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Background: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD., Methods: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials., Results: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias., Conclusions: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers., (© 2024 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia., Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns., Results: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort., Conclusions: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD., Methods: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors., Results: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning., Conclusions: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions., Methods: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist., Results: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred., Conclusions: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical samples with cross-sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life-story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Objectives: Increasing evidence supports a bidirectional relationship between major depressive disorder (MDD) and obesity, but the role of visceral adipose tissue (VAT) as a measure of obesity in relation to MDD is not well understood. Here we review literature investigating the link between MDD and VAT in terms of biomarkers, sex differences, and aging., Methods: PubMed, EMBASE, PsycINFO, and CINAHL searches were conducted on December 11, 2020. No date or language limits were imposed. Major concepts searched were Depressive Disorder linked with Adipose Tissue, White, Hypothalmo-Hypophyseal System, and Pituitary-Adrenal System in addition to keywords. A final set of 32 items meeting criteria for inclusion., Results: Converging biological evidence suggests a significant bidirectional relationship between VAT and MDD across the lifespan. In adulthood, greater VAT was associated with increased risk for depression, especially in vulnerable groups such as individuals who are overweight/obese, postmenopausal women, and individuals with comorbid medical or psychiatric illness. In older adults, sarcopenia had an impact on the relationship between abnormal VAT and risk of depression. Additionally, sex differences emerged as a potential factor affecting the strength of the association between VAT and depression., Conclusions: Elucidating the pathophysiological mechanisms associated with increased rates of depression in obese individuals will be crucial for developing specific treatment strategies that seek to improve outcomes in individuals with comorbid depression and obesity. Moreover, identifying age- and sex-specific risk factors may contribute to a more personalized medicine approach, thereby improving the quality of clinical care., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations., Methods: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials., Results: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking., Conclusions: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Objectives: We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed neuropsychological profile., Methods: We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive function in OABD (age ≥50 years ) containing, at a minimum, the domains of attention/processing speed, memory, and executive functions were included. A random-effects meta-analysis was conducted to summarize differences between patients and matched controls in each cognitive domain. We also conducted meta-regressions to estimate the impact of clinical and socio-demographic variables on these differences., Results: Eight articles, providing data for 328 euthymic OABD patients and 302 healthy controls, were included in the meta-analysis. OABD showed worse performance in comparison with healthy controls, with large significant effect sizes (Hedge's g from -0.77 to -0.89; p < 0.001) in verbal learning and verbal and visual delayed memory. They also displayed statistically significant deficits, with moderate effect size, in processing speed, working memory, immediate memory, cognitive flexibility, verbal fluency, psychomotor function, executive functions, attention, inhibition, and recognition (Hedge's g from -0.52 to -0.76; p < 0.001), but not in language and visuoconstruction domains. None of the examined variables were associated with these deficits., Conclusions: Cognitive dysfunction is present in OABD, with important deficits in almost all cognitive domains, especially in the memory domain. Our results highlight the importance of including a routine complete neuropsychological assessment in OABD and also considering therapeutic strategies in OABD., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Cognitive dysfunction affects a significant proportion of people with bipolar disorder (BD), but the cause, trajectory and correlates of such dysfunction remains unclear. Increased understanding of these factors is required to progress treatment development for this symptom dimension., Methods: This paper provides a critical overview of the literature concerning the trajectories and emerging correlates of cognitive functioning in BD. It is a narrative review in which we provide a qualitative synthesis of current evidence concerning clinical, molecular, neural and lifestyle correlates of cognitive impairment in BD across the lifespan (in premorbid, prodromal, early onset, post-onset, elderly cohorts)., Results: There is emerging evidence of empirical links between cognitive impairment and an increased inflammatory state, brain structural abnormalities and reduced neuroprotection in BD. However, evidence regarding the progressive nature of cognitive impairment is mixed, since consensus between different cross-sectional data is lacking and does not align to the outcomes of the limited longitudinal studies available. Increased recognition of cognitive heterogeneity in BD may help to explain some inconsistencies in the extant literature., Conclusions: Large, longitudinally focussed studies of cognition and its covariation alongside biological and lifestyle factors are required to better define cognitive trajectories in BD, and eventually pave the way for the application of a precision medicine approach for individual patients in clinical practice., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta-analyses., Methods: The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018., Results: A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait-related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye-tracking and facial emotion analysis revealed subtle trait-related abnormalities in emotional reactivity., Conclusion: The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta-analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2017 The Authors Bipolar Disorders Published by John Wiley & Sons Ltd.)

Objectives: Cognitive dysfunction affects a substantial proportion of patients with bipolar disorder (BD), and genetic-imaging paradigms may aid in the elucidation of mechanisms implicated in this symptomatic domain. The Val allele of the functional Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working memory in BD., Methods: Sixty-four outpatients with BD in full or partial remission were stratified according to COMT Val158Met genotype (ValVal [n=13], ValMet [n=34], and MetMet [n=17]). The patients completed a spatial n-back working memory task during fMRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory test outside the scanner., Results: During high working memory load (2-back vs 1-back), Val homozygotes displayed decreased activity relative to ValMet individuals, with Met homozygotes displaying intermediate levels of activity in the right dorsolateral prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes., Conclusions: The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive impairments in BD., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Several studies have documented the prevalence and effects of cigarette smoking on cognition in psychotic disorders; fewer have focused on bipolar disorder (BD). Cognitive and social dysfunction are common in BD, and the severity of these deficits may be related both to illness features (e.g., current symptoms, psychosis history) and health-related behaviors (e.g., smoking, alcohol use). The current study assessed the influence of cigarette smoking on general and social cognition in a BD cohort, accounting for illness features with a focus on psychosis history., Methods: We assessed smoking status in 105 euthymic patients with BD, who completed a comprehensive battery including social (facial affect recognition, emotional problem-solving, and theory of mind) and general (the MATRICS Consensus Cognitive Battery and executive functioning) cognitive measures. We compared smokers vs nonsmokers on cognitive performance and tested for the effects of psychosis history, premorbid intellectual functioning, substance use, and current affective symptoms., Results: Within the nonpsychotic subgroup with BD (n=45), smokers generally outperformed nonsmokers; by contrast, for subjects with BD with a history of psychosis (n=41), nonsmokers outperformed smokers. This pattern was noted more globally using a general composite cognitive score and on social/affective measures assessing patients' ability to identify emotions of facial stimuli and solve emotional problems., Conclusions: Cigarette smoking differentially affects performance on both general and social cognition in patients with BD as a function of psychosis history. These results suggest that there may be at least partially divergent underlying neurobiological causes for cognitive dysfunction in patients with BD with and without psychosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Atypical age-associated changes in white matter integrity may play a role in the neurobiology of bipolar disorder, but no studies have examined the major white matter tracts using nonlinear statistical modeling across a wide age range in this disorder. The goal of this study was to identify possible deviations in the typical pattern of age-associated changes in white matter integrity in patients with bipolar disorder across the age range of 9-62 years., Methods: Diffusion tensor imaging was performed in 57 (20 male and 37 female) patients with a diagnosis of bipolar disorder and 57 (20 male and 37 female) age- and sex-matched healthy volunteers. Mean diffusivity and fractional anisotropy were computed for the genu and splenium of the corpus callosum, two projection tracts, and five association tracts using probabilistic tractography., Results: Overall, patients had lower fractional anisotropy and higher mean diffusivity compared to healthy volunteers across all tracts (while controlling for the effects of age and age(2) ). In addition, there were greater age-associated increases in mean diffusivity in patients compared to healthy volunteers within the genu and splenium of the corpus callosum beginning in the second and third decades of life., Conclusions: Our findings provide evidence for alterations in the typical pattern of white matter development in patients with bipolar disorder compared to healthy volunteers. Changes in white matter development within the corpus callosum may lead to altered inter-hemispheric communication that is considered integral to the neurobiology of the disorder., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Impulsivity is a core feature in bipolar disorder. Although mood symptoms exacerbate impulsivity, self-reports of impulsivity are elevated, even during euthymia. Neurocognitive processes linked to impulsivity (e.g., attention, inhibition) are also impaired in patients with bipolar disorder, and a high frequency of comorbidities associated with impulsivity, such as substance use disorders, further highlights the clinical relevance of this dimension of the illness. Our objective was to assess the relationship between impulsivity and cognition in bipolar disorder., Methods: We evaluated impulsivity in 98 patients with bipolar disorder and its relationship with symptoms, cognition, and substance use history. We assessed self-reports of trait impulsivity [Barrett Impulsiveness Scale (BIS)] and impulsive behaviors on the Iowa Gambling Task (IGT). A comprehensive clinical and neurocognitive battery was also completed. Patients were compared with 95 healthy controls., Results: Patients with bipolar disorder had higher scores versus healthy controls on all BIS scales. Performance on the IGT was significantly impaired and patients showed a tendency toward more erratic choices. Depressive symptoms were positively correlated with trait impulsivity and with an increased tendency to attend more readily to losses versus gains on the IGT. We found no significant associations between impulsivity and neurocognition in the full bipolar sample; however, when sub-grouped based on substance abuse history, significant relationships were revealed only in subjects without a substance abuse history., Conclusions: Our data support prior reports of increased trait impulsivity and impairment on behavioral tasks of impulsiveness in bipolar disorder and suggest a differential relationship between these illness features that is dependent upon history of substance abuse., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Schizophrenia and bipolar disorder may share common neurobiological mechanisms, but few studies have directly compared gray and white matter structure in these disorders. We used diffusion-weighted magnetic resonance imaging and a region of interest based analysis to identify overlapping and distinct gray and white matter abnormalities in 35 patients with schizophrenia and 20 patients with bipolar I disorder in comparison to 56 healthy volunteers., Methods: We examined fractional anisotropy within the white matter and mean diffusivity within the gray matter in 42 regions of interest defined on a probabilistic atlas following non-linear registration of the images to atlas space., Results: Patients with schizophrenia had significantly lower fractional anisotropy in temporal (superior temporal and parahippocampal) and occipital (superior and middle occipital) white matter compared to patients with bipolar disorder and healthy volunteers. By contrast, both patient groups demonstrated significantly higher mean diffusivity in frontal (inferior frontal and lateral orbitofrontal) and temporal (superior temporal and parahippocampal) gray matter compared to healthy volunteers, but did not differ from each other., Conclusions: Our study implicates overlapping gray matter frontal and temporal lobe structural alterations in the neurobiology of schizophrenia and bipolar I disorder, but suggests that temporal and occipital lobe white matter deficits may be an additional risk factor for schizophrenia. Our findings may have relevance for future diagnostic classification systems and the identification of susceptibility genes for these disorders., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well-investigated., Methods: Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract-Based Spatial Statistics method in the FSL software package., Results: Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity., Conclusions: Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder., (© 2012 John Wiley and Sons A/S.)

Objectives: Bipolar disorder (BD) has been associated with impairment in affective processing during depressive and manic states; however, there are limited data as to whether this population exhibits such difficulty during stable periods. We examined the pattern of affective processing in stable BD patients and compared their profile to that of healthy controls (HC) and patients diagnosed with schizophrenia (SZ)., Methods: A total of 336 subjects were administered an Affective Go/No-go test to evaluate target detection of negatively valenced, positively valenced, and neutral stimuli. Accuracy and response bias served as dependent variables in a series of multivariate analyses of covariance to test for group differences., Results: The BD group relative to the HC group exhibited response biases toward negatively valenced information (p<0.01). Deficits were also evident in discrimination of and accurate responses to positively valenced information in the BD group versus the HC group (p<0.05). In contrast to the controls, the SZ group performed poorly on all task components and was less accurate across all conditions regardless of affective valence (p<0.01). Patients with SZ evidenced reverse biases for positive information, as they were less likely to respond to positive words (p<0.05) despite comparable response bias on neutral and negative conditions., Conclusions: Affective processing impairment evident in BD is a feature of the disorder that is present even during stable periods. Prior studies comparing BD with SZ have highlighted clear quantitative but inconsistent qualitative differences in cognitive functioning. Our data suggest that a response bias toward negative stimuli may be a critical and relatively specific feature of BD., (© 2011 John Wiley and Sons A/S.)

Background: Cognitive and functional impairments occur in patients diagnosed with bipolar disorder (BPD), although they are usually less severe and far less studied than in schizophrenia. There may be value in applying approaches developed in schizophrenia research to study cognitive functioning among BPD patients in areas including performance-based disability assessment, cognitive remediation treatments, enhancement of the accuracy of real-world functioning, and studying cognition and disability in relatives., Methods: We reviewed current research on cognitive and functional disability in BPD, noted areas of similarity and discrepancy to research on schizophrenia, and highlighted methods and approaches used to study schizophrenia that can be applied to study unmet needs of BPD patients., Results: Research in schizophrenia increasingly separates potential functional capacity from real-world outcome status, and has assessed contributions of cognitive impairment and other illness factors to functional outcomes. For schizophrenia, various behavioral and pharmacological treatments aimed at cognitive enhancement have been attempted, with moderate success, compared to rare studies of treatment effects on cognitive impairment in BPD. Very little research has been performed in the occurrence of cognitive impairments in first-degree relatives of people with BPD, despite evidence that cognitive impairments may be stable traits across symptomatic status in people with BPD., Conclusions: Research and treatment approaches developed for schizophrenia can productively be applied to the study and treatment of patients diagnosed with BPD, notably including studies of the characteristics of and treatments for functional impairment related to cognitive deficits.

Objectives: Although cognitive impairment is recognized as an important clinical feature of bipolar disorder, there is no standard cognitive battery that has been developed for use in bipolar disorder research. The aims of this paper were to identify the cognitive measures from the literature that show the greatest magnitude of impairment in bipolar disorder, to use this information to determine whether the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), developed for use in schizophrenia, might be suitable for bipolar disorder research, and to propose a preliminary battery of cognitive tests for use in bipolar disorder research., Methods: The project was conducted under the auspices of the International Society for Bipolar Disorders and involved a committee that comprised researchers with international expertise in the cognitive aspects of bipolar disorder. In order to identify cognitive tasks that show the largest magnitude of impairment in bipolar disorder, we reviewed the literature on studies assessing cognitive functioning (including social cognition) in bipolar disorder. We further provided a brief review of the cognitive overlap between schizophrenia and bipolar disorder and evaluated the degree to which tasks included in the MCCB (or other identified tasks) might be suitable for use in bipolar disorder., Results: Based on evidence that cognitive deficits in bipolar disorder are similar in pattern but less severe than in schizophrenia, it was judged that most subtests comprising the MCCB appear appropriate for use in bipolar disorder. In addition to MCCB tests, other specific measures of more complex verbal learning (e.g., the California Verbal Learning Test) or executive function (Stroop Test, Trail Making Test-part B, Wisconsin Card Sorting Test) also show substantial impairment in bipolar disorder., Conclusions: Our analysis reveals that the MCCB represents a good starting point for assessing cognitive deficits in research studies of bipolar disorder, but that other tasks including more complex verbal learning measures and tests of executive function should also be considered in assessing cognitive compromise in bipolar disorder. Several promising cognitive tasks that require further study in bipolar disorder are also presented.

Objectives: Bipolar disorder (BPD) is an affective disorder characterized by episodes of depression and mania. Cognitive impairment in patients with BPD is common and recent data suggest that it may represent a trait-like feature of the illness, as it persists during periods of wellness and co-segregates in families of bipolar patients. This suggests an underlying genetic predisposition towards cognitive impairment in patients with BPD; however, there have been few studies investigating the effects of candidate genes on this symptom domain. The catechol-O-methyl transferase (COMT) gene is located on chromosome 22q11 and is involved in the metabolism of dopamine and norepinephrine. A large body of evidence suggests that COMT is associated with cognitive performance in patients with schizophrenia and in healthy volunteers but there have been no reports of its relationship to cognition in BPD., Methods: We genotyped 52 Caucasian bipolar I probands and 102 Caucasian healthy controls across four single nucleotide polymorphisms (SNPs) within the COMT gene and administered a cognitive screening battery. We first assessed the relationship between COMT genotype and diagnosis and then tested for effects on cognition., Results: We observed a modest but significant association between SNP rs165599 and BPD I, with the g allele being over-represented in cases versus controls (odds ratio, OR = 2.41; allelic p = 0.02; genotypic p = 0.04). Further, we found a relationship between the risk allele at this SNP and poorer performance on measures of verbal memory [California Verbal Learning Test (CVLT) Trials 1-5; p = 0.005, eta(2) = 0.07] particularly with regard to prefrontal aspects of learning (CVLT semantic cluster; p = 0.037, eta(2) = 0.04) in patients with BPD and in healthy controls. The common Val158Met polymorphism was not associated with diagnosis (p = 0.32) or cognition in our sample., Conclusions: These data suggest that COMT genetic variation at SNP rs165599 is associated with BPD I and influences prefrontal aspects of verbal memory in bipolar patients and healthy controls.