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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. [ABSTRACT FROM AUTHOR]

This study sought to assess the differences in mental health conditions among the general population, quarantined population and healthcare workers during the COVID-19 outbreak in China. An online rapid assessment captured depressive and anxiety symptoms, and sleep quality data. A total of 2689 participants (n=374 general population, n=403 healthcare workers, n=1912 quarantined population) were included in the final statistical analysis. The proportion of individuals with mild and/or serious depression and anxiety were higher in the general population when compared to the quarantined population and healthcare workers (58.6% vs. 25.1%vs. 48.6%, P<0.001; 41.2% vs. 18.5% vs. 35.7%, P<0.001). The prevalence of sleep disturbance was higher among healthcare workers than the general population and quarantined population (29.8% vs. 24.1% vs. 22.7%, P=0.013). Logistic regression analysis showed that, perceived effect on daily life was associated with depression, anxiety and sleep disturbance in the general population, quarantined population and the healthcare workers. The general population had a greater risk of developing psychological problems. The healthcare workers suffered the poorest sleep quality. Future research must further explorethe targeted measures for the general population and healthcare workers while combating COVID-19. [ABSTRACT FROM AUTHOR]

Background: Herein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized antidepressant therapy. Methods: Adults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity [ i.e. , Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20] were treated with open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB). Results: After 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (e.g. , processing speed) (p = 0.031). A subdomain measure of working memory (i.e. , symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively. Conclusion: The THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03053362. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to their effect on anhedonia in MDD. Methods: This is a post-hoc analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20] were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed. Results: A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (p < 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (p < 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (p = 0.026). Conclusion: The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the validity of using social media for depression screening.Method: Article searches on PubMed and PsycINFO from database inception to August 20, 2019 were completed with a search string and filters.Results: 15 articles made the inclusion criteria. Facebook, Twitter, and Instagram profiles of depressed people were distinguishable from nondepressed people shown by social media markers. Facebook studies showed that having fewer Facebook friends and mutual friends, posting frequently, and using fewer location tags positively correlated with depressive symptoms. Also, Facebook posts with explicit expression of depressive symptoms, use of personal pronouns, and words related to pain, depressive symptoms, aggressive emotions, and rumination predicted depression. Twitter studies showed that the use of "past focus" words, negative emotions and anger words, and fewer words per Tweet positively correlated with depression. Finally, Instagram studies showed that differences in follower patterns, photo posting and editing, and linguistic features between depressed people and nondepressed people could serve as a marker.Limitations: The primary articles analyzed had different methods, which constricts the amount of comparisons that can be made. Further, only four social media platforms were explored.Conclusion: Social media markers like number and content of Facebook messages, linguistic variability in tweets and tweet word count on Twitter, and number of followers, frequency of Instagram use and the content of messages on Instagram differed between depressed people and nondepressed people. Therefore, screening social media profiles on these platforms could be a valid way to detect depression. [ABSTRACT FROM AUTHOR]

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]

Background: As a major virus outbreak in the 21st century, the Coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented hazards to mental health globally. While psychological support is being provided to patients and healthcare workers, the general public's mental health requires significant attention as well. This systematic review aims to synthesize extant literature that reports on the effects of COVID-19 on psychological outcomes of the general population and its associated risk factors.Methods: A systematic search was conducted on PubMed, Embase, Medline, Web of Science, and Scopus from inception to 17 May 2020 following the PRISMA guidelines. A manual search on Google Scholar was performed to identify additional relevant studies. Articles were selected based on the predetermined eligibility criteria.Results: Relatively high rates of symptoms of anxiety (6.33% to 50.9%), depression (14.6% to 48.3%), post-traumatic stress disorder (7% to 53.8%), psychological distress (34.43% to 38%), and stress (8.1% to 81.9%) are reported in the general population during the COVID-19 pandemic in China, Spain, Italy, Iran, the US, Turkey, Nepal, and Denmark. Risk factors associated with distress measures include female gender, younger age group (≤40 years), presence of chronic/psychiatric illnesses, unemployment, student status, and frequent exposure to social media/news concerning COVID-19.Limitations: A significant degree of heterogeneity was noted across studies.Conclusions: The COVID-19 pandemic is associated with highly significant levels of psychological distress that, in many cases, would meet the threshold for clinical relevance. Mitigating the hazardous effects of COVID-19 on mental health is an international public health priority. [ABSTRACT FROM AUTHOR]

Background: Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes.Methods: Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2-6 days, 7-20 days, 21-28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine.Results: The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591-1.903, p < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p = 0.139). At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499-1.538, p < 0.01). At 21-28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368-0.898, p < 0.01).Limitations: Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery.Conclusions: The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD. [ABSTRACT FROM AUTHOR]

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 (χ2 = 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. [ABSTRACT FROM AUTHOR]

Highlights • MDD is a mental disorder characterized by aberrant emotion regulation. • Abnormal emotional control may result from dysfunctional cognitive processing. • The emotional response is comprised of affective and expressive components. • Lower limbic structures direct the expressive and affective components. • Higher cognitive structures allow for context-based emotional response modulation. Abstract 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 dys regulation. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is a principal determinant of functional impairment in major depressive disorder (MDD) and often persists during periods of euthymia. Abnormalities in the glutamate system, particularly in N -methyl- d -aspartate receptors (NMDARs) activity, have been shown to contribute to both mood and cognitive symptoms in MDD. The current narrative review aims to evaluate the potential pro-cognitive effects of targeting the glycine site of NMDARs in the treatment of psychiatric disorders, with a special focus on how these results may apply to MDD. Literature databases were searched from inception to May 2018 for relevant pre-clinical and clinical studies evaluating antidepressant and pro-cognitive effects of NMDAR glycine site modulators in both MDD and non-MDD samples. Six glycine site modulators with pro-cognitive and antidepressant properties were identified: d -serine (co-agonist), d -cycloserine (partial agonist), d -alanine (co-agonist), glycine (agonist), sarcosine (co-agonist) and rapastinel (partial agonist). Preclinical animal studies demonstrated improved neuroplasticity and pro-cognitive effects with these agents. Numerous proof-of-concept clinical trials demonstrated pro-cognitive and antidepressant effects trans-diagnostically (e.g., in healthy participants, MDD, schizophrenia, anxiety disorders, major neurocognitive disorders). The generalizability of these clinical studies was limited by the small sample sizes and the paucity of studies directly evaluating cognitive effects in MDD samples, as most clinical trials were in non-MDD samples. Taken together, preliminary results suggest that the glycine site of NMDARs is a promising target to ameliorate symptoms of depression and cognitive dysfunction. Additional rigorously designed clinical studies are required to determine the cognitive effects of these agents in MDD. • The NMDAR has been previously implicated in cognitive dysfunction in MDD • Pro-cognitive effects of targeting the glycine site of NMDARs was evaluated • Preclinical studies demonstrated improved neuroplasticity and pro-cognitive effects • Preliminary clinical trials demonstrated pro-cognitive and antidepressant effects • Preliminary results suggest that the glycine site of NMDARs is a promising target [ABSTRACT FROM AUTHOR]

• Early change in cognition was a non-significant predictor of treatment response. • Signal-to-noise ratio was low due to high heterogeneity in the cognitive data. • Future studies should stratify patients to produce more homogenous samples. • Early cognitive change may predict response in stratified MDD subpopulations. • Early change in MADRS and baseline MADRS scores were correlated with response. 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. [ABSTRACT FROM AUTHOR]