Sex-differential cognitive performance on MCCB of youth with BD-II depression.

BACKGROUND: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. METHOD: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. RESULT: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. CONCLUSION: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder.

BACKGROUND: It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. METHODS: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. RESULTS: In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. CONCLUSIONS: Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

The effectiveness of vortioxetine on neurobiochemical metabolites and cognitive of major depressive disorders patients: A 8-week follow-up study.

OBJECTIVE: Vortioxetine has been shown to improve cognitive performance in people with depression. This study will look at the changes in neurobiochemical metabolites that occur when vortioxetine improves cognitive performance in MDD patients, with the goal of determining the neuroimaging mechanism through which vortioxetine improves cognitive function. METHODS: 30 depressed patients and 30 demographically matched healthy controls (HC) underwent MCCB cognitive assessment and 1H-MRS. After 8 weeks of vortioxetine medication, MCCB and 1H-MRS tests were retested in the MDD group. Before and after therapy, changes in cognitive performance, NAA/Cr, and Cho/Cr were examined in the MDD group. RESULTS: Compared with the HC group, the MDD group had significant reduced in verbal learning, social cognition, and total cognition (all p < 0.05). And the MDD group had lower NAA/Cr in Right thalamus and Left PFC; the Cho/Cr in Right thalamus was lower than HC; the Cho/Cr in Left ACC had significantly increase (all p < 0.05). The MDD group showed significant improvements in the areas of verbal learning, attention/alertness, and total cognitive function before and after Vortioxetine treatment (all p < 0.05). The NAA/Cr ratio of the right PFC before and after treatment (t = 2.338, p = 0.026) showed significant changes. CONCLUSIONS: Vortioxetine can enhance not just the depression symptoms of MDD patients in the initial period, but also their verbal learning, social cognition, and general cognitive capacities after 8 weeks of treatment. Furthermore, vortioxetine has been shown to enhance cognitive function in MDD patients by altering NAA/Cr and Cho/Cr levels in the frontal-thalamic-ACC.

Finite-time tolerant containment control for IT2 T-S fuzzy network multi-agent systems with actuator faults, packet dropouts and DoS attacks.

This article studies finite-time tolerant containment control issue for uncertain nonlinear networked multi-agent systems (MASs) with actuator faults, denial-of-service (DoS) attacks and packet dropouts, under the framework of interval type-2 (IT2) Takagi-Sugeno (T-S) fuzzy method. Firstly, based on establishing the actuator fault models and introducing Bernoulli random distribution to represent the packet dropouts phenomenon, the IT2 T-S fuzzy network MASs under actuator faults and packet dropouts are constructed as switchable systems according to the attack situations on the communication channels. Secondly, the slack matrix with more information of lower and upper membership functions is introduced in the stability analysis to reduce conservatism. And on basis of Lyapunov stability theory and average dwell-time method, finite-time tolerant containment control protocol is proposed, which makes the follower' states converge to the convex hull controlled by the leaders in finite time. Finally, the effectiveness of the control protocol designed in this article is verified by numerical simulation.

Alterations of insular dynamic functional connectivity and psychological characteristics in unmedicated bipolar depression patients with a recent suicide attempt.

BACKGROUND: Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA). METHODS: Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality. RESULTS: Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group. CONCLUSIONS: Our findings indicated that the dysfunction of insula-cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.

Effects of virtual reality working memory training on event-based prospective memory in patients with major depressive disorder.

BACKGROUND: Event-based prospective memory (EBPM) refers to remembering to perform delayed intention when specific events occur. EBPM deficit is present in patients with major depressive disorder (MDD) and hinders recovery from the illness. Working memory training (WMT) has been reported to enhance EBPM but its effect on EBPM in MDD remains unclear. We investigated whether virtual reality (VR)-based WMT can improve EBPM in MDD patients. METHODS: Forty-six MDD patients and 41 healthy controls (HC) were recruited. Among the former ones, the first 23 consecutive patients were allocated to the experimental group (MDD-VR) and the next 23 consecutive patients to the waitlist control group (MDD-W). EBPM accuracy was used to assess EBPM performance. Hamilton Depression Rating Scale (HDRS) and Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) were employed to assess the cognitive functions and the depressive symptoms. RESULTS: At baseline, EBPM accuracy did not significantly differ between MDD-VR and MDD-W but was lower in both of these two groups than in HC (both p < 0.001). Group-by-time interactions on EBPM accuracy (F = 4.614, p = 0.031) and CPFQ score (F = 5.754, p = 0.021) were present, whereas no significant group-by-time interaction or group effects were observed for HDRS score (both p > 0.05). After VR intervention, MDD-VR showed an increase in EBPM accuracy (Cohen's d = 1.20 [95% CI: 0.53, 1.86], p = 0.001). CONCLUSIONS: Our results demonstrated that VR-based WMT could improve EBPM deficits in MDD patients. Large-scale studies of a VR-based WMT program are indicated.

The prevalence and characteristics of MCCB cognitive impairment in unmedicated patients with bipolar II depression and major depressive disorder.

BACKGROUND: Cognitive impairment has been acknowledged as a core clinical manifestation of bipolar disorder (BD) as well as major depressive disorder (MDD). Determining the prevalence and characteristics of cognitive impairment is important for clinical interventions. This study investigated the prevalence and characteristics of cognitive impairment based on the Measurement and Treatment Research to Improve Cognition Schizophrenia Consensus Cognitive Battery (MCCB) in both BD and MDD. METHOD: One hundred and forty-nine BD II depression, 147 MDD, and 124 demographically matched healthy controls (HC) underwent MCCB cognitive assessment. The prevalence of MCCB cognitive impairment and group difference comparisons were performed. Additionally, association analysis was performed to investigate the relationship between cognitive performance and clinical variables. RESULTS: Compared to the HC group, both BD II depression and MDD groups had a significantly reduced performance for all MCCB cognitive domains (all p < 0.05). The numerical scores for visual learning were lower in the BD II depression group compared to the MDD group. 32.89% of the BD II depression patients had clinically significant impairment (>1.5 SD below the normal mean) in two or more MCCB domains compared to 23.13% for MDD patients. CONCLUSIONS: A high percent of patients in the BD II depression and MDD group exhibited MCCB cognitive impairments with clinical significance. Cognitive impairments were more common in BD II depression patients compared to MDD patients, particularly for visual learning. These findings suggest that clinicians should be aware of the severe cognitive impairment in mood disorders and establish effective cognitive screening and intervention strategies.

Similarities and differences in working memory and neurometabolism of obsessive-compulsive disorder and major depressive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD. METHODS: A total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (1H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships. RESULTS: Compared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003). CONCLUSIONS: Both OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD.

Correlations between facial emotion processing and biochemical abnormalities in untreated adolescent patients with major depressive disorder: A proton magnetic resonance spectroscopy study.

BACKGROUND: Studies show that disturbances of the fronto-striato-thalamic-cerebellar circuit could be correlated to facial emotion processing (FEP) biases in major depressive disorder (MDD). Nevertheless, the underlying mechanism of natural metabolism-emotion relationships in adolescent MDD remains unclear. METHODS: Thirty-seven adolescent patients with MDD and 30 healthy controls completed FEP tasks using the Chinese Facial Affective Picture System (CAFPS). Proton magnetic resonance spectroscopy (1H-MRS) was also used to obtain ratios of N-acetylaspartate (NAA) /creatine (Cr) and choline (Cho) /Cr ratios in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), putamen, thalamus and cerebellum. Correlations between abnormal neurometabolic ratios and FEP were also computed. RESULTS: Compared with the control group, the MDD group had significantly lower accuracy and perception intensity of happiness, and significantly higher accuracy of disgust and perception intensity of sad and fearful faces in FEP tasks. Compared to healthy controls, adolescent patients with MDD showed significantly lower NAA/Cr ratios in the left PFC, higher NAA/Cr ratios in the right thalamus, and higher Cho/Cr ratios in the right putamen, although there were no significant differences in metabolites in the ACC and cerebellum between two groups. In the MDD group, NAA/Cr ratios of the right thalamus were negatively correlated with happy reaction time and positively correlated with sad, anger, and fear intensity; Cho/Cr ratios in the right putamen were positively correlated with fear reaction time. CONCLUSIONS: Our findings suggest that FEP bias may exist in adolescents with MDD, while the impairment of FEP may be associated with abnormal metabolites in the fronto-striato-thalamic circuit.

Associations between executive function impairment and biochemical abnormalities in depressed adolescents with non-suicidal self-injury.

BACKGROUND: H protons magnetic resonance spectroscopy (1H-MRS) has been used to detect the biochemical metabolism changes and the mechanism of executive dysfunction in major depressive disorder (MDD). While, finding information associated with non-suicidal self-injury (NSSI) among adolescents with MDD is challenging. The present study aimed to examine the executive function and biochemical metabolism alterations, as well as to elucidate their associations in depressed adolescents with NSSI. METHODS: A total of 86 adolescents with MDD (40 with NSSI, and 46 without NSSI) and 28 healthy controls were recruited in the current study. The executive function was assessed by Digital symbol test (DST), Wisconsin Card Sorting Test (WCST), Trail Making Test, part B (TMT-B), and Verbal fluency (VF). Bilateral metabolite levels of the prefrontal cortex (PFC), anterior cingulated cortex (ACC), lenticular nucleus (LN) of basal ganglia and thalamus were obtained by 1H-MRS at 3.0 T, and then the ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) were determined, respectively. Finally, association analysis was conducted to investigate their relationships. RESULTS: The depressed adolescents with NSSI showed significantly lower VF scores than those without NSSI and healthy controls. We also found significantly higher NAA/Cr ratios in the right thalamus, while significantly lower Cho/Cr ratios in the right thalamus of NSSI group than the MDD without NSSI group and healthy controls. And NSSI group also showed lower NAA/Cr ratio in the right LN than the MDD without NSSI group. For MDD with NSSI, the NAA/Cr ratios of the left thalamus were positively correlated with the time of TMTB and the Cho/Cr ratios of the left ACC were positively correlated with the VF scores. CONCLUSIONS: Depressed adolescents with NSSI may have executive dysfunction and NAA and Cho metabolism abnormalities in the thalamus. And the NAA/Cr ratios of the right LN could distinguish NSSI from depressed adolescents. Further, the executive dysfunction may be associated with the abnormal NAA metabolism in the left thalamus and ACC.

The Effectiveness of Eye Movement Desensitization and Reprocessing Toward Adults With Major Depressive Disorder: A Meta-Analysis of Randomized Controlled Trials.

The practice-based evidence suggests that it is possible to use eye movement desensitization and reprocessing (EMDR) to treat major depressive disorder (MDD), but its specific efficacy is unknown. A systematic search was carried out for randomized controlled trials comparing EMDR with a control condition group in MDD patients. Two meta-analyses were conducted, with symptom reduction as primary outcome and remission as exploratory outcome. Eight studies with 320 participants were included in this meta-analysis. The first meta-analysis showed that EMDR outperformed "No Intervention" in decreasing depressive symptoms (standardized mean difference [SMD] = -0.81, 95% CI = -1.22 to -0.39, p < 0.001, low certainty), but statistically significant differences were not observed in improving remission (risk ratio = 1.20, 95% CI = 0.87-1.66, p = 0.25, very low certainty). The second showed the superiority of EMDR over CBT in reducing depressive symptoms (mean difference [MD] = -7.33, 95% CI = -8.26 to -6.39, p < 0.001, low certainty), and improving remission (risk ratio = 1.95, 95% CI = 1.24-3.06, p = 0.004, very low certainty). Besides, anxiety symptoms and level of functioning could not be included as secondary outcome due to the lack of data. The present meta-analysis suggests that EMDR is more effective in treating MDD than "No Intervention" and CBT, particularly in individuals who have traumatic experience. However, this result should be considered with caution due to small sample size and low quality of trails.