Influence of pre-treatment structural brain measures on effects of action-based cognitive remediation on executive function in partially or fully remitted patients with bipolar disorder.

Cognitive impairment is an emerging treatment target in patients with bipolar disorder (BD) but so far, no evidence-based treatment options are available. Recent studies indicate promising effects of Cognitive Remediation (CR) interventions, but it is unclear who responds most to these interventions. This report aimed to investigate whether pre-treatment dorsal prefrontal cortex (dPFC) thickness predicts improvement of executive function in response to Action-Based Cognitive Remediation (ABCR) in patients with BD. Complete baseline magnetic resonance imaging (MRI) data were available from 45 partially or fully remitted patients with BD from our randomized controlled ABCR trial (ABCR: n = 25, control group: n = 20). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. Multiple linear regression analysis was conducted to assess the influence of dPFC thickness on ABCR-related executive function improvement, reflected by change in the One Touch Stocking of Cambridge performance from baseline to post-treatment. We also conducted whole brain vertex wise analysis for exploratory purposes. Groups were well-matched for demographic and clinical variables. Less pre-treatment dPFC thickness was associated with greater effect of ABCR on executive function (p = 0.02). Further, whole-brain vertex analysis revealed an association between smaller pre-treatment superior temporal gyrus volume and greater ABCR-related executive function improvement. The observed associations suggest that structural abnormalities in dPFC and superior temporal gyrus are key neurocircuitry treatment targets for CR interventions that target impaired executive function in BD.

Effect of electroconvulsive therapy on neural response to affective pictures: A randomized, sham-controlled fMRI study.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression but its neurocognitive mechanisms are unclear. This randomized, sham-controlled functional magnetic resonance imaging (fMRI) study explored the effects of a single ECT on neural response to affective pictures. Twenty-seven patients with major depressive disorder were randomized to a single active ECT (N = 15) or sham (N = 12) session in a double-blind, parallel-group design. On the following day, patients underwent fMRI during which they viewed pleasant, unpleasant and neutral pictures and performed a free recall test after the scan. Mood symptoms were assessed before ECT/sham and at the time of fMRI. Subsequently, all patients continued active ECT as usual. Mood symptoms were reassessed after six active ECT sessions. A single ECT vs. sham session reduced neural response to unpleasant vs. pleasant pictures in the medial prefrontal cortex, a region showing greater response in the more depressed patients. This effect occurred in the absence of between-group differences in picture recall, mood symptoms or concomitant medication. In conclusion, modulation of medial prefrontal hyper-activity during encoding of negative affective information may be a common mechanism of distinct biological depression treatments.

Systematic review of randomized controlled trials of candidate treatments for cognitive impairment in depression and methodological challenges in the field.

Cognitive impairment is a core feature of Major Depressive Disorder (MDD) but treatments targeting cognition are lacking. Numerous pre-clinical and clinical studies have investigated potential cognition treatments, but overall the evidence is conflicting. We conducted a systematic search following the PRISMA guidelines on PubMed and PsychInfo to evaluate the extant evidence and methodological challenges in randomized controlled trials (RCTs) of biological, psychological and behavioural candidate treatments targeting cognition in MDD. Inclusion criteria were RCTs with a placebo control assessing potential pro-cognitive effects of candidate treatments in MDD. Two independent authors reviewed the studies and assessed their risk of bias with the Cochrane Collaboration׳s Risk of Bias tool. Twenty-eight eligible studies (24 biological and four psychological or behavioural studies) were identified. Cognition was the primary treatment target in ten (36%) trials and an additional treatment outcome together with mood symptoms in 18 (64%) trials. The risk of bias was high or unclear in 93% of trials due to potential selective outcome reporting or 'pseudospecificity' (unspecific cognitive improvement due to reduced depression severity), and/or insufficient details on how the allocation sequence was generated or how blinding was maintained. Several promising treatments were identified, including vortioxetine, erythropoietin, transcranial direct current stimulation and cognitive remediation. However, several common methodological challenges may impede advances in the field. In particular, future trials should select one cognitive composite score as primary outcome, screen for cognitive impairment before inclusion of participants and address 'pseudospecificity' issues. Together, these strategies may improve the success of future cognition trials in MDD.

Predictors of the discrepancy between objective and subjective cognition in bipolar disorder: a novel methodology.

OBJECTIVE: The poor relationship between subjective and objective cognitive impairment in bipolar disorder (BD) is well-established. However, beyond simple correlation, this has not been explored further using a methodology that quantifies the degree and direction of the discrepancy. This study aimed to develop such a methodology to explore clinical characteristics predictive of subjective-objective discrepancy in a large BD patient cohort. METHODS: Data from 109 remitted BD patients and 110 healthy controls were pooled from previous studies, including neuropsychological test scores, self-reported cognitive difficulties, and ratings of mood, stress, socio-occupational capacity, and quality of life. Cognitive symptom 'sensitivity' scores were calculated using a novel methodology, with positive scores reflecting disproportionately more subjective complaints than objective impairment and negative values reflecting disproportionately more objective than subjective impairment ('stoicism'). RESULTS: More subsyndromal depressive and manic symptoms, hospitalizations, BD type II, and being male positively predicted 'sensitivity', while higher verbal IQ predicted more 'stoicism'. 'Sensitive' patients were characterized by greater socio-occupational difficulties, more perceived stress, and lower quality of life. CONCLUSION: Objective neuropsychological assessment seems especially warranted in patients with (residual) mood symptoms, BD type II, chronic illness, and/or high IQ for correct identification of cognitive deficits before commencement of treatments targeting cognition.