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Antidepressant pharmacotherapy dominates current treatment in psychiatry, including treatment for major depressive disorder (MDD). However, the current trial-and-error process of medication selection contributes to treatment failure and unnecessarily exposes patients to lengthy and insufficient treatment trials. Notably, improvements in measures of cognition have been demonstrated to occur early during treatment and prior to improvements in clinical state. Cognitions have been categorized based on emotional valence (i.e., cold versus hot cognitions). Cold cognitions describe cognitive operations that are relevant to the processing of non-emotional information. The current analysis investigates whether early changes in cold cognition can predict response after 8 weeks of vortioxetine treatment in adults with MDD. This was secondary analysis of an 8-week, open-label study. Cognition was assessed at week 0 and week 2 to measure early cognitive change. Depressive symptom severity was assessed at week 0 and week 8 to measure treatment response. Eighty-one subjects were analyzed using binomial logistic regression models. Early change in cognition was a non-significant predictor of response (p = 0.845, SE = 0.599, OR = 1.124), which may have resulted from high data variability. The overall predictive accuracy of the model was low (sensitivity = 37.5%, specificity = 89.8%, PPV = 70.6%, NPV = 68.8%). Future studies should include larger samples and stratify patients based on potentially moderating variables, such as baseline cognitive impairment and occupation. Stratification would likely produce more homogenous samples, reducing the amount of variability observed for early cognitive change., Competing Interests: Declaration of Competing Interest Roger S. McIntyre is a consultant to speak on behalf for, and/or has received research support from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Stanley Medical Research Institute, and CIHR/GACD/Chinese National Natural Research Foundation. All other authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: It is well established that deficits in motivation, reward, and cognition are common during and in between syndromal episodes of depression as part of Major Depressive Disorder (MDD). Informed by evidence indicating functional and structural interconnectivity between cognitive and reward brain circuits, we preliminarily evaluate the association between measures of cognitive performance and reward/motivation., Methods: This is a post-hoc analysis of a primary study (i.e. the THINC-it sensitivity to change study). Adults (18-65 years of age) meeting DSM-5 criteria for MDD, single-episode or recurrent confirmed by M.I.N.I. with moderate severity or greater (i.e. Montgomery Asberg Depression Rating Scale ≥20). All eligible subjects received vortioxetine 10-20 mg open-label for 8 weeks. The Effort Expenditure Reward Task (EEfRT) was the principal measure of motivation and reward. We directly compare the effects of cognitive measures and depressive symptoms on effort-based decision-making using the THINC-it composite score and MADRS total score., Results: Twenty-one participants with MDD (Mean age = 38.47, SD = 12.85) and 20 healthy volunteers (Mean age = 41.50, SD = 14.21) completed the optional EEfRT task. Amongst individuals with MDD, performance in processing speed, executive function (i.e. Trails B) and overall composite cognitive score was positively associated with the proportion of hard-task choices in the high reward condition (i.e. greater reward valuation). Across both groups, a greater probability (χ 2  = 1.137) and magnitude of reward (χ 2  = 0.045) was associated with increased effort (i.e. choosing the hard task more frequently). Using fully factored GEE models, we observed a positive association between performance on the Trails test (β = 2.223, SE = 0.928, p = 0.017) as well as the composite score (β = 0.978, SE = 0.0.459, p = 0.033), and greater effort for high rewards. In addition, it was observed that a positive association (i.e. greater effort for reward in higher probability) was observed with depressive symptoms and overall cognitive measures., Conclusion: Herein, we observed that an association exists between overall cognitive function, notably processing speed and executive function and reward function. Specifically, a greater effort for hard task rewards (using the EEfRT task) was manifested in individuals exhibiting higher levels of cognitive performance in a well-characterized sample of MDD treated with Vortioxetine., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.

Background: Despite the widespread use of antidepressants in clinical practice, the current trial-and-error approach to medication selection contributes to treatment failure and underscores the need to identify reliable predictors of antidepressant response. Since changes in measures of cognition have been reported to occur early in treatment and prior to improvements in overall mood symptoms, the present review aims to determine whether early changes in measures of cognition can predict response in individuals with MDD., Methods: A systematic review of studies evaluating early cognitive change as a predictor of later treatment response in MDD was conducted using PubMed/Medline, Embase and PsychINFO., Results: A total of seven articles were identified. The available evidence suggests the early changes in cognition may predict treatment response in individuals with MDD. This was shown across antidepressant classes (i.e., SSRIs, SNRIs, NRIs, melatonergic antidepressants) and forms of therapy (i.e., pharmacotherapy, rTMS). The results depict an emerging trend towards early changes in facial emotion recognition (i.e., a hot cognitive process) as a predictor of treatment outcome., Limitations: Our qualitative analysis reflects a very limited number of studies. Moreover, there was significant heterogeneity in the evaluation of cognition across studies. Future research should aim to parse out this heterogeneity by evaluating the relative predictive value of different measures of cognition., Conclusion: The identification of reliable early treatment predictors of antidepressant response would be clinically significant, enabling clinicians to more accurately evaluate the efficacy of selected treatment avenues., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To assess the effect of insulin resistance (IR) on treatment response to the antidepressant, vortioxetine, in patients with Major Depressive Disorder (MDD).Methods: This is a secondary analysis of an 8-week, open-label clinical trial. Ninety-five adults in a primary care setting experiencing a major depressive episode were included. Response to vortioxetine was measured using the THINC-integrated tool, Montgomery Åsberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Perceived Deficits Questionnaire (PDQ-5), and the Sheehan Disability Scale (SDS). Generalized estimating equation models were utilized for data analysis.Results: When adjusted for age, gender, dose, and BMI, there was a significant baseline IR by time interaction for SHAPS (p = 0.022), PDQ-5 (p = 0.037), and SDS (p = 0.013). Higher baseline IR predicted decreased early improvements in anhedonia. It also predicted poorer subjective assessments of cognition and increased functional impairment at the endpoint of treatment. For functional capacity (i.e. SDS) other covariates including severity of symptoms, illness course, other metabolic factors (e.g. cholesterol), and physical activity were included with no changes to the moderating effect of baseline IR.Limitations: This was a post-hoc analysis of a primarily non-diabetic sample. Also, only one agent was assessed.Conclusions: IR was a predictor of response to vortioxetine. This persisted after controlling for other factors including, but not limited to, BMI. These findings strengthen the link between depression and IR and may point to another novel metabolic predictor of response. These findings should be replicated using other antidepressants. [ABSTRACT FROM AUTHOR]