Effects of electroconvulsive therapy on functional brain networks in patients with schizophrenia.

BACKGROUND: Schizophrenia is a kind of intractable brain disorder. Electroconvulsive therapy (ECT) has been used to rapidly improve the clinical symptoms of patients with schizophrenia, but the effect of ECT on topological attributes of brain functional network in patients with schizophrenia has not been clear. The purpose of this study was to investigate the brain functional network mechanism of ECT against schizophrenia. METHODS: Thirty-one patients with schizophrenia and fifty healthy controls matching age, gender, and years of education were included. All participants underwent general data collection and magnetic resonance imaging scanning before ECT, and clinical symptoms were assessed using the Positive And Negative Syndrome Scale (PANSS). MRI and clinical symptoms were collected again after the first and eighth ECT application. The functional brain network was constructed on the basis of magnetic resonance imaging, and the global and node topological properties were analyzed. Repeated measure variance analysis was used to explore the changes of the topological attribute values and clinical symptom scores before and after ECT, and Bonferroni post hoc analysis was performed. The independent sample t-test was used to compare the differences in the topological attribute values between patients and healthy controls at three time points before and after ECT. Partial correlation analysis was performed for topological attribute values and clinical symptom scores of abnormal brain regions in the patient groups and their changes during ECT. A general linear regression model was used to predict the outcome after the final eighth ECT using the patient's response to the first ECT. RESULTS: (1) One ECT can restore the gamma(γ), lamuda(λ), sigma(σ), nodal global efficiency (Ne) of right insular gyrus ventral agranular insula (INS_R_vIa) and nodal local efficiency (NLe) of bilateral fusiform gyrus medioventral area37 (FuG_A37mv). Eight ECT can also restore the NLe of cortex rostral lingual gyrus (MVOcC _R_rLinG). Eight ECT did not improve the Ne of right superior parietal lobule rostral area 7 (SPL_R_A7r) and NLe of left superior frontal gyrus medial area 6 (SFG_L_A6m). (2) Even after only the first use of ECT, total PANSS scores began to decrease (mean ΔPANSSECT1 was 11.7%; Range, 2%-32.8%), decreased significantly after the eighth application (mean ΔPANSSECT8 was 86.0%; Range,72.5% to 97.9%). Five patients met the response criteria after ECT1 (20% reduction in PANSS total score), and all patients met the response criteria after ECT8. (3) Linear regression analysis showed that ΔPANSSECT1 was a significant predictor of ΔPANSSECT8 (F=5.387, P=0.028), and ΔPANSSECT1 explained 15.7% of the variance of ΔPANSSECT8 (R2=0.157). CONCLUSIONS: ECT was able to normalize γ, λ, σ, Ne of INS_R_vIa, NLe of bilateral FuG_A37mv in SZ patients after the first treatment, and NLe of MVOcC_R_rLinG after the eighth ECT. ECT significantly alleviates psychotic symptoms in patients with SZ, and its efficacy after eight sessions can be predicted by the patient's response to the first session of ECT.

Resting-state cerebral blood flow and functional connectivity abnormalities in depressed patients with childhood maltreatment: Potential biomarkers of vulnerability?

AIM: Childhood maltreatment (CM) is an important risk factor for major depressive disorder (MDD). This study aimed to explore the specific effect of CM on cerebral blood flow (CBF) and brain functional connectivity (FC) in MDD patients. METHODS: A total of 150 subjects were collected including 55 MDD patients with CM, 34 MDD patients without CM, 19 healthy controls (HC) with CM, and 42 HC without CM. All subjects completed MRI scans and neuropsychological tests. Two-way analysis of covariance was used to detect the main and interactive effects of disease and CM on CBF and FC across subjects. Then, partial correlation analyses were conducted to explore the behavioral significance of altered CBF and FC in MDD patients. Finally, a support vector classifier model was applied to differentiate MDD patients. RESULTS: MDD patients represented increased CBF in bilateral temporal lobe and decreased CBF in right visual cortex. Importantly, significant depression-by-CM interactive effects on CBF were primarily located in the frontoparietal regions, including orbitofrontal cortex (OFC), lateral prefrontal cortex (PFC), and parietal cortex. Moreover, significant FC abnormalities were seen in OFC-PFC and frontoparietal-visual cortex. Notably, the abnormal CBF and FC were significantly associated with behavioral performance. Finally, a combination of altered CBF and FC behaved with a satisfactory classification ability to differentiate MDD patients. CONCLUSIONS: These results highlight the importance of frontoparietal and visual cortices for MDD with CM experience, proposing a potential neuroimaging biomarker for MDD identification.

Progressive Changes in Brain Regional Homogeneity Induced by Electroconvulsive Therapy Among Patients With Schizophrenia.

OBJECTIVES: Electroconvulsive therapy (ECT) has significant effects on improving psychotic symptoms in schizophrenia (SZ), but the changes of brain function induced by it are unclear. The purpose of the study was to explore progressive ECT-induced changes in regional homogeneity (ReHo) at multiple time points before, during, and after a course of ECT. METHODS: The 27 in-patients with SZ (SZ group) who met the recruitment criteria accepted clinical evaluations and resting-state functional magnetic resonance imaging scans before the first ECT (pre-ECT), after the first ECT (ECT1), and after the eighth ECT (ECT8), all conducted within 10 to 12 hours. Forty-three healthy controls (HCs; HC group) who matched well with the patients for age, sex, and years of education were recruited. For Positive and Negative Syndrome Scale (PANSS) and ReHo, progressive changes were examined. RESULTS: Pair-wise comparisons of patient pre-ECT, ECT1, and ECT8 ReHo values with HC ReHo values revealed that ECT normalized the ReHo values in bilateral superior occipital gyrus (SOG), right lingual gyrus (LG), left medial prefrontal cortex. Furthermore, improved ReHo in bilateral SOG and right LG appeared after the first ECT application. The ReHo values in right middle occipital gyrus, right middle temporal gyrus, and right inferior parietal lobule were not significantly altered by ECT. The total PANSS score was lower even after the first ECT application (mean ΔPANSSECT1, 11.7%; range, 2%-32.8%) and markedly reduced after the eighth application (mean ΔPANSSECT8, 86.3%; range, 72.5%-97.9%). CONCLUSIONS: The antipsychotic effects of ECT may be achieved through regulating synchronization of some regions such as bilateral SOG, right LG, and left medial prefrontal cortex. Furthermore, the enhanced synchronizations also take place in other regions.

Identification of microRNA-9 linking the effects of childhood maltreatment on depression using amygdala connectivity.

Childhood maltreatment (CM) is regarded as an important risk factor for major depressive disorder (MDD). However, the neural links corresponding to the process of early CM experience producing brain alterations and then leading to depression later remain unclear. To explore the neural basis of the effects of CM on MDD and the potential role of microRNA-9 (miR-9) in these processes, we recruited 40 unmedicated MDD patients and 34 healthy controls (HCs) to complete resting-state fMRI scans and peripheral blood miR-9 tests. The neural substrates of CM, miR-9, and depression, as well as their interactive effects on intrinsic amygdala functional connectivity (AFC) networks were investigated in MDD patients. Two-step mediation analysis was separately employed to explore whether AFC strength mediates the association among CM severity, miR-9 levels, and depression. A support vector classifier (SVC) model of machine learning was used to distinguish MDD patients from HCs. MDD patients showed higher miR-9 levels that were negatively correlated with CM scores and depressive severity. Overlapping effects of CM, miR-9, and depressive severity on bilateral AFC networks in MDD patients were primarily located in the prefrontal-striatum pathway and limbic system. The connection of amygdala to prefrontal-limbic circuits could mediate the effects of CM severity on the miR-9 levels, as well as the impacts of miR-9 levels on the severity of depression in MDD patients. Furthermore, the SVC model, which integrated miR-9 levels, CM severity, and AFC strength in prefrontal-limbic regions, had good power in differentiating MDD patients from HCs (accuracy 85.1%). MiR-9 may play a crucial role in the process of CM experience-produced brain changes targeting prefrontal-limbic regions and that subsequently leads to depression. The present neuroimaging-epigenetic results provide new insight into our understanding of MDD pathophysiology.

The reduced left hippocampal volume related to the delayed P300 latency in amnestic mild cognitive impairment.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is characterized by delayed P300 latency and reduced grey matter (GM) volume, respectively. The relationship between the features in aMCI is unclear. This study was to investigate the relationship between the altered P300 latency and the GM volume in aMCI. METHODS: Thirty-four aMCI and 34 well-matched normal controls (NC) were studied using electroencephalogram during a visual oddball task and scanned with MRI. Both tests were finished in the same day. RESULTS: As compared with the NC group, the aMCI group exhibited delayed P300 latency in parietal cortex and reduced GM volumes in bilateral temporal pole and left hippocampus/parahippocampal gyrus. A remarkable negative correlation was found between delayed P300 latency and reduced left hippocampal volume only in the aMCI group. Interestingly, the mediating analysis found P300 latency significantly mediated the association between right supramarginal gyrus volume and information processing speed indicated by Stroop Color and Word Test A scores. CONCLUSIONS: The association between delayed P300 latency and reduced left hippocampal volume in aMCI subjects suggests that reduced left hippocampal volume may be the potential structural basis of delayed P300 latency.

Desynchronized Functional Activities Between Brain White and Gray Matter in Major Depression Disorder.

BACKGROUND: Alterations in gray matter (GM) have been recognized as playing an important role in the neurobiological mechanism underlying major depressive disorder (MDD) and antidepressant responses. However, little is known about white matter (WM) connectivity in MDD, leaving an incomplete understanding of the pathophysiology of the disorder. PURPOSE: To examine the functional connectivity (FC) of WM, GM, and WM-GM in MDD patients and explore the relationship between FC and antidepressant response. STUDY TYPE: Longitudinal study. SUBJECTS: In all, 129 MDD patients and 89 healthy controls (HC). FIELD STRENGTH/SEQUENCE: Whole-brain blood oxygen level-dependent (BOLD) single-shot echo planar imaging was acquired at 3.0T. ASSESSMENT: At baseline, all participants received Hamilton depression rating scale (HAMD) assessment and an fMRI scan. After 2- and 8-week antidepressant treatment, patients completed the HAMD again. The HAMD reductive rate of 2- and 8-weeks were calculated. STATISTICAL TESTS: The comparisons of age, education, HAMD scores, and FC values (false discovery rate correction) between patients and controls were calculated with a two-sample t-test. The chi-square test was employed to compare the differences of gender between these two groups. Correlations between FC and HAMD, as well as the reductive rate of HAMD, were analyzed with Pearson or Spearman correlation. Receiver operator curve analysis was performed to predict the antidepressant response. RESULTS: Compared to HC, MDD patients exhibited widespread decreases in FC of WM-GM. Furthermore, 28 GM regions and 11 WM bundles had lower connectivity in MDD patients. At baseline, four FC of WM-GM showed negative correlations with the HAMD scores. Six FC of WM-GM correlated with the 2-week reductive rate of HAMD. Moreover, FC in GM, WM, and WM-GM also exhibited significantly positive correlations with an 8-week reductive rate of HAMD. DATA CONCLUSION: The FC of WM-GM was decreased in MDD and may play a role in its pathophysiology and antidepressant responses. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

CircDYM ameliorates depressive-like behavior by targeting miR-9 to regulate microglial activation via HSP90 ubiquitination.

Circular RNAs (circRNAs), highly expressed in the central nervous system, are involved in various regulatory processes and implicated in some pathophysiology. However, the potential role of circRNAs in psychiatric diseases, particularly major depressive disorder (MDD), remains largely unknown. Here, we demonstrated that circular RNA DYM (circDYM) levels were significantly decreased both in the peripheral blood of patients with MDD and in the two depressive-like mouse models: the chronic unpredictable stress (CUS) and lipopolysaccharide (LPS) models. Restoration of circDYM expression significantly attenuated depressive-like behavior and inhibited microglial activation induced by CUS or LPS treatment. Further examination indicated that circDYM functions as an endogenous microRNA-9 (miR-9) sponge to inhibit miR-9 activity, which results in a downstream increase of target-HECT domain E3 ubiquitin protein ligase 1 (HECTD1) expression, an increase of HSP90 ubiquitination, and a consequent decrease of microglial activation. Taken together, the results of our study demonstrate the involvement of circDYM and its coupling mechanism in depression, providing translational evidence that circDYM may be a novel therapeutic target for depression.

Increased subcortical region volume induced by electroconvulsive therapy in patients with schizophrenia.

Electroconvulsive therapy (ECT) has been widely used to treat patients with schizophrenia. However, the underlying mechanisms of ECT remain unknown. In the present study, the treatment effects of ECT on brain structure in patients with schizophrenia were explored. Seventy patients with schizophrenia were scanned using structural magnetic resonance imaging. Patients in the drug group were scanned at baseline (time 1) and follow-up (time 2, 6 weeks of treatment). Patients in the ECT group were scanned before ECT treatment (baseline, time 1) and 10-12 h after the last ECT treatment (time 2). Voxel-based morphometry was applied to analyze the imaging data. Patients in the ECT group showed significantly increased gray matter volume (GMV) in the bilateral hippocampus/amygdala and left superior temporal gyrus (STG)/middle temporal gyrus (MTG) after ECT combined with antipsychotic therapy at time 2. In contrast, patients in the drug group showed decreased GMV in widespread brain regions. Correlation analysis results showed significantly negative correlations between the increased GMV in the bilateral hippocampus/amygdala and PANSS scores at baseline in the ECT group. ECT may modulate brain structure in patients with schizophrenia. The GMV in distinct subcortical regions was related to the individual therapeutic response in patients with schizophrenia.

[Association of gene polymorphisms with the susceptibility of schizophrenia in Han Chinese population].

OBJECTIVE: To investigate the potential association of carbonic anhydrase I (CA1) anterior pharynx-defective 1A ( APH1A), neurodevelopment protein 1-like 1 (NDEL1) and serine racemase (SRR) gene polymorphisms with the susceptibility of schizophrenia (SZ). METHODS: A case-control study was performed to identify polymorphisms of the CA1, APH1A, NDEL1 and SRR gene that may confer susceptibility to SZ in the Han Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped in 516 paranoid SZ patients and 516 control subjects by real time quantitative polymerase chain reaction. The association between genotypes and positive and negative symptoms scale was also explored. RESULTS: No significant differences in genotype or allele frequencies of five SNPs were observed between schizophrenic patients and healthy controls (P = 0.163, 0.322, 0.494, 0.338, 0.545; 0.259, 0.149, 0.417, 0.527, 0.720; respectively). However, the frequency of CA haplotypes in SZ group was higher than control group (P = 0.041). The scores of depression/anxiety, positive and excited/hostile factors in SZ patients with genotype of rs2298161 (AG), rs4523957 (CC) and rs8081273 (GG) were higher than other genotypes (P = 0.008, 0.001, 0.000, respectively). CONCLUSIONS: These data suggests that the CA1, APH1A, NDEL1 and SRR gene may not be association with susceptibility to SZ in the Han Chinese population. However, the haplotype of CA may be the susceptible factor of SZ. Rs2298161, rs4523957 and rs8081273 may be associated with some phenotypes of SZ.

Glucose-insulin-potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND: Glucose-insulin-potassium (GIK) has been advocated in the setting of acute coronary syndrome (ACS) to reduce ischemia-related arrhythmias and myocardial injury. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess whether the use of GIK infusions >3 or <3 hours after the onset of symptoms reduce mortality or cardiac arrest. METHODS: Electronic databases (Medline, EMBASE, and Cochrane Central Register of Controlled Trials) and references of retrieved articles were searched for RCTs evaluating the effect of GIK infusions, <3 hours or >3 hours after the onset of symptoms, on mortality and/or cardiac arrest. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each outcome. RESULTS: Nine trials were identified and eligible for review. The summary OR for in-hospital mortality was 1.01 (95% CI 0.94 to 1.09), based on 2,542 deaths among 27,294 patients. The subgroup analysis according to the study enrollment time (within 3 hours [OR, 0.77, 95% CI 0.50-1.16], vs. >3 hours [OR, 0.90; 95% CI, 0.67-1.21]) did not reveal any difference in mortality. CONCLUSIONS: Administration of GIK in ACS patients does not significantly reduce mortality whether or not GIK administration >3 or <3 hours after the onset of symptoms.

Serum S100B protein and white matter changes in schizophrenia before and after medication.

Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain. It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. To investigate WM and S100B changes and associations and determine the effect of quetiapine on WM and S100B in schizophrenia patients, we determined serum S100B levels with solid phase immunochromatography and fractional anisotropy（FA）values of 36 patients and 40 healthy controls. Patients exhibited significantly higher serum concentrations of S100B and decreased FA values in left postcentral，right superior frontal，right thalamus, and left inferior occipital gyrus, while higher in right temporal cortex WM compared with healthy controls. Following treatment with quetiapine, patients had decreased S100B and higher FA values in right cerebellum，right superior frontal，right thalamus, and left parietal cortex，and decreased FA values in right temporal cortex WM compared with pre-treatment values. Furthermore, S100B were negatively correlated with PANSS positive scores and positively correlated with FA values in the left postcentral cortex. In addition，the percentage change in FA values in the right temporal cortex was positively correlated with the percentage change in the S100B, percentage reduction in PANSS scores, and percentage reduction in PANSS-positive scores. Our findings demonstrated abnormalities in S100B and WM microstructure in patients with schizophrenia. These abnormalities may be partly reversed by quetiapine treatment.

Occipital connectivity networks mediate the neural effects of childhood maltreatment on depressive symptoms in major depressive disorder.

BACKGROUND: Childhood maltreatment (CM) is a well-established risk factor for major depressive disorder (MDD). The neural mechanisms linking childhood maltreatment experiences to changes in brain functional networks and the onset of depression are not fully understood. METHODS: In this study, we enrolled 66 patients with MDD and 31 healthy controls who underwent resting-state fMRI scans and neuropsychological assessments. We employed multivariate linear regression to examine the neural associations of CM and depression, specifically focusing on the bilateral occipital functional connectivity (OFC) networks relevant to MDD. Subsequently, a two-step mediation analysis was conducted to assess whether the OFC network mediated the relationship between CM experiences and the severity of depression. RESULTS: Our study showed that patients with MDD exhibited reduced OFC strength, particularly in the occipito-temporal, parietal, and premotor regions. These reductions were negatively correlated with CM scores and the severity of depression. Notably, the overlapping regions in the bilateral OFC networks, affected by both CM experiences and depressive severity, were primarily observed in the bilateral cuneus, left angular and calcarine, as well as the right middle frontal cortex and superior parietal cortex. Furthermore, the altered strengths of the OFC networks were identified as positive mediators of the impact of CM history on depression symptoms in patients with MDD. CONCLUSION: We have demonstrated that early exposure to CM may increase vulnerability to depression by influencing the brain's network. These findings provide new insights into understanding the pathological mechanism underlying depressive symptoms induced by CM.

MicroRNA-124 influenced depressive symptoms via large-scale brain connectivity in major depressive disorder patients.

This study aimed to investigate the neurobiological mechanisms by which microRNA 124 (miR-124) is involved in major depressive disorder (MDD). We enrolled 53 untreated MDD patients and 38 healthy control (HC) subjects who completed behavior assessments and resting-state functional MRI (rs-fMRI) scans. MiR-124 expression levels were detected in the peripheral blood of all participants. We determined that miR-124 levels could influence depressive symptoms via disrupted large-scale intrinsic intra- and internetwork connectivity, including the default mode network (DMN)-DMN, dorsal attention network (DAN)-salience network (SN), and DAN-cingulo-opercular network (CON). This study deepens our understanding of how miR-124 dysregulation contributes to depression.

Linking individual variability in functional brain connectivity to polygenic risk in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disease, which brings great difficulties to clinical diagnosis and therapy. Its mechanism is still unknown. Prior neuroimaging studies mainly focused on mean differences between patients and healthy controls (HC), largely ignoring individual differences between patients. METHODS: This study included 112 MDD patients and 93 HC subjects. Resting-state functional MRI data were obtained to examine the patterns of individual variability of brain functional connectivity (IVFC). The genetic risk of pathways including dopamine, 5-hydroxytryptamine (5-HT), norepinephrine (NE), hypothalamic-pituitary-adrenal (HPA) axis, and synaptic plasticity was assessed by multilocus genetic profile scores (MGPS), respectively. RESULTS: The IVFC pattern of the MDD group was similar but higher than that in HCs. The inter-network functional connectivity in the default mode network contributed to altered IVFC in MDD. 5-HT, NE, and HPA pathway genes affected IVFC in MDD patients. The age of onset, duration, severity, and treatment response, were correlated with IVFC. IVFC in the left ventromedial prefrontal cortex had a mediating effect between MGPS of the 5-HT pathway and baseline depression severity. LIMITATIONS: Environmental factors and differences in locations of functional areas across individuals were not taken into account. CONCLUSIONS: This study found MDD patients had significantly different inter-individual functional connectivity variations than healthy people, and genetic risk might affect clinical manifestations through brain function heterogeneity.

Episodic Memory-Related Imaging Features as Valuable Biomarkers for the Diagnosis of Alzheimer's Disease: A Multicenter Study Based on Machine Learning.

BACKGROUND: Individualized and reliable biomarkers are crucial for diagnosing Alzheimer's disease (AD). However, lack of accessibility and neurobiological correlation are the main obstacles to their clinical application. Machine learning algorithms can effectively identify personalized biomarkers based on the prominent symptoms of AD. METHODS: Episodic memory-related magnetic resonance imaging (MRI) features of 143 patients with amnesic mild cognitive impairment (MCI) were identified using a multivariate relevance vector regression algorithm. The support vector machine classification model was constructed using these MRI features and verified in 2 independent datasets (N = 994). The neurobiological basis was also investigated based on cognitive assessments, neuropathologic biomarkers of cerebrospinal fluid, and positron emission tomography images of amyloid-ß plaques. RESULTS: The combination of gray matter volume and amplitude of low-frequency fluctuation MRI features accurately predicted episodic memory impairment in individual patients with amnesic MCI (r = 0.638) when measured using an episodic memory assessment panel. The MRI features that contributed to episodic memory prediction were primarily distributed across the default mode network and limbic network. The classification model based on these features distinguished patients with AD from normal control subjects with more than 86% accuracy. Furthermore, most identified episodic memory-related regions showed significantly different amyloid-ß positron emission tomography measurements among the AD, MCI, and normal control groups. Moreover, the classification outputs significantly correlated with cognitive assessment scores and cerebrospinal fluid pathological biomarkers' levels in the MCI and AD groups. CONCLUSIONS: Neuroimaging features can reflect individual episodic memory function and serve as potential diagnostic biomarkers of AD.

Insula network connectivity mediates the association between childhood maltreatment and depressive symptoms in major depressive disorder patients.

Childhood maltreatment (CM) is a major risk factor for developing the major depressive disorder (MDD), however, the neurobiological mechanism linking CM and MDD remains unclear. We recruited 34 healthy controls (HCs) and 44 MDD patients to complete the childhood maltreatment experience assessment with Childhood Trauma Questionnaire (CTQ) and resting-state fMRI scan. Multivariate linear regression analysis was employed to identify the main effects of CM and depressive symptoms total and subfactors scores on bilateral anterior and posterior insula functional connectivity (IFC) networks, respectively. Mediation analysis was performed to investigate whether IFC strength mediates the association between CM and depressive symptoms. MDD patients showed significantly decreased connectivity in the dorsal medial prefrontal cortex and increased connectivity in the medial frontal gyrus in the bipartite IFC networks, compared to HCs. The main effects of CM and depressive symptoms showed a large discrepancy on the anterior and posterior IFC networks, which primarily located in the frontal-limbic system. Further, conjunction analysis identified the overlapping regions linking CM and depressive symptoms were mainly implicated in self-regulation and cognitive processing circuits. More important, these IFC strengths could mediate the association between different types of CM, especially for childhood abuse and childhood neglect, and depressive symptoms in those overlapping regions. We demonstrated that early exposure to CM may increase the vulnerability to depression by influencing brain's self-regulating and cognitive processing circuitry. These findings provide new insight into the understanding of pathological mechanism underlying CM-induced depressive symptoms.

Neural effects of childhood maltreatment on dynamic large-scale brain networks in major depressive disorder.

Emerging evidence suggests that childhood maltreatment (CM) alters trajectories of brain development to affect network architecture and is a risk factor for the development and maintenance of depression. The current study aimed to explore the association between CM and depressive severity on the large-scale resting-state networks (RSNs) level in major depressive disorder (MDD) patients and explored the network basis of clinical symptoms. 42 healthy controls without childhood maltreatment, 13 healthy controls with CM, 35 MDD without CM and 50 MDD with CM were included in the study population. Group differences in ten large-scale RSNs, associations between CM and depressive symptom dimensions and network variables were tested. And we explored whether symptom-related networks might discriminate between the four groups. We found one-versus-all-others-network showed an inverted U-shaped curve across groups. Network variables were significantly associated with Hamilton Depression Scale subscores and Childhood Trauma Questionnaire subscores. Different symptoms showed different imaging patterns, and overlapping connections of patterns had better ability to distinguish groups. Our findings suggest that CM could lead to significant changes in both network measures and connections in healthy individuals and MDD. These results deepen our understanding of the neuroimaging mechanisms of CM and MDD.

COMT Val158Met Polymorphism Influences the Cerebral Blood Flow Changes Related to Psychomotor Retardation in Major Depressive Disorder.

Background: Previous studies revealed different cerebral blood flow (CBF) changes of major depressive disorder (MDD) patients with psychomotor retardation (PMR). These different changes might result from the modulation of other factors, such as genes. This study aimed to investigate the influence of COMT Val158Met polymorphism on the CBF alterations in MDD patients with PMR. Methods: COMT Val158Met genotypes and arterial spin labeling-magnetic resonance imaging (ASL-MRI) data of 103 Chinese Han participants (63 MDD, 40 NCs) were collected in this study. MDD patients were divided into PMR group (N = 23) and NPMR group (N = 40) according to the Salpetriere Retardation Rating Scale score. PMR, NPMR and NCs groups were further divided into two subgroups, respectively, based on the COMT Val158Met genotype. CBF throughout the whole brain was calculated based on the ASL-MRI data. A two-way factorial analysis of covariance was used to investigate the main effects of PMR, COMT Met allele, as well as the interactions between COMT genotype and PMR on the CBF in a voxel-wise manner. Partial correlation analyses were also applied to evaluate the association between the CBF of significant brain regions and the PMR severity. Results: Main effect of PMR mainly influenced the CBF of the prefrontal cortex (PFC). Main effect of COMT Met allele mainly influenced the CBF of the thalamus. The interaction between PMR and COMT Met allele primarily influenced the CBF of left precuneus and right caudate. The CBF of PFC was positively correlated with the PMR severity. Conclusion: Our findings indicate that the COMT Met allele could modulate the CBF changes of the left precuneus and right caudate in MDD patients with PMR, providing additional layer of information regarding earlier reports for different CBF changes of MDD patients with psychomotor retardation in the literature, which were assessed irrespective of polymorphisms among patients.

Altered resting-state cerebral blood flow and functional connectivity mediate suicidal ideation in major depressive disorder.

The relationships among cerebral blood flow (CBF), functional connectivity (FC) and suicidal ideation (SI) in major depressive disorder (MDD) patients have remained elusive. In this study, we characterized the changes in CBF and FC among 175 individuals including 47 MDD without SI (MDDNSI), 59 MDD with SI (MDDSI), and 69 healthy control (HC) who underwent arterial spin labeling and resting-state functional MRI scans. Then the voxel-wise CBF, seed-based FC and partial correlation analyses were measured. Mediation analysis was carried out to reveal the effects of FC on the association between CBF and behavioral performances in both subgroups. Results showed that CBF was higher in MDDSI patients in the bilateral precuneus compared to HC and MDDNSI participants. MDDSI patients exhibited enhanced FC in the prefrontal-limbic system and decreased FC in the sensorimotor cortex (SMC) relative to MDDNSI patients. CBF and FC were significantly correlated with clinical variables. More importantly, exploratory mediation analyses identified that abnormal FC can mediate the association between regional CBF and behavioral performances. These results highlight the potential role of precuneus gyrus, prefrontal-limbic system as well as SMC in the process of suicide and provide new insights into the neural mechanism underlying suicide in MDD patients.

Abnormal brain gray matter volume in patients with major depressive disorder: Associated with childhood trauma?

BACKGROUND: Patients with major depressive disorders (MDD) have abnormalities in the frontal-limbic structures of the brain. Childhood trauma is a risk factor for both structural brain alterations and MDD. However, the relationships among the three have not been confirmed. METHODS: Sixty-four patients with MDD and sixty-one healthy controls (HC) were checked by using MRI, the Hamilton Depression Scale (HAMD) and Childhood Trauma Questionnaire (CTQ). Voxel-based morphometry (VBM) was used to compare gray matter volume (GMV) differences between the two groups. Moreover, partial correlation and mediation analyses were conducted to test for potential associations between CTQ scores, different GMV, and clinical variables. RESULTS: Compared to the HC group, the MDD patients showed decreased GMV in the right middle frontal gyrus (rMFG) and right precentral gyrus (rPreCG). In the patient group, reduced GMV in rMFG was associated with CTQ scores (r = -0.30, P = 0.019) and HAMD scores (r = -0.53, P < 0.001). Finally, in the patient group, mediation analysis revealed that the indirect effect of rMFG GMV in CTQ scores and HAMD scores was 0.115 and the proportion of indirect effect to total effect was 23.86%. LIMITATIONS: This study used a cross-sectional collection, and it is unclear whether at the longitudinal level the brain GMV mediates the relationship between childhood trauma and depression. CONCLUSIONS: Abnormalities in the frontal GMV were presented in the MDD patients. It is possible that childhood traumatic experiences cause inefficient GMV and ultimately lead to an increased susceptibility to depression.