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Background Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD. Methods We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan–Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group. Results Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen's f2 = 0.361; p = 1.78 × 10−13). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups. Conclusions These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.

Objective A growing body of evidence reports on the effect of different types of childhood abuse on the structural and functional architecture of the brain. In the present study, we aimed to investigate the differences in cortical thickness according to specific types of childhood abuse between patients with major depressive disorder (MDD) and healthy controls (HCs).Methods A total of 61 patients with MDD and 98 HCs were included in this study. All participants underwent T1-weighted magnetic resonance imaging, and the occurrence of childhood abuse was assessed using the Childhood Trauma Questionnaire. We investigated the association between whole-brain cortical thickness and exposure to any type of childhood abuse and specific type of childhood abuse in the total sample using the FreeSurfer software.Results No significant difference was reported in the cortical thickness between the MDD and HC groups nor between the “any abuse” and “no abuse” groups. Compared to no exposure to childhood sexual abuse (CSA), exposure to CSA was significantly associated with cortical thinning in the left rostral middle frontal gyrus (p=0.00020), left (p=0.00240), right fusiform gyri (p=0.00599), and right supramarginal gyrus (p=0.00679).Conclusion Exposure to CSA may lead to cortical thinning of the dorsolateral prefrontal cortex, which is deeply involved in emotion regulation, to a greater extent than other types of childhood abuse.

Major depressive disorder (MDD) is one of the most common psychiatric disorders, and present various symptoms such as the dysregulation of mood, cognition, and behavior. The purpose of the present study was to investigate the morphometric change in MDD patients by voxel-based morphometry (VBM) and sulcal depth analyses. Forty-six MDD patients (mean age, SD; 36.07±14.34), and 23 age- and sex-matched normal controls (NML) (mean age, SD; 36.78±14.42) were included. Coronal 3D T1 magnetic resonance imaging (MRI) was obtained with the resolution of isotropic 1.0 mm. To check morphological changes of brain, T1 MRIs were objectively processed by VBM and sulcal depth methods. In sulcal depth analysis, depressed patients showed reduced sulcal depth in the areas of left posterior ramus of the lateral sulcus, superior frontal sulcus, supramarginal gyrus, central sulcus (Rolando's fissure), and Heschl's gyrus. And right posterior ramus of the lateral sulcus, temporal plane of the superior temporal gyrus, anterior transverse collateral sulcus, and central sulcus (Rolando's fissure) were also reduced compared to NML. But, VBM analyses did not showed significant finding. Reduced sulcal depth in the motor and emotion related areas were found in patients with MDD. Especially reduced sulcal depth in bilateral central sulci which are connecting between primary motor cortex and primary sensory cortex seems to be related with social and physical anhedonia in MDD.

Objective Considerable evidence suggests that neuroinflammation plays an important role in the pathophysiology of major depressive disorder (MDD). However, the relationship between serum C4 binding protein (C4BP) and white matter (WM) tract integrity in MDD has not been investigated.Methods We obtained diffusion tensor images of 44 patients with MDD and 44 healthy controls and performed TRActs Constrained by UnderLying Anatomy (TRACULA) analysis to assess WM tract integrity. Serum C4-binding protein alpha chain (C4BPA) and C4- binding protein beta chain (C4BPB) levels were measured and in-between group comparisons were obtained. The correlation between serum C4BP levels and WM tract integrity was examined.Results In comparison to healthy controls, both serum C4BPA and C4BPB were higher in MDD. Also, fractional anisotropy (FA) was increased in the left cingulum-angular bundle (CAB) in MDD, but not healthy controls (HCs). A significant correlation was found between serum C4BP and FA levels in the right cingulum-cingulate gyrus bundle (CCG) in MDD.Conclusion This study is the first to investigate the correlation between serum C4BP levels and WM tract integrity in MDD. We identified an increase in WM integrity in the left CAB region in MDD. Furthermore, serum C4BP levels were higher in MDD, and this finding correlated with increased WM integrity in the right CCG region.

Background: Late-life depression (LLD) is one of the most common psychiatric disorders. However, LLD is often undetected or inadequately treated by clinicians. This review summarizes the recent research on pharmacotherapy for LLD, updates information on monotherapy using recommended antidepressants, and discusses the clinical features and diagnostic criteria for LLD.Current Concepts: The diagnostic criteria for depression in both elderly and young adults are identical. Clinical features of the elderly with depression more likely include more comorbid medical conditions and cognitive impairment than those of young adults. Depression in the elderly tends to have a more chronic course with frequent recurrences or relapses.Discussion and Conclusion: The current pharmacological treatment guidelines for LLD recommend the use of selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor, bupropion, mirtazapine, and vortioxetine as first-line medications. SSRIs, among them, are recommended first because they present fewer serious adverse effects and more clinical evidence than those of other antidepressants. Before starting antidepressant treatment for LLD, clinicians should consider patients’ comorbid medical conditions, drug interactions, possible adverse effects of antidepressants, and polypharmacy. The starting dose of antidepressants for elderly patients should be half of that prescribed for young adults to minimize the adverse effects; however, most elderly patients need the same antidepressant doses as that prescribed for young patients. After remission, a 1-year maintenance treatment is required to prevent recurrence or relapse of LLD.

Objective Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD.Methods A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups.Results We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased.Conclusion Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.

Objective Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes.Methods We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors.Results We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients.Conclusion Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Alexithymia is characterized by impairments in the processing of emotions. Although the disruptions in the white matter (WM) integrity in Major depressive disorder (MDD) has frequently been reported, the underlying relationship with alexithymia remains unclear. In the present study, we investigated WM tracts with Tracts Constrained by UnderLying Anatomy approach to discover potential associations between alexithymia and WM integrity to identify the neural basis of impaired emotional self-awareness in MDD. 101 patients with MDD and 99 healthy sex- and age-matched individuals underwent diffusion-weighted imaging. All participants were assessed with the 20-item Toronto Alexithymia Scale (TAS). TAS scores were significantly higher in MDD patients than in controls. Patients with MDD exhibited significantly lower FA values in the left inferior longitudinal fasciculus and it also showed negative associations with TAS. These results contribute to the neurobiological evidence on the association between MDD and alexithymia. Additionally, they suggest that reduced white matter integrity in the regions constitutes a principal pathophysiology underlying impaired emotional recognition and description in MDD.

Background Long working hours can be a risk factor for poor mental health; however, little is known about the potential factors moderating their relation. This study investigates the association between working hours and depressive symptoms, and explores the potential moderating effect of gender, income level, and job status on this association using a nationally representative sample of working population in South Korea. Methods Data of 7,082 workers aged 19 years or above were obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted in 2014, 2016, and 2018 in South Korea. Working hours were categorized into 35–39, 40, 41–52, 53–68, and ≥69 hours/week. Depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). Results Individuals working ≥69 hours/week were more likely to have moderate to severe depressive symptoms compared to those working 40 hours/week. The association between longer working hours and depressive symptoms was especially prominent in female workers, standard wage workers, and workers with low income levels. We observed significant partial mediation pathways between working hours and PHQ-9 scores through both perceived usual stress level and self-rated health in the total sample. Limitations The cross-sectional design of the study limits causal interpretation of the findings. Conclusion Working longer than the legal upper limit of 52 hours/week puts workers at a greater risk for depression. Females, low-income workers, and wage workers are more vulnerable to the negative consequences of long working hours on mental health.

Despite the growing number of refugees and their mental health issues, neurobiological mechanisms to explain clinical symptoms resulting from traumatic events, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD), have not been extensively investigated. Research on the mental health of North Korean refugees (NKRs) who defected to South Korea for resettlement is still at an early stage but commonly reports structural and functional abnormalities in brain regions related to reward and motivational processing. The nucleus accumbens (NAc) and ventral pallidum (VP) are the major sites in subcortical structures that play key roles in reward and motivation.The present study examined subcortical structural abnormalities of 28 NKRs and age-, sex- matched South Korean Controls (SKCs) using shape analysis at the vertex level.Among the 28 NKRs, 18 had psychiatric disorders, including PTSD and MDD. The NKRs showed significantly reduced volumes in the right NAc and bilateral VP compared to the SKRs. The volume of the right VP showed a significant negative correlation with current PTSD severity in the NKR group.Our findings demonstrated that structural alterations of the NAc and VP may explain PTSD and MDD observed in the refugees and further suggest that the aftereffect of trauma, manifested as anhedonia and anxiety, may show chronically.

The Nod-like receptor pyrin containing 3 (NLRP3) inflammasome has been reported to be a convergent point linking the peripheral immune response induced by psychological stress and neuroinflammatory processes in the brain. We aimed to identify differences in the methylation profiles of the NLRP3 gene between major depressive disorder (MDD) patients and healthy controls (HCs). We also investigated the correlation of the methylation score of loci in NLRP3 with cortical thickness in the MDD group using magnetic resonance imaging (MRI) data. A total of 220 patients with MDD and 82 HCs were included in the study, and genome-wide DNA methylation profiling of the NLRP3 gene was performed. Among the total sample, 88 patients with MDD and 74 HCs underwent T1-weighted structural MRI and were included in the neuroimaging–methylation analysis. We identified five significant differentially methylated positions (DMPs) in NLRP3. In the MDD group, the methylation scores of cg18793688 and cg09418290 showed significant positive or negative correlations with cortical thickness in the occipital, parietal, temporal, and frontal regions, which showed significant differences in cortical thickness between the MDD and HC groups. Our findings suggest that NLRP3 DNA methylation may predispose to depression-related brain structural changes by increasing NLRP3 inflammasome-related neuroinflammatory processes in MDD.

We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.

Background Numerous studies have suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). We aimed to investigate differences in the volume and cortical thickness of the cerebellar subregions between patients with BD and healthy controls (HCs). Methods Ninety patients with BD and one hundred sixty-six HCs participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed the volume and cortical thickness of each cerebellar hemisphere divided into 12 subregions using T1-weighted images of participants. One-way analysis of covariance was used to evaluate differences between the groups, with age, sex, medication, and total intracranial cavity volume used as covariates. Results The BD group had significantly increased cortical thickness of the cerebellum in all cerebellar subregions compared to the HC group. The cortical thicknesses of the whole cerebellum and each hemisphere were also significantly thicker in the BD group than in the HC group. The volume of the left lobule IX was significantly lower in patients with BD than in HCs, whereas no significant differences in the volumes were observed in the other subregions. Limitations Our cross-sectional design cannot provide a causal relationship between the increased cortical thickness of the cerebellum and the risk of BD. Conclusions We observed widespread and significant cortical thickening in all the cerebellar subregions. Our results provide evidence for the involvement of the cerebellum in BD. Further studies are required to integrate neurobiological evidence and structural brain imaging to elucidate the pathophysiology of BD.

Although structural alterations have been reported in patients with major depressive disorder (MDD), very few studies have compared the shape alterations of the subcortical regions between drug-naïve MDD patients and healthy controls (HCs). Therefore, we investigated and compared the subcortical shape alterations and volumetric changes between drug-naïve MDD patients and HCs in this study.This study included 45 drug-naïve MDD patients and 83 HCs, who underwent three-dimensional (3-D) T1-weighted structural magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nuclei accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. SVA revealed regional contractions of the thalamus (bilateral medial and lateral nuclei) and right caudate nucleus (medial wall and anterosuperior areas) in the drug-naïve MDD patients when compared to HCs RESULTS: In volume analysis, the drug-naïve MDD patients showed a significant decrease in the volume of bilateral thalami compared with HCs (after Bonferroni correction p 0.003). We identified morphometric contractions in bilateral thalami and right caudate nucleus in the drug-naïve MDD patients (p 0.05).The present study implied that with cortical shape changes, the subcortical brain alterations could contribute to emotional dysregulation in the drug-naïve MDD patients.

Trait impulsivity is a known risk factor for suicidality, and the prefrontal cortex plays a key role in impulsivity and its regulation. However, the relationship between trait impulsivity, neural basis, and suicidality has been inconsistent. Therefore, this study aimed to explore the relationship between impulsivity and its structural correlates (prefrontal gray matter volume), suicidal ideation, and actual suicide attempts. A total of 87 individuals with major depressive disorder participated in study, and the gray matter volume of the prefrontal regions was extracted from T1 images based on region of interest masks. The variables for the mediation models were selected based on correlation analysis and tested for their ability to predict suicide attempts, with impulsivity and suicidal ideation as the mediation variables and gray matter volume as the independent variable. A significant correlation was observed between suicidal ideation and the left dorsolateral prefrontal cortex and right dorsomedial prefrontal cortex. The dual-mediation model revealed a significant indirect relationship between gray matter volume in both regions and suicide attempts mediated by motor impulsivity and suicidal ideation. The counterintuitive positive relationship between gray matter volume and suicidality was also discussed.

Workplace gender discrimination (WGD) may have long-term negative impacts on female workers' mental health. We aimed to investigate the association between WGD and the prevalence of depressive symptoms using a nationally representative sample of female employees in South Korea.Data of 3190 adult female employees were obtained from the 2018 nationwide Korean Longitudinal Survey of Women and Families. Women's perception of WGD was assessed using a 6-item questionnaire. Respondents were classified into high, medium, and low levels of WGD according to the 25th and 75th percentile scores. A score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale was defined as having significant depressive symptoms.A high level of WGD was significantly associated with a higher odds ratio (OR) for depressive symptoms compared to the low level (OR = 1.87, 95% confidence interval = 1.45-2.41). In the subgroup analyses, high WGD levels were associated with the highest OR for depressive symptoms in the following subgroups: younger age (19-39 years), those with a college degree, non-standard workers, pink collar workers, those with a workplace size of 10-29 employees, those with high levels of job autonomy, or low levels of emotional labor.Causal interpretation is limited owing to the study's cross-sectional design.A high level of perceived WGD was associated with depressive symptoms among female employees. Certain groups of female employees may be particularly vulnerable to the detrimental effects of WGD on depression.

This cohort study uses data from the Korean National Health Insurance Service database to assess the association of depression with the development of new-onset atrial fibrillation., Key Points Question Is depression associated with increased risk of new-onset atrial fibrillation (AF)? Findings In this cohort study of 5 031 222 individuals with a follow-up of 43 115 042 person-years, depression was associated with a higher cumulative incidence of new-onset AF. Recurrent episodes of depression were associated with an even higher risk of new-onset AF, and young age and female sex had a significant interaction with depression. Meaning Results of this study suggest that depression is associated with an increased risk of new-onset AF, suggesting the need for adequate screening for AF in people with depression., Importance The risk of atrial fibrillation (AF) in people with depression is not fully known. Depression is associated with sympathetic activation and emotional stress, which might increase the risk of new-onset AF. Objective To assess the incidence of new-onset AF in those with and without depression using data from a nationwide health care database. Design, Setting, and Participants This cohort study obtained data from the Korean National Health Insurance Service database and enrolled people who underwent a nationwide health checkup in 2009. People younger than 20 years and those with a history of heart valve surgery, previous diagnosis of mitral stenosis, or who were diagnosed with AF between January 1, 2002 and December 31, 2008 were excluded. The risk of new-onset AF (occurring between 2009 and 2018) was compared in people who were and were not diagnosed with depression within a year before the 2009 nationwide health checkup. Data were analyzed between August 1, 2020 and October 31, 2020. Exposure Previous diagnosis of depression. Main Outcomes and Measures Cumulative incidence and risk of new-onset AF between 2009 and 2018 in participants with and without depression. Kaplan-Meier analysis was conducted to assess incidence of AF, and Cox proportional hazards regression was used to calculate adjusted and unadjusted hazard ratios (HRs) and 95% CIs. Results A total of 5 031 222 individuals with a mean (SD) age of 46.99 (14.06) years (2 771 785 men [55.1%]) were included in the analysis; of these individuals, 148 882 (3.0%) had a diagnosis of depression in the year before the 2009 health checkup and 4 882 340 (97%) did not. People with depression vs those without depression were older (aged 56.7 vs 46.7 years) and more likely to be women (96 472 [64.8%] vs 2 162 965 [44.3%]). Prevalence of hypertension, diabetes, dyslipidemia, and heart failure was higher in the depression group. The cumulative incidence of new-onset AF was significantly higher in people with depression vs without depression in the Kaplan-Meier analysis and showed steady divergence throughout 10 years of follow-up (cumulative incidence, 4.44% vs 1.92%; log-rank P

Childhood abuse is associated with brain structural alterations; however, few studies have investigated the association between specific types of childhood abuse and cortical volume in patients with major depressive disorder (MDD). We aimed to investigate the association between specific types of childhood abuse and gray matter volumes in patients with MDD. Seventy-five participants with MDD and 97 healthy controls (HCs) aged 19-64 years were included. Cortical gray matter volumes were compared between MDD and HC groups, and also compared according to exposure to each type of specific childhood abuse. Emotional, sexual, and physical childhood abuse were assessed using the 28-item Childhood Trauma Questionnaire. Patients with MDD showed a significantly decreased gray matter volume in the right anterior cingulate gyrus (ACG). Childhood sexual abuse (CSA) was associated with significantly decreased gray matter volume in the right middle occipital gyrus (MOG). In the post-hoc comparison of volumes of the right ACG and MOG, MDD patients with CSA had significantly smaller volumes in the right MOG than did MDD patients without CSA or HCs. The right MOG volume decrease could be a neuroimaging marker associated with CSA and morphological changes in the brain may be involved in the pathophysiology of MDD.

Work-family conflict (WFC), an inter-role conflict between work and family, negatively affects mental health. Using a nationally representative systematic sample, this study aimed to investigate the association between WFC, depressive symptoms, and potential moderators in the association of adult female workers. Data of 4714 female workers (aged ≥19 years) were obtained cross-sectionally from the 2018 nationwide Korean Longitudinal Survey of Women and Families (KLoWF). WFC was assessed using a 7-item questionnaire, based on which scores were classified into high (75th percentile score) and low (≤75th percentile score) levels of WFC. Significant depressive symptoms were defined as a score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale. Female workers with high WFC levels were more likely to have depressive symptoms than those with low WFC levels (odds ratio = 2.29, 95% confidence interval = 1.91-2.74). In stratified analyses, high WFC levels were associated with the highest odds of depressive symptoms in the following groups: young adults (19-39 years), those with a college degree or above or with high income, never-married individuals, those with a family size of three or a single child, nonstandard workers, and pink-collar workers. This study replicated and extended previous findings on the association between WFC and depressive symptoms. The association was moderated by age, education and income levels, marital status, family size, number of children, and job conditions.

Depressive symptoms have been found to be associated with decreased hand-grip strength (HGS) and low socioeconomic status (SES) in older adults. We aimed to investigate the potential moderating effect of SES on the association between HGS and depressive symptoms and the potential mediating effect of HGS on the association between SES and depressive symptoms using a nationally representative sample of older adults.Data from 3169 community-dwelling adults aged 60 years or older were acquired from the Korea National Health and Nutrition Examination Survey conducted in 2014 and 2016. HGS was measured using a digital hand-grip dynamometer. Depressive symptoms were evaluated using the 9-item version of the Patient Health Questionnaire-9 (PHQ-9). SES was assessed using equivalent monthly household income and education level.Older adults in the lowest tertile of HGS measures were more likely to have experienced depressive symptoms compared to those in the highest tertile (odds ratio = 1.95, 95% confidence interval = 1.25-2.74). A significant moderating effect of household income level was observed on the association between HGS and PHQ-9 score (P = 0.014). Older adults with a low income had a stronger inverse correlation between HGS and PHQ-9 score compared to those with a high income (low income: beta = -0.162, P 0.001; high income: beta = -0.119, P = 0.036). HGS partially mediated the association between low income and depressive symptoms.Our findings indicate that there may be a stronger relationship between low HGS and depressive symptoms in socioeconomically deprived older people. Further research on muscle strength and income level in older adults is required regarding depression risk assessment.

Objective This study aimed to demonstrate that the Patient Health Questionnaire (PHQ)-8 is not less useful than the PHQ-9 as a screening test for major depressive disorder (MDD). Methods We performed a retrospective analysis of 567 patients in psychiatric outpatient units. The Mini International Neuropsychiatric Interview was used to diagnose MDD. We derived the validity and reliability of the PHQ-8 and PHQ-9. To evaluate the ability of the PHQ-8 and PHQ-9 to discriminate MDD, we drew receiver operating characteristic (ROC) curves and compared the areas under the curves (AUCs). Results Of the 567 participants, 207 (36.5%) were diagnosed with MDD. Cronbach's αs for the PHQ-8 and PHQ-9 were 0.892 and 0.876, respectively. Similar to the PHQ-9, the PHQ-8 was also associated with scores on the Hamilton Depression Rating Scale in a correlation analysis. When we drew ROC curves for the PHQ-8 and PHQ-9, there was no statistically significant difference in the AUCs. With a cutoff score of 10, the PHQ-8 showed a sensitivity of 58.3%, specificity of 83.1%, positive predictive value of 53.4%, and negative predictive value of 85.7%. Conclusion In a psychiatric outpatient sample, the PHQ-8 was as useful as the PHQ-9 for MDD screening.

The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression. Childhood adversity is associated with structural changes in the hippocampus, amygdala, anterior cingulate cortex (ACC), and prefrontal cortex (PFC), as well as white matter tracts such as the corpus callosum, cingulum, and uncinate fasciculus. Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population. Individuals with the Met allele of BDNF Val66Met and a history of childhood adversity had reduced volume in the hippocampus and its subfields, amygdala, and PFC and thinner rostral ACC in a study of depressed patients and healthy controls. The S allele of 5-HTTLPR combined with exposure to childhood adversity or a poorer parenting environment was associated with a smaller hippocampal volume and subsequent onset of depression. The FKBP5 gene rs160780 had a significant interaction with childhood adversity in the white matter integrity of brain regions involved in emotion processing. This review identified that imaging genetic studies on childhood adversity may deepen our understanding on the neurobiological background of depression by scrutinizing complicated pathways of genetic factors, early psychosocial environments, and the accompanying morphologic changes in emotion-processing neural circuitry.

s Background Bipolar disorder (BD) is one of the most heritable psychiatric disorders. A growing number of whole-exome sequencing (WES) studies for BD has been performed, however, no research has examined the association between single nucleotide variants (SNVs) from WES and structural magnetic resonance imaging (MRI) data. Methods We sequenced whole-exomes in 53 patients with BD and 82 healthy control participants at an initial discovery stage and investigated the impacts of SNVs in risk genes from WES analysis on the cortical gray-matter thickness and integrity of white matter tracts and in the following stage. Cortical thickness and white matter integrity were investigated using the FreeSurfer and TRACULA (Tracts Constrained by UnderLying Anatomy). Results We identified 122 BD-related genes including KMT2C, AHNAK, CDH23, DCHS1, FRAS1, MACF1 and RYR3 and observed 27 recurrent copy number alteration regions including gain on 8p23.1 and loss on 15q11.1 - q11.2. Among them, single nucleotide polymorphism (SNP) rs4639425 in KMT2C gene, which regulates histone H3 lysine 4 (H3K4) methylation involved in chromatin remodeling, was associated with widespread alterations of white matter integrity including the cingulum, uncinate fasciculus, cortico-spinal tract, and superior longitudinal fasciculus. Limitation The small sample size of patients with BD in the genome data may cause our study to be underpowered when searching for putative rare mutations. Conclusion This study first combined a WES approach and neuroimaging findings in psychiatric disorders. We postulate the rs4639425 may be associated with BD-related microstructural changes of white matter tracts.

Substance P, which is encoded by tachykinin precursor 1 gene (TAC1), has been implicated in the regulation of stress responses and the pathogenesis of major depressive disorder (MDD). We evaluated the association of 10 SNPs on TAC1 with MDD susceptibility in 111 patients with MDD and 79 control subjects, and with 17-item Hamilton depression rating scale (HAMD17) score in MDD patients. In all subjects, haplotype (ht) 2 homozygous individuals showed higher plasma substance P levels than subjects carrying one or no copy of ht2. The minor allele frequency of rs1397202 was higher in patients with MDD than that in control subjects. Patients homozygous for the minor allele of rs1397202 showed significantly lower HAMD17 scores than patients carrying the common allele. Our results suggest a possible involvement of genetic variants of TAC1 with the plasma level of substance P and symptom severity of MDD.

Background:The hippocampus is not a uniform structure, but rather consists of multiple, functionally specialized subfields. Few studies have explored hippocampal subfield volume difference in the same sample of major depressive disorder (MDD) and bipolar disorder (BD) cases. We aimed to investigate the difference of hippocampal subfield volume between patents with MDD and BD and healthy controls (HCs).Methods:A total of 102 MDD and 55 BD patients and 135 HCs were recruited and underwent T1-weighted image. Hippocampal subfield volume was calculated by automated segmentation and volumetric procedures developed by Iglesias et al. and implemented in FreeSurfer. Volume differences between the groups were analyzed using the analysis of covariance and controlling for age, sex, and total intracranial cavity volume.Results:Patients with MDD had significantly reduced volumes in the bilateral cornu ammonis 1 (CA1), CA4, the granule cell layer (GCL), molecular layer (ML), whole hippocampus, the left CA2/3, and right presubiclum and subiculum. Patients with BD had significantly reduced volumes in the right CA1, GCL, and the whole hippocampus as compared to HCs. No significant volume differences were observed between the MDD and BD groups. Illness duration was negatively correlated with volumes of the left CA1, CA4, ML, presubiculum, subiculum, and the whole hippocampus in patients with BD.Conclusion:We observed hippocampal subfield volume reductions in both MDD and BD, a finding which more prominent in MDD. The inverse correlation between BD illness duration and hippocampal subfield volume may evidence the neuroprogressive nature of BD.

Disasters have numerous harmful effects on the mental health status of trauma-exposed people. We investigated the differences in the association between trauma-related psychopathologies and posttraumatic growth according to the perceived social support level among victims of the Sewol Ferry disaster on April 16, 2014, in South Korea. Data from 241 bereaved family members, survivors, and family members of survivors were used. The Duke-UNC Functional Social Support Questionnaire, Posttraumatic Growth Inventory, PTSD Checklist-5, Posttraumatic Embitterment Disorder Self-Rating Scale, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 were used to evaluate perceived social support, posttraumatic growth, and trauma-related psychopathologies. We found that the severity of depression and anxiety showed inverse correlations with posttraumatic growth only in the low-social support group, while they did not demonstrate significant correlations in the high-social support group. The social support level had correlations with posttraumatic growth and the severity of posttraumatic stress disorder and posttraumatic embitterment disorder only in female respondents. Furthermore, there was a mediation pathway from social support level to posttraumatic growth through depressive symptoms. This study explored the complex relationship between social support, posttraumatic growth, trauma-related psychopathologies, and gender among trauma-exposed individuals in the aftermath of the Sewol Ferry disaster.

Background Although major depressive disorder (MDD) has been associated with volumetric abnormalities in the amygdala, studies investigating the association between structural alterations of the amygdala and depression have yielded varying results. Since the amygdala comprises several subregions, it is difficult to detect subtle regional changes by measuring the total amygdala volume. This study aimed to examine the volume in each amygdala subregion in adults with and without a diagnosis of MDD. Methods A total of 147 participants with a current history of major depression and 144 healthy participants ranging in age from 19 to 64 years underwent 3T magnetic resonance imaging scanning. Automatic segmentation of the nine nuclei of the amygdala was performed using FreeSurfer. One-way analysis of covariance, with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates, was performed to analyze volume differences. Results Patients with MDD had significantly lower volumes of the entire amygdala and subregions, including the lateral nucleus and anterior amygdaloid area, than healthy volunteers (HCs). There were no significant associations between subregion volumes and antidepressant use, illness duration, or depression severity. Limitations Our cross-sectional design cannot provide a causal relationship between the volume change in the amygdala subregion and the risk of MDD. Conclusion Our findings suggest that specific amygdala subregions are more susceptible to volumetric alterations in patients with MDD than in HCs. These findings may advance our understanding of the neuroanatomic basis on MDD.

A leading goal in the field of biological psychiatry for depression is to find a promising diagnostic biomarker and selection of specific psychiatric treatment mode that is most likely to benefit patients with depression. Recent neuroimaging studies have characterized the pathophysiology of major depressive disorder (MDD) with functional and structural alterations in the neural circuitry involved in emotion or reward processing. Particularly, structural and functional magnetic resonance imaging (MRI) studies have reported that the brain structures deeply involved in emotion regulation or reward processing including the amygdala, prefrontal cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and hippocampus are key regions that provide useful information about diagnosis and treatment outcome prediction in MDD. For example, it has been consistently reported that elevated activity of the ACC is associated with better antidepressant response in patients with MDD. This chapter will discuss a growing body of evidence that suggests that diagnosis or prediction of outcome for specific treatment can be assisted by a neuroimaging-based biomarker in MDD.

A leading goal in the field of biological psychiatry for depression is to find a promising diagnostic biomarker and selection of specific psychiatric treatment mode that is most likely to benefit patients with depression. Recent neuroimaging studies have characterized the pathophysiology of major depressive disorder (MDD) with functional and structural alterations in the neural circuitry involved in emotion or reward processing. Particularly, structural and functional magnetic resonance imaging (MRI) studies have reported that the brain structures deeply involved in emotion regulation or reward processing including the amygdala, prefrontal cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and hippocampus are key regions that provide useful information about diagnosis and treatment outcome prediction in MDD. For example, it has been consistently reported that elevated activity of the ACC is associated with better antidepressant response in patients with MDD. This chapter will discuss a growing body of evidence that suggests that diagnosis or prediction of outcome for specific treatment can be assisted by a neuroimaging-based biomarker in MDD.

BackgroundAn aberrant neural connectivity has been known to be associated with bipolar disorder (BD). Local gyrification may reflect the early neural development of cortical connectivity and has been studied as a possible endophenotype of psychiatric disorders. This study aimed to investigate differences in the local gyrification index (LGI) in each cortical region between patients with BD and healthy controls (HCs).MethodsLGI values, as measured using FreeSurfer software, were compared between 61 patients with BD and 183 HCs. The values were also compared between patients with BD type I and type II as a sub-group analysis. Furthermore, we evaluated whether there was a correlation between LGI values and illness duration or depressive symptom severity in patients with BD.ResultsPatients with BD showed significant hypogyria in various cortical regions, including the left inferior frontal gyrus (pars opercularis), precentral gyrus, postcentral gyrus, superior temporal cortex, insula, right entorhinal cortex, and both transverse temporal cortices, compared to HCs after the Bonferroni correction (p < 0.05/66, 0.000758). LGI was not associated with clinical factors such as illness duration, depressive symptom severity, and lithium treatment. No significant differences in cortical gyrification according to the BD subtype were found.ConclusionsBD appears to be characterized by a significant regionally localized hypogyria, in various cortical areas. This abnormality may be a structural and developmental endophenotype marking the risk for BD, and it might help to clarify the etiology of BD.

Previous studies have documented the protective effects of social participation on depression in older adults. In this study, we investigated the association between social participation and depressive symptoms and the associated gender difference in older adults. In addition, we explored the mediating role of emotional social support in the association between social participation and depressive symptoms. We collected data from 4751 community-dwelling adults aged 60 and above from the Korean Retirement and Income Study (KReIS) conducted in 2017 and 2018. The relationship between social participation (participation in different types of activities, frequency of participation, and the number of activities participated) and the risk for depressive symptoms was examined. Older adults who participated in social activity, volunteer work, and donation had decreased risk of depressive symptoms. More frequent and more diverse participation in activities further reduced the risk. Overall, women benefited more from social participation than men. Importantly, emotional social support significantly mediated the relationship between social participation and depressive symptoms. Social participation was associated lower odds for depression in older adults, particularly in older women. Our findings provided one of very few pieces of evidence that documents the mediating role of emotional social support in the relationship between social participation and depression among the elderly.

Chronic low-grade inflammation contributes to the pathophysiology of major depressive disorder (MDD). This study aimed to examine the association between serum levels of FAM19A5, a novel chemokine-like peptide that reflects reactive astrogliosis and inflammatory activation in the brain, and the neurodegenerative changes of MDD by investigating the correlation between serum FAM19A5 levels and cortical thickness changes in patients with MDD. We included 52 drug-naive patients with MDD and 60 healthy controls (HCs). Serum FAM19A5 levels were determined in peripheral venous blood samples using a sandwich enzyme-linked immunosorbent assay. All participants underwent T1-weighted structural magnetic resonance imaging. Serum FAM19A5 levels were greater in patients with MDD than in HCs. In the MDD group, there were significant inverse correlations between serum FAM19A5 levels and cortical thickness in the prefrontal regions (i.e., the left inferior and right medial superior frontal gyri), left posterior cingulate gyrus, right cuneus, and both precunei, which showed significantly reduced thickness in patients with MDD compared to HCs. However, no correlation between serum FAM19A5 level and cortical thickness was observed in the HC group. The results of our study indicate that serum FAM19A5 levels may reflect reactive astrogliosis and related neuroinflammation in MDD. Our findings also suggest that serum FAM19A5 may be a potential biomarker for the neurodegenerative changes of MDD.

Background We investigated the interactive effects of depressive symptoms and chronic diseases on health care utilization among elderly people and explored the potential moderating effect of gender and the mediating effect of self-rated health (SRH) on the association between depressive symptoms and health care utilization. Method We analyzed data from 5223 people aged 60 years or older living in the community from the Korea Welfare Panel Study in 2015. Depressive symptoms were measured using an 11-item version of the Center for Epidemiologic Studies Depression (CES-D-11) Scale and morbidity within 28 disease categories was assessed. Health care utilization was evaluated as the number of outpatient visits (OV), number of hospitalizations (NH), and number of days spent in the hospital (DH) during past year. Hierarchical moderated regression analyses were applied to investigate the interactive effects. We also adopted the mediation analysis method by Hayes and Preacher. Results A significant interactive effect of CES-D-11 score and chronic disease on OV was found. A positive correlation between CES-D-11 score and OV was only observed in those with chronic disease. Gender had a moderating effect on the association of depression symptoms with OV, NH, and DH among elderly people with chronic disease. SRH had mediating effects on the association of CES-D-11 with OV, NH, and DH only among those with chronic disease. Limitations The severity or multimorbidity of chronic diseases, which could affect health care utilization among elderly were not considered. Conclusions We elucidated the complex aspects of the relationship between depressive symptoms and chronic disease and their interactive effects on health care utilization among elderly people, and identified important roles of gender and SRH.

Emotional labor is strongly correlated with negative consequences in psychological well-being and mental health status in workers. We investigated the associations of emotional labor with depressive mood and perceived usual stress level according to gender and its interactions with job autonomy in service and sales workers. The data from 2,055 service and sales workers from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2007 to 2009 were analyzed. High emotional labor was associated with increased risk for depressive mood in female workers (adjusted odds ratio [aOR] = 2.19, 95%, confidence interval [CI] = 1.56–3.07). Emotional labor and job autonomy showed interactive effects on depressive mood in that high emotional labor was associated with depressive mood only in the presence of low job autonomy in male workers (aOR = 2.85, 95% CI = 1.13–7.17). A significant mediation pathway between high emotional demand and prevalence of depressive mood through higher stress level was observed in female workers. In conclusion, female workers had high vulnerability to depressive symptoms due to emotional labor, and high job autonomy can act as a buffer against the detrimental effect of emotional labor in male workers.

A growing body of evidence has suggested that social capital is an upstream social determinant of mental health. We investigated the association of cognitive social capital, including interpersonal trust and reciprocity, with depressive symptoms in the elderly. We also explored the mediating role of cognitive social capital in the association between socioeconomic status (SES) and depressive symptoms and the moderating effect of SES on the relationship between social capital and depressive symptoms. Data from the 2012 Korea Welfare Panel Study (KOWEPS) was analyzed for 5969 participants aged 60 years or older. Cognitive components of social capital, including interpersonal trust and reciprocity, were evaluated using single-item questionnaires. Socioeconomic and health-related characteristics were investigated and depressive symptoms were evaluated by an 11-item version of the Center for Epidemiologic Studies Depression Scale. Low interpersonal trust and reciprocity levels were significantly associated with depressive symptoms in the elderly. Reciprocity level mediated the association between household income level and depressive symptoms. We did not observe any significant moderating effect of SES on the association between cognitive social capital and depressive symptoms. A significant association between cognitive social capital and depressive symptoms in Korean elderly was found. We elucidated how SES interacted with depressive symptoms through the mediation pathway of cognitive social capital using a representative sample of the Korean elderly population.

The serotonin-transporter-linked polymorphic region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have been implicated in the pathophysiology of major depressive disorder (MDD). We aimed to investigate the effects of genetic variants of the 5-HTTLPR and BDNF Val66Met polymorphisms and their interactions with MDD on cortical volume and white matter integrity. Ninety-five patients with MDD and 65 healthy participants aged 20-65 years were recruited. The subjects were genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms and scanned with T1-weighted and diffusion tensor imaging. The gray matter volumes of 24 gyri in the prefrontal and anterior cingulate cortices and the fractional anisotropy values of nine white matter tracts in both hemispheres were determined. In the pooled sample of subjects from both groups, 5-HTTLPR L-allele carriers had significantly decreased cortical volume in the right anterior midcingulate gyrus compared to S-allele homozygotes. A significant effect of the interaction of the BDNF Val66Met polymorphism and MDD on the fractional anisotropy values of the right uncinate fasciculus was observed. Our results suggested that these genetic polymorphisms play important roles in the neurostructural changes of emotion-processing regions in subjects with MDD.

Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919. A total of 105 patients with MDD and 85 healthy control subjects underwent T1-weighted structural magnetic resonance imaging and diffusion tensor imaging. The rs7294919 was genotyped and its DNA methylation status was assessed in all the participants. We analyzed the hippocampal subfield volumes and PHC integrity using FreeSurfer and the Tracts Constrained by Underlying Anatomy (TRACULA) respectively. Significant interactive effects of rs7294919 and MDD were observed in the volumes of the dentate gyrus and CA4. The patients with MDD had increased methylation in two of the three CpG loci of rs7294919, and the methylation of CpG3 was significantly correlated with right PHC integrity in the MDD group. Our results provide neurobiological evidence for the association of rs7294919 with brain structural changes in MDD.