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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive functioning in bipolar disorder is heterogeneous with evidence for multiple subgroups. However, cognitive subgroup change patterns over time remains unknown. While prior work suggests minimal differences in cognitive functioning patterns over time between those with bipolar disorder and controls, group‐based analyses may obscure unique subgroup‐based changes. Material and Methods: Participants diagnosed with bipolar disorder (I, II, NOS; n = 568) and unaffected controls (n = 234) completed baseline, one‐ and five‐year neuropsychological assessments. Data reduction techniques were used to limit the number of neuropsychological variables. Bipolar disorder participant baseline neuropsychological data were entered into hierarchical cluster analyses and resultant clusters were entered in multilevel models, which tested for differences in baseline and longitudinal cognitive changes in cognition among the cluster groups and with controls. Results: Results were consistent with bipolar disorder participants forming three subgroups with high (n = 209), mid (n = 259), and low (n = 100) cognition. These groups were associated with unique clinical characteristics. Multilevel models demonstrated that over a five‐year period, the low group improved, relative to the high and mid groups, and with controls, in auditory memory. Over the five‐year period, the mid group, in comparison with the high group, improved in visual memory; additionally, the high group remained stable, in comparison with a slight decline in the control group, in inhibitory control. Conclusion: These results demonstrate that cognition‐based subgroups of bipolar disorder participants have minimal differences in their longitudinal course in relation to each other and with unaffected controls. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Using a self‐administered questionnaire (the five‐item Brief Symptom Rating Scale, BSRS‐5), determine the prevalence of suicide ideation (SI), psychiatric morbidity (PM), and the factors associated with these conditions in a general hospital in Taiwan. All individuals aged 12 years or older, who were admitted to a Medical University Hospital between August 2014 and December 2016, were asked to fill out the BSRS‐5 at admission. The study was conducted in a medical inpatient setting, excluding Intensive Care Units and the Emergency Service Department. The 93,129 participants were recruited for analysis. Pearson's correlation, regression analysis and path analysis were performed to test the association between SI and each item of psychopathology and to determine the discrimination validity of individual BSRS‐5 items for predicting SI. The prevalence rate was 2.3% for SI and 2.0% for PM among all participants. PM was more prevalent in females and those aged 25–54 years. Individuals with PM had a significantly higher rate of SI (44.6%) than did others (1.4%). The prevalence of PM was varied by department, e.g., Psychiatry (44.3%), Rehabilitation Medicine (7.9%), and Nephrology (5.2%). The regression analysis and path analysis with structural equation model indicated that depression, hostility, anxiety, and inferiority were significant independent predictors of SI. The BSRS‐5 is an efficient and useful screening tool to identify psychological distress and SI among inpatients in a general hospital. Its integration into the electronic medical chart facilitates identifying patients at risk. [ABSTRACT FROM AUTHOR]

Obsessive–compulsive disorder (OCD) is highly heterogeneous. While obsessions often involve fear of harm, many patients report uncomfortable sensations and/or urges that drive repetitive behaviors in the absence of a specific fear. Prior work suggests that urges in OCD may be similar to everyday "urges‐for‐action" (UFA) such as the urge to blink, swallow, or scratch, but very little work has investigated the pathophysiology underlying urges in OCD. In the current study, we used an urge‐to‐blink approach to model sensory‐based urges that could be experimentally elicited and compared across patients and controls using the same task stimuli. OCD patients and controls suppressed eye blinking over a period of 60 s, alternating with free blinking blocks, while brain activity was measured using functional magnetic resonance imaging. OCD patients showed significantly increased activation in several regions during the early phase of eyeblink suppression (first 30 s), including mid‐cingulate, insula, striatum, parietal cortex, and occipital cortex, with lingering group differences in parietal and occipital regions during late eyeblink suppression (last 30 s). There were no differences in brain activation during free blinking blocks, and no conditions where OCD patients showed reduced activation compared to controls. In an exploratory analysis of blink counts performed in a subset of subjects, OCD patients were less successful than controls in suppressing blinks. These data indicate that OCD patients exhibit altered brain function and behavior when experiencing and suppressing the urge to blink, raising the possibility that the disorder is associated with a general abnormality in the UFA system that could ultimately be targeted by future treatments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article offers information on causes of the cognitive deficits in Bipolar Disorder (BD), which is the fourth leading cause of disability worldwide among young people of age range between 10-24. It is noted that "The International Consortium Investigating Cognition in Bipolar Disorder" (ICONIC-BD) was organized to bring together an international team of experts in BD to analyze various issues.

Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self-reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self-reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self-rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp 38:6068-6082, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 age2). 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. [ABSTRACT FROM AUTHOR]

Cognitive impairment is emerging as an important therapeutic target in patients with psychiatric illnesses, including major depressive disorder (MDD). The objective of this general overview is to briefly review the evidence for cognitive impairment in MDD and to summarize a representative sample of cognitive assessment tools currently available to assess cognitive function in depressed patients. Study results in MDD patients with cognitive dysfunction are somewhat inconsistent, likely due to the heterogeneity of the disorder as well as the use of diverse assessment tools. Measuring cognitive changes in this population is challenging. Cognitive symptoms are typically less severe than in patients with schizophrenia and bipolar disorder, requiring greater sensitivity than afforded by existing tools. Preliminary evidence suggests antidepressant treatments may improve cognitive functioning as a direct result of ameliorating depressive symptoms; however, any procognitive effects have not been elucidated. To evaluate antidepressant efficacy in MDD patients with cognitive dysfunction, a standardized cognitive battery for use in clinical trials is essential. [ABSTRACT FROM AUTHOR]

The Royal Australian and New Zealand College of Psychiatrists (RANZCP) is to be commended for setting forth clear and detailed directions regarding the management of bipolar disorder's (BD) mood symptomatology and episode recurrence in its 2020 clinical practice guidelines.1 We were surprised, however, that cognitive dysfunction was only briefly mentioned as an aspect of BD's symptom profile (in the context of the ACE model). Hence, awareness that there is potential for sustained cognitive dysfunction in patients with BD is important, and should be considered by clinicians when setting tasks, examining cognitive biases and in interacting with patients generally. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mahon K, Burdick KE, Wu J, Ardekani BA, Szeszko PR. Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study. Bipolar Disord 2012: 14: 80-89. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. 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. [ABSTRACT FROM AUTHOR]

Gopin CB, Burdick KE, DeRosse P, Goldberg TE, Malhotra AK. Emotional modulation of response inhibition in stable patients with bipolar I disorder: a comparison with healthy and schizophrenia subjects. Bipolar Disord 2011: 13: 164-172. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. 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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

Yatham LN, Torres IJ, Malhi GS, Frangou S, Glahn DC, Bearden CE, Burdick KE, Martínez-Arán A, Dittmann S, Goldberg JF, Ozerdem A, Aydemir O, Chengappa KNR. The International Society for Bipolar Disorders–Battery for Assessment of Neurocognition (ISBD-BANC). Bipolar Disord 2010: 12: 351–363. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. 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. [ABSTRACT FROM AUTHOR]

Harvey PD, Wingo AP, Burdick KE, Baldessarini RJ. Cognition and disability in bipolar disorder: lessons from schizophrenia research. Bipolar Disord 2010: 12: 364–375. © 2010 The Authors. Journal compilation © 2010 John Wiley & 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. [ABSTRACT FROM AUTHOR]

Dystrobrevin binding protein 1 (DTNBP1) has been identified as putative schizophrenia susceptibility gene, but it remains unknown whether polymorphisms relate to altered cerebral structure. We examined relationships between a previously implicated DTNBP1 risk variant [P1578] and global and segmented brain tissue volumes and regional cortical thickness in schizophrenia ( n = 62; 24 risk carriers) and healthy subjects ( n = 42; 11 risk carriers), across ethnic groups and within Caucasians. Schizophrenia patients showed similar brain volumes, but significantly reduced brain-size adjusted gray matter and CSF volumes and cortical thinning in a widespread neocortical distribution compared to controls. DTNBP1 risk was found associated with reduced brain volume, but not with tissue sub-compartments. Cortical thickness, which was weakly associated with brain size, showed regional variations in association with genetic risk, although effects were dominated by highly significant genotype by diagnosis interactions over broad areas of cortex. Risk status was found associated with regional cortical thinning in patients, particularly in temporal networks, but with thickness increases in controls. DTNBP1 effects for brain volume and cortical thickness appear driven by different neurobiological processes. Smaller brain volumes observed in risk carriers may relate to previously reported DTNBP1/cognitive function relationships irrespective of diagnosis. Regional cortical thinning in patient, but not in control risk carriers, may suggest that DTNBP1 interacts with other schizophrenia-related risk factors to affect laminar thickness. Alternatively, DTNBP1 may influence neural processes for which individuals with thicker cortex are less vulnerable. Although DTNBP1 relates to cortical thinning in schizophrenia, morphological changes in the disorder are influenced by additional genetic and/or environmental factors. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Thalamic abnormalities have been implicated in the pathogenesis of schizophrenia, although the majority of studies used chronic samples treated extensively with antipsychotics. Moreover, the clinical and neuropsychological correlates of these abnormalities remain largely unknown. Using high-resolution MR imaging and novel methods for shape analysis, we investigated thalamic subregions in 35 (25 M/10 F) first-episode schizophrenia patients compared with 33 (23 M/10 F) healthy volunteers. The right and left thalami were traced bilaterally on coronal brain slices and volumes were compared between groups. In addition, regional abnormalities were identified by comparing distances, measured from homologous thalamic surface points to the central core of each individual's surface model, between groups in 3D space. Patients had significantly less total thalamic volume compared with healthy volunteers. Statistical mapping demonstrated most pronounced shape abnormalities in the pulvinar; however, estimated false discovery rates in these regions were sizable. Smaller thalamus volume was significantly correlated with worse overall neuropsychological functioning and specific deficits were observed in the language, motor, and executive domains. There were no significant associations between thalamus volume and positive or negative symptoms. Our findings suggest that thalamic abnormalities are evident at the onset of a first episode of schizophrenia prior to extensive pharmacologic intervention and that these abnormalities have neuropsychological correlates. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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, η2 = 0.07] particularly with regard to prefrontal aspects of learning (CVLT semantic cluster; p = 0.037, η2 = 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. [ABSTRACT FROM AUTHOR]

The recently published debate article by Douglas et al.[1] contends to introduce new terminology for therapeutic interventions on cognition in patients with major mood disorders. REFERENCES 1 Douglas KM, Peckham A, Porter R, Hammar A. Cognitive enhancement therapy for mood disorders: A new paradigm?. [Extracted from the article]

Background Methods Results Conclusion Effective treatment of bipolar disorder (BD) requires prompt response to mood episodes. Preliminary studies suggest that predictions based on passive sensor data from personal digital devices can accurately detect mood episodes (e.g., between routine care appointments), but studies to date do not use methods designed for broad application. This study evaluated whether a novel, personalized machine learning approach, trained entirely on passive Fitbit data, with limited data filtering could accurately detect mood symptomatology in BD patients.We analyzed data from 54 adults with BD, who wore Fitbits and completed bi‐weekly self‐report measures for 9 months. We applied machine learning (ML) models to Fitbit data aggregated over two‐week observation windows to detect occurrences of depressive and (hypo)manic symptomatology, which were defined as two‐week windows with scores above established clinical cutoffs for the Patient Health Questionnaire‐8 (PHQ‐8) and Altman Self‐Rating Mania Scale (ASRM) respectively.As hypothesized, among several ML algorithms, Binary Mixed Model (BiMM) forest achieved the highest area under the receiver operating curve (ROC‐AUC) in the validation process. In the testing set, the ROC‐AUC was 86.0% for depression and 85.2% for (hypo)mania. Using optimized thresholds calculated with Youden's J statistic, predictive accuracy was 80.1% for depression (sensitivity of 71.2% and specificity of 85.6%) and 89.1% for (hypo)mania (sensitivity of 80.0% and specificity of 90.1%).We achieved sound performance in detecting mood symptomatology in BD patients using methods designed for broad application. Findings expand upon evidence that Fitbit data can produce accurate mood symptomatology predictions. Additionally, to the best of our knowledge, this represents the first application of BiMM forest for mood symptomatology prediction. Overall, results move the field a step toward personalized algorithms suitable for the full population of patients, rather than only those with high compliance, access to specialized devices, or willingness to share invasive data. [ABSTRACT FROM AUTHOR]

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness., (© 2015 Wiley Periodicals, Inc.)