Health Research (IRYCIS) CIBERSAM, Department of psychiatry, Madrid, Spain Purpose of the study: Functional impairment among bipolar patients is very frequent even during periods of clinical remis-
S439
sion [1]. Longitudinal reports confirm that cognitive and psychosocial functioning are correlated with each other [2]. Interventions in order to improve cognitive and psychosocial impairment are needed. A recent multicentre, randomized, controlled trial confirmed the short-term efficacy of a novel group intervention, named functional remediation, by improving the functional outcome of bipolar I and II patients [3]. To date, no long-term data of the efficacy of a psychosocial intervention in affective disorders exists. This study aims to report whether the positive effects of the above mentioned functional remediation intervention were maintained on long-term as well. Methods: This is the continuation study of a published randomized clinical trial. 239 euthymic bipolar I and II patients were recruited at baseline in this multi-centre study. Subjets had age between 18−55 years and presented with a moderate to severe degree of functional impairment. Excluded were patients with an IQ<85, any medical and comorbid psychiatric disturbance condition affecting neuropsychological performance or having received electroconvulsive therapy within the past year. At baseline and at one year follow-up patients were evaluated with the following symptom rating scales: Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D). The Functioning Assessment Short Test (FAST), was used to assess psychosocial functioning, the primary outcome of the study. All patients completed at baseline and follow-up a comprehensive neuropsychological battery grouped into six cognitive domains: estimated IQ, processing speed index, executive functions, visual and verbal memory, working memory index and attention. Composite scores for verbal memory and executive functions were calculated by converting the subject’s raw score to standard z-scores. Repeated measures analyses of covariance (MANCOVAs) were employed to analyse the longitudinal changes on the primary efficacy outcome. Results: Of 239 patients at baseline, 174 completed the followup phase (72%). The baseline and follow-up group did not differ on demographic and clinical data. Longitudinal repeated-measures analyses addressing the treatment effect on the primary outcome measure showed significant differences between groups (Pillai’s Trace = 0.032; F = 3.071; df = 2; p = 0.049), suggesting that the effect of the intervention is maintained over time. When analyzing each of the domains of functioning in detail, only one of six domains was found to be significantly different between groups, this domain is autonomy (F = 5.54, df = 2, p = 0.005). Concerning neuropsychological performance, repeated-measures analyses showed one trend toward improvement in memory (composite verbal memory) in patients who where enrolled in the functional remediation group. Conclusions: The main finding of the study is the confirmation that the effectiveness of functional remediation remained over time, furthermore a significant enhancement in autonomy was observed. Longer follow-up studies are needed to confirm the results and to evaluate whether or not the inclusion of some regular booster sessions to keep the effect of the intervention at a longer term. References [1] Sanchez-Moreno J, Martinez-Aran A, Tabar´es-Seisdedos et al., 2009. Functioning and disability in bipolar disorder. Psychother Psychosom 78, 285–297. [2] Bonnin CM, Martinez-Aran A, Torrent C et al., 2010. Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term follow-up study. J Affect Disord 121, 156–160. [3] Torrent C, Bonnin CM, Martinez-Aran A et al., 2013. Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study. Am J Psychiatry, 170: 852–859.
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)
(Sibling–control: time × group F 7,476 = 2.2, p = 0.111) and alphaamylase (Sibling vs. control: time × group interaction F 7,469 = 1.6, p = 0.170) levels as healthy controls, suggesting that genetic predisposition for BD1 did not have a large effect on stress system functionality. In summary, in the current study euthymic BD1 patients had a substantially blunted endocrine stress response and exaggerated autonomic stress response. Antipsychotic use has a profound blunting effect on the cortisol response of BD1 patients, suggesting that the blunted cortisol response may be the result of antipsychotic use rather than constitute a specific BD1 phenotype. References [1] Bender, R.E., Alloy, L.B., 2011. Life stress and kindling in bipolar disorder: review of the evidence and integration with emerging biopsychosocial theories. Clin Psychol Rev 31, 383–398. [2] Cervantes, P., Gelber, S., Kin, F.N., Nair, V.N., Schwartz, G., 2001. Circadian secretion of cortisol in bipolar disorder. J Psychiatry Neurosci. 26, 411–416. [3] Lake, C.R., Pickar, D., Ziegler, M.G., Lipper, S., Slater, S., Murphy, D.L., 1982. High plasma norepinephrine levels in patients with major affective disorder. Am J Psychiatry. 139, 1315–1318.
P.2.d.042 Identification and semi-quantification of potential biomarkers for bipolar disorder with a novel mass spectrometric methodology
controls. The results are based on four different technical replicates of LC-MS runs. Among these 37 proteins, there are several proteins involved in CNS processes as e.g. neurite outgrowth, synaptic plasticity and neurotransmitter release, and some of them have previously been implicated in neuropsychiatric disorders. A few examples [fold change (FC) is reported as the ratio between the BP1 patients and the controls] are: Cadherin 13 (p = 0.005, FC = 0.82), Neuronal pentraxin receptor (p = 0.015, FC = 0.81), Voltage-dependent calcium channel subunit alpha-2/delta-1 (p = 0.015, FC = 0.88), SLIT- and NTRK-like protein 1 (p = 0.015, FC = 0.87), Ly-6/neurotoxin-like protein (p = 0.023, FC = 0.89) and Chromogranin A (p = 0.029, FC = 0.84). Patients with type 1 BP disorder have decreased CSF levels of these proteins as compared to controls. The findings in this study will be followed up and validated in larger patient cohorts by additional TMT semiquantitative studies but also with immunoassays and a targeted MS method called selected reaction monitoring (SRM). Conclusions: The results from this study clearly demonstrate that this approach is promising in order to find relevant biomarkers for BD. A panel of biological markers would be very helpful in the diagnostic assessment of patients and to predict and evaluate treatment responses.
P.2.d.043 A naturalistic study of antipsychotic-induced weight gain in bipolar disorder
J. Holm´en Larsson1 ° , J. Gobom1 , J. Jakobsson1 , M. H¨oltt¨a1 , K. Blennow1 , H. Zetterberg1 , M. Land´en1 1 University of Gothenburg, Institute of Neurosence and Physiology, G¨oteborg, Sweden
H. Najar1 ° , E. Palsson1 , M. Land´en1 1 University of Gothenburg, Psychiatry and neurochemistry, G¨oteborg, Sweden
Aims and purpose: There is a great need for expanding our knowledge on molecular mechanisms that underlie common neuropsychiatric disorders as Bipolar disorder (BD) and to find new biological markers, biomarkers, for disease diagnosis and for monitoring the effects of therapies. One valuable source for biomarkers is cerebrospinal fluid (CSF), as it is in close contact with the CNS and contains large numbers of endogenous proteins with great potential value as biomarkers. In the search for new potential biomarkers in CSF from BD patients, we have developed a new sensitive exploratory proteome-wide approach (proteomics) based on high-resolution liquid chromatography-mass spectrometry (LCMS) combined with Tandem Mass Tag (TMT) labeling, enabling a multiplexed semi-quantification approach. No previous semiquantitative proteome-wide studies on CSF have been performed in BD, giving this study a unique scope. Methodology: LC-MS analysis was performed on a Q-Exactive instrument with Orbitrap detection and the combination with stable isotope labeling of proteins has greatly improved the ability to perform quantitative proteomic analyses of hundreds of endogenous proteins in small quantities of biological samples (50 ul CSF) in a single experiment. Six different isobaric TMT reagents (TMT 6-plex), each with a unique reporter mass, are utilized and this makes it possible to multiplex the analysis. A pool of all samples in the study is used as a comparative control in every sample set (5 samples + 1 pool) for the semi-quantification. To prepare the protein samples, we use tryptic digestion to cleave the proteins into shorter peptides and this methodology has now been employed on a CSF patient material from 15 bipolar type 1 (BP1) patients and 15 controls (Ctrls). Results: In this exploratory proteome-wide study we identified 37 proteins that show significantly (Mann–Whitney test, p < 0.05) different CSF protein levels in the BD patients as compared to
Purpose: Mood stabilizers such as lithium or valproic acid are the first line of treatment in bipolar disorder. However, a significant proportion of patients are also treated with atypical antipsychotics. Both mood stabilizer and atypical antipsychotics can induce weight gain as a side effect [1]. This contributes to poor health in the afflicted individuals and jeopardizes adherence to treatment. However not all patients experience adverse metabolic side effects when treated with antipsychotic medication. Further, little is known about the interactive effects of mood stabilizers and atypical antipsychotics on weight gain in clinical practice. Our aim was to investigate how weight gain is affected by atypical antipsychotics, when used as an add-on treatment to a mood stabilizer, in everyday clinical practice. Methods: We collected patient data from the national quality register for bipolar disorder in Sweden. Patients in the register who began add-on treatment with atypical antipsychotics between two yearly follow-up visits were included. We excluded cases with a diagnosis of schizoaffective disorder, age <18 years, treatment with typical antipsychotics or missing BMI data. Further, we added a reference group matched for age and sex and only treated with a mood stabilizer. The final analysis included 1180 patients with 575 patients in the group receiving treatment with atypical antipsychotics and 605 patients in the reference group. The primary outcome measure was change in body weight measured either as absolute weight or BMI (body mass index) between the two yearly visits. As a secondary outcome measure the prevalence of clinically significant weight gain, defined as 7% gain in body weight [2], was also analyzed. We also evaluated the effect of different confounders including age, sex, starting BMI, total number of mood episodes, subdiagnosis, global assessment of functioning (GAF) score, treatment with antidepressants and previous treatment with antipsychotics on weight gain in the two groups.
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical) Results: There was no difference in weight gain measured either as absolute weight (p = 0.69) or BMI (p = 0.53) between the group treated with atypical antipsychotics and the reference group. 18.1% of patients receiving atypical antipsychotics as an add on treatment had a clinically significant weight gain compared to 11.4% in the reference group. This difference was statistically significant (p = 0.001) with an odds ratio of 1.7. The effect remained statistically significant when controlling for potential confounders (p = 0.020, odds ratio 1.5). Furthermore, patients with a clinically significant weight gain were younger [2], had lower baseline BMI [2], had more mood episodes and were more likely to also self-report an increase in body weight as a side effect (5.6% compared to 2.1%). Conclusions: Our findings suggest that add-on treatment with atypical antipsychotics in patients with bipolar disorder is not associated with weight gain. Add-on treatment was associated with a modest increase in the risk of gaining clinically significant weight. Although no general effect of antipsychotics was found further studies are needed to identify risk factors such as genetic variation that could help identify vulnerable patients to avoid treatment with antipsychotics or to allocate more resources to prevent weight gain. References [1] Torrent C, Amann B, Sanchez-Moreno J, Colom F, Reinares M, Comes M, Rosa AR., Scott J, Vieta E. Weight gain in bipolar disorder: pharmacological treatment as a contributing factor. Acta Psychiatr Scand 2008: 118: 4−18. [2] Kinon BJ, Kaiser CJ, Ahmed S, Rotelli MD, Kollack-Walker S. Association between early and rapid weight gain and change in weight over one year of olanzapine therapy in patients with schizophrenia and related disorders. J Clin Psychopharmacol 2005; 25: 255–258.
P.2.d.044 Functional remediation in bipolar disorder: results of the one-year follow-up C. Torrent1 ° , C.M. Bonnin2 , A. Martinez-Aran2 , C. Arango3 , B.L. Amann4 , B. Sol´e2 , A. Gonz´alez-Pinto5 , J.M. Crespo6 , R. Tabar´es-Seisdedos7 , M. Reinares8 , J. Valle9 , P. GarciaPortilla10 , A. Iba˜nez11 , E. Vieta8 1 Clinical Institute of Neuroscience, IDIBAPS CIBERSAM. ENBREC Bipolar Disorders Program, Barcelona, Spain; 2 Clinical Institute of Neuroscience, IDIBAPS, Bipolar Disorders Program, Barcelona, Spain; 3 Gregorio Mara˜ no´ n University General Hospital, Health Research Institute (IISGM) CIBERSAM, Madrid, Spain; 4 FIDMAG Hermanas Hospitalarias Research Foundation ´ CIBERSAM Barcelona Spain, Barcelona, Spain; 5 Alava University Hospital CIBERSAM, University of the Basque Country Kronikgune, Vitoria, Spain; 6 Department of Psychiatry University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL) CIBERSAM, Barcelona, Spain; 7 University of Valencia CIBERSAM, Deaptment of medicine, Valencia, Spain; 8 Clinical Institute of Neuroscience, IDIBAPS, CIBERSAM, Bipolar Disorders Program, Barcelona, Spain; 9 Autonomous University of Madrid Research Institute of the Hospital de la Princesa CIBERSAM, Department of psychiatry, Madrid, Spain; 10 University of Oviedo. CIBERSAM, Department of psychiatry, Oviedo, Spain; 11 Ramon y Cajal Hospital Ramon y Cajal Institute of Health Research (IRYCIS) CIBERSAM, Department of psychiatry, Madrid, Spain Purpose of the study: Functional impairment among bipolar patients is very frequent even during periods of clinical remis-
S439
sion [1]. Longitudinal reports confirm that cognitive and psychosocial functioning are correlated with each other [2]. Interventions in order to improve cognitive and psychosocial impairment are needed. A recent multicentre, randomized, controlled trial confirmed the short-term efficacy of a novel group intervention, named functional remediation, by improving the functional outcome of bipolar I and II patients [3]. To date, no long-term data of the efficacy of a psychosocial intervention in affective disorders exists. This study aims to report whether the positive effects of the above mentioned functional remediation intervention were maintained on long-term as well. Methods: This is the continuation study of a published randomized clinical trial. 239 euthymic bipolar I and II patients were recruited at baseline in this multi-centre study. Subjets had age between 18−55 years and presented with a moderate to severe degree of functional impairment. Excluded were patients with an IQ<85, any medical and comorbid psychiatric disturbance condition affecting neuropsychological performance or having received electroconvulsive therapy within the past year. At baseline and at one year follow-up patients were evaluated with the following symptom rating scales: Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D). The Functioning Assessment Short Test (FAST), was used to assess psychosocial functioning, the primary outcome of the study. All patients completed at baseline and follow-up a comprehensive neuropsychological battery grouped into six cognitive domains: estimated IQ, processing speed index, executive functions, visual and verbal memory, working memory index and attention. Composite scores for verbal memory and executive functions were calculated by converting the subject’s raw score to standard z-scores. Repeated measures analyses of covariance (MANCOVAs) were employed to analyse the longitudinal changes on the primary efficacy outcome. Results: Of 239 patients at baseline, 174 completed the followup phase (72%). The baseline and follow-up group did not differ on demographic and clinical data. Longitudinal repeated-measures analyses addressing the treatment effect on the primary outcome measure showed significant differences between groups (Pillai’s Trace = 0.032; F = 3.071; df = 2; p = 0.049), suggesting that the effect of the intervention is maintained over time. When analyzing each of the domains of functioning in detail, only one of six domains was found to be significantly different between groups, this domain is autonomy (F = 5.54, df = 2, p = 0.005). Concerning neuropsychological performance, repeated-measures analyses showed one trend toward improvement in memory (composite verbal memory) in patients who where enrolled in the functional remediation group. Conclusions: The main finding of the study is the confirmation that the effectiveness of functional remediation remained over time, furthermore a significant enhancement in autonomy was observed. Longer follow-up studies are needed to confirm the results and to evaluate whether or not the inclusion of some regular booster sessions to keep the effect of the intervention at a longer term. References [1] Sanchez-Moreno J, Martinez-Aran A, Tabar´es-Seisdedos et al., 2009. Functioning and disability in bipolar disorder. Psychother Psychosom 78, 285–297. [2] Bonnin CM, Martinez-Aran A, Torrent C et al., 2010. Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term follow-up study. J Affect Disord 121, 156–160. [3] Torrent C, Bonnin CM, Martinez-Aran A et al., 2013. Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study. Am J Psychiatry, 170: 852–859.