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Background: Insulin resistance (IR) is a potential predictor of antidepressant treatment response., Aims: We assess changes in IR after antidepressant treatment and whether these changes have any effect on treatment response. Also, to see whether changes in IR mediates relationship between C-reactive protein (CRP) and antidepressant efficacy., Methods: This is a secondary analysis of an 8-week, open-label clinical trial with 95 adults experiencing a major depressive episode. Response to vortioxetine was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). Generalized estimating equation models were utilized for this intent-to-treat analysis., Results: When adjusted for age, sex, and body mass index, there was a significant increase in IR following treatment in the overall sample (p = 0.035). This finding was detected in treatment non-responders (p = 0.019), whereas it was not observed in responders (p = 0.329). Mediation analysis revealed that change in IR during treatment was responsible for change in MADRS as well as the relationship between baseline CRP and treatment response., Conclusions: Exacerbation of IR during antidepressant treatment mediated non-response. Conversely in treatment responders IR reduced. Like previous studies, baseline CRP moderated treatment response. This relationship was also mediated by changes in IR. These findings further elucidate the role of IR in terms of antidepressant response as well as potentially explain inflammation's relationship with the latter.

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., (Copyright © 2020. Published by Elsevier B.V.)

Background: Major Depressive Disorder (MDD) is a common and debilitating mood disorder. Individuals with MDD are often misdiagnosed or diagnosed in an untimely manner, exacerbating existing functional impairments. Ecological momentary assessment (EMA) involves the repeated sampling of an individual's symptoms within their natural environment and has been demonstrated to assist in illness assessment and characterization. Capturing data in this way would set the stage for improved treatment outcomes and serve as a complementary resource in the management and treatment of depressive symptoms., Methods: Online databases PubMed/MedLine and PsycINFO were searched using PRISMA guidelines and combinations of the following keywords: EMA, depression, smartphone app, diagnosing, symptoms, phone, app, ecological momentary assessment, momentary assessment, data mining, unobtrusive, passive data, GPS, sensor., Results: A total of nineteen original articles were identified using our search parameters and ten articles met the inclusion criteria for full-text review. Among the ten relevant studies, three studies evaluated feasibility, seven evaluated detection, and three evaluated treatment of MDD., Limitations: Limitations include that the design of all of the studies included in this review are non-randomized. It should be noted that most of the studies included were pilot studies and/or exploratory trials lacking a control group., Conclusions: Available evidence suggests that the use of passive smartphone-based applications may lead to improved management of depressive symptoms. This review aids the creation of new EMA applications, highlights the potential of EMA usage in clinical settings and drug development, emphasizes the importance for regulation of applications in the mental health field, and provides insight into future directions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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: Sleep disturbances are frequently reported in patients with major depressive disorder. We aimed to investigate the effects of vortioxetine on sleep quality and association between changes in sleep and treatment response., Methods: This study is a post-hoc analysis of a clinical trial that sought to evaluate the sensitivity to cognitive change of THINC-integrated tool in patients with major depressive disorder. In total, 92 patients (aged 18 to 65) meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for moderate or severe major depressive disorder and 54 healthy controls were included. All patients received open-label vortioxetine (10-20 mg/day, flexibly dosed) for 8 weeks. Herein, the primary outcomes of interest were changes in sleep, as measured by the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index, between weeks 0, 2, and 8. The association between changes in sleep and depressive symptom severity was secondarily assessed., Results: We observed that sleep, as indicated by scores of Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index, was significantly poorer in patients with major depressive disorder compared to healthy controls at weeks 0, 2, and 8 ( p < 0.05). Among patients with major depressive disorder, we observed significant improvements on the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Insomnia Severity Index between weeks 0 and 8 ( p < 0.05). We observed a significant association between improvements on the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Insomnia Severity Index and improvement of depressive symptoms., Conclusion: Improvement of depressive symptoms in major depressive disorder patients treated with vortioxetine was associated with significant improvements in sleep. Furthermore, improvements in sleep were predictive of antidepressant response and were linearly correlated with improvement in overall depressive symptom severity.

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.)

Background: Anhedonia and abnormalities in reward behavior are core features of major depressive disorder (MDD). Convergent evidence indicates that overweight/obesity (OW), a highly prevalent condition in MDD, is independently associated with reward disturbances. We therefore aimed to investigate the moderating effect of OW on the willingness to expend efforts for reward in individuals with MDD and healthy controls (HC)., Methods: Forty-one adults (HC n = 20, MDD n = 21) completed the Effort Expenditure for Rewards Task (EEfRT), clinical and cognitive measures. Anthropometric parameters were assessed in all participants, and an additional evaluation of laboratorial parameters were conducted solely on those with MDD. Individuals with MDD were all on vortioxetine monotherapy (10-20 mg/day)., Results: Interactions between reward magnitude, group and OW were observed (χ 2  = 9.192, p = 0.010); the OW-MDD group chose the hard task significantly less than normal weight (NW)-HC (p = 0.033) and OW-HC (p = 0.034), whereas there were no differences between NW-MDD and HCs. Within individuals with MDD, the proportion of hard task choices was more strongly correlated with body mass index (BMI) (r = -0.456, p = 0.043) and insulin resistance (HOMA2-IR) (r = -0.467, p = 0.038), than with depressive symptoms (r = 0.290, p = 0.214)., Conclusions: OW significantly moderated the association between MDD and willingness to make efforts for rewards. These findings offer novel evidence on the potential role of metabolic factors on the basis of anhedonia, and for the heuristic models proposing a pathophysiological connection between mood and metabolic disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) is a mental disorder characterized by aberrant emotion regulation. The capacity for emotion regulation stems from diverse neural circuits including higher level cognitive structures involved in processing contextual information, and lower level limbic structures involved in triggering emotional expression. Cognitive theories of depression posit that the MDD-specific abnormalities in emotional control derive itself from dysfunctional cognitive processes including biased attention, rumination, and altered information processing and memory. The main objectives of the current narrative review are to summarize the major neural systems involved in emotion regulation in humans, and to describe how these systems are dysregulated in MDD. The findings will be briefly discussed in the context of a conceptual framework of depression (i.e., Beck's cognitive model of depression), and neural targets of conventional treatments for depression will also be discussed. MDD exemplifies the critical importance of appropriate emotion regulation to human health and wellbeing, and demonstrates the personal and social impact of emotion dysregulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR, LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Compared to the 17-Item Hamilton Rating Scale for Depression (HAMD-17), the 7-Item Hamilton Rating Scale for Depression (HAMD-7) would be more practical for use in busy clinical settings. Herein, we aim to evaluate (1) whether the HAMD-7 is a reliable and valid measure that is sensitive to changes in depressive symptoms, and (2) whether early improvement of depressive symptoms, as measured by the HAMD-7, is capable of predicting response and remission in patients with major depressive disorder (MDD) during acute treatment with fluoxetine or electroconvulsive therapy (ECT)., Methods: This is a post-hoc analysis of two clinical trials in MDD. Internal consistency, validity, and sensitivity-to-change of the HAMD-17 and HAMD-7 were compared during acute treatment and at 3-month follow-up. Receiver operating characteristic analyses were used to evaluate the discriminative capacity of the HAMD-17 and HAMD-7., Results: The HAMD-7 is a reliable and valid measure that is sensitive to changes in depressive symptoms. Early improvement, as measured by either the HAMD-17 or HAMD-7, was capable of predicting response and remission to acute treatment with fluoxetine or ECT with good discriminative capacity., Limitations: This is a post-hoc analysis of two open-label clinical trials with limited sample sizes. All patients were Taiwanese, which limits the generalizability of our results., Conclusions: HAMD-7 is a clinically useful measure that is capable of detecting early improvement of depressive symptoms. The HAMD-7 may have the potential to inform clinical assessment as part of measurement-based care., (Copyright © 2019. Published by Elsevier B.V.)

Anhedonia is defined as a diminished ability to experience interest or pleasure, and is a critical psychopathological dimension of major depressive disorder (MDD). The purpose of the current systematic review is to evaluate the therapeutic efficacy of pharmacological treatments on measures of anhedonia in adults with MDD. Electronic databases Cochrane Library (CENTRAL), Ovid MEDLINE, PubMed, PsycINFO, and Google Scholar were searched from inception to June 1, 2018 for longitudinal studies utilizing pharmacotherapy for the treatment of anhedonia in patients with MDD. A total of 17 eligible studies were identified (i.e., evaluated the effects of pharmacotherapy on a measure of anhedonia). Among the identified studies, the efficacy of 14 different pharmacotherapies on measures of anhedonia were evaluated, including melatonergic agents (i.e. agomelatine), monoaminergic agents (i.e. moclobemide, clomipramine, bupropion, venlafaxine, fluoxetine, amitifadine and levomilnacipran, escitalopram, and sertraline), glutamatergic agents (i.e., ketamine and riluzole), stimulants (i.e., methylphenidate), and psychedelics (i.e., psilocybin). Based on the available evidence, most antidepressants demonstrated beneficial effects on measures of anhedonia as well as the other depressive symptoms. Only escitalopram/riluzole combination treatment was ineffective in treating symptoms of anhedonia in MDD. Continued research is warranted to further support the efficacy of mechanistically-distinct antidepressants in treating symptoms of anhedonia in MDD. Future research should also aim to parse out the heterogeneous effects of different pharmacotherapies on anhedonic symptoms., (Copyright © 2019 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.)

Objectives: To explore differences in adipokine levels (i.e., leptin and adiponectin levels) between adults with Major Depressive Disorder (MDD) and healthy controls (HC), and to discuss the possible role of adipokine regulation in the development and progression of MDD., Methods: A systematic review and meta-analysis were conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic search was conducted for all English and Chinese peer-reviewed articles from inception to November 2017. A random effects model was used to calculate the standardized mean difference (SMD) of leptin and/or adiponectin levels in subjects diagnosed with MDD versus HC within a 95% confidence interval (CI)., Results: Thirty-three studies were included in this meta-analysis. In total, 4,372 (52.3%) subjects with MDD and 3,984 (47.7%) HC were compared. We identified significant lower adiponectin levels in MDD compared to HC with a small effect size (ES) (SMD = -0.25; 95% CI: -0.48, -0.02; P < 0.001). However, no significant difference was observed in leptin levels between MDD subjects and HC (SMD = 0.13; 95% CI: -0.06, 0.31; P = 0.170). The heterogeneity in the results of our meta-analysis could not be completely explained by dividing subjects into subgroups. Results from subgroup analyses suggested that studies involving samples with BMI ≥ 25 had lower adiponectin levels in subjects with MDD compared to HC, and older age samples (i.e., age ≥ 40) with BMI ≥ 25 had both higher leptin levels and lower adiponectin levels in MDD subjects as compared to HC., Limitations: The heterogeneity of included studies, small sample sizes, and potential publication bias were significant limitations., Conclusions: The current systematic review and meta-analysis indicated that lower adiponectin levels may be associated with MDD. Moreover, the results suggest that males expressing lower adiponectin and leptin levels have an increased likelihood of developing MDD. Future studies should aim to investigate the manifestation of depressive phenotypes in older, obese populations with altered metabolic profiles resulting from adipokine dysregulation. The review has been registered with PROSPERO (registration number CRD42018082733)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Learning Objectives: After participating in this activity, learners should be better able to:• Characterize cognitive dysfunction in patients with major depressive disorder.• Evaluate approaches to treating cognitive dysfunction in patients with major depressive disorder., Abstract: Cognitive dysfunction is a core psychopathological domain in major depressive disorder (MDD) and is no longer considered to be a pseudo-specific phenomenon. Cognitive dysfunction in MDD is a principal determinant of patient-reported outcomes, which, hitherto, have been insufficiently targeted with existing multimodal treatments for MDD. The neural structures and substructures subserving cognitive function in MDD overlap with, yet are discrete from, those subserving emotion processing and affect regulation. Several modifiable factors influence the presence and extent of cognitive dysfunction in MDD, including clinical features (e.g., episode frequency and illness duration), comorbidity (e.g., obesity and diabetes), and iatrogenic artefact. Screening and measurement tools that comport with the clinical ecosystem are available to detect and measure cognitive function in MDD. Notwithstanding the availability of select antidepressants capable of exerting procognitive effects, most have not been sufficiently studied or rigorously evaluated. Promising pharmacological avenues, as well as psychosocial, behavioral, chronotherapeutic, and complementary alternative approaches, are currently being investigated.

Objectives: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD., Method: Electronic search engines PubMed/MEDLINE, ClinicalTrials.gov, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors , and response and/or remission ., Results: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI), history of suicide, family history of alcohol use disorder), peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels), polysomnography (abnormalities in delta sleep ratio), neurochemistry (i.e., glutamine/glutamate ratio), neuroimaging (i.e., anterior cingulate cortex activity), genetic variation (i.e., Val66Met BDNF allele), and cognitive functioning (i.e., processing speed). High BMI and a positive family history of alcohol use disorder were the most replicated predictors., Conclusions: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.

Background: Psychosocial impairment represents an important treatment target in major depressive disorder (MDD). The majority of patients with MDD do not regain premorbid levels of psychosocial functioning despite the resolution of core depressive symptoms. This study aimed to investigate the respective effects of cognitive function and depression severity on impaired psychosocial function in MDD., Methods: Adults aged 18-65 with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls participated in a cross-sectional study validating the THINC-integrated tool (THINC-it), a cognitive screening tool comprised of objective and subjective measures of cognitive function. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale and psychosocial function was assessed using the Sheehan Disability Scale (SDS)., Results: Subjects with MDD reported greater impairment in psychosocial function than healthy controls, with significant differences in SDS total and domain scores (ps < .01) after controlling for age, sex, and education. Generalized linear models indicated that subjective cognitive function was most strongly associated with SDS total score (RR = .14, p = .01) and SDS domains of work/school (RR = .15, p = .03), family and home responsibilities (RR = .15, p = .02), and economic days lost (RR = .18, p =.03). Depression severity was most strongly associated with SDS social life (RR = .08, p < .01) and economic days underproductive (RR = .07, p < .01). Objective cognitive function was not significantly associated with any SDS outcomes., Limitations: The cross-sectional, observational study design limits temporal inferences. The self-report nature of measures included may have influenced associations observed. Potential medication effects are not noted., Conclusions: Cognitive deficits, as measured by the THINC-it, are associated with significant psychosocial impairment in MDD. These results provide empirical support for the assessment of both subjective and objective measures of cognition, as they are not associated with each other and have differential effects on functional trajectory., (Copyright © 2017 Elsevier B.V. All rights reserved.)