Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt.

INTRODUCTION: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. METHODS: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. CONCLUSION: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

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.

Association between serum copper, zinc, and selenium concentrations and depressive symptoms in the US adult population, NHANES (2011-2016).

BACKGROUND: Evidence suggests that alterations in serum trace element concentrations are closely associated with mental illness. However, ​studies on the relationship between serum copper, zinc, and selenium concentrations and depressive symptoms are limited and with controversial results. We aimed to investigate the association between serum concentrations of these trace elements and depressive symptoms in US adults. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) (2011-2016) were used in this cross-sectional study. The Patient Health Questionnaire-9 Items (PHQ-9) was employed to assess depressive symptoms. Multiple logistic regression was performed to determine the relationship between the serum concentrations of copper, zinc, and selenium and depressive symptoms. RESULTS: A total of 4552 adults were included. Subjects with depressive symptoms had higher serum copper concentrations (123.88 ± 1.87) than those without depressive symptoms (116.99 ± 0.86) (p < 0.001). In Model 2, weighted logistic regression analysis showed that the second (Q2) quartile of zinc concentrations (odds ratio [OR] = 1.534, 95% confident interval [CI]: 1.018 to 2.313) were significantly associated with an increased risk of depressive symptoms. Subgroup analysis revealed that the third (Q3) and fourth (Q4) quartiles of copper concentrations (Q3: OR = 2.699, 95% CI: 1.285 to 5.667; Q4: OR = 2.490, 95% CI: 1.026 to 6.046) were also positively associated with depressive symptoms in obese individuals after controlling for all confounders. However, no significant relationship between serum selenium concentrations and depressive symptoms was observed. CONCLUSIONS: Obese US adults with high serum copper concentrations, as well as US adults in general with low serum zinc concentrations, were susceptible to depressive symptoms. Nevertheless, the causal mechanisms underlying these relationships need to be further explored.

Variation in Thyroid-Stimulating Hormone and Cognitive Disorders in Unmedicated Middle-Aged Patients with Major Depressive Disorder: A Proton Magnetic Resonance Spectroscopy Study.

Background: Middle-aged (45-59 years old) patients with major depressive disorder (MDD) have a predilection for dementia and cognitive disorders (CDs); however, the characteristics and mechanisms of CDs in these patients remain unclear. There are also known connections between thyroid-stimulating hormone (TSH), brain biochemical metabolism, and cognitive function (CF); however, there is scanty of information about these connections in middle-aged MDD patients. Methods: Cognitive assessment was performed on 30 first-episode, untreated middle-aged patients with MDD and 30 well-matched healthy controls (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in the prefrontal cortex (PFC) and cerebellum were also obtained via proton magnetic resonance spectroscopy (1H-MRS), and the TSH level was measured by chemiluminescence analysis. Results: MDD patients presented significantly lower processing speed, working memory, verbal learning, reasoning problem-solving, visual learning, and composite cognition scores than controls, with a statistically lower NAA/Cr ratio in the right cerebellum. Age was positively related to reasoning problem-solving in the MDD group (r = 0.6249, p = 0.0220). Education also showed a positive association with visual learning, social cognition, and composite cognition. The 24-item Hamilton Depression Rating Scale (HDRS-24) score was negatively related to all domains of CF. TSH levels were markedly decreased in the MDD group, and a positive connection was determined between the NAA/Cr ratio in the right PFC and the TSH level. Conclusions: Middle-aged MDD patients have multidimensional CDs. There are changes in PFC and cerebellar biochemical metabolism in middle-aged patients with MDD, which may be related to CDs or altered TSH levels.

[Advances in Imaging Genetics of Suicidal Behavior].

Suicide,a major public health problem,is the death caused by injuring oneself with the intent to die.In this paper,we reviewed the genes encoding serotonin system,calcium voltage-gated channel subunit alpha1 C,γ-aminobutyric acid,and spindle and kinetochore associated complex subunit 2,as well as their related brain regions,from the perspective of imaging genetics,aiming to provide new ideas for the research and intervention on suicidal behavior.

Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model.

BACKGROUND: Major depressive disorder (MDD) is frequently associated with cognitive deficits and high copper levels. Dysfunction of N-methyl-d-aspartate (NMDA) receptors has been postulated to underlie MDD pathogenesis. This study sought to investigate the curative effect of the NMDA receptor antagonist memantine on cognitive deficits in depression and the underlying mechanisms. METHODS: Adult male Sprague-Dawley rats received corticosterone (CORT) (20 mg/kg) bi-weekly via subcutaneous injection and/or copper gluconate (7 mg/kg) via daily intragastric administration. After 3 weeks, sucrose preference tests and open field tests showed anhedonia and high anxiety in both the CORT and CORT+Cu groups. Memantine intervention (20 mg/kg daily via intragastric administration for 14 days) led to recovery of anhedonia and anxiety behaviors. Memantine also remarkably suppressed serum copper ion levels. Moreover, memantine treatment effectively rescued depression-related spatial memory deficits as shown by the Morris water maze task. RESULTS: Compared to the pre-memantine treatment results, the results of behavioral tests and cognitive function after memantine treatment were significantly normalized, and the copper concentration was decreased in all groups. CONCLUSIONS: Collectively, our findings suggest that the NMDA receptor antagonist memantine may improve symptoms of anhedonia and anxiety and the cognitive deficits associated with depression, likely be related to suppress serum copper ion levels.

Characteristics of temporal dynamics of intrinsic brain activity in unmedicated bipolar disorder with suicidality.

BACKGROUND: Bipolar disorder is associated with a high risk of suicide. Routine neuroimaging examination exhibited that bipolar disorder with suicidality was associated with brain structural and functional changes. However, the alterations of brain dynamics have still remained elusive. PURPOSE: To investigate the alterations of brain dynamics in unmedicated bipolar disorder II depression with suicidality and predict the severity of suicidality. MATERIALS AND METHODS: This prospective study included 106 bipolar disorder II participants (20 with suicidal attempt, 35 with suicidal ideation, 51 without suicidal ideation) and 50 healthy controls who underwent resting-state functional magnetic resonance imaging between February 2016 and December 2017. We first used sliding window analysis to evaluate the dynamic amplitude of low-frequency fluctuations. Then, we predicted the severity of suicidality using a multivariate regression model. RESULTS: One-way analysis of covariance revealed that the dynamic amplitude of low-frequency fluctuations in the right temporal pole, inferior temporal gyrus, superior temporal gyrus and the bilateral precuneus/posterior cingulate cortex was significantly different among the four groups. Post hoc pairwise comparisons revealed that dynamic amplitude of low-frequency fluctuations was remarkably decreased in the bilateral precuneus/posterior cingulate cortex in the three bipolar disorder II groups compared with that in healthy controls group. Increased dynamic amplitude of low-frequency fluctuations was found in the right superior temporal gyrus and inferior temporal gyrus in the suicidal attempt group compared with that in the other groups, and in the right temporal pole in the suicidal attempt group compared with that in the suicidal ideation and healthy controls groups. Importantly, these temporal variabilities could be used to predict the severity of suicidality (r = 0.330, p = 0.036), whereas static amplitude of low-frequency fluctuations couldn't (r = -0.050, p = 0.532). CONCLUSION: Our findings indicated that alterations of temporal variability in the precuneus/posterior cingulate cortex are such a common feature of bipolar disorder patients. Besides, the severity of suicidality could be predicted by the dynamic amplitude of low-frequency fluctuations abnormalities rather than static amplitude of low-frequency fluctuations abnormalities, which is the first evidence of dynamic brain alterations in bipolar disorder patients with suicidality. The proposed predictive model may be advantageous for clinical applications.

Sex differences in serum trace elements and minerals levels in unmedicated patients with major depressive episode: The role of suicidal ideation.

BACKGROUND: We aimed to examine the influence of gender on serum trace elements and minerals levels in depression, as well as the impact of suicidal ideation (SI) on these gender dimorphisms. METHODS: A total of 260 unmedicated patients with a current major depressive episode were enrolled. The Beck Scale for Suicide Ideation was utilized to evaluate SI. The serum levels of copper, zinc, iron, calcium, phosphorus, and magnesium were quantified. RESULTS: Within the non-SI (NSI) group, females exhibited higher levels of copper (p = 0.001) and phosphorus (p = 0.008), and lower levels of zinc (p = 0.022) and calcium (p = 0.008) compared to males. Conversely, no discernible gender disparities were observed in the SI group (all p > 0.05). Also, no group differences in these trace elements/minerals were observed between the SI and NSI groups (all p > 0.05). Notably, serum iron levels exhibited a significant group-by-sex interaction effect (p = 0.024). Further analysis revealed that iron levels were higher in the SI group than in the NSI group among females (p = 0.048), but lower in females than in males within the NSI group (p < 0.001). Moreover, a positive association between the fourth quantile of serum iron and SI was detected in females (odds ratio [OR] = 2.88, 95 % confidence interval [CI]: 1.08-8.11). CONCLUSIONS: Gender effects on serum trace element/mineral levels were different in depressed patients with and without SI. Female patients were susceptible to SI when serum iron was at the upper end of normal.

Personality traits as predictors for treatment response to sertraline among unmedicated obsessive-compulsive Disorder: A 12-weeks retrospective longitudinal study.

The effectiveness of selective serotonin reuptake inhibitors (SSRIs) as a primary treatment for obsessive-compulsive disorder (OCD) remains uncertain. Even after undergoing standard SSRIs treatment, 40%-60% of individuals with OCD persistently endure symptoms. Recent studies proposed that personality traits may influence the diversity of OCD treatment results. Thus, in this retrospective study, we evaluated the Eysenck Personality Questionnaire (EPQ) scores of 51 untreated patients with OCD and 35 healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed to assess OCD symptom severity at weeks 0, 2, 4, 8, and 12 of sertraline treatment. The primary outcome focused on the reduction rate of Y-BOCS scores (response: ≥25%; marked response: ≥50%). Our findings revealed that individuals with OCD demonstrated a significantly higher neuroticism score compared to healthy controls. Correlation analyses exposed a positive link between psychoticism and the duration of the disease. Moreover, family history strongly correlated with both obsessive thoughts and the total Y-BOCS score. Subsequent univariate Cox proportional analyses indicated that both low neuroticism and high extraversion traits could forecast the response to sertraline. Furthermore, only a high extraversion trait was linked to a marked response. Our results support the idea that personality traits may contribute to OCD vulnerability and predict sertraline treatment outcomes.

Cognitive impairment in major depressive disorder with non-suicidal self-injury: Association with the functional connectivity of frontotemporal cortex.

BACKGROUND: Non-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI. METHOD: Thirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest. RESULTS: MDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI. CONCLUSION: In MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI.

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.

Effects of virtual reality-based cognitive training for adolescents with depressive episodes: A pilot randomized controlled study.

Cognitive impairment is a common symptom in depression, yet few intervention strategies target adolescents. This study investigated the effects of an attention and working memory cognitive training system based on virtual reality (VRCT) in adolescents with mild to moderate depressive episodes. Adolescents with depression were randomized into a VR training group (VRG, n = 47) or a waitlist control group (WT, n = 46). The VR training consisted of three 10-min tasks per session, conducted three sessions per week for 20 sessions over 7 weeks. Forty-four healthy adolescents participated as a comparison group for baseline cognitive assessment. Cognitive functions and depressive symptoms were assessed using the Das-Naglieri cognitive assessment system, driven by the Planning, Attention, Simultaneous, and Successive (PASS) processing theory, and the Hamilton Depression Rating Scale-24 at pre- and post-intervention. Baseline results indicated significantly lower cognitive scores in patients compared to healthy adolescents. Post-intervention, the VRG demonstrated significant improvements in all four cognitive scales (effect sizes 0.56 to 0.76) and a significant reduction in depressive symptoms compared to the WT. These findings suggest that VRCT holds potential for improving cognitive impairments and alleviating depressive symptoms in adolescents with depression. Further large-scale and follow-up studies are necessary to confirm long-term benefits.

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.

Association between serum zinc levels and suicidal ideation in US adults: A population-based cross-sectional study.

BACKGROUND: Evidence suggests that the homeostatic disruption of zinc, copper, and selenium might contribute to the pathophysiology of mental disorders. However, the specific relationship between the serum levels of these trace elements with suicidal ideation remains poorly understood. This study aimed to investigated the association among suicidal ideation on serum levels of zinc, copper, and selenium. METHODS: The cross-sectional study was conducted using data from a nationally representative sample of the National Health and Nutrition Examination Survey (NHANES) 2011-2016. Suicidal ideation was assessed using Item #9 of the Patient Health Questionnaire-9 Items. Multivariate regression models and restricted cubic splines were performed and E-value was calculated. RESULTS: A total of 4561 participants aged 20 years and older were analyzed, of whom 4.08 % had suicidal ideation. The serum zinc levels were lower in the suicidal ideation group than in the non-suicidal ideation group (P = 0.021). In Crude Model, the serum zinc levels were associated with a higher suicidal ideation risk in the second quartile compared with the highest quartile [odds ratio (OR) = 2.63; 95 % confidence interval (CI): 1.53-4.53]. The association persisted (OR = 2.35; 95 % CI: 1.20-4.58) after full adjustment, with E-value 2.44. A nonlinear relationship was observed between serum zinc levels and suicidal ideation (P = 0.028). No relationship was observed between suicidal ideation and serum copper or selenium levels (all P > 0.05). CONCLUSIONS: Decreased serum zinc levels may increase susceptibility to suicidal ideation. Future studies are needed to validate the findings of this study.

The effect of exogenous estrogen on depressive mood in women: A systematic review and meta-analysis of randomized controlled trials.

Sex differences exist in the prevalence of major depressive disorder (MDD). Comparing with males, females are at a higher risk of depression, especially in some reproductive statuses with significant changes in sex hormones. Based on the positive effect on menopausal symptoms in human and on depression-like behaviors in animals, exogenous estrogen was considered as a potential therapeutic approach to the treatment of female depression, however, with inconsistent conclusions in previous studies. In the present systematic review and meta-analysis, 14 eligible randomized controlled trials (RCTs) were included to investigate the effect of exogenous estrogen on depressive mood in women. The results indicated that exogenous estrogens were superior to the control group either alone or in combination with progesterone or antidepressants. Female individuals in perimenopause are more sensitive to estrogen than those in other reproductive statuses, which might be the reason that depressive mood during this stage is more associated with estrogen fluctuations, and exogenous estrogen supplementation can moderate these drastic changes. The finding of meta-regressions that the effect of exogenous estrogen was associated with age in perimenopause and post-menopause rather than the dose or administration of exogenous estrogen, showed again that a stable level of estrogen is more beneficial than a high serum level. This study provides strong evidence of the important role of estrogen fluctuations but not estrogen levels in female depression.

Cognitive dysfunction and neurometabolic alternations in major depressive disorder with gastrointestinal symptoms.

BACKGROUND: Brain biochemical abnormalities have been associated with major depressive disorder (MDD) and cognitive impairments. However, the cognitive performance and neurometabolic alterations of MDD patients accompanied by gastrointestinal (GI) symptoms remain to be elucidated. We aimed to reveal the features and correlation between cognitive impairments and brain biochemical abnormalities of depressed patients with GI symptoms. METHODS: Fifty MDD patients with GI symptoms (GI group), 46 patients without GI symptoms (NGI group) and 50 demographically matched healthy controls (HCs) underwent Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) assessments. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the thalamus, putamen and anterior cingulate cortex (ACC). Finally, association analysis was conducted to investigate the relationships of these measurements. RESULTS: Compared to HCs, participants in both the GI and NGI groups had significantly reduced performance in the six MCCB cognitive domains (all p < 0.05), except for reasoning and problem solving. Higher Cho/Cr ratios in the right thalamus (p < 0.05) and lower NAA/Cr ratios in the left putamen (p < 0.05) were found in the NGI group than in the GI group. The severity of GI symptoms was negatively correlated with Cho/Cr ratios in the right ACC (r = -0.288, p = 0.037). In addition, the T-scores of visual learning were negatively correlated with NAA/Cr ratios in the right ACC (r = -0.443, p = 0.001) and right thalamus (r = -0.335, p = 0.015). CONCLUSION: Our findings suggest that MDD patients with GI symptoms may exhibit greater neurometabolic alternations than those without GI symptoms, while both show similar cognitive dysfunction. In addition, neurometabolic alterations in the ACC and thalamus may underlie the neural basis of GI symptoms and cognitive impairment in MDD.

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

BACKGROUND: Major 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). METHOD: Fifty-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. RESULTS: Compared 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. CONCLUSION: Patients 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.

Association between cognitive impairments and aberrant dynamism of overlapping brain sub-networks in unmedicated major depressive disorder: A resting-state MEG study.

OBJECTIVE: Little is known about the pathogenesis underlying cognitive impairment in major depressive disorder (MDD). We aimed to explore the mechanisms of cognitive impairments among patients with MDD by investigating the dynamics of overlapping brain sub-networks. METHODS: Forty unmedicated patients with MDD and 28 healthy controls (HC) were enrolled in this study. Cognitive function was measured using the Chinese versions of MATRICS Consensus Cognitive Battery (MCCB). All participants were scanned using a whole-head resting-state magnetoencephalography (MEG) machine. The dynamism of neural sub-networks was analyzed based on the detection of overlapping communities in five frequency bands of oscillatory brain signals. RESULTS: MDD demonstrated poorer cognitive performance in six domains compared to HC. The difference in community detection (functional integration mode) in MDD was frequency-dependent. MDD showed significantly decreased community dynamics in all frequency bands compared to HC. Specifically, differences in the visual network (VN) and default mode network (DMN) were detected in all frequency bands, differences in the cognitive control network (CCN) were detected in the alpha2 and beta frequency bands, and differences in the bilateral limbic network (BLN) were only detected in the beta frequency band. Moreover, community dynamics in the alpha2 frequency band were positively correlated with verbal learning and reasoning problem solving abilities in MDD. CONCLUSIONS: Our study found that decreasing in the dynamics of overlapping sub-networks may differ by frequency bands. The aberrant dynamics of overlapping neural sub-networks revealed by frequency-specific MEG signals may provide new information on the mechanism of cognitive impairments that result from MDD.

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.

Development of a Novel Retina-Based Diagnostic Score for Early Detection of Major Depressive Disorder: An Interdisciplinary View.

Background: Clinically effective markers for the diagnosis of major depressive disorder (MDD) are lacking. Alterations in retinal features are closely related to the pathophysiological progression of MDD. However, the reliable retina-related diagnostic model for MDD remains to be developed. Thus, our study aimed to quantitatively evaluate retinal vascular and structural changes in MDD patients and to develop a reliable diagnostic model of MDD based on retinal parameters. Methods: Seventy-eight patients with MDD and 47 healthy controls (HCs) underwent retinal vessel density and structure examination using optical coherence tomography angiography and visual field examination using perimetry. Independent-sample t test was used to assess the differences in retinal parameters between the groups. Meanwhile, we constructed the corresponding retina-based diagnostic model by LASSO logistic regression. Finally, the diagnostic ability of the model was evaluated by area under the curve (AUC) of receiver operating characteristic curves and calibration plot of nomogram. Results: MDD patients showed lower retinal vessel density (including radial peripapillary capillary vessel density, superficial and deep capillary plexus vessel density), thinner subfoveal choroidal thickness, and poorer visual fields compared to HCs (all p < 0.05). Furthermore, a retina-based diagnostic model was constructed and shows a strong diagnostic capability for MDD (AUC = 0.9015, p < 0.001). Conclusion: Patients with MDD showed distinct retinal features compared to HCs. The retina-based diagnostic model is expected to be a necessary complement to the diagnosis of MDD.