A longitudinal study of cognition, functional outcome and quality of life in bipolar disorder and major depression.

OBJECTIVE: Cognitive impairments are known to be a frequent cause of disability in bipolar disorder (BD) and major depression (MDD). Yet there is no consensus regarding the particular cognitive functions whose impairments can lead to disability in each domain of functioning. The aim of this study was to perform a longitudinal evaluation of working memory, inhibition, cognitive flexibility and attention in BD and MDD, investigate the relationship of these cognitive functions to disability and quality of life, and evaluate the impact of variables related to cognitive reserve (education and daily cognitive stimulation) on cognitive performance. METHOD: 31 participants (MDD = 12; BD = 19) were evaluated at baseline and after an average time of 2 years. RESULTS: the BD group showed improvements in attention while patients with MDD improved on measures of attention and working memory. In BD working memory performance was associated with the cognition and mobility domains of functioning, and with physical and environmental quality of life. In MDD, cognitive flexibility was related to social relationships and environmental quality of life. CONCLUSION: working memory and cognitive flexibility may be an interesting target for interventions aiming to improve everyday functioning and quality of life in BD and MDD.

Lysosomal cathepsins act in concert with Gasdermin-D during NAIP/NLRC4-dependent IL-1ß secretion.

The NAIP/NLRC4 inflammasome is classically associated with the detection of bacterial invasion to the cytosol. However, recent studies have demonstrated that NAIP/NLRC4 is also activated in non-bacterial infections, and in sterile inflammation. Moreover, in addition to the well-established model for the detection of bacterial proteins by NAIP proteins, the participation of other cytosolic pathways in the regulation of NAIP/NLRC4-mediated responses has been reported in distinct contexts. Using pharmacological inhibition and genetic deletion, we demonstrate here that cathepsins, well known for their involvement in NLRP3 activation, also regulate NAIP/NLRC4 responses to cytosolic flagellin in murine and human macrophages. In contrast to that observed for NLRP3 agonists, cathepsins inhibition did not reduce ASC speck formation or caspase-1 maturation in response to flagellin, ruling out their participation in the effector phase of NAIP/NLRC4 activation. Moreover, cathepsins had no impact on NF-κB-mediated priming of pro-IL-1ß, thus suggesting these proteases act downstream of the NAIP/NLRC4 inflammasome activation. IL-1ß levels secreted in response to flagellin were reduced in the absence of either cathepsins or Gasdermin-D (GSDMD), a molecule involved in the induction of pyroptosis and cytokines release. Notably, IL-1ß secretion was abrogated in the absence of both GSDMD and cathepsins, demonstrating their non-redundant roles for the optimal IL-1ß release in response to cytosolic flagellin. Given the central role of NAIP/NLRC4 inflammasomes in controlling infection and, also, induction of inflammatory pathologies, many efforts have been made to uncover novel molecules involved in their regulation. Thus, our findings bring together a relevant contribution by describing the role of cathepsins as players in the NAIP/NLRC4-mediated responses.

Cognitive reserve may outperform age, mood and psychiatric comorbidities as a predictor of executive functioning in bipolar disorder and healthy adults.

INTRODUCTION: Cognitive reserve plays a protective role against executive dysfunction in healthy adults and individuals with psychiatric illnesses such as bipolar disorder. However, the magnitude of the influence of cognitive reserve on specific executive functions (EFs), and its impact relative to variables such as depressive symptoms, age and psychiatric comorbidities, is unexplored. This study aimed to quantify the influence of cognitive reserve on specific EFs, and compare its impact with that of depressive symptoms, age and psychiatric comorbidities, in separate models for patients with bipolar disorder and healthy adults. METHOD: This was a cross-sectional study of 121 adults with no mood disorders and 109 with bipolar disorder, all of whom underwent a comprehensive psychiatric assessment and evaluation of the EFs. Cognitive reserve was measured using years of education, IQ and reading and writing habits. The association between EFs and predictors (cognitive reserve, depressive symptoms, age and psychiatric comorbidities) was evaluated through structural equation modeling. Four models were constructed for each group independently (bipolar disorder and control), one each for working memory, verbal fluency, inhibition and flexibility, due to group differences in age and cognitive reserve. RESULTS: Working memory, inhibition and flexibility were most significantly predicted by cognitive reserve and age. Verbal fluency was only predicted by cognitive reserve. Comorbidities and depressive symptoms were not significant in any of the models. Cognitive reserve had a positive influence on all EFs in models for patients with bipolar disorder and models for control participants. Age had a negative impact on three of the four EFs tested. CONCLUSION: Fostering cognitive reserve through continued education and cognitively stimulating leisure activities may be an effective intervention for executive dysfunction in patients and non-patients alike. In some cases, the effects of these interventions may outweigh the negative cognitive impact of aging, depressive symptoms and psychiatric conditions.

Cognitive abilities underlying performance on the modified card sorting test: novel and traditional scores.

The Modified Card Sorting Test (MCST) is a widely used variation of the Wisconsin Card Sorting Test. It is faster to administer, less frustrating for respondents and less ambiguous in its scoring but has been criticized for its task impurity and low discriminability between control participants and clinical groups prone to executive dysfunction. This study aimed to examine the executive functions (EF) underlying traditional (number of categories completed, perseverative errors) and novel scores for the MCST, and compare their ability to differentiate between control and clinical samples. Novel and traditional MCST scores were compared between 94 control participants, 87 with bipolar disorder and 64 with major depression. The relationship between MCST scores and traditional EF tasks was examined through correlation and regression analyses. All MCST scores were associated with at least one measure of EF, the most common of which were the Trail Making or Hayling Tests. IQ predicted most scores on the MCST, save for nonperseverative errors and categorizing efficiency. Traditional and novel scores differentiated between clinical and control groups. These findings support the utility of the MCST in detecting executive dysfunction and highlight the importance of new scoring methods in increasing the specificity and interpretability of this task.

Extracellular vesicles derived from head and neck squamous cells carcinoma inhibit NLRP3 inflammasomes.

The content of tumor-derived extracellular vesicles (EVs) can regulate the tumor microenvironment and functionally acts in favor of cancer aggressiveness. To better elucidate the role of EVs in the interplay between immune system and tumor microenvironment, the purpose of this study was to analyze the effect of head and neck squamous cells carcinoma (HNSCC)-derived EVs on the modulation of inflammasomes - mediators of pyroptosis and secretion of inflammatory factors by macrophages. Our results showed that macrophages treated with the Vesicular Secretome Fraction (VSF) isolated from patient-derived HNSCC presented a reduction in the secretion of mature IL-1ß and caspase-1 without affecting cell viability. An analysis of the protein content of HNSCC-derived VSF by antibody array revealed that some of the most expressed proteins share a correlation with Transforming Growth Factor-beta (TGF-ß) activity. Since TGF-ß is related to the inhibition of the NF-kB-related pathways, including those required for the priming phase of the inflammasomes, we sought to evalute the interference of the VSF in the induction of inflammasome components. In fact, HNSCC-derived VSF inhibited the induction of pro-IL-1ß and pro-caspase-1 proteins and NLRP3 gene expression during the priming phase of inflammasome activation. Thus, our findings contribute to a better understanding of how tumor-derived EVs modulate inflammatory response by demonstrating their role in inhibiting NLRP3 inflammasomes.

"Influence of modifiable and non-modifiable variables on functioning in bipolar disorder: a path analytical study".

OBJECTIVE: The aim of this study was to investigate the influence of modifiable (mood, cognitive reserve, cognitive performance) and non-modifiable factors (diagnosis, suicide attempts, substance use, age) on self-reported functioning in BD. METHODS: 103 adults with no mood disorders and 95 individuals with BD completed the WHODAS 2.0, in addition to a neuropsychological battery and diagnostic assessments. Path analysis was then used to analyse the relationships between modifiable and non-modifiable predictors of functioning in the sample. RESULTS: Cognitive reserve and age had an indirect influence on individual functioning, mediated by cognitive performance. The influence of diagnosis and depressive symptoms on functioning was partly direct, and partly mediated by cognition. The presence of psychiatric comorbidities in addition to BD also had a significant influence on individual functioning. CONCLUSIONS: Initiatives focussed on modifiable factors such as depressive symptoms and cognitively stimulating activities, which increase cognitive reserve, may be a useful complement to existing treatments and help patients achieve functional recovery. KEY POINTS Individual functioning was influenced by cognitive performance, cognitive reserve, age, diagnosis and depressive symptoms. Executive functioning mediated the influence of age and cognitive reserve on individual functioning. Interventions focussed on depressive symptoms and cognitive stimulation may help patients achieve functional recovery.

The effects of cognitive reserve and depressive symptoms on cognitive performance in major depression and bipolar disorder.

BACKGROUND: Significant heterogeneity is observed in the cognitive profiles of bipolar disorder (BD) and major depression (MDD), characterized in part by differences in individual and clinical variables such as cognitive reserve (CR) and depression severity. However, no other study evaluated how this variables may interact regarding neurocognitive functioning. The aim of the present exploratory study was to evaluate the interaction between different depressive symptoms severity, CR and diagnosis with neurocognitive functioning. METHOD: 202 participants (MDD=91; BD=111) classified either as euthymic, with mild depression or moderate to severe depression, and low or high CR completed a neuropsychological evaluation of verbal fluency, working memory (WM), inhibitory control (IC), cognitive flexibility (CF) and attention (Att). RESULTS: Neuroprotective effects of CR were observed in patients with BD within a major depressive episode in WM, IC, FC and Att. In MDD, CR acted as a neuroprotective factor during euthymia and moderate to severe depression in the same cognitive functions. CR and depression severity differentiated the cognitive profiles of individuals with BD and MDD. LIMITATIONS: Some variables related to neurocognitive performance like medication use, number of mood episodes, illness duration or previous hospitalizations were not controlled. CONCLUSION: CR may be protective against cognitive impairment in both BD and MDD, and these effects were observed in euthymia and during depressive episodes of varying severity. These findings highlight the importance of investigating such variables in the neuropsychological evaluation of mood disorders, which may help to understand the cognitive heterogeneity within these populations.

Annexin A1 Regulates NLRP3 Inflammasome Activation and Modifies Lipid Release Profile in Isolated Peritoneal Macrophages.

Annexin A1 (AnxA1) is a potent anti-inflammatory protein that downregulates proinflammatory cytokine release. This study evaluated the role of AnxA1 in the regulation of NLRP3 inflammasome activation and lipid release by starch-elicited murine peritoneal macrophages. C57bl/6 wild-type (WT) and AnxA1-null (AnxA1-/-) mice received an intraperitoneal injection of 1.5% starch solution for macrophage recruitment. NLRP3 was activated by priming cells with lipopolysaccharide for 3 h, followed by nigericin (1 h) or ATP (30 min) incubation. As expected, nigericin and ATP administration decreased elicited peritoneal macrophage viability and induced IL-1ß release, more pronounced in the AnxA1-/- cells than in the control peritoneal macrophages. In addition, nigericin-activated AnxA1-/- macrophages showed increased levels of NLRP3, while points of co-localization of the AnxA1 protein and NLRP3 inflammasome were detected in WT cells, as demonstrated by ultrastructural analysis. The lipidomic analysis showed a pronounced release of prostaglandins in nigericin-stimulated WT peritoneal macrophages, while ceramides were detected in AnxA1-/- cell supernatants. Different eicosanoid profiles were detected for both genotypes, and our results suggest that endogenous AnxA1 regulates the NLRP3-derived IL-1ß and lipid mediator release in macrophages.

Predictors of quality of life in bipolar disorder: A path analytical study.

Quality of life (QoL) is an important outcome in psychiatric illnesses like bipolar disorder (BD). However, little is known about the variables that affect it, and therefore contribute to prognosis and treatment outcomes in these populations. This study aimed to explore QoL in BD and investigate its relationship with modifiable (cognitive reserve, cognitive ability, mood symptoms) and non-modifiable factors (diagnosis, previous suicide attempts, substance misuse, age). The WHOQOL-bref was administered to 121 control participants and 109 patients with BD, who also underwent clinical and neuropsychological assessments. Factor analysis was used to identify latent constructs underlying WHOQOL-bref domains, and structural equation models were used to examine predictors of each latent construct. Two latent constructs were identified in the WHOQOL-bref, and labeled 'Personal' and 'Social' QoL. Both were directly predicted by depression symptoms and a diagnosis of BD, and indirectly predicted by (hypo)manic symptoms. Cognitive reserve was a stronger predictor of social QoL than a diagnosis of BD. Our findings suggest that the management of depression symptoms and fostering of cognitive reserve may improve QoL in BD. A diagnosis of BD and/or substance use disorders were risk factors for poor QoL, and may signal the need for preventive interventions to promote well-being.

Regulation of Innate Immune Responses by Platelets.

The role of platelets has been extensively studied in the context of coagulation and vascular integrity. Their hemostatic imbalance can lead to known conditions as atherosclerotic plaques, thrombosis, and ischemia. Nevertheless, the knowledge regarding the regulation of different cell types by platelets has been growing exponentially in the past years. Among these biological systems, the innate immune response is remarkably affected by the crosstalk with platelets. This interaction can come from the formation of platelet-leukocyte aggregates, signaling by direct contact between membrane surface molecules or by the stimulation of immune cells by soluble factors and active microparticles secreted by platelets. These ubiquitous blood components are able to sense and react to danger signals, guiding leukocytes to an injury site and providing a scaffold for the formation of extracellular traps for efficient microbial killing and clearance. Using several different mechanisms, platelets have an important task as they regulate the release of different cytokines and chemokines upon sterile or infectious damage, the expression of cell markers and regulation of cell death and survival. Therefore, platelets are more than clotting agents, but critical players within the fine inflammatory equilibrium for the host. In this review, we present pointers to a better understanding about how platelets control and modulate innate immune cells, as well as a summary of the outcome of this interaction, providing an important step for therapeutic opportunities and guidance for future research on infectious and autoimmune diseases.

Pattern Recognition Receptors and the Host Cell Death Molecular Machinery.

Pattern Recognition Receptors (PRRs) are proteins capable of recognizing molecules frequently found in pathogens (the so-called Pathogen-Associated Molecular Patterns-PAMPs), or molecules released by damaged cells (the Damage-Associated Molecular Patterns-DAMPs). They emerged phylogenetically prior to the appearance of the adaptive immunity and, therefore, are considered part of the innate immune system. Signals derived from the engagement of PRRs on the immune cells activate microbicidal and pro-inflammatory responses required to eliminate or, at least, to contain infectious agents. Molecularly controlled forms of cell death are also part of a very ancestral mechanism involved in key aspects of the physiology of multicellular organism, including the elimination of unwanted, damaged or infected cells. Interestingly, each form of cell death has its particular effect on inflammation and on the development of innate and adaptive immune responses. In this review article, we discuss some aspects of the molecular interplay between the cell death machinery and signals initiated by the activation of PRRs by PAMPs and DAMPs.

Adaptation and validation of the Melbourne Decision Making Questionnaire to Brazilian Portuguese / Adaptação e validação do Melbourne Decision Making Questionnaire em português brasileiro

Abstract Introduction: Decision making (DM) is among the most important abilities for everyday functioning. However, the most widely used measures of DM come from behavioral paradigms, whose ecological validity and standalone use has been criticized in the literature. Though these issues could be addressed by the use of DM questionnaires as a complementary assessment method, no such instruments have been validated for use in Brazilian Portuguese. Therefore, the aim of this study was to conduct the translation and validation of the Melbourne Decision Making Questionnaire (MDMQ) for use in a Brazilian population. Methods: The adaptation of the MDMQ involved the following steps: translation, back-translation, expert review and pilot study. These steps were followed by factor analysis and internal consistency measurements, which led to the exclusion of 4 items from the scale. The 18-item version of the MDMQ was then administered to a validation sample consisting of healthy adults, as well as patients with bipolar disorder (BD) and major depressive disorder (MDD). Results: The instrument displayed good internal consistency, with the hypervigilance subscale showing the lowest, though still acceptable, Cronbach's alpha value. Its factor structure was comparable to that of the original MDMQ according to confirmatory factor analysis. Nevertheless, the MDMQ was sensitive to both depression severity and the presence of MDD and BD, both of which are known to have an impact on DM ability. Conclusion: The version of the MDMQ produced in the present study may be an important addition to neuropsychological assessment batteries with a focus on DM and related abilities

Resumo Introdução: A tomada de decisão (TD) é uma das habilidades mais relevantes para a funcionalidade. No entanto, esta habilidade é geralmente avaliada por meio de tarefas comportamentais, cuja validade ecológica tem sido questionada. De acordo com a literatura, a avaliação da TD deve ser complementada por questionários ou escalas, instrumentos estes que não estão disponíveis no português brasileiro. Desta forma, o objetivo deste estudo foi a tradução e validação de uma versão do Melbourne Decision Making Questionnaire (MDMQ), o instrumento mais amplamente utilizado na avaliação da TD, para uso em português. Métodos: A adaptação da MDMQ foi realizada através da tradução, retrotradução, avaliação por painel de juízes e estudo piloto. A versão da escala produzida neste processo foi submetida a análise fatorial e avaliação de consistência interna, levando a exclusão de 4 itens da escala original. A versão resultante da MDMQ, contando com 18 itens no total, foi então utilizada em estudo de validação, em que a TD foi comparada entre adultos saudáveis e portadores de depressão e transtorno bipolar. Resultados: O instrumento demonstrou consistência interna satisfatória, apesar da obtenção de alfas de Cronbach relativamente baixos para a subescala de hipervigilância. A estrutura fatorial do questionário traduzido foi semelhante a observada no instrumento original. Todas as medidas derivadas da MDMQ, mostraram-se discriminativas na comparação entre adultos saudáveis e portadores de transtornos mentais. Conclusão: A versão da MDMQ produzida neste estudo poderá realizar uma importante contribuição para a prática clínica e pesquisa neuropsicológica acerca da TD.

Self-reported inhibition predicts history of suicide attempts in bipolar disorder and major depression.

BACKGROUND: Studies have reliably identified an association between suicide attempts and executive functions such as decision making (DM) and inhibitory control (IC) in patients with mood disorders. As such, the present study aimed to investigate the association between inhibition, DM, impulsivity and the history of suicide attempts in individuals with bipolar (BD) or major depressive disorder (MDD), identifying which assessment instruments may be most strongly associated with suicide in clinical samples. METHODS: The sample included 80 control subjects and two groups of patients with BD and MDD, matched by age and education (26 with a history of suicide attempts [MD+], and 26 with no such history [MD-]). Participants completed behavioral and self-report measures of DM and IC, which were compared between groups using ANCOVA, followed by logistic regression for patients with mood disorders only, and the presence or absence of a history of suicide as the outcome. RESULTS: Cognitive performance did not differ between groups. The MD+ group showed significantly higher motor and attentional impulsivity on the BIS-11 than the MD- and control groups. A regression analysis containing these scores showed that motor impulsivity was the only significant predictor of a history of suicide (OR = 1.14; 95%CI 1.00-1.30). CONCLUSIONS: Self-reported motor impulsivity was a significant predictor of suicide. These findings underscore the importance of self-report measures in neuropsychological assessment, and their contributions to the management and prognosis of patients with mood disorders. Lastly, they point to the role of impulsivity as a target for interventions and public policy on suicide prevention.

Adaptation and validation of the Melbourne Decision Making Questionnaire to Brazilian Portuguese.

INTRODUCTION: Decision making (DM) is among the most important abilities for everyday functioning. However, the most widely used measures of DM come from behavioral paradigms, whose ecological validity and standalone use has been criticized in the literature. Though these issues could be addressed by the use of DM questionnaires as a complementary assessment method, no such instruments have been validated for use in Brazilian Portuguese. Therefore, the aim of this study was to conduct the translation and validation of the Melbourne Decision Making Questionnaire (MDMQ) for use in a Brazilian population. METHODS: The adaptation of the MDMQ involved the following steps: translation, back-translation, expert review and pilot study. These steps were followed by factor analysis and internal consistency measurements, which led to the exclusion of 4 items from the scale. The 18-item version of the MDMQ was then administered to a validation sample consisting of healthy adults, as well as patients with bipolar disorder (BD) and major depressive disorder (MDD). RESULTS: The instrument displayed good internal consistency, with the hypervigilance subscale showing the lowest, though still acceptable, Cronbach's alpha value. Its factor structure was comparable to that of the original MDMQ according to confirmatory factor analysis. Nevertheless, the MDMQ was sensitive to both depression severity and the presence of MDD and BD, both of which are known to have an impact on DM ability. CONCLUSION: The version of the MDMQ produced in the present study may be an important addition to neuropsychological assessment batteries with a focus on DM and related abilities.

Attentional impairments following right hemisphere damage with and without hemispatial neglect: A comparative study.

This study aimed to evaluate the performance of patients with right hemisphere damage (RHD) with or without hemispatial neglect (HN) on a cancellation task. The study involved 31 control participants and 31 patients with RHD, matched by age, education, and frequency of reading and writing habits. The numbers of omission and random errors as well as the mean time to task completion were compared between adults with and without RHD, as well as between patients with and without HN. The latter made more left-sided omission errors, and more overall omission errors, than patients with RHD and no HN. The location of the first target canceled differed between subjects with RHD and control participants, as well as between patients with and without hemineglect. The use of organized vs. disorganized search strategies did not differ between groups. Further studies are required to investigate the performance of patients with HN of different levels of severity.

Reliability and construct validity of the bells test / Confiabilidad y validez de constructo del test de cancelación de las campanas / Fidedignidade e validade de construto do teste de cancelamento dos sinos

The Bells Test (BT) is widely used to aid in the diagnosis of heminegligence. The objective of this study was to evaluate the convergent validity of the BT, comparing it with tools that evaluate similar constructs, and to investigate its test-retest reliability. The sample included 66 healthy adults age 19-75 years. The reliability was evaluated through a test-retest procedure, with correlations and t-tests for paired samples, while validity was investigated through comparisons between the performance on the BT and scores in the Concentrated Attention test (CA-15), the Sustained Attention test (SA), and the WAIS-III Symbols and Codes subtests. Positive correlations were found between test and retest in both BT versions, as well as between the number of BT omissions and other attention measures. These results corroborate the validity and reliability of the two BT versions in the Brazilian population. (AU)

O Teste de Cancelamento dos Sinos (TCS) é amplamente utilizado para auxiliar o diagnóstico de heminegligência. O objetivo deste estudo foi avaliar a validade convergente do TCS, comparando-o a ferramentas que avaliam construtos similares, e investigar sua fidedignidade teste-reteste. A amostra incluiu 66 adultos saudáveis com idades entre 19 e 75 anos. A fidedignidade foi avaliada por meio de procedimento teste-reteste, com correlações e testes t para amostras pareadas, enquanto a validade foi investigada através de comparações entre o desempenho no TCS e escores no teste de Atenção Concentrada (AC-15), teste de Atenção Sustentada (AS) e os subtestes Símbolos e Códigos do WAIS-III. Correlações positivas foram encontradas entre teste e reteste nas duas versões do TCS, assim como entre o número de omissões no TCS e demais medidas de atenção. Esses resultados corroboram a validade e fidedignidade das duas versões do TCS na população Brasileira. (AU)

El Test de las Campanas (TC) es un instrumento ampliamente utilizado para auxiliar en el diagnóstico de heminegligencia. El objetivo de este estudio fue evaluar la validez convergente del TCS, comparándolo con otras herramientas que evalúan constructos similares, e investigar su confiabilidad test-retest. La muestra incluyó 66 adultos con buena salud, de 19 a 75 años. La confiabilidad fue evaluada a través de procedimientos de test-retest, con correlaciones y tests-t para muestras pareadas, y la validez fue investigada a través de comparaciones entre el desempeño del TCS y los resultados en el test de Atención Concentrada (AC-15), test de Atención Sostenida (AS) y los sub-tests Símbolos y Códigos del WAIS-III. Correlaciones positivas fueron encontradas entre test y retest en las dos versiones del TCS así como entre el número de omisiones en el TCS y otras medidas de atención. Estos resultados corroboran validez y confiabilidad de las dos versiones del TCS en la población brasileña. (AU)

Neuropsychological Clustering in Bipolar and Major Depressive Disorder.

OBJECTIVES: Cognitive dysfunction is a key feature of major depressive (MDD) and bipolar (BD) disorders. However, rather than a single cognitive profile corresponding to each diagnostic categories, recent studies have identified significant intra- and cross-diagnostic variability in patterns of cognitive impairment. The goal of this study was to contribute to the literature on cognitive heterogeneity in mood disorders by identifying cognitive subprofiles in a population of patients with MDD, BD type I, BD type II, and healthy adults. METHODS: Participants completed a neuropsychological battery; scores were converted into Z-scores using normative data and submitted to hierarchical cluster analysis. RESULTS: Three distinct neuropsychological clusters were identified: (1) a large cluster containing mostly control participants, as well as some patients with BD and MDD, who performed at above-average levels on all neuropsychological domains; (2) a cluster containing some patients from all diagnostic groups, as well as healthy controls, who performed worse than cluster 1 on most tasks, and showed impairments in motor inhibition and verbal fluency; (3) a cluster containing mostly patients with mood disorders with severe impairments in verbal inhibition and cognitive flexibility. CONCLUSIONS: These findings revealed multiple cognitive profiles within diagnostic categories, as well as significant cross-diagnostic overlap, highlighting the importance of developing more specific treatment approaches which consider patients' demographic and cognitive profiles in addition to their diagnosis. (JINS, 2017, 23, 584-593).

The predictive role of daily cognitive stimulation on executive functions in bipolar disorder.

This study aimed to estimate the predictive role of clinical and demographic variables on the three core executive functions (EF) - working memory (WM), inhibitory control (IC) and cognitive flexibility (CF) - in bipolar disorder (BD). The sample consisted of 38 patients with BD type I, 39 with BD type II, and 106 control participants with no mood disorders. Subjects completed the Hayling Test, Trail Making Test, Digit Span Backwards, Sentence Word Span Test, and Stroop Color-Word Test. Composite scores for WM, IC and CF were calculated, and their correlations with clinical and demographic variables were analyzed. Stepwise hierarchical regression models including all significant correlates, gender, and diagnosis, revealed that the frequency of reading and writing habits (FRWH), IQ and diagnosis predicted 38.1% of the variance in IC. Diagnosis and IQ predicted 24.9% of the variance in WM scores. CF was predicted by the FRWH only, which accounted for 7.6% of the variance in this construct. These results suggest that daily cognitive stimulation through reading and writing make a significant positive contribution to executive functioning in BD, even in the absence of continued education. These and other forms of routine cognitive stimulation should be further emphasized in intervention programs for BD.