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Lockdown caused by COVID-19 pandemic has a negative impact on mental health. The aim was to assess self-reported neurocognitive symptoms during the lockdown and identify associated vulnerable and protective factors in a sample of psychiatric patients in a Spanish population. These results are part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Neurocognitive symptoms were assessed through an online survey considering the five items that represented self-reported neurocognitive complaints. We split the sample into two groups based on the severity of the self-reported neurocognitive complaints: intact cognitive function/mild cognitive impairment (CI-) and moderate/severe cognitive impairment (CI+). Univariate analyses were used to compare both groups in terms of sociodemographic and clinical variables. Multiple logistic regression models were carried out to identify clinical variables and coping strategies associated with neurocognitive symptoms. 198 patients with different psychiatric diagnoses were included in this study. One hundred seventeen patients were classified in the CI- group and 81 in the CI+ group. Depressive symptoms and negative psychotic-like symptoms were vulnerable factors for neurocognitive impairment. Coping strategies of performing physical activity, carrying out relaxing activities and maintaining a routine were protective factors against cognitive impairment. Lockdown situation negatively impact on neurocognitive function. Psychopathological symptoms and coping strategies were associated with neurocognitive symptoms during lockdown in subjects with psychiatric illness. The early treatment of psychopathological symptoms in psychiatric patients and promoting coping strategies during lockdown should be considered an intervention strategy against cognitive impairment.

Background The efficacy of adjunctive group psychoeducation in bipolar disorder has been proven although treatment response differ among individuals. The aim of this study was to characterize responders and non-responders to group psychoeducation in order to identify baseline variables that could predict treatment response. Methods The sample was composed of 103 medicated euthymic patients with bipolar disorder referred to 21 sessions of group psychoeducation (6 months). Sociodemographic and clinical variables, temperament, circadian rhythms, BDNF, cognitive and psychosocial functioning were collected. At the 18-month endpoint, the patients were split in two groups on the basis of having suffered any recurrence. Significant group differences were included in a logistic regression analysis. Results Ninety patients out of 103 engaged in group psychoeducation, 47 of whom (52.2%) responded to psychoeducation and 43 (47.8%) did not. Recurrences occurred more often in the follow-up, the most common being depression. Responders and non-responders differed in gender, age at diagnosis, latency of diagnosis, temperament, attention composite score and BDNF. Lower age at diagnosis of bipolar disorder, lower cyclothimic temperament scores and being male -which was associated with bipolar type I and a trend to more previous manic episodes- were significantly related to a better response to psychoeducation in the regression analysis. Limitations No control group. Conclusions This study identifies age at diagnosis as a significant modifiable risk factor of treatment response, highlighting the need for early identification of bipolar disorder. Existing programs should be adjusted to the characteristics of specific subpopulations in the framework of a personalized approach.

Introduction Bipolar disorder is related to a high level of personal, familial, social and economic burden. There is a need for feasible adjunctive psychological interventions easy to implement in clinical practice in order to enhance aspects that medication alone cannot achieve. This study aims to evaluate the impact of a 12-session adjunctive integrative program designed for patients with bipolar disorder. Methods This is a single-blind prospective, randomized controlled trial involving a total of 132 outpatients with bipolar disorder who will be recruited from the Hospital Clinic of Barcelona. All participants will be randomly assigned to two arms. All the patients will receive treatment as usual (TAU) but in addition the experimental group will receive an integrative approach consisting of 12-sessions of 90 min each in which contents of psychoeducation for patients have been combined with a session for family members, and complemented with aspects related to health promotion, mindfulness training, and strategies for cognitive and functional enhancement. The whole sample will be assessed at baseline, after completion (3-months) and at 12 months from baseline regarding demographic and clinical variables, psychosocial and cognitive functioning, wellbeing and quality of life. The primary outcome measure will be improvement in psychosocial functioning. Conclusions If the integrative approach is effective, it would allow clinicians to cover different areas that may be affected by bipolar disorder, by means of a brief intervention that can therefore be easily generalized to clinical practice. Trial registration NCT04031560 . Date registered July 24, 2019.

The main aim of this study is to evaluate the impact of functional remediation (FR) in serum brain derived neurotrophic factor (BDNF) levels in euthymic adult patients with Bipolar Disorder (BD). A total of 128 participants were recruited at the Hospital Clinic of Barcelona. They were assessed at baseline and at the end of follow-up by the means of Hamilton Depression Scale (HAM-D), Young Mania Rating Scale (YMRS) and Functioning Assessment Short Test (FAST), as well as a clinical structured interview to collect clinical and demographic variables of interest. Blood samples were also collected to assess BDNF levels. After baseline assessment, patients received FR, Psychoeducation or treatment as usual (TAU). One hundred and two out of 126 participants finished the study distributed as follows: FR group (n = 39); Psychoeducation group (n = 47) and TAU group (n = 16). Longitudinal repeated-measures analyses addressing the treatment effect on BDNF levels showed non-significant differences between the three groups (Pillai's trace = 0.06; F(2,97)= 0.28; p = 0.75), suggesting no interaction between treatment allocation and time on BDNF levels. The results of this study suggest that FR has no effect on peripheral BDNF levels in euthymic patients with BD, despite the improvement in psychosocial functioning.

Background Offspring of patients diagnosed with bipolar disorder and schizophrenia (Off-BDSZ) have a high genetic risk of developing a mental illness. The aim of this project is to develop and investigate the efficacy of an intervention aimed at this population, based on the concept of cognitive reserve. Methods This is a multicenter randomized trial with an experimental test–retest design study with control group. Two groups will be included: a community comparison group (CC) and a Off-BDSZ group. A total of 108 Off-BDSZ and 65 CC aged between 6 and 25 years will be recruited. Off-BDSZ participants will be randomized to receive either Cognitive Reserve EnhAncement ThErapy (CREATE) (n = 54), or a supportive approach (n = 54). The CC group will be assessed at baseline. The duration of the intervention will be 3 months, with 12 weekly group sessions. The primary outcome will be the improvement in CR measured according to change in the Cognitive Reserve Assessment Scale in Health (CRASH) and Cognitive Reserve scale for Adolescents (CORE-A). All participants will be blindly evaluated using clinical, cognitive and neuroimaging measures at baseline, at three months (after the psychological intervention), and at twelve-month follow-up after treatment completion. Discussion The results will provide insight into whether the CREATE-Offspring version may enhance cognitive reserve (CR) in child, adolescent and young adult Off-BDSZ as well as advance knowledge about changes in clinical manifestations, neuropsychological performance and brain structure and function associated with improving CR. This novel and cost-effective intervention represents an advance in the framework of preventive interventions in mental health. Trial registration Clinicaltrials.gov, NCT03722082 . Registered on 26 October 2018.

Highlights • Survey comparing data from community controls and psychiatric illnesses. • Lockdown had a higher psychological impact in psychiatric patients. • Patients with depression or anxiety symptoms reported more psychological distress. • Psychiatric patients used less adaptive copings strategies to face the lockdown., Background : The aim of this study was to evaluate potential differences about the effects of the COVID-19 pandemic and lockdown between community controls (CC) and patients with a mental illness (MI) in a Spanish population during the state of emergency. Methods : Individuals with a psychiatric condition and the general population were invited to complete an anonymous online survey. Bivariate analyses were used to compare them in a broad range of measures: sociodemographic, clinical variables, behavioral changes related to the lockdown and coping strategies to face it. Two groups of different psychiatric disorders were compared: depression or anxiety disorders (D+A) versus bipolar disorder and schizophrenia related disorders (BD+SCZ). Results : 413 CC and 206 MI were included in the study. CC reported to use more adaptive coping strategies as following a routine, talking to friends/relatives, practicing physical exercise and maintaining a balanced diet. MI reported significantly more anxiety and depression symptoms during the lockdown when compared to CC. Gaining weight, sleep changes, and tobacco consumption were more prevalent in the MI group. The D+A group showed significantly more psychological distress and negative expectations about the future, suffered more sleep disturbances when compared to BD+SCZ, whilst reported to practice more exercise. Limitations : psychiatric disorders were self-reported. Conclusions : Imposed restrictions and uncertainty during confinement had a higher psychological impact in individuals with a psychiatric illness, with less healthy behavior strategies to face the situation. Developing interventions to mitigate negative mental health outcomes among this vulnerable population will be essential in the coming months.

Clinical and epidemiological research suggests that behavioral addictions (BA) are associated with a wide range of psychiatric disorders. However, the relationship between BA and bipolar disorders (BD) has not been thoroughly explored. The aim of this systematic review was to critically summarize and evaluate the current available evidence regarding a possible association between BA and BD. A systematic review of major electronic databases according to PRISMA guidelines was conducted from inception to 31st December 2017. We sought quantitative studies data concerning prevalence of comorbidity, features and treatment related to BA-BD comorbidity. Data were narratively synthesized. Of the 1250 studies returned from the search, a total of 28 articles were included in this review. BA may be overrepresented in BD samples, and the other way around. Pathological gambling and kleptomania were the most prevalent conditions followed by compulsive buying, compulsive sexual behavior and internet addiction. BA was also associated with other mood disorders, anxiety disorders and substance use disorder. BD-BA comorbidity was related with more severe course of illness. Studies on treatment strategies for BD–BA comorbidity are rather limited; only one randomized controlled trial that fulfilled inclusion criteria was identified. Methodological heterogeneity in terms of design and results among studies was found. BD-BA commonly co-occurs although there is a need for rigorous studies. Routine screening and adequate assessment may be helpful in BD patients to identify individuals at risk for BA and to effectively manage the complex consequences associated with BA-BD comorbidity.

It is well established that patients with either bipolar disorder (BD) or attention-deficit/hyperactivity disorder (ADHD) present functional impairment even when in remission. Nevertheless, research on functional impairment with adult patients with bipolar disorder comorbid to ADHD (BD+ADHD) is very scarce. The main objective of the current report was to evaluate the overall and specific domains of functioning, in patients with BD+ADHD compared to patients with pure bipolar disorder (pBD) and healthy controls (HCs).162 subjects from 3 groups were compared: 63 pBD, 23 BD+ADHD and 76 HCs. All the patients with BD had been euthymic for at least 6 months and they were recruited at the Hospital Clinic of Barcelona. All the participants were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical, and sociodemographic data were also recorded.Clinical groups, pBD and BD+ADHD, showed lower overall functioning (p0.001) in each domain of the FAST scale compared to the HCs. Moreover, the Tukey post hoc test revealed that the BD+ADHD group showed a worse score than pBD in the cognitive domain of the FAST. However, after controlling for potential confounding variables, only the HDRS scores (p0.026) remained significant for the cognitive domain of the FAST.The small sample size of the comorbid BD+ADHD group.Adult patients with BD+ADHD showed the worst scores in functioning compared with the HCs, but did not show more severe functional impairment than the pBD group except for the cognitive domain. Therefore our findings suggest that depressive symptoms in adults with BD+ADHD may negatively influence cognitive functioning. Further studies are needed to confirm our findings for the management of BD+ADHD.

Background The present study aims to characterize emotional intelligence (EI) variability in a sample of euthymic bipolar disorder (BD) patients through the Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT). Method A total of 134 euthymic BD outpatients were recruited and divided into three groups according to the total Emotional Intelligence Quotient (EIQ) score of the MSCEIT, following a statistical criterion of scores 1.5 SDs above/below the normative group mean, as follows: a low performance (LP) group (EIQ 115). Afterwards, main sociodemographic, clinical, functional and neurocognitive variables were compared between the groups. Results Three groups were identified: 1) LP group (n=16, 12% ), 2) NP group (n=93, 69% ) and 3) HP group (n=25, 19% ). There were significant differences between the groups in premorbid intelligence quotient (IQ) (p=0.010), axis II comorbidity (p=0.008), subthreshold depressive symptoms (p=0.027), general functioning (p=0.013) and in four specific functional domains: autonomy, occupation, interpersonal relations and leisure time. Significant differences in neurocognitive performance were found between groups with the LP group showing the lowest attainments. Limitations The cross-sectional design of the study. Conclusion Our results suggest that EI variability among BD patients, assessed through MSCEIT, is lower than expected. EI could be associated with premorbid IQ, subthreshold depressive symptoms, neurocognitive performance and general functioning. The identification of different profiles of SC may help guide specific interventions for distinct patient subgroups aimed at improving social cognition, neurocognitive performance and psychosocial functioning.

In the paraventricular nucleus of the mammalian hypothalamus, hypophysiotropic thyrotropin releasing hormone (TRH) neurons integrate metabolic information and control the activity of the thyroid axis. Additional populations of TRH neurons reside in various hypothalamic areas, with poorly defined connections and functions, albeit there is evidence that some may be related to energy balance. To establish extracellular modulators of TRH hypothalamic neurons activity, we performed a screen of neurotransmitters effects in hypothalamic cultures. Cell culture conditions were chosen to facilitate the full differentiation of the TRH neurons; these conditions had permitted the characterization of the effects of known modulators of hypophysiotropic TRH neurons. The major end-point of the screen was Trh mRNA levels, since they are generally rapidly (0.5-3h) modified by synaptic inputs onto TRH neurons; in some experiments, TRH cell content or release was also analyzed. Various modulators, including histamine, serotonin, β-endorphin, met-enkephalin, and melanin concentrating hormone, had no effect. Glutamate, as well as ionotropic agonists (kainate and N-Methyl-d-aspartic acid), increased Trh mRNA levels. Baclofen, a GABAB receptor agonist, and dopamine enhanced Trh mRNA levels. An endocannabinoid receptor 1 inverse agonist promoted TRH release. Somatostatin increased Trh mRNA levels and TRH cell content. Orexin-A rapidly increased Trh mRNA levels, TRH cell content and release, while orexin-B decreased Trh mRNA levels. These data reveal unaccounted regulators, which exert potent effects on hypothalamic TRH neurons in vitro.

BACKGROUND: Scarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD. METHODS: Assessment of VM by Rey-Osterrieth Complex Figure Test (ROCF) was carried out on a sample of 317 subjects, including 140 patients with BD, 60 unaffected first-degree relatives (BD-Rel), and 117 genetically-unrelated healthy controls (HC), on three occasions over a 5-year period (T1, T2, and T3). BD-Rel group scores were analyzed only at T1 and T2. RESULTS: Performance of BD patients was significantly worse than the HC group (p < 0.01). Performance of BD-Rel was also significantly different from HC scores at T1 (p < 0.01) and T2 (p?=?0.05), and showed an intermediate profile between the BD and HC groups. Only among BD patients, there were significant differences according to sex, with females performing worse than males (p?=?0.03). Regarding other variables, education represented significant differences only in average scores of BD-Rel group (p?=?0.01). LIMITATIONS: Important attrition in BD-Rel group over time was detected, which precluded analysis at T3. CONCLUSIONS: BD patients show significant deficits in VM that remain stable over time, even after controlling sociodemographic and clinical variables. Unaffected relatives also show stable deficits in VM. Accordingly, the deficit in VM could be considered a potential endophenotype of BD, which in turn may be useful as a predictor of the evolution of the disease. Further studies are needed to confirm these findings. VB-M is supported by the national grant PI16/01770 (PROBILIFE Study), from the ISCIII. RTS was supported in part by grant PROMETEOII/2015/021 from Generalitat Valenciana and the national grands PI14/00894, PI17/00719 and PIE14/00031 from ISCIII-FEDER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.

BackgroundCognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD).MethodsOne hundred and two patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS ≤ 6 and HDRS ≤ 8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR.ResultsParticipants with BD with high CR displayed a better performance in measures of attention (digits forward: F = 4.554, P = 0.039); phonemic and semantic verbal fluency (FAS: F = 9.328, P = 0.004; and Animal Naming: F = 8.532, P = 0.006); and verbal memory (short cued recall of California Verbal Learning Test: F = 4.236, P = 0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms.ConclusionsHigh cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.Disclosure of interestDr. I. Grande has received a Juan Rodés Contract (JR15/00012), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Barcelona, Spain and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag.Disclosure of interestDr. I. Grande has received a Juan Rodés Contract (JR15/00012), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Barcelona, Spain and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag.

Functional improvement has become one of the aims of the treatment of bipolar disorder. However, scant attention has been given to family functioning, even though it has a role in the illness outcome and is affected by the disorder. The aims of this study were to compare family functioning reported by euthymic patients with bipolar disorder and healthy controls; explore the level of congruence in the perception of family environment between patients with bipolar disorder and their relatives; and analyse the relationship between clinical variables and family functioning. The sample comprised 82 adult euthymic subjects with bipolar disorder, 82 family caregivers of these patients and 47 healthy controls. Participants completed the Family Environment Scale. Results showed moderate correlations and a mean pattern almost identical between relatives' and patients' reported scores in family functioning subscales. There were significant differences between patients and controls, favourable for the latter, in the subscales cohesion (p

Background Despite its importance, no distinction between none, mild, moderate and severe functional impairment is available. Categorization of functional impairment could help to better assess randomized controlled trials (RCT) and to study the correlates of functional impairment according to severity. The Functional Assessment Short Test (FAST) is one of the most widely used measures of functional impairment in bipolar disorder and related conditions, but to date no severity cut-offs have been determined for their use in clinical research and practice. Method FAST and Global Functioning Assessment (GAF) ratings from 65 euthymic outpatients with bipolar disorder at the Hospital Clinic in Barcelona were analyzed. A linear regression was computed using the FAST as the independent variable and the GAF as the dependent variable. Cut-offs scores for the FAST were estimated taking into account the GAF scores as a reference. Results Linear regression analysis with GAF scores as the dependent variable yielded the following equation: GAF score = 91,41–1,031 * FAST score. The cut-off scores for the FAST scale derived from this equation were as follows: scores from 0 to 11 included patients with no impairment. Scores from 12 to 20, represented the category of mild impairment. Moderate impairment comprised scores from 21 to 40. Finally, scores above 40 represent severe functional impairment. Further, the 4 × 4 cross-tabulation resulted in a significant association of FAST and GAF severity gradation: (Chi2= 95,095; df = 9; p Limitations In the absence of a better alternative, the GAF, a broad clinical measure, was used as gold standard for establishing FAST categories according to severity. Conclusion The categorization of functional impairment in four categories based on empirical data shows that 12, 20 and 40 represent clinically meaningful cut-offs of the FAST for mild, moderate, and severe functional impairment and for functional recovery, remission, and improvement. The proposed categories are suitable to be further implemented in clinical studies and RCTs.

Sexual development prior to gonadal sex differentiation is regulated by various molecular mechanisms. In fish, a "molecular sex-differentiation period" has been identified in species for which sex can be ascertained prior to gonadal sex differentiation. The present study was designed to identify such a period in a species for which no genetic sex markers or monosex populations are available. Siberian sturgeons undergo a slow sex-differentiation process over several months, so gonad morphology and gene expression was tracked in fish from ages 3-27 months to identify the sex-differentiation period. The genes amh, sox9, and dmrt1 were selected as male gonad markers; cyp19a1a and foxl2a as female gonad markers; and cyp17a1 and ar as markers of steroid synthesis and steroid receptivity. Sex differentiation occurred at 8 months, and was preceded by a molecular sex-differentiation period at 3-4 months, at which time all of the genes except ar showed clear expression peaks. amh and sox9 expression seemed to be involved in male sexual development whereas dmrt1, a gene involved in testis development in metazoans, unexpectedly showed a pattern similar to those of the genes known to be involved in female gonadal sex differentiation (cyp19a1 and foxl2a). In conclusion, the timing of and gene candidates involved with molecular sex differentiation in the Siberian sturgeon were identified.

Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric illness often accompanied of cognitive dysfunction which may persist even when patients achieve clinical remission. Currently, cognitive deficits emerge as a potential target because they compromise the functional outcome of depressed patients. The aim of this study was to review data for several potential pharmacological treatments targeting cognition in MDD, resulting from monotherapy or adjunctive treatment. An extensive and systematic Pubmed/Medline search of the published literature until March 2014 was conducted using a variety of search term to find relevant articles. Bibliographies of retrieved papers were further examined for publications of interest. Searches were limited to articles available in English language. We describe studies using modafinil, lisdexamfetamine, ketamine, lanicemine, memantine, galantamine, donepezil, vortioxetine, intranasal oxytocin, omega-3, s-adenosyl-methionine, scopolamine and erythropoietin. From these articles, we determined that there are a number of promising new therapies, pharmacological agents or complementary medicines, but data are just emerging. Drugs and therapies targeting cognitive dysfunction in MDD should prove effective in improving specific cognitive domains and functioning, while ruling out pseudospecificity.

OBJECTIVES: To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus-based guidance paper for the methodology and design of cognition trials in bipolar disorder.METHODS: The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face-to-face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.RESULTS: Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non-study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.CONCLUSIONS: This ISBD task force guidance paper provides the first consensus-based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.

Objective Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). Methods This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. Results Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. Conclusions Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.

The purpose of this study was to compare the psychometric properties of the Screen for Cognitive Impairment in Psychiatry (SCIP) when applied to patients diagnosed with schizophrenia (n=126) or bipolar I disorder (n=76), and also to compare the cognitive impairment in both samples of patients and a control group (n=83) using the SCIP and a complete neuropsychological battery. The SCIP is a scale intended to quickly and easily assess cognitive impairment in patients with severe psychiatric disorders. The results showed firstly that, in terms of internal consistency, temporal stability, dimensional structure, and criterion-referenced validity, the SCIP provides reliable and valid scores at an equivalent level in both schizophrenia and bipolar I disorder samples. Secondly, it showed that differential cognitive impairment between the two patient groups occurs only in verbal memory, although the effect size of the difference is small. Finally, compared with the control group, cognitive impairment was present at all levels in both groups of patients using both the SCIP and the neuropsychological battery, which indicates that the SCIP is a good screening tool for cognitive deficits in schizophrenia and bipolar and useful in clinical practice for healthcare professionals.ResumenEl objetivo del estudio fue comparar las propiedades psicométricas del test Screen for Cognitive Impairment in Psychiatry (SCIP) en pacientes diagnosticados de esquizofrenia (n=126) o trastorno bipolar I (n=76). Además, el deterioro cognitivo se comparó con un grupo control (n=83) empleando el SCIP y una batería neuropsicológica completa. El test SCIP es una escala que evalúa rápida y fácilmente el deterioro cognitivo en trastornos psiquiátricos graves. En términos de consistencia interna, estabilidad temporal, estructura dimensional y validez de criterio, el SCIP proporciona resultados al mismo nivel de fiabilidad y validez en pacientes con esquizofrenia o trastorno bipolar I. Además, demostró que el deterioro cognitivo diferencial entre los dos grupos de pacientes se produce solo en la memoria verbal, aunque el tamaño del efecto de esta diferencia es pequeño. Por último, y frente al grupo control, se confirma el deterioro cognitivo a todos los niveles en ambos grupos de pacientes utilizando tanto el SCIP como la batería neuropsicológica, lo que indica que el SCIP es una buena herramienta de detección para los déficits cognitivos en esquizofrenia y trastorno bipolar, y útil en la práctica clínica habitual para profesionales de la salud.

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.

Background Psychomotor agitation (PMA) is a state of motor restlessness and mental tension that requires prompt recognition, appropriate assessment and management to minimize anxiety for the patient and reduce the risk for escalation to aggression and violence. Standardized and applicable protocols and algorithms can assist healthcare providers to identify patients at risk of PMA, achieve timely diagnosis and implement minimally invasive management strategies to ensure patient and staff safety and resolution of the episode. Methods Spanish experts in PMA from different disciplines (psychiatrists, psychologists and nurses) convened in Barcelona for a meeting in April 2016. Based on recently issued international consensus guidelines on the standard of care for psychiatric patients with PMA, the meeting provided the opportunity to address the complexities in the assessment and management of PMA from different perspectives. The attendees worked towards producing a consensus for a unified approach to PMA according to the local standards of care and current local legislations. The draft protocol developed was reviewed and ratified by all members of the panel prior to its presentation to the Catalan Society of Psychiatry and Mental Health, the Spanish Society of Biological Psychiatry (SEPB) and the Spanish Network Centre for Research in Mental Health (CIBERSAM) for input. The final protocol and algorithms were then submitted to these organizations for endorsement. Results The protocol presented here provides guidance on the appropriate selection and use of pharmacological agents (inhaled/oral/IM), seclusion, and physical restraint for psychiatric patients suspected of or presenting with PMA. The protocol is applicable within the Spanish healthcare system. Implementation of the protocol and the constituent algorithms described here should ensure the best standard of care of patients at risk of PMA. Episodes of PMA could be identified earlier in their clinical course and patients could be managed in the least invasive and coercive manner, ensuring their own safety and that of others around them. Conclusion Establishing specialized teams in agitation and providing them with continued training on the identification of agitation, patient management and therapeutic alternatives might reduce the burden of PMA for both the patient and the healthcare system.

Background: Cognitive remediation is accepted as an important therapeutic intervention in schizophrenia, but few studies provide data on whether the benefits extend to affective disorders. Objectives: To review quantitatively studies of cognitive remediation with samples that included cases of schizoaffective disorder, affective psychosis, unipolar and/or bipolar disorders. Methods: Twenty one studies met preliminary inclusion criteria, comprising a total of 940 participants of which 35% had an affective or schizoaffective disorder. Effect sizes (ES) for pre- to post-intervention change in cognitive performance were estimated. Results: A meta-analysis of 16 studies gave a pooled ES for change in cognitive function of 0.32 (95% Confidence Intervals 0.20 to 0.43) and produced statistical homogeneity. Overall, ES were significantly positively correlated with higher proportion of schizo-affective and affective cases (r¼ 0.61; p¼ 0.007), even when age, gender and duration of therapy were included as covariates in the analysis (r¼ .59, p¼ 0.017). Limitations: The quality of and small number of affective disorder only studies mean the fi ndings must be treated with caution. Conclusions: The estimated ES reflect those reported in the literature on cognitive remediation for schizophrenia. As such a conservative interpretation is that cognitive remediation has at least equivalent benefits in affective and schizo-affective disorder as demonstrated in schizophrenia. Further studies are urgently required to examine the durability of any gains with cognitive remediation in affective populations and to determine if any changes in cognitive deficits lead to improvements in symptoms or functioning and/ or whether post-intervention cognitive changes differ in character or magnitude from those reported in schizophrenia.

Rosa AR, Gonzalez-Ortega I, Gonzalez-Pinto A, Echeburua E, Comes M, Martinez-Aran A, Ugarte A, Fernandez M, Vieta E. One-year psychosocial functioning in patients in the early vs. late stage of bipolar disorder. Objective: The aim of this 1-year follow-up study was to compare functional outcome as well as clinical differences between patients with first- and multiple-episode bipolar disorder. Method: Bipolar disorder patients with first (n = 60) and multiple episodes (n = 59) were recruited from two hospitals in Spain. The Functioning Assessment Short Test (FAST) was used to assess functioning. The Hamilton Depression Rating Scale (HAMD) and the Young Mania Rating Scale (YMRS) were administered to assess mood symptoms. Results: As expected, patients with first episode experienced a greater functioning compared to patients with multiple episodes (11.26 ± 10.94 vs. 26.91 ± 13.96; t = 6.436, P

Bipolar disorder is a severe mental illness that affects nearly 4.4% of the general population when bipolar spectrum disorders are taken into account. Neurocognitive impairment is thought to be a core deficit of this illness since it is present during euthymia. In fact, 40–60% of euthymic patients present with neurocognitive disturbances. Not only the clinical factors but also disturbances in neurocognition can influence the functional outcome of BD patients. Hence, further research is needed in order to clarify the relationship between these variables. Despite the growing body of evidence that has emerged during the last decade, no unique neurocognitive profile has been proposed yet for either BD subtype. The majority of the studies recluted heterogeneous samples (including both bipolar I and II) or focused on BD‐I patients only. The aim of this review is to give an overall picture of the main neurocognitive disturbances found in the bipolar spectrum and particularly in BD‐II, where the findings are more ambiguous. An extensive review of all the literature has been done regarding this subtype (from 1980 until July 2009). Data available until now suggest that deficits are present across the bipolar spectrum (BD‐I and BD‐II), but they seem slightly more severe in BD‐I. The extent to which either subtype share—or not—some similarities is still unknown. More studies are required but it would also be interesting to reach a consensus in the neuropsychological assessment of BD to facilitate comparisons between the different studies.

Sole B, Bonnin CM, Torrent C, Balanza-Martinez V, Tabares-Seisdedos R, Popovic D, Martinez-Aran A, Vieta E. Neurocognitive impairment and psychosocial functioning in bipolar II disorder. Objective: There is a growing body of evidence on neurocognitive impairment in euthymic bipolar patients, but this issue has been studied mostly in bipolar I disorder, data on bipolar II (BD-II) are scant and discrepant. The two aims of this study were to ascertain whether strictly defined euthymic BD-II patients would present neurocognitive disturbances and to evaluate their impact on functional outcome. Method: Forty-three BD-II patients and 42 demographically and educationally matched healthy subjects were assessed with a comprehensive neuropsychological test battery and with the Social and Occupational Functioning Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating Scale for Depression score ≤6 and a Young Mania Rating Scale score ≤6) to minimize the influence of subdepressive symptomatology on cognition and functioning. Results: BD-II patients showed a significantly lower performance on several measures of attention, learning and verbal memory, and executive function compared with healthy controls. The presence of subthreshold depressive symptomatology and one measure related to executive function (Trail Making Test, part B) was the variables that best predicted psychosocial functioning measured with the SOFAS. Conclusion: This report provides further evidence that euthymic BD-II patients present cognitive impairment which may impact psychosocial functioning.

Lopez-Jaramillo C, Lopera-Vasquez J, Gallo A, Ospina-Duque J, Bell V, Torrent C, Martinez-Aran A, Vieta E. Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Bipolar Disord 2010: 12: 557–567. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective: To determine if the repeated occurrence of manic episodes in bipolar I disorder (BD-I) patients is associated with reduced cognitive performance, which could in turn imply a worsening in the disorder’s evolution. Method: Cognitive performance in euthymic patients was assessed using attention, memory, and executive function tests on 24 BD-I patients who had experienced only 1 manic episode, on 27 BD-I patients with 2 manic episodes, on 47 BD-I patients with 3 or more manic episodes, and on 66 healthy control subjects. Results: In BD-I patients, number of manic episodes was positively associated with poorer performance on neurocognitive tests, an association that was not accounted for by depression, disease chronicity, onset, or medication. Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more. Conclusion: The number of manic episodes predicted poor cognitive performance, suggesting that the recurrence of mania may have a long-term neuropsychological impact. Prospective follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function.

Background There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms, especially the course of comorbid alcohol/substance abuse. Method A naturalistic sample of bipolar I patients ( n = 120) was followed prospectively for up to 10 years. At baseline, number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes, respectively. 25 patients were excluded from the analyses. Outcomes including episodes, hospitalisations and suicide attempts were recorded at bimonthly visits. Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients. Results Of the 95 patients analyzed, 44 (46.3%) had predominantly manic episodes and 51 (53.7%) had predominantly depressive episodes. At baseline, the predominantly depressive group had more history of suicide attempts (45.1% vs. 20.5%; p = 0.021) and more family history of affective disorders (64.7% vs. 38.6%; p = 0.020), but they had fewer previous hospitalisations than the manic group (mean 0.38 vs. 0.50; p = 0.025). During the 10-year follow-up, the predominantly depressive group was associated with more episodes ( p = 0.001), more hospitalisations ( p = 0.004) and more suicide attempts ( p = 0.002). At baseline, there were no differences between the manic and depressive groups in the frequency of alcohol abuse (43.2% and 35.3%, p = 0.565) or other substance abuse (13.6% and 9.8%, p = 0.794). During the 10-year follow-up, the frequency of alcohol and other substance abuse decreased significantly in the manic group only, after controlling by age at onset and civil (marital) status. Conclusion Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients, with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse. These differences should be considered when designing treatment approaches for bipolar patients with comorbid alcohol/substance abuse.

To demonstrate the ability of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) to discriminate between cognitively-impaired individuals and those with adequate functioning in a sample of schizophrenic and bipolar patients, as well as in a control group.The SCIP-S, together with a full neuropsychological battery, was administered to three groups: patients with schizophrenia, patients diagnosed with bipolar disorder I, and controls. The battery scores were used to perform a standardization with respect to the control group and this served to determine the comparison groups (cognitively impaired versus unimpaired) for each of the subtests of the SCIP-S. A full analysis of decision validity was conducted on the basis of receiver operating characteristic curves (sensitivity and specificity, +LR and -LR, PPV and NPV).All the subtests yielded adequate values for sensitivity and specificity with the proposed cut-off points, while the total score of the SCIP (70) was associated with a sensitivity of 87.9 and specificity of 80.6.The SCIP-S shows adequate decision validity as a screening tool for cognitive deficit in patients diagnosed with schizophrenia or bipolar disorder.

Objective To identify clinical and neurocognitive predictors of long-term functional outcome in patients with bipolar disorder Methods A total of 32 subjects who met criteria for bipolar I or II disorder were recruited from the Barcelona Bipolar Disorder Program and were assessed clinically and neuropsychologically at baseline. After an average 4-year follow-up, they were interviewed with the Functioning Assessment Short Test (FAST) to assess functional outcome. Multivariate analyses were applied to identify clinical and neurocognitive predictors of functional outcome. Results The main regression model for predictors of overall psychosocial functioning identified subclinical depressive symptoms ( s = 0.516, t = 3.51, p = 0.002), and free delayed recall in a verbal memory task ( s = − 0.314, t = − 2.144, p = 0.041), accounting for 36% of the variance. Specific predictors of occupational functioning were, again, subthreshold depression ( s = 0.435, t = 2.8, p = 0.009) and a measure of executive function, digits backwards ( s = − 0.347, t = − 2.23, p = 0.034). This model explained around 28% of the variance (corrected R 2 = 0.28; F = 6.38, gl = 2, p = 0.004). Conclusions Subdepressive symptomatology together with neurocognitive impairments related to verbal memory and executive functions are predictor variables of long-term functional outcome in bipolar disorder.

The last decade has witnessed a growing interest in the neuropsychological study of bipolar disorder (BD). This chronic mood disorder is associated with persistent neurocognitive impairments even during periods of euthymia, particularly in the broad domains of attention, verbal memory and executive functions. More interestingly, cognitive dysfunction seems to predict a poorer functional outcome among BD patients and thus represents an important target for future therapies. The aetiology of cognitive dysfunction is probably multifactorial, including gene-environment interactions with potentially confounding variables as well. Drug-induced cognitive adverse effects represent an important and difficult to examine confounder. This review provides an overview of selected aspects of neurocognition in bipolar disorder with a focus on the relative contributions of medications as well as medical and psychiatric comorbid conditions to cognitive dysfunction. Finally, recommendations for future research in the field are provided including collaborative studies with larger samples, observational follow-up studies, as well as randomized clinical trials comparing head-to-head the neurocognitive impact of different medications.

Objectives: A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample. Methods: The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome. Results: Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables-older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations-were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance (F - 12.54, df = 58, p < 0.001). Conclusions: A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.

Background: Bipolar disorder has generally been regarded as having a better functional outcome than schizophrenia. However, studies have suggested low functioning in bipolar patients even when they are in clinical remission. Our aim was to determine the degree of functioning and disability in bipolar patients. Secondly, we reviewed factors potentially associated with the low functioning of bipolar patients. Method: The authors conducted an extensive Medline and Pubmed search of the published literature from 1980 up to December 2007, using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Articles that reported clinically significant findings on functioning and disability, and research reports were reviewed in detail. Results: From these articles, we determined that bipolar disorder is associated with significant impairment in work, family and social life, beyond the acute phases of the illness. The aspects that appear to increase the risk of low functioning and disability in bipolar patients are mainly subsyndromal symptoms and neurocognitive impairment, among others. Conclusions: Suitable pharmacological and psychological interventions may improve the level of functioning and reduce the disability in bipolar patients. Potential targets to be considered for intervention should be residual symptoms, comorbid conditions and neurocognitive deficits. Further research is required to better identify the factors that best predict functioning in bipolar patients.

We describe issues encountered in implementing the International Classification of Functioning, Disability, and Health (ICF) in a comprehensive psychiatric rehabilitation settings for people with Serious Mental Illness (SMI), with the goal of facilitating other implementation projects and stimulating international discussion.In 2006, the Hospital Mellino Mellini Department of Mental Health undertook a 2-year evaluation of the applicability of the ICF to its community-based program for people with SMI, in collaboration with the Neurological Institute Carlo Besta Foundation. An ICF-based assessment of functional status was administered at intake, 3 months, and at 6 months, using an extended checklist of ICF codes determined to reflect the most important aspects of functioning among the SMI client population. All project focused on three important aspects of participation of these persons: housing, working, and socialization.Issues encountered during the project related to: (1) the identification of a relevant code set for the population; (2) difficulty in administering the checklist as a primary functional status measure; (3) whose perspective would be followed in rating functional status; (4) how to conceptualize the ICF Capacity qualifier; and (5) the need for teamwork and culture change for successful ICF implementation.On the basis of this experience and input from an international workshop convened by the Department, the project team concluded that the ICF is a helpful conceptual frame for functional status among people with SMI, promotes a common language and integrated treatment model, supports the development of individual rehabilitation plans, and can be used to improve services for this population.

Objective:The aim of the present study was to assess the association between previous suicide attempts and functional impairment among euthymic patients with bipolar disorder (BD).Methods:Seventy-one Diagnostic Statistical Manual IV (DSM-IV) patients with BD and 61 healthy volunteers were recruited from the Bipolar Disorder Program at the Clinic Hospital of Barcelona. Patients with (n = 36, 50.7%) and without (n = 35, 49.3%) previous suicide attempts were assessed using the Structured Clinical Interview for DSM-IV-TR (SCID-P). Previous suicide attempts were carefully investigated by means of patient and caregiver interview and by a standard structured interview from the protocol of our BD Program. The Functioning Assessment Short Test (FAST) was employed to assess functional impairment.Results:Euthymic patients with previous suicide attempts showed functional impairment, particularly in occupational (F = 30.39; p = 0.001) and cognitive functioning (F = 18.43; p = 0.001). In addition, family history of psychiatric illness (χ2: 6.49; degrees of freedom (df) = 2;132; p = 0.010), family history of affective disorders (χ2 = 5.57; p = 0.017), psychotic symptoms (χ2 = 5.88; p = 0.014) and axis II comorbidity were associated with previous suicide attempts (χ2 = 5.16; p = 0.021).Conclusion:Bipolar patients with previous suicide attempts had lower overall functioning than patients who did not attempt suicide. Previous suicide attempts were particularly associated with the occupational and cognitive domains of functioning.

Objective Many studies have reported that cognitive ability may be predictive of the functional outcome for patients with schizophrenia. However, no study has prospectively examined these aspects in schizophrenia and bipolar disorders simultaneously. The present study attempted to analyze if neurocognition and clinical status predicts the real-life functioning for patients with schizophrenia or bipolar I disorder, using a longitudinal design. Method Forty-seven schizophrenic and 43 bipolar I outpatients were assessed twice with a neurocognitive battery (Executive Functions, Working Memory, Verbal Memory, Visual Memory, Visual-Motor Processing, Vigilance, Vocabulary and Motor Speed tasks), clinical scales (the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression and the Clinician Administered Rating Scale for Mania) and functional outcome measures (the Global Assessment of Functioning Scale, the WHO's Disability Assessment Scale and occupational adaptation level) over a one-year follow-up period. The cognitive performance of the patients was compared, at baseline and one year later, with that of 25 healthy subjects. Results In schizophrenia patients, global functioning one year later was predicted by a composite neurocognitive score and three specific domain (verbal memory, motor speed, vocabulary). Symptoms appeared to explain less of the variance in functioning. In bipolar I patients, changes in the composite neurocognitive score over one year, deficits in the visual/motor processing domain, severity of symptoms (psychotic, excitatory and affective symptoms) and premorbid adjustment at the first assessment were the variables that better predicted functioning or disability changes over follow-up period. Conclusions Although the relationships between cognition, symptoms and functional capacity differ for schizophrenia or bipolar I patients, neuropsychological performance seems to be a principal longitudinal predictor of functioning in both disorders. Baseline neurocognition and cognitive changes over 12 months predicted changes in functioning over the same period, but only in bipolar I patients. These cognitive domains could be potential neurocognitive endophenotypes (endophenocognitypes) with regard to bipolar I disorder.

Objective Although there are some randomized controlled trials that highlight the positive role of family-focused treatment added to pharmacotherapy in bipolar disorder, no trials using contemporary methodologies have analyzed the specific effect of working with caregiver-only groups. The aim of this study was to assess the efficacy of a psychoeducational group intervention focused on caregivers of euthymic bipolar patients. Method A total of 113 medicated euthymic bipolar outpatients who lived with their caregivers were randomized into an experimental and a control group. Caregivers in the experimental group received twelve 90-min group psychoeducation sessions focused on knowledge of bipolar disorder and training in coping skills. The patients did not attend the groups. Caregivers assigned to the control group did not receive any specific intervention. Patients were assessed monthly during both the intervention and the 12 months of follow-up. The primary outcome was time to any mood recurrence. Results Psychoeducation group intervention focused on the caregivers of bipolar patients carried a reduction of the percentage of patients with any mood recurrence (chi2 = 6.53; p = 0.011) and longer relapse-free intervals (log-rank chi(2) = 4.04; p = 0.044). When different types of episodes were analyzed separately, the effect was significant for both the number of patients who experienced a hypomanic/manic recurrence (chi2 = 5.65; p = 0.017) and the time to such an episode (log-rank chi2 = 5.84; p = 0.015). The differences in preventing depressive and mixed episodes were not significant. Conclusions A psychoeducation group intervention for the caregivers of bipolar patients is a useful adjunct to usual treatment for the patients in reducing the risk of recurrences, particularly mania and hypomania, in bipolar disorder.

Objective: Little is known regarding the impact of psychotic symptoms on the cognitive functioning of bipolar patients. Findings from previous reports are controversial and mainly focused on current psychotic symptoms. The main aim of this study was to ascertain whether the history of psychotic symptoms was associated with greater cognitive impairment in euthymic bipolar patients. Method: Sixty-five euthymic bipolar disorder patients (DSM-IV criteria; 35 with a history of psychotic symptoms and 30 without such a history) were assessed through a neuropsychological battery targeting attention, psychomotor speed, verbal memory, and executive functions. Thirty-five healthy controls were also included in the study in order to compare the neuropsychological performance among groups. Multivariate analysis of covariance was performed controlling for the effect of residual depressive symptoms as a co-variate. The study was conducted from June 2005 to June 2006. Results: Bipolar patients with a history of psychotic symptoms showed a higher number of manic episodes and more hospitalizations than patients without such a history (both p

Objectives Although it is well established that euthymic patients with bipolar disorder can have cognitive impairment, substantial heterogeneity exists and little is known about the extent and severity of impairment within the bipolar II disorder subtype. Therefore, the main aim of this study was to analyze cognitive variability in a sample of patients with bipolar II disorder. Methods The neuropsychological performance of 116 subjects, including 64 euthymic patients with bipolar II disorder and 52 healthy control subjects, was examined and compared by means of a comprehensive neurocognitive battery. Neurocognitive data were analyzed using a cluster analysis to examine whether there were specific groups based on neurocognitive patterns. Subsequently, subjects from each cluster were compared on demographic, clinical, and functional variables. Results A three-cluster solution was identified with an intact neurocognitive group (n = 29, 48.3%), an intermediate or selectively impaired group (n = 24, 40.0%), and a globally impaired group (n = 7, 11.6%). Among the three clusters, statistically significant differences were observed in premorbid intelligence quotient (p = 0.002), global functional outcome (p = 0.021), and leisure activities (p = 0.001), with patients in the globally impaired cluster showing the lowest attainments. No differences in other clinical characteristics were found among the groups. Conclusions These results confirm that neurocognitive variability is also present among patients with bipolar II disorder. Approximately one-half of the patients with bipolar II disorder were cognitively impaired, and among them 12% were severely and globally impaired. The identification of different cognitive profiles may help to develop cognitive remediation programs specifically tailored for each cognitive profile.

Objective To study the prevalence of attention-deficit and hyperactivity disorder (ADHD) in adult patients with bipolar disorder (BD) and identify differential clinical features for a better diagnosis. Method A total of 163 euthymic bipolar out-patients were screened for ADHD with the ASRS.V1 and the WURS at a BD Unit. Patients with a positive screening were assessed with the CAADID, at an ADHD unit. Sociodemographic and clinical features of the groups with and without ADHD were compared. Results Lifetime prevalence of comorbid ADHD was 17.9% (10.5% for adult ADHD and 7.4% for childhood ADHD). The BD + ADHD group showed more suicidal behaviour although less severe. Comorbidity was also more common, especially regarding substance use disorders. Nevertheless, these patients did not show more affective episodes or hospitalizations and suffered more atypical but less melancholic depression. However, they required more treatment with psychotherapy and valproate. One-third of positive screenings at the ASRS were false; a severe course of BD was the hallmark of this subgroup. Conclusion Adult patients with BD and ADHD show differential clinical features, but not a more severe course of BD. Comorbidity with substance abuse is a big issue, deserving special clinical attention. Better screening tools are necessary to avoid overdiagnosis of comorbid ADHD in BD.

Objective To conduct the first randomized, controlled trial assessing the prophylactic efficacy of gabapentin in bipolar disorder. Method We conducted a 1-year, double-blind, randomized, comparative, placebo-controlled, parallel-group, multicenter study. As this was a pure prophylactic trial, only euthymic bipolar I and II patients (DSM-IV) were randomly assigned in a 1:1 ratio to gabapentin (N = 13) or placebo (N = 12) added to the current treatment (lithium, valproate, carbamazepine, or any combination but not antipsychotics or antidepressants). Subjects participated in the study for 12 months. The primary efficacy parameter was the Clinical Global Impressions scale for Bipolar Illness, Modified (CGI-BP-M), which was assessed at all visits. Other assessments were the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the systematic collection of reported adverse events. Data were collected from May 1999 to February 2004. Results The change from baseline to month 12 in mean CGI-BP-M scores between groups was statistically significant (p = .0046). Mean score change from baseline to endpoint in the gabapentin group was -2.1, and the mean score change in the placebo group was -0.6. No emerging manic or depressive symptoms were seen in either group as measured with the YMRS, HAM-D, HAM-A, and PSQI. In the PSQI-6 subscale (use of sleeping medication), the mean score change at month 12 in the gabapentin group was 0.9, and the mean score change in the placebo group was 0.05 (p = .0267). Overall, gabapentin was well tolerated. Conclusion This small, randomized clinical trial comparing the prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute efficacy, treatment with gabapentin might provide some benefit on the long-term outcome of bipolar disorder.

Background: More and more epidemiological, genetic and neuroimaging studies show similarities between bipolar disorder (BD) and schizophrenia (SZ). Cognitive functions are known to be highly impaired in SZ and are increasingly studied in BD. When both populations are compared, the conclusions appear to be contradictory. The purpose of this review is to help define the profile of cognitive deficits in BD and in SZ. Methods: A systematic review of the literature of neuropsychological studies comparing BD and SZ was made, beginning in January 1990 and ending in January 2005. Thirty-eight studies met the required quality criteria and were included in this review. Results: Bipolar patients exhibit extensive cognitive abnormalities with a pattern of deficits that is not unique to this disease. However, when compared to schizophrenic patients, bipolar patients demonstrate a lesser degree of deficits, particularly concerning premorbid and current intelligence quotient and perhaps attention, verbal memory and executive functions. When looking into effect sizes, there seem to be different profiles even in studies finding no significant differences. Conclusions: The neuropsychological differences reported between both groups could be due to the presence of psychotic features, to environmental factors (stressful events, duration of the disease and number of hospitalisations) and could also be related to differences during the neurodevelopmental phase. Further studies should confirm whether these results are truly related to different neurobiological backgrounds.

Objective: To determine and correlate alterations in neuropsychological function and cerebral blood flow in bipolar patients. Method: Assessments included the Positive and Negative Symptom Scale, Global Assessment Functioning, Wechsler Adult Intelligence Scale (WAIS), Wisconsin Card Sorting Test (WCST), Stroop test, Trail Making Test (TMT), California Verbal Learning Test (CVLT), Wechsler Memory Scale (WMS) and phonetic verbal fluency/controlled oral word association tests. Single photon emission computed tomography (SPECT) was carried out with the administration of 99mTc-HMPAO. Forty-three outpatients out of 85 fulfilling RDC diagnostic criteria for bipolar disorder and six healthy subjects were included in the study. SPECT and neuropsychological assessments were performed in 30 patients in manic (n = 7), hypomanic (n = 8), depressed (n = 12) or euthymic (n = 3) states. All assessments were carried out before starting treatment. Result: Several corrected correlations between neuropsychological function and cerebral blood flow (CBF) were identified: executive function (WCST) and striatal, frontal, temporal, cerebellum, parietal and cingulate CBF; memory (WMS, WAIS-Digits) and striatal, frontal, temporal and parietal CBF; attentional tasks (Stroop) and striatal, temporo-medial and parietal CBF; verbal learning (CVLT) and frontal, posterior temporal, cingulate and occipital CBF; psychomotor disturbances (TMT) and anterior temporal CBF; poorer intelligence performance scores (WAIS-Vocabulary) and cerebellum and parietal CBF. Conclusions: This study confirms the presence of functional disturbances in frontosubcortical structures, the cerebellum and limbic system in bipolar patients.