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Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.
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Transtorno Depressivo Maior , Microbioma Gastrointestinal , Hipocampo , Imageamento por Ressonância Magnética , Humanos , Transtorno Depressivo Maior/microbiologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Masculino , Hipocampo/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/microbiologia , Adulto , Feminino , Disbiose/microbiologia , Disbiose/fisiopatologia , Adulto Jovem , Estudos de Casos e Controles , Pessoa de Meia-Idade , Fezes/microbiologiaRESUMO
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.
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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.
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Ácido Aspártico , Transtorno Depressivo Maior , Giro do Cíngulo , Ferro , Oligoelementos , Zinco , Humanos , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Masculino , Feminino , Giro do Cíngulo/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Adulto , Oligoelementos/sangue , Oligoelementos/metabolismo , Zinco/sangue , Zinco/metabolismo , Ferro/metabolismo , Ferro/sangue , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Ácido Aspártico/sangue , Pessoa de Meia-Idade , Fatores Sexuais , Fosfocreatina/metabolismo , Fosfocreatina/sangue , Ceruloplasmina/metabolismo , Cobre/sangue , Cobre/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Magnésio/sangue , Magnésio/metabolismo , Fósforo/sangue , Creatina/metabolismo , Creatina/sangue , Cálcio/sangue , Cálcio/metabolismo , Estudos de Casos e ControlesRESUMO
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: âCompared 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.
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Transtorno Bipolar , Disfunção Cognitiva , Humanos , Masculino , Feminino , Transtorno Bipolar/psicologia , Transtorno Bipolar/complicações , Estudos Transversais , Adolescente , Disfunção Cognitiva/psicologia , Fatores Sexuais , Testes Neuropsicológicos , Adulto Jovem , Escalas de Graduação Psiquiátrica , Cognição/fisiologiaRESUMO
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.
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Transtorno Depressivo Maior , Humanos , Vortioxetina/uso terapêutico , Transtorno Depressivo Maior/psicologia , Seguimentos , Cognição , MotivaçãoRESUMO
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.
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Transtorno Obsessivo-Compulsivo , Sertralina , Humanos , Sertralina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Estudos Retrospectivos , Estudos Longitudinais , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico , Resultado do Tratamento , NeuroticismoRESUMO
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.
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Transtorno Bipolar , Humanos , Ideação Suicida , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal , Hormônio Adrenocorticotrópico/metabolismo , Hipocampo/metabolismo , Personalidade , Imageamento por Ressonância MagnéticaRESUMO
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.
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Transtorno Depressivo Maior , Oligoelementos , Humanos , Feminino , Masculino , Ideação Suicida , Cobre , Caracteres Sexuais , Cálcio , Minerais , Zinco , Ferro , FósforoRESUMO
The goal of this study was to discern the neural activation patterns associated with anorexia nervosa (AN) in response to tasks related to body-, food-, emotional-, cognitive-, and reward- processing. A meta-analysis was performed on task-based fMRI studies, revealing that patients with AN showed increased activity in the left superior temporal gyrus and bilaterally in the ACC during a reward-related task. During cognitive-related tasks, patients with AN also showed increased activity in the left superior parietal gyrus, right middle temporal gyrus, but decreased activity in the MCC. Additionally, patients with AN showed increased activity bilaterally in the cerebellum, MCC, and decreased activity bilaterally in the bilateral precuneus/PCC, right middle temporal gyrus, left ACC when they viewed food images. During emotion-related tasks, patients with AN showed increased activity in the left cerebellum, but decreased activity bilaterally in the striatum, right mPFC, and right superior parietal gyrus. Patients with AN also showed increased activity in the right striatum and decreased activity in the right inferior temporal gyrus and bilaterally in the mPFC during body-related tasks. The present meta-analysis provides a comprehensive overview of the patterns of brain activity evoked by task stimuli, thereby augmenting the current comprehension of the pathophysiology in AN.
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Anorexia Nervosa , Humanos , Anorexia Nervosa/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo , Compreensão/fisiologia , Mapeamento EncefálicoRESUMO
BACKGROUND: Evidence suggests that alterations in serum trace element concentrations are closely associated with mental illness. However, âstudies 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.
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Desnutrição , Selênio , Oligoelementos , Adulto , Humanos , Zinco , Inquéritos Nutricionais , Cobre , Estudos Transversais , Depressão/diagnóstico , ObesidadeRESUMO
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.
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Disfunção Cognitiva , Transtorno Depressivo Maior , Distúrbios do Início e da Manutenção do Sono , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Giro do Cíngulo , Cognição/fisiologia , Disfunção Cognitiva/etiologiaRESUMO
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.
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Depressão , Transtorno Depressivo , Masculino , Feminino , Humanos , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Afeto , Transtorno Depressivo/tratamento farmacológicoRESUMO
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.
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Selênio , Adulto , Humanos , Estudos Transversais , Inquéritos Nutricionais , Cobre , Fatores de Risco , ZincoRESUMO
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.
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Transtorno Bipolar , Esquizofrenia , Humanos , Tentativa de Suicídio/psicologia , Encéfalo , Ideação Suicida , Imageamento por Ressonância MagnéticaRESUMO
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.
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Disfunção Cognitiva , Transtorno Depressivo Maior , Humanos , Magnetoencefalografia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologiaRESUMO
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.
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Disfunção Cognitiva , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Creatina , Ácido Aspártico/análise , Espectroscopia de Prótons por Ressonância Magnética/métodos , Colina , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologiaRESUMO
BACKGROUND: Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions - including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. METHODS: Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. RESULTS: Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. CONCLUSIONS: These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.
Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Depressão , Memória de Curto Prazo , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/etiologiaRESUMO
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.
Assuntos
Transtorno Depressivo Maior , Memória Episódica , Humanos , Transtorno Depressivo Maior/terapia , Treino Cognitivo , MassachusettsRESUMO
BACKGROUND: The underlying neurobiological mechanisms on suicidal behavior in bipolar disorder remain unclear. We aim to explore the mechanisms of suicide by detecting dynamic functional connectivity (dFC) of corticostriatal circuitry and cognition in depressed bipolar II disorder (BD II) with recent suicide attempt (SA). METHODS: We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 68 depressed patients with BD-II (30 with SA and 38 without SA) and 35 healthy controls (HCs). The whole-brain dFC variability of corticostriatal circuitry was calculated using a sliding-window analysis. Their correlations with cognitive dysfunction were further detected. Support vector machine (SVM) classification tested the potential of dFC to differentiate BD-II with SA from HCs. RESULTS: Increased dFC variability between the right vCa and the right insula was found in SA compared to non-SA and HCs, and negatively correlated with speed of processing. Decreased dFC variability between the left dlPu and the right postcentral gyrus was found in non-SA compared to SA and HCs, and positively correlated with reasoning problem-solving. Both SA and non-SA exhibited decreased dFC variability between the right dCa and the left MTG, and between the right dlPu and the right calcarine when compared to HCs. SVM classification achieved an accuracy of 75.24 % and AUC of 0.835 to differentiate SA from non-SA, while combining the abnormal dFC features between SA and non-SA. CONCLUSIONS: Aberrant dFC variability of corticostriatal circuitry may serve as potential neuromarker for SA in BD-II, which might help to discriminate suicidal BD-II patients from non-suicidal patients and HCs.