THINC-integrated Tool Research Articles

The feasibility and effectiveness of remote cognitive training on cognitive function and work performance in workers.

We aimed to determine whether remote cognitive training (CT) is feasible and has the potential to improve cognitive function and work performance in Japanese workers. From June to September 2020, this intervention time series study enrolled workers aged 18-65 years from 10 companies located in a metropolitan area of Japan. Cognitive function tests and self-administered questionnaires were completed by the participants three times: at baseline, after 12 weeks of CT, and after a further 12 weeks following cessation. We measured work performance with the question: "How would you rate your performance (compared with your optimum performance) over the past 4 weeks?" Responses were made via a visual analog scale (0-100). Cognitive function was assessed using the THINC-integrated tool, which is a brief, objective computerized cognitive assessment battery. For our computerized remote CT intervention, BrainHQ was used on the basis of our scientific rationale and the empirical literature. We recommended three 20-min sessions of BrainHQ per week and sent participants three reminders. In total, 119 participants were recruited to this study. Only 22.7% of the subjects achieved the recommended training time of 720 min over 12 weeks. The median training time was used to divide participants into long and short- training groups. The long-training group showed a greater improvement in attention and executive function than the short-training group but there was no significant improvement in work performance after CT compared to baseline. Our results suggest that although remote CT was not feasible enough, the effects on cognitive function can be expected by increasing training time and motivation.

Tablet-Based Cognitive and Eye Movement Measures as Accessible Tools for Schizophrenia Assessment: Multisite Usability Study.

Schizophrenia is a complex mental disorder characterized by significant cognitive and neurobiological alterations. Impairments in cognitive function and eye movement have been known to be promising biomarkers for schizophrenia. However, cognitive assessment methods require specialized expertise. To date, data on simplified measurement tools for assessing both cognitive function and eye movement in patients with schizophrenia are lacking. This study aims to assess the efficacy of a novel tablet-based platform combining cognitive and eye movement measures for classifying schizophrenia. Forty-four patients with schizophrenia, 67 healthy controls, and 41 patients with other psychiatric diagnoses participated in this study from 10 sites across Japan. A free-viewing eye movement task and 2 cognitive assessment tools (Codebreaker task from the THINC-integrated tool and the CognitiveFunctionTest app) were used for conducting assessments in a 12.9-inch iPad Pro. We performed comparative group and logistic regression analyses for evaluating the diagnostic efficacy of the 3 measures of interest. Cognitive and eye movement measures differed significantly between patients with schizophrenia and healthy controls (all 3 measures; P<.001). The Codebreaker task showed the highest classification effectiveness in distinguishing schizophrenia with an area under the receiver operating characteristic curve of 0.90. Combining cognitive and eye movement measures further improved accuracy with a maximum area under the receiver operating characteristic curve of 0.94. Cognitive measures were more effective in differentiating patients with schizophrenia from healthy controls, whereas eye movement measures better differentiated schizophrenia from other psychiatric conditions. This multisite study demonstrates the feasibility and effectiveness of a tablet-based app for assessing cognitive functioning and eye movements in patients with schizophrenia. Our results suggest the potential of tablet-based assessments of cognitive function and eye movement as simple and accessible evaluation tools, which may be useful for future clinical implementation.

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (±2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Long-term follow-up of brain regional changes and the association with cognitive impairment in quarantined COVID-19 survivors.

This study aimed to evaluate the neuropsychiatric symptoms of quarantined COVID-19 survivors 15months after discharge and explore its potential association with structural and functional brain changes and inflammation. A total of 51 quarantined COVID-19 survivors and 74 healthy controls were included in this study. Cognitive function was assessed using the THINC-integrated tool. Structural brain changes were examined through both surface- and volume-based analyses, and functional changes were assessed using resting-state amplitude low-frequency fluctuation (ALFF). Serum inflammatory markers were measured by a multiplexed flow cytometric assay. COVID-19 survivors exhibited subjective cognitive decline compared to healthy controls, despite no significant differences in objective cognitive tasks. Structural analysis revealed significantly increased gray matter volume and cortical surface area in the left transverse temporal gyrus (Heschl's gyrus) in quarantined COVID-19 survivors. This enlargement was negatively correlated with cognitive impairment. The ALFF analysis showed decreased neural activity in multiple brain regions. Elevated levels of serum inflammatory markers were also found in COVID-19 survivors, including MIP-1a, MIP-1b, TNF-a, and IL-8, which correlated with functional abnormalities. Our findings indicate a subjective cognitive decline in quarantined COVID-19 survivors 15months after discharge, which is associated with brain structural alterations in the left Heschl's gyrus. The observed elevation of inflammatory markers suggests a potential mechanism involving inflammation-induced neurogenesis. These results contribute to our understanding of the possible mechanisms underlying long-term neuropsychiatric consequences of COVID-19 and highlight the need for further research to develop targeted interventions.

Psychometric Properties of the Korean Version of THINC-integrated Tool (THINC-it-K): A Tool for Screening Assessment of Cognitive Function in Patients with Major Depressive Disorder.

: The present study was performed to investigate the validity and reliability of the Korean version of the THINC-it tool (THINC-it-K) in adult patients with major depressive disorder (MDD). : Subjects aged 19-65 years with recurrent MDD experiencing moderate to severe major depressive episode (n = 44) were evaluated and compared to age and sex matched healthy controls (n = 44). Subjects completed the THINC-it-K which includes variants of the Identification Task (IDN) using Choice Reaction Time, One-Back Test, Digit Symbol Substitution Test, Trail Making Test-Part B, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). : A total of 75.0% of patients with MDD exhibited cognitive performance 1 standard deviation or below. The differences in Spotter (p = 0.001), Codebreaker (p = 0.001), PDQ-5-D (p ＜ 0.001) and objective THINC-it-K composite score (p = 0.002) were significant between the two groups. Concurrent validity of the THINC-it-K based on a calculated composite score was good (r = 0.856, p ＜ 0.001), and ranges for each component tests were from 0.076 (IDN) to 0.928 (PDQ-5-D). : The THINC-it-K exhibits good reliability and validity in adults with MDD. It could be a useful tool for the measurement of cognitive deficits in persons with MDD and should be implemented in clinical practice.

Effect of aripiprazole on promoting cognitive function and enhancing clinical efficacy in patients with first-episode depression on escitalopram: A randomized controlled trial

ObjectivesTo explore the effect of escitalopram combined with aripiprazole on cognitive function in patients with major depressive disorder (MDD), and to evaluate the clinical efficacy of the combination therapy. MethodA total of 70 patients with first-episode MDD were randomly divided into the study group or the control group, receiving escitalopram combined with aripiprazole (5 mg/day) or escitalopram monotherapy respectively for 8 weeks. The severity of illness was assessed by using the Hamilton Rating Scale for Depression (HAMD) at baseline, at the end of 4th and 8th week, and cognitive function was assessed by using the THINC integrated tool (THINC-it), the Wisconsin Card Sorting Test (WCST), and the Continuous Performance Test (CPT). Rating Scale for Extrapyramidal Side Effects (RSESE) was applied to assess adverse reactions. ResultsThe average HAMD-17 and HAMA scores decreased over time in both the control and the study groups, but the reductions were not statistically different between two groups with the passage of time. In WCST, total number of response (TR) of the study group decreased relative to the baseline at the end of the eighth week, but the control group did not significantly change during whole eight weeks. Perseverative errors (PE) in the control group eventually decreased at the end of Week 8 compared to that at Week 4, but in the study group, it was a continuous trend of decrease. In CPT, the decrease of leakage responses (LR) in the study group was higher than that of the control group in 2-digit number, and LR of the control group was higher than that of the study group at the end of Week 8 in 4-digit number. The downtrend of LR in 4-digit number kept for the whole period in study group, while in the control group, the LR did not decrease significantly until the end of Week 8 compared to that at baseline. ConclusionEscitalopram combined with a low-dose of aripiprazole, and escitalopram monotherapy could both enhance cognitive function of MDD patients, while the improvements of combination therapy might happen relatively earlier. The combined use of escitalopram and aripiprazole might be more beneficial to the domains of executive function (EF) and continuous attention compared to escitalopram monotherapy. There was no significant differences between two treatment options in alleviating depressive and anxiety symptoms.

Targeted visual cortex stimulation (TVCS): a novel neuro-navigated repetitive transcranial magnetic stimulation mode for improving cognitive function in bipolar disorder

A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), as a potential site for improving cognitive function in BD. Seed-based functional connectivity (FC) analysis was used to locate targets in the V1 that had significant FC with the DLPFC and ACC. Subjects were randomly assigned to 4 groups, namely, the DLPFC active-sham rTMS (A1), DLPFC sham-active rTMS (A2), ACC active-sham rTMS (B1), and ACC sham-active rTMS groups (B2). The intervention included the rTMS treatment once daily, with five treatments a week for four weeks. The A1 and B1 groups received 10 days of active rTMS treatment followed by 10 days of sham rTMS treatment. The A2 and B2 groups received the opposite. The primary outcomes were changes in the scores of five tests in the THINC-integrated tool (THINC-it) at week 2 (W2) and week 4 (W4). The secondary outcomes were changes in the FC between the DLPFC/ACC and the whole brain at W2 and W4. Of the original 93 patients with BD recruited, 86 were finally included, and 73 finished the trial. Significant interactions between time and intervention type (Active/Sham) were observed in the scores of the accuracy of the Symbol Check in the THINC-it tests at baseline (W0) and W2 in groups B1 and B2 (F = 4.736, p = 0.037) using a repeated-measures analysis of covariance approach. Group B1 scored higher in the accuracy of Symbol Check at W2 compared with W0 (p < 0.001), while the scores of group B2 did not differ significantly between W0 and W2. No significant interactions between time and intervention mode were seen between groups A1 and A2, nor was any within-group significance of FC between DLPFC/ACC and the whole brain observed between baseline (W0) and W2/W4 in any group. One participant in group B1 experienced disease progression after 10 active and 2 sham rTMS sessions. The present study demonstrated that V1, functionally correlated with ACC, is a potentially effective rTMS stimulation target for improving neurocognitive function in BD patients. Further investigation using larger samples is required to confirm the clinical efficacy of TVCS.

Factors associated with objective and subjective cognitive impairment in Chinese patients with acute major depressive disorder

BackgroundPatients diagnosed withmajor depressive disorder (MDD) usually experience impaired cognitive functioning, which might negatively impact their clinical and functional outcomes. This study aimed to investigate the association of specific clinical factors with cognitive dysfunction in a group of MDD patients.MethodsA total of 75 subjects diagnosed with recurrent MDD were evaluated during the acute stage. Their cognitive functions were assessed using the THINC-integrated tool (THINC-it) for attention/alertness, processing speed, executive function, and working memory. Clinical psychiatric evaluations, such as the Hamilton Anxiety Scale (HAM-A), the Young Mania Rating Scale (YMRS), the Hamilton Depression Scale (HAM-D), and the Pittsburgh Sleep Quality Index(PSQI), were used to assess patients’ levels of anxiety, depression and sleeping problems. The investigated clinical variables were age, years of education, age at onset, number of depressive episodes, disease duration, presence of depressive and anxiety symptoms, sleep problems, and number of hospitalizations.ResultsThe results revealed that significant differences were observed between the two groups in the THINC-it total scores, Spotter, Codebreaker, Trails, and PDQ-5-D scores (P < 0.001). The THINC-it total scores, Spotter, Codebreaker, Trails, and Symbol Check were significantly associated with age and age at onset(P < 0.01). In addition, regression analysis found that years of education was positively associated with the Codebreaker total scores (P < 0.05). the THINC-it total scores, Symbol Check, Trails, and Codebreaker were correlated with the HAM-D total scores(P < 0.05). Additionally, the THINC-it total scores, Symbol Check, PDQ-5-D and Codebreaker significantly correlated with the PSQI total scores (P < 0.05).ConclusionWe found a significant statistical association between almost all cognitive domains and different clinical aspects in depressive disorder, such asage, age at onset, severity of depression, years of education, and sleep problems. Additionally, education was shown to be a protective factor against processing speed impairments. Special considerations of these factors might help outline better management strategies to improve cognitive functions in MDD patients.

THINC-Integrated Tool (THINC-it): A Brief Measurement of Changes in Cognitive Functioning and Its Correlation with the Life Quality of Patients with Schizophrenia and Related Disorders-A Pilot Study.

This pilot study aimed to assess patients' cognitive functioning with the Polish version of the THINC-it tool and to analyze its association with self-reported quality of life (QOL). Twenty-one patients (mean age: 37.8 ± 10.4) were assessed at baseline and after six weeks of a standard therapeutic outpatient program. Participants completed the World Health Organization QOL Questionnaire (WHOQOL-BREF) and the THINC-it tool at both visits. The tool consists of tasks evaluating working memory (SYMBOL CHECK), attention (SPOTTER), executive functions (TRIALS), and cognitive skills (CODEBREAKER). During the second visit, patients showed significant improvements in mean latency of correct responses of SPOTTER: p = 0.021, Cohen's d = 0.38 and in the Physical health domain: p = 0.007, Cohen's d = 0.37. The number of correct responses for CODEBREAKER was positively associated with the Physical health domain at visit 1 (r = 0.53, p = 0.014) and visit 2 (r = 0.42, p = 0.058). The number of correct responses at SYMBOL CHECK was positively related to QOL in the Environment domain only at visit 2 (r = 0.45, p = 0.042). These results suggest the THINC-it tool has utility as a cognitive measure in adults with schizophrenia in both clinical and research settings.

Validation of the THINC-It Tool for Assessment of Cognitive Impairment in Patients with Bipolar Depression.

Cognitive impairment is one of the core features of bipolar depression. A unified, reliable, and valid assessment tool is key to screening and assessing cognitive impairment. The THINC-Integrated Tool (THINC-it) is a simple and quick battery for screening cognitive impairment in patients with major depressive disorder. However, the use of the tool has not been validated in patients with bipolar depression. The cognitive functions of 120 patients with bipolar depression and 100 healthy controls were evaluated using the THINC-it tool including Spotter, Symbol Check, Codebreaker, Trials, and the only one subjective test (PDQ-5-D) and five corresponding standard tests. A psychometric analysis of the THINC-it tool was performed. The overall Cronbach's alpha coefficient of the THINC-it tool was 0.815. The intra-group correlation coefficient (ICC) of retest reliability ranged from 0.571 to 0.854 (P<0.001), while the correlation r of parallel validity ranged from 0.291 to 0.921 (P<0.001). There were significant differences in the two groups Z-scores of THINC-it total score, Spotter, Codebreaker, Trails, and PDQ-5-D (P<0.05). Construct validity was analyzed using exploratory factor analysis (EFA). The Kaiser-Meyer-Olkin (KMO) value was 0.749. Using Bartlett's Sphericity test, the χ 2 (10) value was 198.257 (P<0.001). The factor loading coefficients of Spotter, Symbol Check, Codebreaker, and Trails on the common factor 1 were -0.724, 0.748, 0.824, and -0.717, respectively, and the factor loading coefficient of PDQ-5-D on the common factor 2 was 0.957. Results revealed that the correlation coefficient of the two common factors was 0.125. The THINC-it tool has good reliability and validity in assessing patients with bipolar depression.

Decreased hemodynamic response to fearful faces relative to neutral faces in the medial frontal cortex of first-episode drug-naïve major depressive disorder

BackgroundMajor depressive disorder (MDD) is a disabling disease with impaired recognition of emotional facial expressions. However, the evidence is heterogeneous, regarding the mechanism of emotional processing in MDD. Focusing on patients with first-episode drug-naïve MDD, we used functional near-infrared spectroscopy (fNIRS) to investigate whether MDD have characteristic patterns in cerebral activation under facial emotion recognition task (FERT). MethodsThirty-five patients with first-episode drug-naïve MDD and 39 healthy controls (HCs) underwent fNIRS measure to evaluate cerebral hemodynamic response in the frontal and temporal cortex during FERT. The 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale and Inventory of Depressive Symptomatology-Self Report were applied to assess the symptoms of the patients. Cognitive functions were assessed using THINC-integrated tool. ResultsHypoactivation in the medial frontal was observed in patients with MDD during recognition of fearful faces relative to neutral faces (F-N faces). Specifically, we found more right lateralized activation in the medial frontal cortex among patients with MDD compared to HCs. Further, the medial frontal activation under the condition of F-N faces was positively correlated to scores of digit symbol substitution test, and negatively relative to severity of depressive symptoms in MDD group. LimitationsOur study is cross-sectional designed, and has a relatively small sample size. ConclusionsWe found abnormal patterns in the medial frontal activation of patients with first-episode drug-naïve MDD in recognition of F-N faces, which correlates with performance in cognitive function and depressive symptoms.

Relationship between objective cognitive functioning and work performance among Japanese workers.

We aimed to explore the relationship between objective cognitive functioning and work performance among Japanese workers. From February to November 2019, this cross-sectional study enrolled workers aged 18-65 years from 10 companies located in a metropolitan area of Japan. We emailed invitations to participate to employees of companies that had agreed to cooperate with the study. We measured work performance with the question, "How would you rate your performance (compared with your optimum performance) over the past 4 weeks?" Responses were made via a visual analog scale (range: 0-100). Cognitive functioning was assessed using the THINC-integrated tool (THINC-it®). THINC-it® is a brief, objective computerized cognitive assessment battery. Associations between work performance and cognitive functioning tests were examined using logistic regression analysis. In total, 353 individuals provided e-consent to participate, of whom 276 were included in the analysis (after omitting those with missing values). The median work performance was used to divide participants into high- (scoring ≥ 80%) and low- (scoring < 80%) performing groups. The P-values for trends indicated that association between cognitive domains, such as attention, executive functioning and working memory was significant (P < .05). Work performance was significantly associated with cognitive function for the two tests that assess attention, executive functioning, and working memory in general workers. Our results suggest that objective cognitive functioning may be related to work performance. Longitudinal investigations may allow for the establishment of causality.

Further validation of the THINC-it tool and extension of the normative data set in a study of n=10.019 typical controls.

We report further validation and normative data for the THINC-Integrated Tool (THINC-it), a measure of cognitive function designed for use with individuals living with Major Depressive Disorder, but which is finding use in further psychiatric and neurological diseases. THINC-it comprises four objective computerised cognitive tests based on traditional psychological paradigms and a version of the Perceived Deficits Questionnaire assessment. Sample size of n=10.019 typical control study participants were tested on one to two occasions to further validate the reliability of THINC-it. Temporal reliability was assessed across 120-180days. Test-retest reliability correlations varied between r=0.50 and 0.72 for the component measures and r=0.75 (95% confidence intervals 0.74, 0.76) forthe THINC-it composite score. Normative data categorised by Age, Sex and Years of Education were calculated and the effect on task performance was reported. Our analysis confirms previously reported levels of reliability and validates previously reported normative data values.

The Relationship Between Cognitive Dysfunction Through THINC-Integrated Tool (THINC-it) and Psychosocial Function in Chinese Patients With Major Depressive Disorder.

Background: Herein, we validate the psychometric properties of the Chinese version of the THINC-integrated tool (THINC-it) as a screening tool for cognitive deficits in patients with major depressive disorder. The primary aim of this study is to determine whether cognitive deficits as detected by the THINC-it tool in adults with major depressive disorder (MDD) are associated with workplace productivity and/or psychosocial function.Methods: Subjects aged 18–65 (n = 91) with MDD were evaluated and compared to age-, sex- and education- matched healthy controls (n = 95). Symptoms of cognitive dysfunction, workplace productivity, and psychosocial function were measured using the THINC-it tool, Hamilton Depression Scale (HAMD), Sheehan Disability Scale (SDS), The Work Productivity and Activity Impairment questionnaire- Specific Health Problem (WPAI-SHP).Results: There were significant differences in THINC-it scores (p < 0.01), the average of HAMD total score (p < 0.01) and all aspects of SDS (p < 0.01) between two groups. There were significant differences in the four aspects of WPAI between the two groups in the employed status (p <0.01). THINC-it subjective cognition and SDS total score, SDS work/school, SDS social, SDS family showed significantly correlation (r ranging from 0.255 to 0.386, p <0.01). SDS and THINC-it Objective cognition, THINC-it comprehensive cognition were no correlation between two groups. HAMD total score and SDS total score, SDS social, SDS family showed significantly correlation (r ranging

No evidence for clinical efficacy of adjunctive celecoxib with vortioxetine in the treatment of depression: A 6-week double-blind placebo controlled randomized trial

Given the role of low-grade inflammation in the pathophysiology of major depressive disorder (MDD), anti-inflammatory strategies may improve treatment outcomes in some patients. However, it is controversial whether they can be used as adjunctive treatments and whether pre-treatment levels of inflammation can predict treatment outcomes. This study was conducted to measure the efficacy of anti-inflammatory augmentation of antidepressant treatment in MDD patients; and to investigate whether treatment response was dependent on baseline inflammation levels. This parallel-group randomised, double-blind, placebo-controlled trial was conducted at the University of Adelaide (Australia). Participants with MDD were randomised to receive vortioxetine with celecoxib or vortioxetine with placebo for six weeks, and baseline blood high sensitivity C reactive protein levels were measured. Primary outcome was change in depressive symptoms (Montgomery–Åsberg Depression Rating Scale) and secondary outcomes included change in cognition (THINC-integrated tool – Codebreaker task) and functioning (Functioning Assessment Short Test) over 6 weeks. There was no evidence of superior efficacy of celecoxib augmentation over placebo on depressive symptom severity, response and remission rates, cognition and psychosocial functioning. There was also no evidence that pre-treatment inflammation levels modified the effect of celecoxib augmentation versus placebo. This observed lack of efficacy of celecoxib add-on does not support the use of celecoxib augmentation of antidepressants in the treatment of MDD in a cohort that mostly comprises treatment-resistant individuals. Additionally, C-reactive protein may not be suitable to predict treatment selection and response in MDD.The study was registered on the Australian New Zealand Clinical Trials Registry: ACTRN12617000527369 (www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p).

Insulin resistance is associated with deficits in hedonic, self-reported cognitive, and psychosocial functional response to antidepressant treatment in individuals with major depressive disorder

BackgroundTo assess the effect of insulin resistance (IR) on treatment response to the antidepressant, vortioxetine, in patients with Major Depressive Disorder (MDD). MethodsThis 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. ResultsWhen 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. LimitationsThis was a post-hoc analysis of a primarily non-diabetic sample. Also, only one agent was assessed. ConclusionsIR 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.

Reliability and Validity of THINC-it in Evaluating Cognitive Function of Patients with Bipolar Depression.

PurposeThe THINC-integrated tool (THINC-it) as a brief screening tool can assesses cognitive impairment in patients with major depressive depression (MDD). Here, we aim to evaluate the reliability and validity of the THINC-it in a bipolar depression (BD-D) group in comparison with a healthy control (HC) group.Materials and MethodsBoth groups were matched according to age, gender, years of education, and IQ. All participants completed the THINC-it test, including Spotter, Symbol Check, Codebreaker, Trails, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). The concurrent validity and internal consistency of the THINC-it test were analyzed, and 30 healthy controls were randomly sampled to retest THINC-it to verify the reliability of the THINC-it retest. The correlation between THINC-it and Hamilton Depression Scale (HAMD-17) and Sheehan Disability Scale (SDS) was also analyzed.ResultsFifty-eight patients with BD-D and 61 HCs were included for final analysis. There were significant mean difference (MD) standard errors (SE) between two groups in PDQ-5-D, Spotter and Codebreaker (all P<0.01), Trails (P=0.015). There was no significant difference in Symbol Check (MD (SE)=−0.01 (0.18), P=0.938; 95% CI=−0.38 to 0.35). The Cronbach’s α of PDQ-5-D was 0.640. The intraclass correlation coefficient (ICC) was between 0.440 and 0.757. The highest concurrent validity was PDQ-5-D (r=0.812, P<0.001). PDQ-5-D was positively correlated with HAMD-17 and SDS score (P<0.01). The objective test had no significant correlation with HAMD-17 and SDS scores (P>0.05).ConclusionThis study found that THINC-it can accurately present the cognitive impairment of patients with BD-D. It can be potentially applied in assessing the cognitive function of patients with BD-D although Symbol Check may not accurately reflect the level of cognitive function. The concurrent validity and retest reliability are lower than expected, we need to further increase the sample size to study.

Exploratory study of association between blood immune markers and cognitive symptom severity in major depressive disorder: Stratification by body mass index status

BackgroundA subset of patients with Major Depressive Disorder (MDD) have shown differences relative to healthy controls in blood inflammatory and immune markers. Meanwhile, MDD and comorbid obesity appear to present with distinct biological and symptom characteristics, categorised as “atypical” or “immunometabolic” depression, although the relevant underlying biological mechanisms are still uncertain. Therefore, this exploratory study aimed to better characterise the relationship between peripheral blood immune markers and symptoms of MDD, as well as the extent to which body mass index (BMI) may alter this relationship. MethodsLinear regression analyses were performed between selected baseline characteristics including clinical scales and blood inflammatory markers in participants with MDD (n = 119) enrolled in the PREDDICT randomised controlled trial (RCT), using age, sex and BMI as covariates, and then stratified by BMI status. Specifically, the Montgomery–Åsberg Depression Rating Scale (MADRS) for symptom severity, Clinical Global Impression scale (CGI) for functional impairment, Oxford Depression Questionnaire (ODQ) for emotional blunting, and THINC integrated tool (THINC-it) for cognitive function were considered as clinical measures. ResultsThere was a significant association between basophil count and THINC-it Codebreaker mean response time (associated with complex attention, perceptual motor, executive function, and learning and memory abilities) in overweight individuals and with THINC-it Trails total response time (associated with executive function ability) in moderately obese individuals, when controlling for age, sex, and years of education. No correlation was found between any tested blood markers and MADRS, CGI or ODQ clinical measures, regardless of BMI. DiscussionAlthough the present study is exploratory, the results suggest that targeting of the immune system and of metabolic parameters might confer benefits, specifically in patients with high BMI and experiencing cognitive impairment associated with MDD. Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017.

The Efficacy of Vortioxetine on Anhedonia in Patients With Major Depressive Disorder.

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.

Recognition and Treatment of Cognitive Dysfunction in Major Depressive Disorder.

Major Depressive Disorder (MDD) is a prevalent, chronic, disabling, and multidimensional mental disorder. Cognitive dysfunction represents a core diagnostic and symptomatic criterion of MDD, and is a principal determinant of functional non-recovery. Cognitive impairment has been observed to persist despite remission of mood symptoms, suggesting dissociability of mood and cognitive symptoms in MDD. Recurrent impairments in several domains including, but not limited to, executive function, learning and memory, processing speed, and attention and concentration, are associated with poor psychosocial and occupational outcomes. Attempts to restore premorbid functioning in individuals with MDD requires regular screenings and assessment of objective and subjective measures of cognition by clinicians. Easily accessible and cost-effective tools such as the THINC-integrated tool (THINC-it) are suitable for use in a busy clinical environment and appear to be promising for routine usage in clinical settings. However, antidepressant treatments targeting specific cognitive domains in MDD have been insufficiently studied. While select antidepressants, e.g., vortioxetine, have been demonstrated to have direct and independent pro-cognitive effects in adults with MDD, research on additional agents remains nascent. A comprehensive clinical approach to cognitive impairments in MDD is required. The current narrative review aims to delineate the importance and relevance of cognitive dysfunction as a symptomatic target for prevention and treatment in the phenomenology of MDD.