Objective: Neuroinflammation’s role is increasingly emphasized in the pathology of major depressive disorder (MDD), and its close association with the risk of suicide is being reported. The Forkhead Box O1 (FoxO1) gene is known to play a role in regulating mood and emotion and is associated with susceptibility to suicidality in relation to environmental stress. This research aims to explore the relationship between FoxO1 and the risk of suicide in individuals with MDD. Methods: We enrolled 127 healthy controls (HC) and 231 patients diagnosed with MDD, including 119 individuals with high suicide risk (HSR). All participants underwent the Hamilton Rating Scale for Depression Assessment and magnetic resonance imaging. Cortical thickness and white matter integrity were evaluated. Results: In the HSR group, cortical thinning was observed in the left triangular part of the inferior frontal gyrus and right transverse frontopolar gyrus compared to HC. Additionally, fractional anisotropy (FA) values were decreased in the left posterior thalamic radiation, sagittal stratum, and uncinate fasciculus. Although no differences were observed based on allele variations for the two FoxO1 single nucleotide polymorphisms (SNPs), those with the minor allele of FoxO1 rs34733279, especially in the HSR group, displayed increased cortical thinning and reduced FA values in the left cingulum. Conclusion Our study reveals close association between the minor allele of the FoxO1 gene rs34733279 and suicide risk in the left cingulum highlights the potential key role of the FoxO1 gene rs34733279 in the context of suicidal vulnerability. Further investigations are warranted to elucidate the underlying biological mechanisms.

Objective: Neuroinflammation’s role is increasingly emphasized in the pathology of major depressive disorder (MDD), and its close association with the risk of suicide is being reported. The Forkhead Box O1 (FoxO1) gene is known to play a role in regulating mood and emotion and is associated with susceptibility to suicidality in relation to environmental stress. This research aims to explore the relationship between FoxO1 and the risk of suicide in individuals with MDD. Methods: We enrolled 127 healthy controls (HC) and 231 patients diagnosed with MDD, including 119 individuals with high suicide risk (HSR). All participants underwent the Hamilton Rating Scale for Depression Assessment and magnetic resonance imaging. Cortical thickness and white matter integrity were evaluated. Results: In the HSR group, cortical thinning was observed in the left triangular part of the inferior frontal gyrus and right transverse frontopolar gyrus compared to HC. Additionally, fractional anisotropy (FA) values were decreased in the left posterior thalamic radiation, sagittal stratum, and uncinate fasciculus. Although no differences were observed based on allele variations for the two FoxO1 single nucleotide polymorphisms (SNPs), those with the minor allele of FoxO1 rs34733279, especially in the HSR group, displayed increased cortical thinning and reduced FA values in the left cingulum. Conclusion Our study reveals close association between the minor allele of the FoxO1 gene rs34733279 and suicide risk in the left cingulum highlights the potential key role of the FoxO1 gene rs34733279 in the context of suicidal vulnerability. Further investigations are warranted to elucidate the underlying biological mechanisms.

Objective: Neuroinflammation’s role is increasingly emphasized in the pathology of major depressive disorder (MDD), and its close association with the risk of suicide is being reported. The Forkhead Box O1 (FoxO1) gene is known to play a role in regulating mood and emotion and is associated with susceptibility to suicidality in relation to environmental stress. This research aims to explore the relationship between FoxO1 and the risk of suicide in individuals with MDD. Methods: We enrolled 127 healthy controls (HC) and 231 patients diagnosed with MDD, including 119 individuals with high suicide risk (HSR). All participants underwent the Hamilton Rating Scale for Depression Assessment and magnetic resonance imaging. Cortical thickness and white matter integrity were evaluated. Results: In the HSR group, cortical thinning was observed in the left triangular part of the inferior frontal gyrus and right transverse frontopolar gyrus compared to HC. Additionally, fractional anisotropy (FA) values were decreased in the left posterior thalamic radiation, sagittal stratum, and uncinate fasciculus. Although no differences were observed based on allele variations for the two FoxO1 single nucleotide polymorphisms (SNPs), those with the minor allele of FoxO1 rs34733279, especially in the HSR group, displayed increased cortical thinning and reduced FA values in the left cingulum. Conclusion Our study reveals close association between the minor allele of the FoxO1 gene rs34733279 and suicide risk in the left cingulum highlights the potential key role of the FoxO1 gene rs34733279 in the context of suicidal vulnerability. Further investigations are warranted to elucidate the underlying biological mechanisms.

Objective: This study investigated the association between white matter tract integrity and frontal executive function in adult non-geriatric patients with major depressive disorder (MDD) and healthy controls (HCs) using diffusion tensor imaging (DTI). Methods: In total, 57 patients with MDD and 115 HCs participated in this study. We calculated the integrity of the white matter tracts using the Tracts Constrained by Underlying Anatomy tool (TRACULA) from FreeSurfer. We performed cognitive function tests. Oneway analysis of covariance was used to investigate the DTI parameters as dependent variables; diagnosis of MDD as an independent variable; and age, sex, and education level as covariates. For correlation analysis between the DTI parameters and cognitive function tests, Pearson’s partial correlation analyses were performed in the MDD and HC groups. Results: The patients with MDD showed significantly decreased axial diffusivity (AD) in forceps major (FMajor), left corticospinal tract (CST), left superior longitudinal fasciculus-parietal bundle (SLFP), right anterior thalamic radiation (ATR), right CST, right inferior longitudinal fasciculus (ILF) and right superior longitudinal fasciculus-temporal bundle (SLFT) and mean diffusivity (MD) in the left CST, right CST, and right SLFT compared to HCs. We found that non-geriatric patients with MDD showed a significant negative correlation between the response time in the Stroop task and the AD value of the FMajor. Conclusion Our findings suggest that impaired structural connectivity in the FMajor may be associated with cognitive dysfunction in non-geriatric patients with MDD.

Objective: Neuroinflammation’s role is increasingly emphasized in the pathology of major depressive disorder (MDD), and its close association with the risk of suicide is being reported. The Forkhead Box O1 (FoxO1) gene is known to play a role in regulating mood and emotion and is associated with susceptibility to suicidality in relation to environmental stress. This research aims to explore the relationship between FoxO1 and the risk of suicide in individuals with MDD. Methods: We enrolled 127 healthy controls (HC) and 231 patients diagnosed with MDD, including 119 individuals with high suicide risk (HSR). All participants underwent the Hamilton Rating Scale for Depression Assessment and magnetic resonance imaging. Cortical thickness and white matter integrity were evaluated. Results: In the HSR group, cortical thinning was observed in the left triangular part of the inferior frontal gyrus and right transverse frontopolar gyrus compared to HC. Additionally, fractional anisotropy (FA) values were decreased in the left posterior thalamic radiation, sagittal stratum, and uncinate fasciculus. Although no differences were observed based on allele variations for the two FoxO1 single nucleotide polymorphisms (SNPs), those with the minor allele of FoxO1 rs34733279, especially in the HSR group, displayed increased cortical thinning and reduced FA values in the left cingulum. Conclusion Our study reveals close association between the minor allele of the FoxO1 gene rs34733279 and suicide risk in the left cingulum highlights the potential key role of the FoxO1 gene rs34733279 in the context of suicidal vulnerability. Further investigations are warranted to elucidate the underlying biological mechanisms.

Objective: Neuroinflammation’s role is increasingly emphasized in the pathology of major depressive disorder (MDD), and its close association with the risk of suicide is being reported. The Forkhead Box O1 (FoxO1) gene is known to play a role in regulating mood and emotion and is associated with susceptibility to suicidality in relation to environmental stress. This research aims to explore the relationship between FoxO1 and the risk of suicide in individuals with MDD. Methods: We enrolled 127 healthy controls (HC) and 231 patients diagnosed with MDD, including 119 individuals with high suicide risk (HSR). All participants underwent the Hamilton Rating Scale for Depression Assessment and magnetic resonance imaging. Cortical thickness and white matter integrity were evaluated. Results: In the HSR group, cortical thinning was observed in the left triangular part of the inferior frontal gyrus and right transverse frontopolar gyrus compared to HC. Additionally, fractional anisotropy (FA) values were decreased in the left posterior thalamic radiation, sagittal stratum, and uncinate fasciculus. Although no differences were observed based on allele variations for the two FoxO1 single nucleotide polymorphisms (SNPs), those with the minor allele of FoxO1 rs34733279, especially in the HSR group, displayed increased cortical thinning and reduced FA values in the left cingulum. Conclusion Our study reveals close association between the minor allele of the FoxO1 gene rs34733279 and suicide risk in the left cingulum highlights the potential key role of the FoxO1 gene rs34733279 in the context of suicidal vulnerability. Further investigations are warranted to elucidate the underlying biological mechanisms.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). Methods: For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). Results: During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. Conclusion Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

Behavioral activation (BA) is a well-established method of evidence-based treatment for depression. There are clear links between the neural mechanisms underlying reward processing and BA treatment for depressive symptoms, including anhedonia; however, integrated interpretations of these two domains are lacking. Here we examine brain imaging studies involving BA treatments to investigate how changes in brain networks, including the reward networks, mediate the therapeutic effects of BA, and whether brain circuits are predictors of BA treatment responses. Increased activation of the prefrontal and subcortical regions associated with reward processing has been reported after BA treatment. Activation of these regions improves anhedonia. Conversely, some studies have found decreased activation of prefrontal regions after BA treatment in response to cognitive control stimuli in sad contexts, which indicates that the therapeutic mechanism of BA may involve disengagement from negative or sad contexts. Furthermore, the decrease in resting-state functional connectivity of the default-mode network after BA treatment appears to facilitate the ability to counteract depressive rumination, thereby promoting enjoyable and valuable activities. Conflicting results suggest that an intact neural response to rewards or defective reward functioning is predictive of the efficacy of BA treatments. Increasing the benefits of BA treatments requires identification of the unique individual characteristics determining which of these conflicting findings are relevant for the personalized treatment of each individual with depression.