Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

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.

Heterogeneity of Cognition in Older Adults with Remitted Major Depressive Disorder: A Latent Profile Analysis.

OBJECTIVES: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. DESIGN: Secondary cross-sectional analysis using latent profile analysis. SETTING: Multisite clinical trial in Toronto, Canada. PARTICIPANTS: One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). MEASUREMENTS: Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. RESULTS: We identified three latent profiles: Profile 1 (poor cognition; n = 75, 42.1%), Profile 2 (intermediate cognition; n = 75, 42.1%), and Profile 3 (normal cognition; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. CONCLUSION: Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups.

Manualized group cognitive behavioral therapy for social anxiety in first-episode psychosis: a randomized controlled trial.

BACKGROUND: Social anxiety (SA), a prevalent comorbid condition in psychotic disorders with a negative impact on functioning, requires adequate intervention relatively early. Using a randomized controlled trial, we tested the efficacy of a group cognitive-behavioral therapy intervention for SA (CBT-SA) that we developed for youth who experienced the first episode of psychosis (FEP). For our primary outcome, we hypothesized that compared to the active control of group cognitive remediation (CR), the CBT-SA group would show a reduction in SA that would be maintained at 3- and 6-month follow-ups. For secondary outcomes, it was hypothesized that the CBT-SA group would show a reduction of positive and negative symptoms and improvements in recovery and functioning. METHOD: Ninety-six patients with an FEP and SA, recruited from five different FEP programs in the Montreal area, were randomized to 13 weekly group sessions of either CBT-SA or CR intervention. RESULTS: Linear mixed models revealed that multiple measures of SA significantly reduced over time, but with no significant group differences. Positive and negative symptoms, as well as functioning improved over time, with negative symptoms and functioning exhibiting a greater reduction in the CBT-SA group. CONCLUSIONS: While SA decreased over time with both interventions, a positive effect of the CBT-SA intervention on measures of negative symptoms, functioning, and self-reported recovery at follow-up suggests that our intervention had a positive effect that extended beyond symptoms specific to SA.ClinicalTrials.gov identifier: NCT02294409.

Combined Cognitive Training and Vortioxetine Mitigates Age-Related Declines in Functional Brain Network Integrity.

OBJECTIVE: Age-related cognitive decline is common and potentially modifiable with cognitive training. Combining cognitive training with pro-cognitive medication offers an opportunity to modify brain networks to mitigate age-related cognitive decline. We tested the hypothesis that the efficacy of cognitive training could be amplified by combining it with vortioxetine, a pro-cognitive and pro-neuroplastic multimodal antidepressant. METHODS: We evaluated the effects of 6 months of computerized cognitive training plus vortioxetine (versus placebo) on resting state functional connectivity in older adults (age 65+) with age-related cognitive decline. We first evaluated the association of functional connectivity with age and cognitive performance (N = 66). Then we compared the effects of vortioxetine plus cognitive training versus placebo plus cognitive training on connectivity changes over the training period (n = 20). RESULTS: At baseline, greater age was significantly associated with lower within-network strength and network segregation, and poorer cognitive function. Cognitive training plus vortioxetine over 6 months positively impacted the relationship between age to mean network segregation. These effects were not observed in the placebo group. In contrast, vortioxetine did not modify the relationship of age to change in mean within-network strength. Exploratory analyses identified the cingulo-opercular network as the network most affected by cognitive training plus vortioxetine. CONCLUSION: This preliminary study provides evidence that combining cognitive training with pro-cognitive medication may modulate the effects of aging on functional brain networks. Results indicate that for older adults experiencing age-related cognitive decline, vortioxetine has a potentially beneficial effect on the correspondence between aging and functional brain network segregation. These results await replication in a larger sample.

Assessing the Longitudinal Relationship between Theta-Gamma Coupling and Working Memory Performance in Older Adults.

Theta-gamma coupling (TGC) is a neurophysiologic mechanism that supports working memory (WM). TGC is associated with N-back performance, a WM task. Similar to TGC, theta and alpha event-related synchronization (ERS) and desynchronization (ERD) are also associated with WM. Few studies have examined the longitudinal relationship between WM performance and TGC, ERS, or ERD. This study aimed to determine if changes in WM performance are associated with changes in TGC (primary aim), as well as theta and alpha ERS or ERD over 6 to 12 weeks. Participants included 62 individuals aged 60 and older with no neuropsychiatric conditions or with remitted Major Depressive Disorder (MDD) and no cognitive disorders. TGC, ERS, and ERD were assessed using electroencephalography (EEG) during the N-back task (3-back condition). There was an association between changes in 3-back performance and changes in TGC, alpha ERD and ERS, and theta ERS in the control group. In contrast, there was only a significant association between changes in 3-back performance and changes in TGC in the subgroup with remitted MDD. Our results suggest that the relationship between WM performance and TGC is stable over time, while this is not the case for changes in theta and alpha ERS and ERD.

Neurocognition and Depressive Symptoms have Unique Pathways to Predicting Different Domains of Functioning in Major Depressive Disorder.

BACKGROUND: Research has established the independent relationships between depressive symptoms to cognition and functioning in depression; however, little is known about the role of mediators in this relationship. We explored the role of neurocognitive abilities, depressive symptom severity, dysfunctional attitudes, and functional capacity in predicting two dimensions of daily functioning in individuals with major depressive disorder (MDD). METHODS: One hundred and twenty-four participants (mean age = 46.26, SD = 12.27; 56% female) with a diagnosis of MDD were assessed on a standard neurocognitive battery, self-reported depressive symptoms, dysfunctional attitudes, and clinician-rated functional impairment. They completed a performance-based assessment of functional competence. RESULTS: Confirmatory path analyses were used to model the independent and mediated effects of variables on two domains of functioning: social (relationships and social engagement) and productive (household and community activities). Cognition and depressive symptoms both predicted productive functioning, and dysfunctional attitudes mediated each of these relationships. Functional competence was a significant mediator in the relationship between neurocognition and productive functioning. Depressive symptoms and cognition were direct predictors of social functioning with no significant mediators. CONCLUSIONS: There are divergent pathways to different dimensions of daily functioning in MDD. Measurement implications include the consideration of multiple levels of predicting productive activities and more direct relationships with social outcomes. Treatments that directly target depressive symptoms and cognition might not generalize to improvements in everyday functioning if additional pathways to functioning are not addressed.

Childhood Adversity, Cognition, and Response to Cognitive Remediation in Major Depressive Disorder.

ABSTRACT: Cognitive impairment is experienced by many individuals with major depressive disorder (MDD) and is significantly related to sustained disability. Recent work has begun to explore the relationship between childhood adversity (CA) and cognitive impairment in MDD, but this work is limited by unreliable measures of CA. Furthermore, no previous research has examined whether CA relates to cognitive remediation response. The current study clarifies how CA and clinical characteristics of illness explain cognitive variance. In addition, we investigate whether CA is associated with response to cognitive remediation. Thirty-nine individuals who completed cognitive remediation were rerecruited to complete a retrospective interview on CA. Results showed that CA, repeated depressive episodes, and earlier age at diagnosis were associated with poorer cognition. We did not observe a difference in treatment response based on CA. Findings suggest that CA is an important variable to consider when examining the expression of depressive illness and areas for intervention.

Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.

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.

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

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.

Diagnostic Precision in the Detection of Mild Cognitive Impairment: A Comparison of Two Approaches.

OBJECTIVE: This study compared diagnostic rates and clinical predictors of discrepancies between diagnoses conferred via: 1) a comprehensive neuropsychological evaluation and National Institute on Aging-Alzheimer's Association (NIA-AA) criteria versus 2) a cognitive screener and Diagnostic Statistical Manual of Mental Disorders (DSM-5) criteria. DESIGN: Cross-sectional examination of baseline data from the Prevention of Alzheimer's dementia (AD) using Cognitive remediation and transcranial direct current stimulation in Mild Cognitive Impairment (MCI) and Depression (PACt-MD; ClinicalTrials.gov Identifier: NCT02386670) trial. SETTING: Five geriatric psychiatry and memory clinics located at academic hospitals affiliated with the Department of Psychiatry, University of Toronto. PARTICIPANTS: Older adults (N = 431) with a history of major depressive disorder (MDD) in remission, MCI, or both. MEASUREMENTS: Main outcome was a comparison of NIA-AA diagnostic rates of MCI or dementia versus DSM-5 rates of mild or major neurocognitive disorder. Secondary analyses examined demographic, race, gender, premorbid intellectual ability, psychosocial, health-related, and genetic predictors of discrepancy between DSM-5 and NIA-AA diagnoses. RESULTS: There were 103 (23.8%) discrepant cases, with most (91; 88.3%) of these discrepant cases reflecting more impairment with the detailed neuropsychological testing and NIA-AA criteria. Discrepancies were more likely in individuals with a history of MDD or who had at least one ApoE4 allele. CONCLUSION: The NIA-AA criteria, in conjunction with comprehensive neuropsychological testing, identified a greater prevalence of cognitive impairment than DSM-5 criteria, in conjunction with the Montreal Cognitive Assessment. Detailed neuropsychological evaluations are recommended for older adults who have a history of MDD or a genetic vulnerability to dementia.

A randomised controlled trial of psychotherapy and cognitive remediation to target cognition in mood disorders.

OBJECTIVE: To examine the impact of a treatment package combining Interpersonal and Social Rhythm Therapy (IPSRT) and cognitive remediation (CR), vs IPSRT alone, on cognition, functioning, and mood disturbance outcomes in mood disorders. METHODS: A pragmatic randomised controlled trial in adults with bipolar disorder (BD) or major depressive disorder (MDD), recently discharged from mental health services in Christchurch, New Zealand, with subjective cognitive difficulties. Individuals were randomised to a 12-month course of IPSRT with CR (IPSRT-CR), or without CR (IPSRT). In IPSRT-CR, CR was incorporated into therapy sessions from approximately session 5 and continued for 12 sessions. The primary outcome was change in Global Cognition (baseline to 12 months). RESULTS: Sixty-eight individuals (BD n = 26, MDD n = 42; full/partial remission n = 39) were randomised to receive IPSRT-CR or IPSRT (both n = 34). Across treatment arms, individuals received an average of 23 IPSRT sessions. Change in Global Cognition did not differ between arms from baseline to treatment-end (12 months). Psychosocial functioning and longitudinal depression symptoms improved significantly more in the IPSRT compared with IPSRT-CR arm over 12 months, and all measures of functioning and mood symptoms showed moderate effect size differences favouring IPSRT (0.41-0.60). At 18 months, small to moderate, non-significant benefits (0.26-0.47) of IPSRT vs IPSRT-CR were found on functioning and mood outcomes. CONCLUSIONS: Combining two psychological therapies to target symptomatic and cognitive/functional recovery may reduce the effect of IPSRT, which has implications for treatment planning in clinical practice and for CR trials in mood disorders.

Randomised controlled trial of Interpersonal and Social Rhythm Therapy and group-based Cognitive Remediation versus Interpersonal and Social Rhythm Therapy alone for mood disorders: study protocol.

BACKGROUND: Individuals with mood disorders frequently experience cognitive impairment, which impacts on the long-term trajectory of the disorders, including being associated with persisting difficulties in occupational and psychosocial functioning, residual mood symptoms, and relapse. Current first-line treatments for mood disorders do little to improve cognitive function. Targeting cognition in clinical research is thus considered a priority. This protocol outlines a prospectively-registered randomised controlled trial (RCT) which examines the impact of adding group-based Cognitive Remediation (CR) to Interpersonal and Social Rhythm Therapy (IPSRT-CR) for individuals with mood disorders. METHODS: This is a pragmatic, two-arm, single-blinded RCT comparing IPSRT-CR with IPSRT alone for adults (n = 100) with mood disorders (Major Depressive Disorder or Bipolar Disorder) with subjective cognitive difficulties, on discharge from Specialist Mental Health Services in Christchurch, New Zealand. Both treatment arms will receive a 12-month course of individual IPSRT (full dose = 24 sessions). At 6 months, randomisation to receive, or not, an 8-week group-based CR programme (Action-based Cognitive Remediation - New Zealand) will occur. The primary outcome will be change in Global Cognition between 6 and 12 months (treatment-end) in IPSRT-CR versus IPSRT alone. Secondary outcomes will be change in cognitive, functional, and mood outcomes at 6, 12, 18, and 24 months from baseline and exploratory outcomes include change in quality of life, medication adherence, rumination, and inflammatory markers between treatment arms. Outcome analyses will use an intention-to-treat approach. Sub-group analyses will assess the impact of baseline features on CR treatment response. Participants' experiences of their mood disorder, including treatment, will be examined using qualitative analysis. DISCUSSION: This will be the first RCT to combine group-based CR with an evidence-based psychotherapy for adults with mood disorders. The trial may provide valuable information regarding how we can help promote long-term recovery from mood disorders. Many issues have been considered in developing this protocol, including: recruitment of the spectrum of mood disorders, screening for cognitive impairment, dose and timing of the CR intervention, choice of comparator treatment, and choice of outcome measures. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12619001080112 . Registered on 6 August 2019.

Comparing cardiovascular risk factors in older persons with mild cognitive impairment and lifetime history of major depressive disorder.

OBJECTIVES: To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study. DESIGN: Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed. SETTING: Community-based multi-centered study based in Toronto across 5 academic sites. PARTICIPANTS: Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls. MEASUREMENTS: We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores. RESULTS: A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD. CONCLUSIONS: This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.

Effect of Action-Based Cognitive Remediation on cognitive impairment in patients with remitted bipolar disorder: A randomized controlled trial.

OBJECTIVES: Cognitive impairment affects many patients with bipolar disorder (BD), and treatments with replicated pro-cognitive effects are lacking. This study aimed to assess the effect of Action-Based Cognitive Remediation (ABCR) vs control treatment on cognitive impairment in patients with BD. METHODS: Patients with remitted BD with objective cognitive impairment were randomized to 10 weeks of ABCR vs control treatment, and assessed at baseline, after 2 weeks of treatment, at treatment completion and at 6 months follow-up. The primary outcome was a cognitive composite score. Secondary outcomes were executive function and observer-rated functional capacity. Tertiary measures included additional neuropsychological tests, performance-based functional capacity and quality of life. Data were analysed with linear mixed effects models. RESULTS: In total, 64 participants were randomized; given three dropouts before the baseline assessments, data were analysed for 61 participants (ABCR: n = 32, control: n = 29). There was no effect on ABCR vs control on the primary cognitive composite score (P-values ≥.60). At treatment completion, there was a large effect of ABCR vs control on the secondary executive function measure (treatment effect= -0.16, 95% CI [-0.27, -0.05], P ≤ .01, d = 0.65), and on subjective cognitive functioning (treatment effect = -5.38, 95% CI [-8.13, -2.67], P ≤ .001, d = 0.80), which disappeared at follow-up. There was no treatment-effect on functioning, and no association between cognitive and functional change. CONCLUSIONS: There was no effect of ABCR on the cognitive composite score. However, there was an effect on executive function and subjective cognitive functioning suggesting that ABCR may be relevant for patients with executive dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03295305.

Systematic review of the effects of evidence-based psychotherapies on neurocognitive functioning in mood disorders.

OBJECTIVE: Neurocognitive impairment is considered a core feature of mood disorders. Research has shown that neurocognitive impairment often persists beyond mood symptom resolution and can have significant deleterious effects on interpersonal relationships, academic achievement, occupational functioning and independent living. As such, neurocognitive impairment has become an important target for intervention. In this systematic review, we aimed to examine the extant literature to ascertain whether current standard evidence-based psychotherapies can improve neurocognitive functioning in mood disorders. METHOD: Studies examining changes in neurocognitive functioning following evidence-based psychotherapy were identified using MEDLINE, PsycINFO and Web of Science databases. Given the heterogeneity of study procedures, treatment protocols and patient samples, a narrative rather than meta-analytic review technique was employed. RESULTS: Nineteen studies (21 articles) met inclusion criteria. There was preliminary evidence of improved executive functioning following evidence-based psychotherapy for Major Depressive Disorder and Bipolar Disorder. There was also some signal of reduced negative biases in emotional information processing following psychotherapy in depression. Due to methodological variability across studies however, it was difficult to draw clear conclusions. CONCLUSION: Findings from the current review suggest that evidence-based psychotherapies may influence some aspects of neurocognitive functioning in mood disorders. This continues to be an ongoing area of importance and warrants further research.

Affective cognition in bipolar disorder: A systematic review by the ISBD targeting cognition task force.

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.

The Canadian Biomarker Integration Network in Depression (CAN-BIND): magnetic resonance imaging protocols

Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging ­ alone or in combination with other variables ­ can predict the outcomes of various treatment modalities.

Activation therapy for the treatment of inpatients with depression - protocol for a randomised control trial compared to treatment as usual.

BACKGROUND: Inpatients with depression have a poor long term outcome with high rates of suicide, high levels of morbidity and frequent re-admission. Current treatment often relies on pharmacological intervention and focuses on observation to maintain safety. There is significant neurocognitive deficit which is linked to poor functional outcomes. As a consequence, there is a need for novel psychotherapeutic interventions that seek to address these concerns. METHODS: We combined cognitive activation and behavioural activation to create activation therapy (AT) for the treatment of inpatient depression and conducted a small open label study which demonstrated acceptability and feasibility. We propose a randomised controlled trial which will compare treatment as usual (TAU) with TAU plus activation therapy for adult inpatients with a major depressive episode. The behavioural activation component involves therapist guided re-engagement with previously or potentially rewarding activities. The cognitive activation aspect utilises computer based exercises which have been shown to improve cognitive function. DISCUSSION: The proposed randomised controlled trial will examine whether or not the addition of this therapy to TAU will result in a reduced re-hospitalisation rate at 12 weeks post discharge. Subjective change in activation and objectively measured change in activity levels will be rated, and the extent of change to neurocognition will be assessed. TRIAL REGISTRATION: Unique trial number: U1111-1190-9517. Australian New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12617000024347p .

Cognitive and functional deficits in bipolar disorder and schizophrenia as a function of the presence and history of psychosis.

OBJECTIVES: Schizophrenia and bipolar disorder overlap considerably. Schizophrenia is a primary psychotic disorder, whereas approximately half of people with bipolar disorder will experience psychosis. In this study, we examined the extent to which cognitive and functional impairments are related to the presence and history of psychosis across the two disorders. METHOD: A total of 633 participants with bipolar disorder I, schizophrenia, and schizoaffective disorder were recruited for a study on the genetics of cognition and functioning in bipolar disorder and schizophrenia. Participants were classified into five groups: bipolar disorder with current psychosis (N = 30), bipolar disorder with a history of psychosis (N = 162), bipolar disorder with no history of psychosis (N = 92), schizophrenia with current psychosis (N = 245), and schizophrenia with past psychosis (N = 104). RESULTS: Cognitive profiles of all groups were similar in pattern; however, both current psychosis (P < .02) and a diagnosis of schizophrenia (P < .03) were associated with greater impairment. Schizophrenia with current psychosis was also associated with a superimposed severe impairment in processing speed. Both psychosis (P < .03) and schizophrenia diagnosis (P < .01) were associated with poorer functional competence. Individuals with bipolar disorder and schizophrenia experienced similar impairments in real-world functioning if they were experiencing current psychosis (P = .32). CONCLUSION: The presence of active psychosis is an important cross-diagnostic factor in cognition and functioning in both schizophrenia and bipolar disorder. Characterization and treatment of cognition and functional deficits in bipolar disorder should consider the effects of both current and history of psychosis.

Associations of Age and Gender with Negative Symptom Factors and Functioning Among Middle-Aged and Older Adults with Schizophrenia.

OBJECTIVE: Gender differences in neurocognition, social skills, and negative symptoms, favoring women, have been documented among young/middle-aged adults with schizophrenia. However, gender differences have rarely been examined among older adults with schizophrenia, when decreases in circulating estrogens may impact outcomes among women. METHODS: Community-dwelling adults (N = 242, ages 40-85) with schizophrenia/schizoaffective disorder completed assessments of negative symptoms (expressive and experiential deficits), neurocognition, and social skills. Mann-Whitney U tests examined gender differences; a regression-based bootstrapped approach to moderation examined gender by age interactions. RESULTS: Female participants had better neurocognition (U = 6,814.00, p = 0.011) and less severe experiential deficits (U = 4,130.50, p = 0.022). There was no gender difference in social skills (U = 5,920.50, p = 0.150). Older age was associated with greater expressive deficits among men but not women (b = -0.04; 95% confidence interval -0.0780, -0.0114; bootstrap p = 0.009). CONCLUSION: Gender differences among adults with schizophrenia may vary depending on age; gender differences in negative symptoms may vary by symptom subgroup.