Function In Major Depressive Disorder Research Articles

A randomized trial of virtual reality eye movement desensitization and reprocessing therapy for major depressive disorder with childhood trauma: A 3-month follow-up study.

Eye movement desensitization and reprocessing therapy (EMDR) is effective in treating major depressive disorder (MDD) with childhood trauma, and virtual reality (VR) can further extend its application form. However, the utilization of VR-EMDR in treating MDD with childhood trauma is still in its infancy, and whether it can improve depressive symptoms and traumatic experience remains unknown. Seventy-two MDD patients were randomly allocated to the intervention group and the wait-list control group on a 1:1 basis. The intervention group received 12-session VR-EMDR, while another group received no intervention. We used Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Rating Scale-24 Version (24-HDRS) to assess the patient's subjective and objective depressive symptoms, the Posttraumatic Stress Disorder Check List-Civilian (PCL-C) to assess the patient's traumatic experience, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, and the MATRICS Consensus Cognitive Battery to assess the patient's subjective and objective cognitive performance. After VR-EMDR, the linear mixed model revealed significantly lower scores in PHQ-9, 24-HDRS total and factor score (including anxiety/somatization, weight, and block), Posttraumatic Stress Disorder Check List-Civilian, and Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire and significantly higher scores in information processing speed, attention/alertness, and working memory in the intervention group (p < .05). Improvements can be maintained in the 3-month follow-up, except for 24-HDRS anxiety/somatization factor score, which showed significantly higher scores in the 3-month follow-up compared with postintervention (p < .05). VR-EMDR is effective in improving depressive symptoms, traumatic experience, and cognitive performance in MDD with childhood trauma. Part of the effects can be maintained 3 months after the intervention. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Cognition-related connectome gradient dysfunctions of thalamus and basal ganglia in drug-naïve first-episode major depressive disorder

BackgroundSubcortical functional abnormalities are believed to contribute to clinical symptoms and cognitive impairments in major depressive disorder (MDD). By introducing functional gradient mapping, the present study evaluated subcortical gradients in MDD patients and their association with cognitive features. MethodsOrganization patterns and between-group differences in the principal subcortical gradient were investigated in 145 never-treated first-episode MDD patients and 145 healthy controls (HCs) across limbic, thalamic, and basal ganglia (BG) systems and their structural and functional subregions. We also assessed the associations between significant gradient alterations and clinical characteristics and neuropsychological functioning. ResultsOverall, MDD patients showed a relatively compressed and disturbed gradient organization than HCs, with limbic and BG regions located at the two extreme ends of the principal gradient. Specifically, MDD patients had lower principal gradient values in thalamus and limbic system but higher values in BG than HCs. These gradient alterations, associated with intrinsic Euclidian distance and functional connectivity patterns, manifested as spatial rearrangements of gradient values within each respective subregion. Lower gradient values in thalamic subregion projecting to default mode network were associated with higher principal gradient values in BG subregion projecting to ventral attention network, and these gradient alterations were correlated with poorer episodic memory performance in MDD patients. LimitationsThe specific neuropathological mechanisms driving the gradient alterations still require further investigation. ConclusionsOpposing gradient alterations in the thalamic and BG regions synergistically impact episodic memory performance in MDD, revealing an internally differentiated and cognition related pattern of subcortical gradient dysfunction in MDD.

Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé.

Major depressive disorder (MDD) is associated with cognitive impairments that persist despite successful treatment. Transcranial magnetic stimulation is a noninvasive treatment for MDD that is associated with small procognitive effects on working memory and executive function. We hypothesized that pairing stimulation with N-methyl-D-aspartate (NMDA) receptor agonism would enhance the effects of stimulation and its procognitive effects. The effect of NMDA receptor agonism (D-cycloserine, 100 mg) on cognitive performance was tested in two randomized double-blind placebo-controlled trials: (1) acute effects of in the absence of stimulation (n = 20 healthy participants) and (2) a treatment study of individuals with MDD (n = 50) randomized to daily intermittent theta-burst stimulation (iTBS) with placebo or D-cycloserine for 2 weeks. Cognitive function was measured using the THINC-it battery, comprised of the Perceived Deficits Questionnaire, the Choice Reaction Time, the Trail Making Test, the Digit Symbol Substitution Test, and the 1-Back tests. D-cycloserine had no acute effect on cognition compared to placebo. iTBS + D-cycloserine was associated with significant improvements in subjective cognitive function and correct responses on the 1-Back when compared to iTBS + placebo. Improvements in subjective cognition paralleled depressive symptoms improvement, however 1-Back improvements were not attributable to improvement in depression. An intersectional strategy pairing iTBS with NMDA receptor agonism may restore cognitive function in MDD.

From antidepressants and psychotherapy to oxytocin, vagus nerve stimulation, ketamine and psychedelics: how established and novel treatments can improve social functioning in major depression.

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions.

Multiple cognition associated multimodal brain networks in major depressive disorder.

Major depressive disorder frequently leads to cognitive impairments, significantly affecting patients' quality of life. However, the neurobiological mechanisms underlying cognitive deficits remain unclear. This study aimed to explore multimodal imaging biomarkers associated with cognitive function in major depressive disorder. Five cognitive scores (sustained attention, visual recognition memory, pattern recognition memory, executive function, and working memory) were used as references to guide the fusion of gray matter volume and amplitude of the low frequency fluctuation. Social function was assessed after 2yr. Linear regression analysis was performed to identify brain features that were associated with social function of patients with major depressive disorder. Finally, we included 131 major depressive disorder and 145 healthy controls. A multimodal frontal-insula-occipital network associated with sustained attention was found to be associated with social functioning in major depressive disorders. Analysis across different cognitive domains revealed that gray matter volume exhibited greater sensitivity to differences, while amplitude of the low frequency fluctuation consistently decreased in the right temporal-occipital-hippocampus circuit. The consistent functional changes across the 5 cognitive domains were related to symptom severity. Overall, these findings provide insights into biomarkers associated with multiple cognitive domains in major depressive disorder. These results may contribute to the development of effective treatment targeting cognitive deficits and social function.

Do enteric glial cells play a role in the pathophysiology of major depression?

Major depressive disorder (MDD) is a common mental disorder associated with significant suffering and disability. Recent evidence has highlighted the role of the gut-brain axis in the pathogenesis of MDD. Enteric glial cells are a structurally and functionally diverse population that plays a key role in regulating enteric nervous function and maintaining intestinal mucosal integrity. These cells may be implicated in the origin of several digestive and extra-digestive disorders, known as enteric neuro-gliopathies (ENG). This paper reviews the evidence that MDD may also belong to the category of ENG. Animal models suggest that environmental adversity can lead to enteric glial dysfunction and depressive-like behaviors. Conditions that are highly comorbid with MDD, both intestinal and extra-intestinal, have been linked to enteric glial alterations. Peripheral blood markers linked to glial integrity and function are altered in patients with MDD, and certain treatments for MDD may have beneficial effects on enteric glial functioning. Though much of this evidence is indirect and provisional, it suggests that MDD may belong to the group of ENG. Further investigation of enteric glial functioning in MDD may yield valuable insights into the pathophysiology and treatment of this disorder.

Atypical Brain Aging and Its Association With Working Memory Performance in Major Depressive Disorder

BackgroundPatients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to those seen in aging. However, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool that quantifies normative neurodevelopmental trajectories. MethodsA total of 304 participants with MDD and 236 control participants without depression were recruited and scanned from 3 studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to generate brain centile scores, which were examined for 1) differences between participants with MDD and control participants; 2) differences between individuals with versus without severe childhood maltreatment; and 3) correlations with depressive symptom severity, neurocognitive assessment domains, and escitalopram treatment response. ResultsBrain centiles were significantly lower in the MDD group than in the control group. Brain centile was also significantly correlated with working memory in the control group but not the MDD group. No significant associations were observed between depression severity or antidepressant treatment response and brain centiles. Likewise, childhood maltreatment history did not significantly affect brain centiles. ConclusionsConsistent with previous work on machine learning models that predict brain age, brain centile scores differed in people diagnosed with MDD, and MDD was associated with differential relationships between centile scores and working memory. The results support the notion of atypical development and aging in MDD, with implications for neurocognitive deficits associated with aging-related cognitive function.

Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis.

Major depressive disorder (MDD) is associated with significant cognitive deficits during the acute and remitted stages. The aim of this systematic review and meta-analysis was to examine the course of cognitive function whilst considering demographic, treatment, or clinical features of MDD that could moderate the extent of cognitive change. Databases were searched to identify studies that reported on cognitive function in MDD with a ≥12-week test-retest interval. Relevant studies were pooled using random effects modelling to generate an inverse-variance, weighted, mean effect size estimate (Hedges' g) of cognitive change for each cognitive variable and for an overall composite cognitive domain. Of 6898 records, 99 eligible studies were identified from which 69 were meta-analysed, consisting of 4639 MDD patients (agemean = 40.25years, female% = 64.62%) across 44 cognitive variables. In over 95% of cognitive variables, improvements were either of non-significant, negligible, or of a small magnitude, and when compared to matched healthy controls, the possibility of practice effects could not be precluded. Depressive symptom improvement and the number of previous depressive episodes moderated the extent of cognitive change, demonstrating state- and scar-like features for one-quarter of the cognitive domains. Further longitudinal studies are required to elucidate the MDD cognitive trajectory from initial onset. Findings nonetheless suggest that following pharmacological and non-pharmacological treatment, cognitive change in MDD is typically small, but the capacity for change may be less with episode recurrence. Targeting cognition early in the course of illness may facilitate better prognosis and support a more complete functional recovery.

Regional decreases of cortical thickness in major depressive disorder and their correlation with illness duration: a case-control study.

Alterations in brain structure and function in major depressive disorder (MDD) have been identified in a number of studies, but findings regarding cortical thickness were various and inconsistent. Our current study aims to explore the differences in cortical thickness between individuals with MDD and healthy controls (HC) in a Chinese population. We investigated T1-weighted brain magnetic resonance imaging data from 61 participants (31 MDD and 30 HC). The cortical thickness between the two groups and analyzed correlations between cortical thickness and demographic variables in the MDD group for regions with significant between-group differences were conducted. Compared with the HC group, patients with MDD had significantly decreased cortical thickness, in left pars triangularis, left pars orbitalis, left rostral middle frontal gyrus, left supramarginal gyrus, right parahippocampal gyrus, right lingual gyrus, right fusiform and right inferior parietal gyrus. The cortical thickness of left rostral middle frontal gyrus was negatively correlated (r = -0.47, p = 0.028) with the illness duration in patients with MDD. Our study distinguished that cortical thickness decreases in numerous brain regions both in the left and right hemisphere in individuals with MDD, and the negative correlation between the cortical thickness of left rostral middle frontal gyrus illness duration. Our current findings are valuable in providing neural markers to identify MDD and understanding the potential pathophysiology of mood disorders.

Dysfunction of circulating endothelial progenitor cells in major depressive disorder.

Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD. We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays. The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups. The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

Relationship of prefrontal cortex activity with anhedonia and cognitive function in major depressive disorder: an fNIRS study.

Major depressive disorder (MDD) is associated with deficits in cognitive function, thought to be related to underlying decreased hedonic experiences. Further research is needed to fully elucidate the role of functional brain activity in this relationship. In this study, we investigated the neurofunctional correlate of the interplay between cognitive function and hedonic experiences in medication-free MDD using functional near-infrared spectroscopy (fNIRS). We examine differences of brain activation corresponding to the verbal fluency test (VFT) between MDD patients and healthy controls (HCs). Fifty-six MDD patients and 35 HCs underwent fMRI scanning while performing the VFT. In exploratory analyses, cognitive performance, as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), four dimensions of hedonic processing (desire, motivation, effort, and consummatory pleasure) measured by the Dimensional Anhedonia Rating Scale (DARS), and relative changes in oxygenated hemoglobin concentration during the VFT were compared across groups. Patients with MDD demonstrated impairments in sustained attention and working memory, accompanied by lower total and subscale scores on the DARS. Compared to healthy controls, MDD patients exhibited reduced activation in the prefrontal cortex (PFC) during the VFT task (t = 2.32 to 4.77, p < 0.001 to 0.02, FDR corrected). DARS motivation, desire, and total scores as well as sustained attention, were positively correlated with activation in the dorsolateral PFC and Broca's area (p < 0.05, FDR corrected). These findings indicate that changes in prefrontal lobe oxygenated hemoglobin levels, a region implicated in hedonic motivation and cognitive function, may serve as potential biomarkers for interventions targeting individuals with MDD. Our results corroborate the clinical consensus that the prefrontal cortex is a primary target for non-invasive neuromodulatory treatments for depression.

Prevalence of sexual dysfunction and its association with psychological symptoms in drug-naive major depressive disorder patients in West China.

Sexual dysfunction is commonly observed in individuals with Major Depressive Disorder (MDD), along with various psychological symptoms such as anxiety, somatic complaints, interpersonal sensitivity, and obsessive-compulsive tendencies. However, there is a research gap in understanding the impact of these psychological symptoms on sexual functioning in MDD. Furthermore, there is limited data on the incidence of sexual dysfunction among drug-naive MDD patients in West China. This study aims to determine the prevalence of sexual dysfunction in this patient population and explore its association with other psychological indicators. We conducted a retrospective analysis of patient data from October 2020 to September 2022 using propensity score matching. A focused group of 165 males and 490 females was selected from a total of 1941 MDD patients. This allowed for a comparative analysis of demographic data, as well as scores from the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Symptom Checklist-90 (SCL-90), the Arizona Sexual Experience Scale (ASEX). Our findings reveal that 46.2% of drug-naive MDD patients experienced sexual dysfunction. Notably, there was a higher prevalence of sexual dysfunction among female patients (50.3%) compared to males (37.5%). MDD patients without sexual dysfunction consistently exhibited higher SDS scores than those with sexual dysfunction (p < 0.01), There were no statistically significant differences between male and female MDD patients with or without concomitant sexual dysfunction in terms of Somatic complaints, Obsessive-compulsive, Interpersonal sensitivity, Anxiety, Phobic anxiety, Paranoid ideation, Psychoticism and Diet/sleep difficulties (p > 0.05). In addition, male MDD patients with sexual dysfunction showed a emerging trend towards elevated Hostility scores on the SCL-90 (p = 0.058), male MDD patients with sexual dysfunction showed an increasing trend in hostility scores on the SCL-90, whereas female MDD patients with sexual dysfunction did not show such a trend. The study highlights a significant gender difference in the prevalence of sexual dysfunction among MDD patients, with females being more susceptible than males. There is a positive correlation between the severity of depression and sexual dysfunction in both genders. Interestingly, male MDD patients demonstrated a potential protective effect of hostility against sexual dysfunction, which was not observed in female patients.

Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder

ObjectiveTo compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). MethodsUsing a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. ResultstDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. ConclusionsAlthough tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SignificanceThis reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Cognitive improvement in patients with major depressive disorder after personalised multi domain training in the CERT-D study

The CERT-D program offers a new treatment approach addressing disturbed cognitive and psychosocial functioning in major depressive disorder (MDD). The current analysis of a randomised controlled trial (RCT) comprises two objectives: Firstly, evaluating the program's efficacy of a personalised versus standard treatment and secondly, assessing the treatment's persistence longitudinally. Participants (N = 112) were randomised into a personalised or standard treatment group. Both groups received 8 weeks of cognitive training, followed by a three-month follow-up without additional training. The type of personalised training was determined by pre-treatment impairments in the domains of cognition, emotion-processing and social-cognition. Standard training addressed all three domains equivalent. Performance in these domains was assessed repeatedly during RCT and follow-up. Treatment comparisons during the RCT-period showed benefits of personalised versus standard treatment in certain aspects of social-cognition. Conversely, no benefits in the remaining domains were found, contradicting a general advantage of personalisation. Exploratory follow-up analysis on persistence of the program's effects indicated sustained intervention outcomes across the entire sample. A subsequent comparison of clinical outcomes between personalised versus standard treatment over a three-month follow-up period showed similar results. First evidence suggests that existing therapies for MDD could benefit from an adjunct administration of the CERT-D program.

Strain-level structure of gut microbiome showed potential association with cognitive function in major depressive disorder: A pilot study

BackgroundAlthough the association between gut microbiota and the pathogenesis of major depressive disorder (MDD) has been well studied, it is unclear whether gut microbiota affects cognitive function in patients with MDD. In this study, we explored the association between gut microbiota and cognitive function in MDD and its possible mechanisms. MethodsWe enrolled 57 patients with MDD and 30 healthy controls (HCs) and used 16S rRNA gene sequencing analysis and shotgun metagenomic sequencing analysis to determine gut microbial composition. ResultsThe richness and diversity of gut microbiota in patients with MDD were the same as those in HCs, but there were differences in the abundance of Bifidobacterium and Blautia. Compared with HCs, two strains (bin_32 and bin_55) were significantly increased, and one strain (bin_31) was significantly decreased in patients with MDD based on the strain-level meta-analysis. Time to complete the Stroop-C had significant negative correlations with bin_31 and bin_32. Bin_55 had significant negative correlations with time to complete the Stroop-C, time to complete the Stroop-CW, and repeated animal words in 60 s but significant positive correlations with correct answers in 120 s on the Stroop-CW. LimitationsThis study only tested the cognitive function of MDD in a small sample, which may have caused some bias. ConclusionsBased on our strain-level analysis, we found that gut microbiota may be associated with the pathogenesis of MDD and may have potential effects on cognitive function.

Effects of a video game intervention on symptoms, training motivation, and visuo-spatial memory in depression.

People with Major Depressive Disorder (MDD) often experience reduced affect, mood, and cognitive impairments such as memory problems. Although there are various treatments for MDD, many of them do not address the cognitive deficits associated with the disorder. Playing 3D video games has been found to improve cognitive functioning in healthy people, but it is not clear how they may affect depressed mood and motivation in people with MDD. The aim of this study was to investigate whether a six-week video game intervention leads to improvements in depressed mood, training motivation, and visuo-spatial (working) memory functions in patients with MDD. A total of 46 clinically depressed individuals were randomly assigned to one of three groups: an experimental "3D video gaming" group (n = 14) which played a video game, an active control group (n = 16) which trained with a computer program "CogPack," and a treatment-as-usual group (n = 16) which received a standard clinical treatment including psychotherapy and/or pharmacotherapy. Participants performed a neuropsychological assessment, including self-report questionnaires asking for depressive symptoms, training motivation, and visuo-spatial (working) memory functions before and after the training intervention. Regarding depressive symptoms, a significant decrease in the proportion of participants who showed clinical levels of depressive symptoms as measured by the Beck Depression Inventory was only found in the 3D video gaming group. Additionally, mean motivational levels of performing the training were significantly higher in the 3D video gaming group when compared with the active control group. Moreover, whereas the 3D Video Gaming group only significantly improved on one visuo-spatial memory test, the active control group improved in all visuo-spatial memory functions. The 3D video gaming group did not perform significantly better than the CogPack group, and the TAU group. Besides a standalone cognitive training, the current findings suggest that cognitive trainings using a video game have potential to increase subjective well-being, show higher levels of training motivation, and lead to improvements in visuo-spatial (working) memory functions in MDD. However, given the mixed and unblinded nature of this study, the results should be interpreted with caution. Further research with larger samples and follow-up measurements is needed.

A pilot study on improvements in attention function in major depressive disorder after 12 weeks of escitalopram monotherapy or combined treatment with agomelatine.

This study aimed to explore both impairments in attention function in patients with major depressive disorder (MDD) and the efficacy of escitalopram monotherapy or combination therapy with agomelatine. A total of 54 patients with MDD and 46 healthy controls (HCs) were included. Patients were treated with escitalopram for 12 weeks; those who presented with severe sleep impairments were also given agomelatine. Participants were evaluated using the Attention Network Test (ANT), which included tests of alerting, orienting, and executive control networks. Concentration, instantaneous memory, and resistance to information interference were tested using the digit span test, and the logical memory test (LMT) was used to evaluate abstract logical thinking. The Hamilton Depression Rating Scale-17 items, Hamilton Anxiety Rating Scale, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep quality, respectively. Patients with MDD were assessed at the end of weeks 0, 4, 8, and 12. HCs were assessed once at baseline. Compared with HCs, patients with MDD showed significantly different alerting, orienting, and executive control functions of attention networks. Treatment with escitalopram alone or combined with agomelatine significantly improved LMT scores at the end of weeks 4, 8, and 12 and restored scores to the level of HCs at the end of week 8. Total Toronto Hospital Test of Alertness scores in patients with MDD increased significantly after 4 weeks of treatment. The ANT executive control reaction time in patients with MDD decreased significantly after 4 weeks of treatment, with this decrease lasting until the end of week 12, but scores did not return to the levels of HCs. Combined treatment with escitalopram and agomelatine led to more improvement in ANT orienting reaction time and was accompanied by a greater reduction of total scores on the Hamilton Depression Rating Scale-17 items and Hamilton Anxiety Rating Scale compared with escitalopram monotherapy. Patients with MDD showed overall impairments in three domains of attention networks as well as the LMT and a test of subjective alertness. Escitalopram monotherapy significantly improved the LMT scores and the executive control function scores in the ANT at the end of the fourth week of treatment, and the improvement was more extensive with combined escitalopram and agomelatine treatment.

Trying to name what doesn't change: Neural nonresponse to Cognitive Therapy for depression.

Theoretical models of neural mechanisms underlying Cognitive Behavior Therapy (CBT) for major depressive disorder (MDD) propose that psychotherapy changes neural functioning of prefrontal cortical structures associated with cognitive-control processes (DeRubeis, Siegle, & Hollon, ); however, MDD is persistent and characterized by long-lasting vulnerabilities to recurrence after intervention, suggesting that underlying neural mechanisms of MDD remain despite treatment. It follows that identification of treatment-resistant aberrant neural processes in MDD may inform clinical and research efforts targeting sustained remission. Thus, we sought to identify brain regions showing aberrant neural functioning in MDD that either (1) fail to exhibit substantive change (nonresponse) or (2) exhibit functional changes (response) following CBT. To identify treatment-resistant neural processes (as well as neural processes exhibiting change after treatment), we collected functional magnetic resonance imaging (fMRI) data of MDD patients (n = 58) before and after CBT as well as never-depressed controls (n = 35) before and after a similar amount of time. We evaluated fMRI data using conjunction analyses, which utilized several contrast-based criteria to characterize brain regions showing both differences between patients and controls at baseline and nonresponse or response to CBT. Findings revealed nonresponse in a cerebellar region and response in prefrontal and parietal regions. Results are consistent with prior theoretical models of CBT's direct effect on cortical regulatory processes but expand on them with identification of additional regions (and associated neural systems) of response and nonresponse to CBT.

Biochemical metabolism in the anterior cingulate cortex and cognitive function in major depressive disorder with or without insomnia syndrome

BackgroundMajor depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC). MethodFifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (1H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups. ResultsCompared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T-score. ConclusionPatients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS.

Mediation Effects of Social Cognition on the Relationship between Neurocognition and Social Functioning in Major Depressive Disorder and Schizophrenia Spectrum Disorders.

In schizophrenia spectrum disorders (SSD), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. Using data obtained through an internet survey, 210 patients with SSD or MDD were selected using propensity score matching based on their demographics and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each group. Invariances of the mediation model across the two groups were then analyzed. The SSD and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. The role of social cognition in patients with MDD was similar to that in SSD. Social cognition could be a common endophenotype for various psychiatric disorders.