Brain alterations in adolescents with first-episode depression who have experienced adverse events: evidence from resting-state functional magnetic resonance imaging.

Introduction: Adverse life events constitute primary risk factors for major depressive disorder (MDD), influencing brain function and structure. Adolescents, with their brains undergoing continuous development, are particularly susceptible to enduring impacts of adverse events. Methods: We investigated differences and correlations among childhood trauma, negative life events, and alterations of brain function in adolescents with first-episode MDD. The study included 23 patients with MDD and 19 healthy controls, aged 10-19 years. All participants underwent resting-state functional magnetic resonance imaging and were assessed using the beck depression inventory, childhood trauma questionnaire, and adolescent self-rating life events checklist. Results: Compared with healthy controls, participants with first-episode MDD were more likely to have experienced emotional abuse, physical neglect, interpersonal relationship problems, and learning stress (all p' < 0.05). These adverse life events were significantly correlated with alterations in brain functions (all p < 0.05). Discussion: This study contributes novel evidence on the underlying process between adverse life events, brain function, and depression, emphasizing the significant neurophysiological impact of environmental factors.

The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder.

BACKGROUND: Inflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear. METHODS: Forty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6-8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1ß, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment. RESULTS: Serum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1ß, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1ß, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents. CONCLUSIONS: Our study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

The Influence of Genetic and Environmental Factors on Anxiety among Chinese Adolescents: A Twin Study.

This study explored the influence of genetic and environmental factors on adolescent anxiety. Ninety-eight monozygotic and dizygotic twins from Chongqing, China (aged 15-18 years) were assessed for anxiety with the Self-Rating Anxiety Scale (SAS). The Parenting Styles and Dimensions Questionnaire (PSDQ) and Strengths and Difficulties Questionnaire (SDQ) were applied to assess environmental factors. Venous blood was drawn from the twins for zygosity determination. Structural equation modeling was performed to evaluate the effects of additive genetic factors (A), common environmental factors (C), and individual-specific environmental factors (E) on adolescent anxiety. The estimates of A and E on adolescent anxiety were 0.34 (95% CI = 0.12-0.53) and 0.66 (95% CI:0.47-0.89), respectively. The environment played an important role in adolescent anxiety. Adolescent anxiety was significantly positively correlated with peer relations (r = 0.606, p < 0.05) and negatively correlated with prosocial behavior (r = 0.207, p < 0. 05). No sex differences were observed. Adolescent anxiety was influenced by both genetic and environmental factors. The individual-specific environmental factors played an important role. Consideration of these variables will facilitate the targeted and individualized implementation of specific interventions for adolescent anxiety.

Interleukin-6 is correlated with amygdala volume and depression severity in adolescents and young adults with first-episode major depressive disorder.

Inflammatory mechanisms may play crucial roles in the pathophysiology of major depressive disorder (MDD), and cytokine concentrations are correlated with brain alterations. Adolescents and young adults with MDD have higher recurrence and suicide rates than adults, but there has been limited research on the underlying mechanisms. In this study, we aimed to investigate the potential correlations among cytokines, depression severity, and the volumes of the amygdala, hippocampus, and nucleus accumbens in Han Chinese adolescents and young adults with first-episode MDD. Nineteen patients with MDD aged 10-21 years were enrolled from the Psychiatry Department of the First Affiliated Hospital of Chongqing Medical University, along with 18 age-matched healthy controls from a local school. We measured the concentrations of interleukin (IL)-4, IL-6, IL-8, and IL-10 in the peripheral blood, along with the volumes of the amygdala, hippocampus, and nucleus accumbens, as determined by magnetic resonance imaging. We observed that patients with MDD had higher concentrations of IL-6 and a trend towards reduced left amygdala and bilateral hippocampus volumes than healthy controls. Additionally, the concentration of IL-6 was correlated with the left amygdala volume and depression severity, while the left hippocampus volume was correlated with depression severity. This study suggests that inflammation is an underlying neurobiological change and implies that IL-6 could serve as a potential biomarker for identifying early stage MDD in adolescents and young adults.

Altered EEG Microstates Dynamics in Individuals with Subthreshold Depression When Generating Negative Future Events.

Negative bias in prospection may play a crucial role in driving and maintaining depression. Recent research suggests abnormal activation and functional connectivity in regions of the default mode network (DMN) during future event generation in depressed individuals. However, the neural dynamics during prospection in these individuals remain unknown. To capture network dynamics at high temporal resolution, we employed electroencephalogram (EEG) microstate analysis. We examined microstate properties during both positive and negative prospection in 35 individuals with subthreshold depression (SD) and 35 controls. We identified similar sets of four canonical microstates (A-D) across groups and conditions. Source analysis indicated that each microstate map partially overlapped with a subsystem of the DMN (A: verbal; B: visual-spatial; C: self-referential; and D: modulation). Notably, alterations in EEG microstates were primarily observed in negative prospection of individuals with SD. Specifically, when generating negative future events, the coverage, occurrence, and duration of microstate A increased, while the coverage and duration of microstates B and D decreased in the SD group compared to controls. Furthermore, we observed altered transitions, particularly involving microstate C, during negative prospection in the SD group. These altered dynamics suggest dysconnectivity between subsystems of the DMN during negative prospection in individuals with SD. In conclusion, we provide novel insights into the neural mechanisms of negative bias in depression. These alterations could serve as specific markers for depression and potential targets for future interventions.

NOD2 silencing promotes cell apoptosis and inhibits drug resistance in chronic lymphocytic leukemia by inhibiting the NF-κB signaling pathway.

Recent years have witnessed increasing studies on the effect of epigenetic silencing of genes in the progression of chronic lymphocytic leukemia (CLL). This study investigates whether the nucleotide binding oligomerization domain containing 2 (NOD2) participates in the cell apoptosis and drug resistance of CLL cells. Cells were treated with adriamycin (ADR), etoposide, aclacinomycin and daunorubicin. After treatment, drug resistance and cell proliferation were examined to detect the inhibitory effect of ADR on cell proliferation; flow cytometry to identify ADR accumulation, the cell cycle distribution and apoptosis after transfection, and rhodamine 123 accumulation and efflux tests to assess P-glycoprotein (P-gp) function. NOD2 silencing or inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway suppressed the multidrug resistance level in CLL, the inhibition rate, and cell proliferation caused by ADR at concentrations of approximately 0.25-1.5 µmol/L. Greater accumulation of ADR was observed in the CLL-AAT cell line than in the CLL-AAT/A02 cell line, but NOD2 silencing or inhibition of the NF-κB signaling pathway further increased the accumulation of ADR drugs in the CLL-AAT cell line and inhibited the drug efflux pump function of P-gp. Additionally, NOD2 silencing or NF-κB signaling pathway inhibition increased the apoptotic rate. The results of this study indicate that NOD2 promotes cell apoptosis and reduces the drug resistance of CLL by inhibiting the NF-κB signaling pathway.

In vivo analyses reveal hippocampal subfield volume reductions in adolescents with schizophrenia, but not with major depressive disorder.

BACKGROUND: Adult studies have reported atypicalities in the hippocampus and subfields in patients with schizophrenia (SCZ) and major depressive disorder (MDD). Both affective and psychotic disorders typically onset in adolescence, when human brain develops rapidly and shows increased susceptibility to adverse environments. However, few in vivo studies have investigated whether hippocampus subfield abnormalities occur in adolescence and whether they differ between SCZ and MDD cases. METHODS: We recruited 150 adolescents (49 SCZ patients, 67 MDD patients, and 34 healthy controls) and obtained their structural images. We used FreeSurfer to automatically segment hippocampus into 12 subfields and analyzed subfield volumetric differences between groups by analysis of covariance, covarying for age, sex, and intracranial volume. Composite measures by summing subfield volumes were further compared across groups and analyzed in relation to clinical characteristic. RESULTS: SCZ adolescents showed significant volume reductions in subfields of CA1, molecular layer, subiculum, parasubiculum, dentate gyrus and CA4 than healthy controls, and almost significant reductions, as compared to the MDD group, in left molecular layer, dentate gyrus, CA2/3 and CA4. Composite analyses showed smaller volumes in SCZ group than in healthy controls in all bilateral composite measures, and reduced volumes in comparison to MDD group in all left composite measures only. CONCLUSIONS: SCZ adolescents exhibited both hippocampal subfield and composite volumes reduction, and also showed greater magnitude of deviance than those diagnosed with MDD, particularly in core CA regions. These results indicate a hippocampal disease process, suggesting a potential intervention marker of early psychotic patients and risk youths.

Transcriptome comparative analysis of amygdala-hippocampus in depression: A rat model induced by chronic unpredictable mild stress (CUMS).

BACKGROUND: Depression is a common and complex mental disease, and its pathogenesis involves several brain regions. Abnormalities in the amygdala-hippocampal neural circuits have been shown to be involved in depression. However, the underlying molecular mechanisms remain unclear. METHODS: A rat model was used to determine the transcriptome changes in the amygdala-hippocampal neural network under chronic unpredictable mild stress (CUMS). Depression-related modules in this neural network were identified using weighted gene co-expression network analysis (WGCNA). Difference and enrichment analyses were used to determine differential gene expression in the two brain regions. RESULTS: The modules in the amygdala and hippocampus associated with depression-like behavior contained 363 and 225 genes, respectively. Forty-two differentially expressed genes were identified in the amygdala candidate module and 37 in the hippocampus. Enrichment analysis showed that candidate genes in the amygdala were associated with neuronal myelination and candidate genes in the hippocampus were associated with synaptic transmission. Finally, based on module hub gene statistics, differential gene expression, and protein-protein interaction networks, 11 central genes were found in the amygdala candidate module, and one central gene was found in the hippocampal module. LIMITATIONS: Our study was based on a rat CUMS model. Further evidence is needed to prove that our results are applicable to patients with depression. CONCLUSION: This study identified critical modules and central genes involved in the amygdala-hippocampal circuit in the context of depression, and may provide further understanding of the pathogenesis of depression and help identify potential targets for antidepressant therapy.

A Bivariate Twin Study of Cortical Surface Area and Verbal and Nonverbal Intellectual Skills in Adolescence.

Understanding the biological basis of cognitive differences between individuals is the goal in human intelligence research. The surface area of the cortex is considered to be a key determinant of human intelligence. Adolescence is a period of development characterized by physiological, emotional, behavioral, and psychosocial changes, which is related to the recombination and optimization of the cerebral cortex, and cognitive ability changes significantly in children and adolescents. This study examined the effects of common genetic and environmental factors between the surface area of the cerebral cortex and intelligence in typical developing adolescents (twins, n = 114, age 12-18 years old). Cortical surface area data were parsed into subregions (i.e., frontal, parietal, occipital, and temporal areas) and intelligence into verbal and nonverbal skills. We found a phenotypic correlation between regional surface areas and verbal intelligence. No correlation was observed between regional surface areas and nonverbal intelligence, except for the occipital lobe and the right hemisphere. In the bivariate twin analyses, the differences in phenotypic correlation between regional surface areas and verbal intelligence were not due to unshared environmental effects or measurement error, but to genetic effects. In summary, the current study has broadened the previous genetic investigations of cognitive ability and cortical surface area.

The Efficacy and Tolerability of Electroconvulsive Therapy in Psychiatric Patients with Arachnoid Cysts: A Retrospective Chart Study.

Electroconvulsive therapy (ECT) is an effective therapy for many psychiatric illnesses. However, intracranial occupying lesions are a relative contraindication to ECT. Arachnoid cysts are benign, congenital, and space-occupying lesions. Our study aimed to evaluate the efficacy and tolerability of ECT in psychiatric patients with arachnoid cysts. We retrospectively identified 62 psychiatric patients with arachnoid cysts; 43 of them underwent ECT and 19 did not. Their conditions were assessed by CGI-S and different scales depending on different diagnoses (PANSS for schizophrenia; HAMD for depression; YMRS for bipolar disorder). The side effect was assessed by TESS. Significant differences were shown in the reduced scores of the CGI-S between patients who underwent ECT and those who did not (p = 0.001), while, at the same time, there was no significant difference in their TESS score (p = 0.297). The current study found that ECT is an effective and tolerable therapy for psychiatric patients with arachnoid cysts.

A retrospective case series of electroconvulsive therapy in the management of depression and suicidal symptoms in adolescents.

OBJECTIVE: Major depressive disorder (MDD) with suicidal symptoms is common in adolescents. Electroconvulsive therapy (ECT) is highly effective in the treatment of MDD. We have described its use and outcome in a case series of adolescents with depression and suicidal symptoms receiving ECT. METHODS: We analyzed 362 adolescents aged from 12 to 17 who had received ECT between year 2015 and 2021. A total of 278 subjects were found to meet the inclusion criteria, where depressive symptoms were assessed by HDRS and suicidal symptoms were assessed by HDRS item 3. Their sociodemographic, clinical, and treatment information were retrieved through these records for this study. RESULTS: The mean ± SD age of subjects was 15.41 ± 1.50 years and male sex was 14.7% (n = 41). Comorbid diagnoses were present in 104 patients (37.4%). The ECT sessions ranged from 6 to 12 times. All the patients took antidepressants, with sertraline (n = 182; 65.5%) being the most widely used. Majority of patients also received benzodiazepines. ECT was significantly effective in adolescents with depression and suicidal symptoms in evaluation by HDRS, HDRS item 3, CGI-S (p < .001) pre/post-ECT. The response rate of MDD patients was 52%, with suicidal ideation (SI) at 49%, and 54% in MDD with suicide attempt (SA). The change of CGI-S scores showed no significant differences between various subgroups of sex and comorbid (p>.05), but there were significant differences between subgroups of suicidal symptoms (p < .001). ECT was generally safe with subjective memory complaint (n = 189, 68.0%), headache (n = 150, 54.0%), body pain (n = 28, 10.1%), delirium (n = 95, 34.2%), and nausea (n = 31, 11.2%) as possible side effects following ECT. CONCLUSION: In this study, ECT was found to decrease depressive and suicidal symptoms in adolescents, and the side effect was acceptable. ECT showed better outcome for MDD with SA compared to MDD with SI.

Is depression the contraindication of anterior cervical decompression and fusion for cervical spondylosis?

Objective: To evaluate whether depression is the contraindication of anterior cervical decompression and fusion (ACDF) for cervical spondylosis. Material and methods: Patients with single-segment cervical spondylosis who underwent ACDF from January 2015 to December 2018 in our department were retrospectively included in this study and divided into two groups. Patients who were diagnosed of depression and prescribed with antidepressant drugs for at least 6 months before surgery were included in the intervention group. Patients without depression were included in the control group. The Beck Depression Inventory (BDI) score was used to evaluate the severity of depression. Visual Analogue Scale (VAS) score, Japanese Orthopeadic Association (JOA) score, Neck Disability Index (NDI), and the 36-Item Short-Form Health Survey (SF-36) were recorded as indexes to assess the pain, cervical spine function, degree of cervical spine injury, and life quality, respectively. The operative time, operative blood loss, hospital stay and complications were also recorded and compared. Results: A total of 117 patients were included in this study, involving 32 patients in the intervention group and 85 patients in the control group. No significant differences were found in operative time, operative blood loss, hospital stay and complications between the two groups (P>0.05). The BDI score, VAS score, JOA score, NDI, SF-36 physical component score (SF-36 PCS) and SF-36 mental component score (SF-36 MCS) were all significantly improved at last follow-up in both the two groups. The intervention group showed higher BDI score and SF-36 MCS than the control group at both preoperative and the last follow-up (P<0.05), and the improvements of BDI score and SF-36 MCS were also higher in the intervention group (P<0.05). Although the intervention group showed higher VAS score, NDI, SF-36 PCS and lower JOA score at preoperative and last follow-up, respectively (P<0.05), there were no significant differences in the improvements of these indexes between the two group (P>0.05). Conclusions: Depression is not the contraindication of ACDF for cervical spondylosis. Depression patients who received preoperative antidepressants can achieve similar improvement of clinical symptoms from ACDF with non-depression patients.

Fabrication of lignin reinforced hybrid hydrogels with antimicrobial and self-adhesion for strain sensors.

Ionic conductive hydrogels prepared from various biological macromolecules are ideal materials for the manufacture of human motion sensors from the perspective of resource regeneration and environmental sustainability. However, it is still challenging to prepare hydrogels with both high toughness and self-healing ability. In this study, lignin-based ß-CD-PVA (LCP) self-healing conductive hydrogels with high tensile properties were prepared by one-step method using alkali lignin as a plasticizer. Compared with PVA hydrogel, the maximum storage modulus and elongation were increased by 2.5 and 20.0 times, respectively. Uniform distribution of lignin can increase the fluidity and distance of polymer molecular chains, thus improving the viscoelastic and tensile properties of the LCP self-healing hydrogel. LCP hydrogels can maintain self-healing ability in both high (45 °C) and low temperature (0 °C) environments, and the self-healing ability is not affected by pH. Moreover, it also has good conductivity, anti-bacterial, thermostability, and anti-UV property, which has a good application prospect in the field of 3D printing and wearable electronic devices, which expands the efficient utilization of lignin in biorefinery.

Depression and stress levels increase risk of liver cancer through epigenetic downregulation of hypocretin.

Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulate neurobiological responses is unknown. Herein, the effects of chronic stress on the epigenetic modification of HCRT and its association with depression were explored with regard to a potential role in cancer progression. In the study, Sprague Dawley (SD) rats were used to establish an animal model of cancer with depression by administrating n-nitrosodiethylamine (DEN) and chronic unpredictable mild stress (CUMS). RNA-sequencing was used to detect differentially expressed genes in the hippocampus of rats and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of RNA-sequencing. The status of HCRT promoter methylation was assessed by methylation specific polymerase chain reaction. Behavioral tests showed that rats exposed to CUMS had significant depressive-like behaviors. The number of liver tumors and tumor load in depressed rats exposed to CUMS was higher than in SD rats without CUMS. RNA-sequencing revealed that HCRT was one of the most siginificantly downregulated gene in the hippocampus of SD rats with CUMS compared to non-stressed group, which was validated by qRT-PCR. HCRT mRNA expression was downregulated and the promoter for HCRT was hyper-methylated in those with depression. These results identified a critical role for chronic psychological stressors in tumorigenesis and cancer progression, via epigenetic HCRT downregulation. Such epigenetic downregulation may be the molecular basis for the association of cancer with depression.

Cortical thickness distinguishes between major depression and schizophrenia in adolescents.

BACKGROUND: Early diagnosis of adolescent psychiatric disorder is crucial for early intervention. However, there is extensive comorbidity between affective and psychotic disorders, which increases the difficulty of precise diagnoses among adolescents. METHODS: We obtained structural magnetic resonance imaging scans from 150 adolescents, including 67 and 47 patients with major depressive disorder (MDD) and schizophrenia (SCZ), as well as 34 healthy controls (HC) to explore whether psychiatric disorders could be identified using a machine learning technique. Specifically, we used the support vector machine and the leave-one-out cross-validation method to distinguish among adolescents with MDD and SCZ and healthy controls. RESULTS: We found that cortical thickness was a classification feature of a) MDD and HC with 79.21% accuracy where the temporal pole had the highest weight; b) SCZ and HC with 69.88% accuracy where the left superior temporal sulcus had the highest weight. Notably, adolescents with MDD and SCZ could be classified with 62.93% accuracy where the right pars triangularis had the highest weight. CONCLUSIONS: Our findings suggest that cortical thickness may be a critical biological feature in the diagnosis of adolescent psychiatric disorders. These findings might be helpful to establish an early prediction model for adolescents to better diagnose psychiatric disorders.

Duodenal adenocarcinoma with skin metastasis as initial manifestation: A case report.

BACKGROUND: Duodenal adenocarcinoma (DA) with skin metastasis as initial manifestation is clinically rare. In this study, we report a rare case of skin metastasis of DA. CASE PRESENTATION: An 84-year-old male patient developed multiple ecchymoses on the trunk and lower extremities. Physical examination showed that the ecchymosis was dark red and had a hard texture, but showed no bulging, rupture, or tenderness. The skin biopsy implied skin metastatic adenocarcinoma. After an endoscopic duodenal biopsy, the patient was finally diagnosed with DA with skin metastasis. The patient received two courses of oral treatment of Tegafur (40 mg, bid d1-d14). However, the patient stopped taking Tegafur because of its poor effect and received Chinese medicine as a replacement treatment. Unfortunately, he was lost to follow-up. CONCLUSIONS: Early diagnosis of DA metastasis is of significant importance as prognosis of these patients is poor.

Functional and Structural Connectivity Between the Left Dorsolateral Prefrontal Cortex and Insula Could Predict the Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is nonuniform across patients. This study aims to determine whether baseline neuroimaging characters can provide a pretreatment predictive effect for rTMS. METHODS: Twenty-seven treatment-naive patients with major depressive disorder (MDD) were enrolled and scanned with resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging. Clinical symptoms were assessed pre- and post-rTMS. Functional and structural connectivity between the left dorsolateral prefrontal cortex (DLPFC) and bilateral insula were measured, and the connectivity strength in each modality was then correlated to the clinical efficacy of rTMS. RESULTS: When the coordinates of left DLPFC were located as a node in the central executive network, the clinical efficacy of rTMS was significantly correlated with the functional connectivity strength between left DLPFC and bilateral insula (left insula: r = 0.66; right insula: r = 0.65). The structural connectivity strength between the left DLPFC and left insular cortex also had a significantly positive correlation with symptom improvement (r s = 0.458). CONCLUSION: This study provides implications that rTMS might act more effectively when the pretreatment functional and structural connectivity between the insula and left DLPFC is stronger.

Author Correction: Predicting individual responses to the electroconvulsive therapy with hippocampal subfield volumes in major depression disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Impact of Whole Brain Global Functional Connectivity Density Following MECT in Major Depression: A Follow-Up Study.

To explore the alteration of global functional connectivity density (gFCD) in depressive patients after modified electroconvulsive therapy (MECT) and analyze the relationship between gFCD and clinical outcome. Thirty-seven subjects were evaluated based on the diagnostic criteria of the International Classification of Diseases-10 (ICD-10), consisting of a depressive group (24 patients after follow-ups) and a healthy control group with 13 normal individuals. All participants received Hamilton Depression Scale (HAMD) scores and resting-state functional magnetic resonance imaging scans. The gFCD significantly increased in the posterior-middle insula, the supra-marginal gyrus and the dorsal medial prefrontal cortex (dmPFC) before MECT treatment compared to healthy controlled patients. The gFCD statistically expanded in the perigenual anterior cingulate cortex (pgACC), the orbitofrontal cortex bilaterally and the left-supra-marginal gyrus after MECT, and it decreased notably in the posterior insula. The gFCD in the pgACC and the right orbital frontal cortex of depressive group before MECT showed a positive correlation with HAMD scores with treatment. Conforming to the impact of gFCD in depressive patients after MECT, the aforementioned brain region may become an indicator of MECT effect.

Comparative efficacy and safety of Crocus sativus L. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials.

PURPOSE: To investigate the efficacy and safety of saffron in the treatment of major depressive disorder (MDD) in comparison to placebo and synthetic antidepressants. PATIENTS AND METHODS: We conducted a systematic search in several electronic databases as well as manual search in bibliographies of relevant studies. We included randomized controlled trials that investigated the efficacy and safety of saffron for treating MDD in adults in comparison to either placebo or synthetic antidepressants. Primary outcome was change in scores on depressive symptoms from baseline. Secondary outcomes included remission rate, response rate, and drop-out rate for all reasons. We chose a random-effects model in order to obtain more conservative results. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated as the overall effect index by inverse variance models. RESULTS: Seven studies were included in this meta-analysis. Overall quality of these included studies was moderate. As for the primary outcome, saffron showed more improvements in depression symptoms when compared with placebo, with an SMD of -1.22 (95% CI -1.94, -0.49, P=0.001). Meanwhile, saffron was as effective as synthetic antidepressants, with an SMD of 0.16 (95% CI -0.25, 0.57, P=0.44). Moderate heterogeneity existed in our analysis. Through subgroup analyses, we found that treatment dosage and duration, types of synthetic antidepressants administered in the comparison group, and outcome measures could explain most of the variance. No differences were found in remission rate, response rate, or drop-out rate. CONCLUSION: Saffron was effective in the treatment of MDD and had comparable efficacy to synthetic antidepressants. Saffron was also a safe drug without serious adverse events reported.