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Objective The aim was to examine the heterogeneity of psychosocial outcomes in euthymic bipolar disorder (BD) patients and analyse the potential influence of distinct variables on functioning. Method Using a hierarchical cluster exploratory analysis, 143 euthymic patients with diagnosis of BD were grouped according to their functional performance based on domains scores of the Functioning Assessment Short Test (FAST). The resulting groups were compared on sociodemographic, clinical and neurocognitive variables to find factors associated with each functional cluster. Results Patients were grouped in three functional profiles: patients with good functioning in all the FAST areas, patients with an intermediate profile showing great difficulties in the occupational domain and milder difficulties in most of the rest domains, and a third group with serious difficulties in almost all functional areas. Both functionally impaired groups were characterized by higher subthreshold symptoms (depressive and manic) and higher unemployment rates. The most functionally impaired group also showed lower scores on some measures of processing speed. Conclusion Two of three functional profiles showed some kind of impairment which was associated with subsyndromal symptoms and cognitive performance. These patterns should be taken into consideration to develop more individualized interventions to restore, or improve, psychosocial outcomes.

Objectives Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. Methods The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges. Consensus-based recommendations were achieved through these exchanges with no need for formal consensus methods. Results The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy-to-administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence-based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments. Conclusions This task force paper provides the first consensus-based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients' functional recovery and improve their quality of life.

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.

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.

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.

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.

Background The aim of this study was to assess the effectiveness and safety of risperidone monotherapy for acute and continuation treatment of mania. Method Ninety-six DSM-IV acutely manic bipolar patients with a Young mania rating score (YMRS) of 20 or more entered this open, multicentre, 6-month study. Efficacy was assessed with the YMRS, the positive and negative syndrome scale (PANSS) and the clinical global impressions scale (CGI). Safety was assessed with the UKU side effect rating scale and with the Hamilton depression rating scale, for the assessment of a switch to depression. Results 80 patients (83.3%) completed the study. Using the last-observation-carried-forward analysis, risperidone produced highly significant improvements (p

Methods: Fourteen rapid cycling bipolar patients were treated with quetiapine, which was added to their ongoing medication regimen for 112 ± 33 days. At the beginning of the study, five were manic, three were in a mixed state, three were depressed, two hypomanic and one was euthymic. Patients were assessed prospectively with a modified version of the Clinical Global Impression Scale for Bipolars (CGI-BP), the Young Scale for mania (YMRS)and the Hamilton Scale for Depression (HDRS). Results: A significant reduction of the following scale scores was observed: • a 1.8 point reduction for the general CGI-BP (p ¼ 0.013), • a –1.3 point for the mania subscale (p ¼ 0.016), • a –1.01 point for the YMRS (p ¼ 0.025). Improvement in depressive symptoms was not significant, neither in the CGI-BP (–1 point, p ¼ 0.074)nor in the HDRS (–5.2 points, p ¼ NS). The most common side-effect was sedation (n ¼ 6, 43%). Doses of quetiapine were significantly reduced by the end of the study (443 ± 235 mg/day versus 268 ± 190 mg/day, p ¼ 0.008)and they also differed according to the initial episode to be treated (720 ± 84 mg/day for mania, and 183 ± 29 mg/day for depression, p ¼ 0.023). Conclusions: Quetiapine could possibly be an effective treatment for rapid cycling bipolar patients. Adequate doses for acute episodes could significantly differ according to the episode polarity and the length of treatment.

OBJECTIVES To ascertain the clinical implications of psychiatric comorbidity in the course and outcome of bipolar I patients. METHODS One hundred and twenty-nine bipolar I outpatients in remission [Young Mania Rating Scale (Y-MRS) < 7, Hamilton Depression Rating Scale (HDRS) < 9] were assessed by means of the Structured Clinical Interview for DSM-III-R axis I and axis II (SCID-I and SCID-II) in order to detect all possible psychiatric comorbid diagnoses. The sample was split according to the presence of psychiatric comorbidity and the groups were compared. RESULTS Psychiatric comorbidity was detected in 31% of the sample. A higher number of mixed features, depressive episodes and suicide attempts and a predominance of depressive onset amongst comorbid bipolar patients were the most relevant differences between the two groups. CONCLUSIONS There is an association between depression, suicidality and comorbidity in bipolar I disorder. As comorbidity had a clear relevance in the course and outcome of bipolar illness, this issue should be specifically assessed in clinical practice.

The annual activity and spatial distribution of Muscidae and Calliphoridae were investigated in a holm-oak (“dehesa”) ecosystem in western Spain over two years using wind-oriented traps baited with a mixture of fresh cattle faeces, liver and sodium sulphide solution. Lucilia sericata (Meigen) was always the dominant species and, with Chrysomya albiceps (Weidemann), Hydrotaea ignava (Harris), Muscina levida (Harris) and Muscina prolapsa (Harris), was more abundant during the second than the first year. By contrast, Calliphora vicina Robineau-Desvoidy, Calliphora vomitoria (L.), Hydrotaea armipes (Fallén), Hydrotaea penicillata (Rondani) and Hydrotaea dentipes (Fabricus) were more numerous during the first than the second year of the study. In summer, the diptera sampled flies were significantly more abundant in a wooded area than a pasture area. However, in autumn, while H. penicillata remained significantly more abundant in woodland, L. sericata became more abundant in the pasture, whereas C. vicina was captured in open and wooded areas in similar proportions. During winter and spring the populations of sampled were relatively small. The changing patterns of abundance are discussed in relation to diffrences in climate within and between years. Generalitat Valenciana GV-C-RN-12-069-96.

Objective: To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2-year longitudinal study. Method: Fifteen DSM-IV-TR bipolar out-patients and 15 healthy-matched controls were cognitively assessed twice over a 2-year follow-up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Conclusion: Our results showed that executive dysfunction is the main long-term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd., Objective: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. Method: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. Results: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps 0.001, E.S. = 0.26–0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. Conclusion: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment., This paper was partially supported by a Seventh Framework Programme grant from the European Union to the European Network of Bipolar Research Expert Centres (ENBREC), Grant No. Health‐F2‐2009‐223102.