Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Development and validation of a nomogram for suicide attempts in patients with first-episode drug-naïve major depressive disorder.

Objective: The risk of suicide can be decreased by accurately identifying high-risk suicide groups and implementing the right interventions. The aim of this study was to develop a nomogram for suicide attempts (SA) in patients with first-episode drug-naïve (FEDN) major depressive disorder (MDD). Methods: This study undertook a cross-sectional analysis of 1,718 patients diagnosed with FEDN MDD, providing comprehensive clinical data from September 2016 to December 2018. Data on anthropometric and sociodemographic factors were gathered, and the severity of depression and anxiety was evaluated using the 17-item Hamilton Depression Scale (HAMD-17) and the Hamilton Anxiety Scale (HAMA), respectively. Additionally, thyroid hormone levels, lipid profile parameters, and fasting blood glucose (FBG) were measured. Suicide attempt (SA) history was verified based on an amalgamation of medical records, patient interviews, and family interviews. Participants were randomly divided into a training group (70%, n = 1,204) and a validation group (30%, n = 514). In the training group, LASSO analysis and multivariate regression were used to identify variables associated with SA. A nomogram was then constructed using the identified risk factors to estimate the likelihood of SA within the training group. To assess the accuracy, the area under the receiver operating characteristic curve (AUC) was utilized, and calibration plots were employed to evaluate calibration. Additionally, decision curve analysis (DCA) was performed to assess the precision of the model. Finally, internal validation was carried out using the validation group. Results: A practical nomogram has been successfully constructed, incorporating HAMD, HAMA, thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and systolic blood pressure (SBP) parameters, to estimate the probability of SA in Chinese patients diagnosed with FEDN MDD. The pooled area under the ROC for SA risk in both the training and validation groups was found to be 0.802 (95% CI: 0.771 to 0.832) and 0.821 (95% CI: 0.774 to 0.868), respectively. Calibration analysis revealed a satisfactory correlation between the nomogram probabilities and the actual observed probabilities. The clinical applicability of the nomogram was confirmed through decision curve analysis. To enhance accessibility for clinicians and researchers, an online version of the nomogram can be accessed at https://doctorjunjunliu.shinyapps.io/dynnomapp/. Conclusions: We constructed and validated a nomogram for the early detection of FEDN MDD patients with a high risk of SA, thereby contributing to the implementation of effective suicide prevention programs.

U-shaped association between fasting blood glucose and suicide attempts in Chinese patients with first-episode drug-naïve major depressive disorder.

BACKGROUND: Evidence regarding the relationship between fasting blood glucose (FBG) and suicide attempts (SA) in patients with major depressive disorder (MDD) was limited. Therefore, the objective of this research was to investigate whether FBG was independently related to SA in Chinese patients with first-episode drug-naïve (FEDN) MDD after adjusting for other covariates. METHODS: The present study was a cross-sectional study. A total of 1718 participants (average age: 34.9 ± 12.4 years, 65.8% females) with FEDN MDD were involved in a hospital in China from September 2016 to December 2018. Multiple logistic regression analysis and smooth curve fitting were used to estimate the association between FBG and the risk of SA. The threshold effect was examined by the two-piecewise linear regression model. Interaction and stratified analyses were conducted according to sex, education, marital status, comorbid anxiety, and psychotic symptoms. RESULTS: The prevalence of SA in patients with FEDN MDD was 20.1%. The result of fully adjusted binary logistic regression showed FBG was positively associated with the risk of SA (odds ratio (OR) = 1.62, 95% CI: 1.13-2.32). Smoothing plots also revealed a nonlinear relationship between FBG and SA, with the inflection point of FBG being 5.34 mmol/l. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.53 (0.32-0.88, P = 0.014) and 1.48 (1.04-2.10, P = 0.030), respectively. CONCLUSIONS: A U-shaped relationship between FBG and SA in FEDN MDD patients was found, with the lowest risk of SA at a FBG of 5.34 mmol/l, indicating that both the lower and higher FBG levels may lead to an increased risk of SA.

Association between triglyceride glucose index (TyG) and psychotic symptoms in patients with first-episode drug-naïve major depressive disorder.

Objective: Major depressive disorder (MDD) sufferers frequently have psychotic symptoms, yet the underlying triggers remain elusive. Prior research suggests a link between insulin resistance (IR) and increased occurrence of psychotic symptoms. Hence, this study sought to investigate the potential association between psychotic symptoms in Chinese patients experiencing their first-episode drug-naïve (FEDN) MDD and the triglyceride glucose (TyG) index, an alternative measure of insulin resistance (IR). Methods: Between September 2016 and December 2018, 1,718 FEDN MDD patients with an average age of 34.9 ± 12.4 years were recruited for this cross-sectional study at the First Hospital of Shanxi Medical University in China. The study collected clinical and demographic data and included assessments of anxiety, depression, and psychotic symptoms using the 14-item Hamilton Anxiety Rating Scale (HAMA), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the positive subscales of the Positive and Negative Syndrome Scale (PANSS), respectively. Measurements of metabolic parameters, fasting blood glucose (FBG), and thyroid hormones were also gathered. To assess the correlation between the TyG index and the likelihood of psychotic symptoms, the study used multivariable binary logistic regression analysis. Additionally, two-segmented linear regression models were employed to investigate possible threshold effects in case non-linearity relationships were identified. Results: Among the patients, 9.95% (171 out of 1,718) exhibited psychotic symptoms. Multivariable logistic regression analysis showed a positive correlation between the TyG index and the likelihood of psychotic symptoms (OR = 2.12, 95% CI: 1.21-3.74, P = 0.01) after adjusting for confounding variables. Moreover, smoothed plots revealed a nonlinear relationship with the TyG index, revealing an inflection point at 8.42. Interestingly, no significant link was observed to the left of the inflection point (OR = 0.50, 95% CI: 0.04-6.64, P = 0.60), whereas beyond this point, a positive correlation emerged between the TyG index and psychotic symptoms (OR = 2.42, 95% CI: 1.31-4.48, P = 0.01). Particularly, a considerable 142% rise in the probability of experiencing psychotic symptoms was found with each incremental elevation in the TyG index. Conclusions: Understanding the non-linear link between the TyG index and the risk of psychotic symptoms in Chinese patients with FEDN MDD highlights the potential for targeted therapeutic approaches. By acknowledging the threshold effect observed, there is an opportunity to mitigate risk factors associated with IR-related psychiatric comorbidities through tailored interventions. These preliminary results stress the need for further longitudinal research to solidify these insights and contribute to more effective therapeutic strategies.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

Gender differences in the association between body mass index and recent suicide attempts in Chinese patients with first-episode drug-naïve major depressive disorder.

Controversial evidence exists on the relationship between body mass index (BMI) and suicide attempts (SA) in patients with major depressive disorder (MDD). This cross-sectional study aimed to explore the association between BMI and SA in first-episode drug-naïve (FEDN) MDD patients in China. The study was conducted from 2016 to 2018 in Taiyuan, China. Univariate and multivariate logistic regression analyzed the BMI-SA association, with subgroup analysis for gender. Threshold effects were examined using two-piecewise regression. In males, BMI was significantly associated with SA (OR = 0.84, 95% CI 0.74-0.94, P = 0.003) after full adjustment, but not in females (OR = 0.97, 95% CI 0.89-1.06, P = 0.541). The interaction with gender was significant (P for interaction < 0.05). Smoothing plots revealed an L-shaped BMI-SA relationship in both genders, with BMI inflection points at 27.3 kg/m2 in males and 21.4 kg/m2 in females. Below the inflection points, BMI is negatively associated with SA in males (OR = 0.75, 95% CI 0.66-0.86, P < 0.001) and females (OR = 0.48, 95% CI 0.32-0.72, P < 0.001). Above the inflection points, no association existed for both genders (all P > 0.05). Results showed an L-shaped nonlinear BMI-SA relationship in FEDN MDD patients but differing BMI inflection points between genders, thus contributing to effective prevention programs for suicide.

Association between triglyceride glucose index and suicide attempts in patients with first-episode drug-naïve major depressive disorder.

Objective: Triglyceride glucose (TyG) index has been suggested as an alternative indicator of insulin resistance (IR); however, the association between TyG index and suicide attempts (SA) in major depressive disorder (MDD) is unclear. The aim of this study was to investigate the relationship between TyG index and SA in Chinese patients with first-episode drug-naïve (FEDN) MDD. Methods: This cross-sectional study enrolled 1,718 patients with FEDN MDD aged 34.9 ± 12.4 years from the First Hospital of Shanxi Medical University (Taiyuan, Shanxi Province, China) from September 2016 to December 2018. Multivariable binary logistic regression analysis was used to estimate the association between TyG index and the risk of SA. A two-piecewise linear regression model was used to investigate the threshold effects if non-linearity associations existed. Interaction and stratified analyses were performed based on sex, education, marital status, comorbid anxiety, and psychotic symptoms. Results: Multivariable logistic regression analysis revealed that TyG index was positively associated with the risk of SA after adjusting for confounders (OR = 1.35, 95% CI: 1.04-1.75, p = 0.03). Smoothing plots also showed a nonlinear relationship between TyG index and SA, with the inflection point of TyG index being 9.29. On the right of the inflection point, a positive association between TyG index and SA was detected (OR = 3.47, 95% CI: 1.81 to 6.66, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 1.14, 95% CI: 0.79 to 1.66, p = 0.476). Conclusion: The relationship between TyG index and SA risk was non-linear and exhibited a threshold effect in Chinese patients with FEDN MDD. When TyG index was greater than 9.29, they showed a significant positive correlation.