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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.

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.

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

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.

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.

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.

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.

Background Previous pharmaco-epidemiological studies have reported increases in the prescription of psychotropic medications after a disaster, reflecting post-disaster changes in psychiatric conditions and mental health service utilization. We investigated changes in the prescription of psychotropic medications in the Danwon district of Ansan city (Ansan Danwon) compared to a control community before and after the Sewol Ferry disaster on April 16, 2014. Methods Data was collected from the Korean Health Insurance Review and Assessment Service database. We analyzed the prescription rates of psychotropic medications including antidepressants, anxiolytics, and sedatives/hypnotics, and investigated whether the time-series pattern of monthly prescriptions per 100,000 people was different in Ansan Danwon compared to that in Cheonan city after the Sewol Ferry disaster through difference-in-differences regression analysis. Results Ansan Danwon showed a significantly greater increase (5.6%) in the prescription rate of antidepressants compared to Cheonan city following the Sewol Ferry disaster. There were no significant differences in changes in the prescription rates of anxiolytics or sedatives/hypnotics. In the secondary analysis, a significantly greater increase in the prescription rate of antipsychotics was observed in Ansan Danwon compared to a control community after the disaster. Limitations We could not exclude the possibility that other events influenced changes in the prescription rates of psychotropic medications during the study period. Conclusions Pharmaco-epidemiological studies on psychotropic medication prescription after a disaster provide important information about population-level mental health. Our results suggest that the Sewol Ferry disaster exerted a harmful effect on the mental health status of the affected community., Highlights • The Sewol Ferry disaster caused 305 deaths in Ansan, Korea on April 16, 2014. • Psychotropic prescriptions rates were examined in Ansan Danwon after the disaster. • Antidepressant prescriptions were increased in Ansan Danwon versus a control city. • There were no differences in anxiolytic or sedative/hypnotic prescription rates. • Post-disaster prescription rates are a useful reflection of community mental health.

Substance P (SP) has been implicated in major depressive disorder (MDD), with SP antagonists being studied as potential antidepressants. Although impaired neural plasticity is considered a key mechanism in MDD pathophysiology, the association between SP and brain structural changes in depression has not been investigated. We investigated the correlations between SP levels and white matter (WM) integrity in 42 medication-naive patients with MDD and 57 healthy controls (HCs). Plasma levels of SP were determined, and diffusion tensor imaging (DTI) was performed to investigate microstructural changes in WM tracts. In patients, negative correlations between SP levels and fractional anisotropy (FA) values of the forceps minor of the corpus callosum, and positive correlations between SP levels and radial diffusivity (RD) and mean diffusivity (MD) values of the right corticospinal tract (CST) were observed, with no significant correlations in HCs. Linear regression analyses showed SP levels to significantly predict FA values of the forceps minor, and RD and MD values of the right CST in patients, but not in HCs. We consider our findings to contribute to the neurobiological evidence on the association between SP and brain structural changes in depression, which may be related with the pathophysiology and treatment of MDD.

The genetic variant of the vesicular monoamine transporter 1 gene (VMAT1) has been suggested to be associated with monoaminergic signaling and neural circuit activity related to emotion processing. We aimed to investigate microstructural changes in white matter tracts of patients with major depressive disorder (MDD), and examined the interaction effect between VMAT1 Thr136Ile (rs1390938) polymorphism and MDD on white matter integrity. Diffusion tensor imaging (DTI) and VMAT1 Thr136Ile (rs1390938) genotyping were performed on 103 patients diagnosed with MDD and 83 healthy control participants. DTI was used to investigate microstructural changes in white matter tracts in patients compared to healthy controls. The possible interaction effect between rs1390938 and MDD on white matter integrity was also assessed. Patients with MDD exhibited lower fractional anisotropy (FA) values of the forceps major (p

Background Morphologic changes of the brainstem in major depressive disorder (MDD) have rarely been reported in neuroimaging studies, even though, monoaminergic neurotransmitters are synthesized in several brainstem regions. We aimed to investigate volume changes in each region of the brainstem and their association with antidepressant use or the remission status of MDD. Methods A total of 126 patients with MDD and 101 healthy controls underwent T1-weighted structural magnetic resonance imaging. We analyzed volumes of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle, and the volume of the whole brainstem using the FreeSurfer. Results The patients with MDD had significantly greater midbrain volumes (P=0.013) compared to healthy controls. In particular, drug-naive patients with MDD had significantly greater brainstem volumes compared to healthy controls (P=0.007), while no significant findings were observed between the antidepressant treatment group and healthy controls. The remitted patient group had reduced pons (P=0.002) and midbrain (P=0.005) volumes compared to healthy controls, while the non-remitted MDD patient group had significantly greater midbrain volumes compared to the healthy controls (P=0.017). Limitations We could not distinguish gray versus white matter volumes changes in our analysis. Conclusions We observed that the midbrain is enlarged in patients with a current depressive episode, who are not undergoing antidepressant treatment. This volume then returns to normal after antidepressant treatment, and is even reduced, when the patient is in remission. Further studies are needed to confirm our observations.

Suicide is among the most important global health concerns; accordingly, an increasing number of studies have shown the risks for suicide attempt(s) in terms of brain morphometric features and their clinical correlates. However, brain studies addressing suicidal vulnerability have been more focused on demonstrating impairments in cortical structures than in the subcortical structures. Using local shape volumes (LSV) analysis, we investigated subcortical structures with their clinical correlates in depressed patients who attempted suicide. Then we compared them with depressed patients without a suicidal history and age‐ and sex‐matched healthy controls (HCs; i.e., 47 suicide attempters with depression, 47 non‐suicide attempters with depression, and 109 HCs). Significant volumetric differences were found between suicidal and nonsuicidal depressed patients in several vertices: 16 in the left amygdala; 201 in the left hippocampus; 1,057 in the left putamen; and 140 in the left pallidum; 1 in the right pallidum; and 6 in the bilateral thalamus. These findings indicated subcortical alterations in LSV in components of the limbic–cortical–striatal–pallidal–thalamic circuits. Moreover, our results demonstrated that the basal ganglia was correlated with perceived stress levels, and the thalamus was correlated with suicidal ideation. We suggest that suicidality in major depressive disorder may involve subcortical volume alterations., Using local shape volumes (LSV) analysis, significant volumetric differences were found between suicidal and nonsuicidal depressed patients in the left amygdala, left hippocampus, left putamen, bilateral pallidum, and thalamus. These findings propose that suicidality in major depressive disorder may involve subcortical volumetric alterations.

Treating patients with major depressive disorder is challenging because it takes several months for antidepressants prescribed for the patients to take effect. This limitation may result in increased risks and treatment costs. To address this limitation, an accurate antidepressant response prediction model is needed. Recently, several studies have proposed models that extract useful features such as neuroimaging biomarkers and genetic variants from patient data, and use them as predictors for predicting the antidepressant responses of patients. However, it is impossible to utilize all the different types of predictors when making a clinical decision on what drugs to prescribe for a patient. Although a machine learning-based antidepressant response prediction model has been proposed to overcome this problem, the model cannot find the most effective antidepressant for a patient. Based on a neural network, we propose an Antidepressant Response Prediction Network (ARPNet) model capturing high-dimensional patterns from useful features. Based on a literature survey and data-driven feature selection, we extract useful features from patient data, and use the features as predictors. In ARPNet, the patient representation layer captures patient features and the antidepressant prescription representation layer captures antidepressant features. Utilizing the patient and antidepressant prescription representation vectors, ARPNet predicts the degree of antidepressant response. The experimental evaluation results demonstrate that our proposed ARPNet model outperforms machine learning-based models in predicting antidepressant response. Moreover, we demonstrate the applicability of ARPNet in downstream applications in use case scenarios.

Background Genetic variations associated with major depressive disorder (MDD) may affect the structural aspects of neural networks mediated by the molecular pathways involved in neuronal survival and synaptic plasticity. However, few studies have applied a novel approach such as whole-exome sequencing (WES) analysis to investigate the genetic contribution to the neurostructural changes in MDD. Methods In the first part of the study, we investigated rare variants of selected genes from previous WES studies using a WES analysis in 184 patients with MDD and 82 healthy controls. In the second part of the study, we explored the association between the common genetic variants from the WES analysis and cortical thickness in 91 patients with MDD and 75 healthy controls. The gray-matter thickness of each cortical region was measured using FreeSurfer. Results We identified recurrent non-silent variants in 24 MDD-related genes including FASN, MYH13, UNC13D, LILRA1, CACNA1B, TRIO, HOMER3, and BCAR3, and observed eleven recurrently altered copy number alternations where a gain on 15q11.2 and losses on 7q34 and 15q11.1-q11.2 in MDD genomes. We also found that rs11592462 in CDH23, a calcium-dependent cell-adhesion molecule encoding gene, was significantly associated with thinning in the right anterior cingulate cortex. Limitation The small sample size may lead our findings to be underpowered regarding rare variants. Conclusion : The present study identified that non-synonymous rare variants were significantly associated with risk of MDD and found that genetic contributions to the development of MDD may be mediated by alterations in cortical thickness of emotion-processing neural circuits.

Study ObjectivesTo investigate the association between weekend catch-up sleep (WCS) and the levels of high-sensitivity C-reactive protein (hsCRP)—a serum inflammatory maker—in adultsMethodsData of 5,506 adults aged 19 years or older were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys conducted in 2016. Serum hsCRP level, weekday and weekend sleep durations, and sociodemographic and health-related characteristics were assessed. Participants whose weekend sleep duration was more than 1 h longer than their weekday sleep duration were included in the WCS group. hsCRP level was categorized into quartiles (i.e. highest, middle-high, middle-low, and lowest). Obesity was defined by body mass index ≥ 25.0 kg/m2.ResultsThe WCS group included 1,901 participants (34.5%). In the logistic regression analysis controlling for all variables, adults in the WCS group were significantly less likely to show the highest hsCRP level (versus the lowest level) compared with those without WCS in the complete sample (adjusted odds ratio = 0.795, 95% confidence interval [CI] = 0.662 to 0.955). In a subgroup analysis, this association was significant only for those with weekday sleep duration of 6 h or lower. Longer WCS (≥3 h) was not associated with hsCRP levels. Non-obese people with WCS demonstrated a lower risk for high hsCRP levels, while there was no significant difference in obese people with WCS.ConclusionsOur findings indicate that WCS may be beneficial for low-grade systemic inflammation in adults, particularly among those with shorter weekday sleep durations. WCS may also interact with obesity.

Background The assessment of comorbid physical illness and metabolic or cardiovascular risk factors as potential risk factors for onset of major depressive disorder (MDD) is crucial. We aimed to investigate potential risk factors for the development of MDD among individuals with chronic medical conditions and metabolic and behavioral risk factors using a large population-based retrospective cohort from the data of the National Health Insurance Service (NHIS) in South Korea. Methods The population-based retrospective cohort included data from 2,370,815 adults (age ≥20 years) diagnosed with MDD between January 1, 2010, and December 31, 2016 and age- and gender-matched 2,370,815 healthy controls obtained from the claims data of the NHIS. The data of the regular health checkup provided by the NHIS were also included (age ≥40 years). Logistic regression analyses were performed to investigate the potential risk factors for the incidence of MDD. Results Chronic medical conditions such as Parkinson's disease (odds ratio [OR] = 7.808, 95% confidence interval [CI] = 7.517–8.11), epilepsy (OR = 6.119, 95% CI = 6.019–6.22), multiple sclerosis (OR = 5.532, 95% CI = 4.976–6.151), Huntington's disease (OR = 5.387, 95% CI = 3.258–8.909), migraine (OR = 4.374, 95% CI = 4.341–4.408), stroke (OR = 4.074, 95% CI = 4.032–4.117), and cancer; metabolic syndrome (OR = 1.049, 95% CI = 1.041–1.057) and several of its components including central obesity, elevated fasting blood glucose and triglyceride levels, and reduced high-density lipoprotein level; and cigarette smoking, frequent alcohol consumption, and low physical activity are potential risk factors for the development of MDD. Conclusion Our results may support previous evidence on the association between physical conditions and the incidence of MDD as reported by individual population-based studies with modest sample sizes.

Background The 15-item geriatric depression scale (GDS-15) is a short form of GDS and is used to screen, diagnose, and evaluate depression in elderly individuals. Most previous studies evaluated the ability of GDS-15 to discriminate between depressive and non-depressive states. In this study, we investigated the multi-stage discriminating ability of GDS-15. Methods A total of 774 participants, over 65 years of age were included (normal, n = 650; minor depressive disorder [MnDD], n = 94; major depressive disorder [MDD], n = 30). Multi-category receiver operating characteristic (ROC) surfaces were evaluated to identify three stages of geriatric depression. The optimal cutoff points were selected based on the volume under the ROC surface (VUS) and the Youden index. Results In the results of multi-category classification analyses, VUS of the GDS-15 of 0.61 was obtained, and optimal cutoff points of the GDS-15 for multiple stages of depression of 4 (between normal and MnDD) and 11 (between MnDD and MDD) were derived. The Youden index for the GDS-15 was 0.49, and the derived optimal cutoff points were 5 and 10, for the multiple stages, respectively. The overall diagnostic accuracy based on the Youden index was superior to that based on the VUS in the GDS-15. Limitations The participants’ cognitive function has potential to affect the GDS-15 score; nevertheless, the study included those with mild cognitive impairment. Conclusions GDS-15 was a useful tool to classify stages of geriatric depression into either minor or major depressive disorder.

Background Suicide is a critical complication of psychiatric disorders. Physical activity has a positive effect on mental health; however, its effects on suicidal ideation have received little attention compared to other psychiatric symptoms. Methods Data were obtained from the Korea National Health and Nutrition Examination Survey 2014. Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. Physical activity was measured by the International Physical Activity Questionnaire (IPAQ) and categorized into three groups by activity level. Multiple logistic regression analysis was performed for the entire sample, men, and women. The following three models were used: Model 1 (adjusted for sociodemographic and health-related variables), Model 2 (additionally adjusted for subjective body image), and Model 3 (additionally adjusted for diagnosed depression). Results Compared to the low IPAQ group, the moderate IPAQ group was significantly associated with decreased suicidal ideation in Model 3 for the entire sample (OR, 0.733; 95% CI, 0.538–0.999) and in all models for women. However, the high IPAQ group showed no significant association. None of the IPAQ groups showed significant associations in men. Limitations This is a cross-sectional study. Therefore, the direction of causality cannot be determined. This study also investigated suicidal ideation over the past two weeks, which may be inconsistent with studies conducted over the past year. Conclusions The beneficial relationship between physical activity and suicidal ideation is weaker in men and individuals with high activity levels. Detailed guidelines on physical activity according to gender and activity level are recommended.

Recent neuroimaging studies have characterized the pathophysiology of late-life depression (LLD) as a dysfunction of the brain networks involved in the regulation of emotion, motivational behavior, cognitive control, executive function, and self-referential thinking. In this article, we reviewed LLD-associated structural neuroimaging markers such as white matter hyperintensity (WMH), white matter integrity measured by diffusion tensor imaging, cortical and subcortical volumes, and cortical thickness, which may provide a structural basis for brain network dysfunction in LLD. LLD was associated with greater severity or volumes of deep, periventricular, or overall WMH and with decreased white matter integrity in the brain regions belonging to the fronto-striatal-limbic circuits and reduced white matter tract integrity which connects these circuits, such as the cingulum, corpus callosum, or uncinate fasciculus. Decreased volumes or cortical thickness in the prefrontal cortex, orbitofrontal cortex, anterior and posterior cingulate cortex, several temporal and parietal regions, hippocampus, amygdala, striatum, thalamus, and the insula were associated with LLD. These structural neuroimaging findings were also associated with cognitive dysfunction, which is a prominent clinical feature in LLD. Several structural neuroimaging markers including the WMH burden, white matter integrity, and cortical and subcortical volumes predicted antidepressant response in LLD. These structural neuroimaging findings support the hypothesis that disruption of the brain networks involved in emotion regulation and cognitive processing by impaired structural connectivity is strongly associated with the pathophysiology of LLD.

We investigated the interactive effects of BclI C/G (rs41423247) allelic variants and the diagnosis of major depressive disorder (MDD) on hippocampal shape and integrity of the left parahippocampal subdivision of the cingulum. Fifty-two patients with MDD and 52 healthy controls (HCs) underwent T1-weighted structural magnetic resonance imaging and BclI C/G (rs41423247) genotyping. We analyzed hippocampal shape using the FIRST module of FSL and analyzed white matter (WM) integrity using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Significant alterations in left hippocampal shape and decreased fractional anisotropy (FA) values of the left parahippocampal cingulum were observed in MDD patients, compared to HCs. In addition, MDD patients of the BclI minor (G-) allele carrier group showed significant alterations in left hippocampal shape and decreased FA values of the left parahippocampal cingulum compared to BclI minor (G-) allele carrier HCs. No significant differences between diagnostic subgroups of the C/C homozygotes were observed. Our study provides evidence for alterations in hippocampal shape and decreased integrity of the WM region associated with the hippocampus in MDD, and for the possible influence of BclI C/G polymorphism (rs41423247) on hippocampal shape and integrity of the parahippocampal subdivision of the cingulum in depression.

Background Intimate partner violence (IPV) has a serious detrimental effect on mental health outcomes. We aimed to investigate the association of verbal or physical IPV with incidence of depressive symptoms in both married women and men according to the victim-perpetrator role. The potential mediating role of verbal or physical IPV in the association between satisfaction level with family relationships or childhood adversity and the incidence of depressive symptoms in married adults was also explored. Methods The Korea Welfare Panel Study (KOWEPS) in 2006 and 2007 dataset was analyzed for 9217 married respondents aged 19 years or older. Physical and verbal IPV was assessed according to victim-perpetrator role in 2006. Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression Scale, 11-item version in 2006 and 2007. Association of IPV with incidental depressive symptoms was investigated with logistic regression analysis fully-adjusted for all potential confounding factors. Results The bidirectional role of verbal IPV and victimization by physical IPV led to incidence of depressive symptoms in married women. Verbal IPV significantly mediated the association between satisfaction level with the family relationship and incidental depressive symptoms in women. Limitations We did not investigate the influence of premorbid depressive symptoms on new-onset IPV. Conclusions This study is the first to demonstrate that gender and the victim-perpetrator role are critical moderating factors in the association between IPV and depressive symptom incidence using a nationally representative sample

Distinguishing depression in bipolar disorder (BD) from unipolar depression (UD) solely based on clinical clues is difficult, which has led to the exploration of promising neural markers in neuroimaging measures for discriminating between BD depression and UD. In this article, we review structural and functional magnetic resonance imaging (MRI) studies that directly compare UD and BD depression based on neuroimaging modalities including functional MRI studies on regional brain activation or functional connectivity, structural MRI on gray or white matter morphology, and pattern classification analyses using a machine learning approach. Numerous studies have reported distinct functional and structural alterations in emotion- or reward-processing neural circuits between BD depression and UD. Different activation patterns in neural networks including the amygdala, anterior cingulate cortex (ACC), prefrontal cortex (PFC), and striatum during emotion-, reward-, or cognition-related tasks have been reported between BD and UD. A stronger functional connectivity pattern in BD was pronounced in default mode and in frontoparietal networks and brain regions including the PFC, ACC, parietal and temporal regions, and thalamus compared to UD. Gray matter volume differences in the ACC, hippocampus, amygdala, and dorsolateral prefrontal cortex (DLPFC) have been reported between BD and UD, along with a thinner DLPFC in BD compared to UD. BD showed reduced integrity in the anterior part of the corpus callosum and posterior cingulum compared to UD. Several studies performed pattern classification analysis using structural and functional MRI data to distinguish between UD and BD depression using a supervised machine learning approach, which yielded a moderate level of accuracy in classification.

Tinnitus is strongly associated with psychiatric symptoms, including depression and suicidality. We aimed to further investigate the association of tinnitus with depressive mood and/or suicidal ideation, and explore the shared risk factors for these within a representative sample of the adult general population. We also investigated potential mediation pathways among tinnitus, suicidal ideation, depression, shared risk factors, and perceived stress levels. We analysed data from 28,930 adults (aged ≥19 years) from the fourth and fifth Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2012 in South Korea. We investigated the presence and severity of tinnitus, depressive mood, suicidal ideation, perceived usual stress level, and socioeconomic and health-related variables. We conducted logistic regression and mediation analyses. Tinnitus and its severity were significantly associated with depressive mood and suicidal ideation. Tinnitus, depressive mood, and suicidal ideation shared common socioeconomic and health-related risk factors. Tinnitus significantly mediated the association of shared risk factors for depressive mood and suicidal ideation. Perceived usual stress level mediates the association of tinnitus with depressive mood and suicidal ideation. The correlation of perceived usual stress levels with depression and suicidal ideation was also mediated by tinnitus. Our findings implicate that tinnitus may contribute substantially to the development of depressive symptom and suicidal ideation in adults via apparent interactions with shared risk factors and stress levels.

A single nucleotide polymorphism of rs1360780 in the FKBP5 gene is associated with a predisposition to developing major depressive disorder (MDD). We investigated the interactive effects of FKBP5 rs1360780 allelic variants, DNA methylation, and the diagnosis of MDD on structural changes of the entire brain. One hundred and fourteen patients with MDD and eighty-eight healthy controls underwent T1-weighted structural magnetic resonance imaging and FKBP5 rs1360780 genotyping, including DNA methylation of intron 7. We analyzed the volume of cortical and subcortical regions and cortical thickness using FreeSurfer. Significant genotype-by-diagnosis interactions were observed for volumes of the left pars triangularis, supramarginal gyrus, superior parietal lobule, right frontomarginal, and posterior midcingulate gyrus. The T allele was associated with significant volume reductions in these brain regions only in the MDD group except for the right posterior midcingulate gyrus. FKBP5 DNA methylation showed a positive correlation with the thickness of the right transverse frontopolar gyrus in the C allele homozygote group. Our findings suggest that the FKBP5 gene and its epigenetic changes could have influence on morphologic changes of several brain regions involved in emotion regulation, and that this process may be associated with the development of MDD.

Background Precarious employment is one of the most important indicators of social disadvantage and is associated with poor mental health. This study aimed to investigate the association of precarious employment with depressive mood and suicidal ideation in adult wage workers, and the possible mediating or moderating effect of socioeconomic factors in the association between precarious work and mental health status. Method Data from the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V) conducted between 2010 and 2012 were analyzed. Among the 24,173 participants, 6266 adult wage workers (3206 precarious and 3060 non-precarious workers) aged ≥19 years were included. Socioeconomic and health-related characteristics as well as depressive mood and suicidal ideation were investigated. Results Precarious employment was significantly associated with depressive mood in the logistic regression analyses adjusting for all potential confounding factors as covariates. The socioeconomic variables including age, gender, education level, marital status, household income, and occupation type were significantly related with depressive mood and suicidal ideation in adult wage workers. We also found that gender and household income had possible moderating effects on the association between precarious employment and suicidal ideation. Precarious work was associated with suicidal ideation only for male workers and worker with low or middle-lower income levels. Limitations Our study is based on a cross-sectional design, thus, we could not elucidate the causal relationship between the variables. Conclusions Our study suggested that precarious employment plays a pivotal role in the mental health status of adult wage workers.

Background The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network. Methods Eighty-six patients with MDD and 64 healthy controls underwent T1-weighted structural magnetic resonance imaging, including diffusion tensor imaging (DTI), and genotype analysis. We selected the genu of the corpus callosum, the uncinate fasciculus, cingulum, and fornix as regions of interest, and extracted fractional anisotropy (FA) values using the FMRIB Diffusion Toolbox software. Results FA values for the left parahippocampal cingulum (PHC) was significantly reduced in the patients with MDD compared to healthy control participants (p = 0.004). We also found that MDD patients with the A allele showed reduced FA values for the left PHC than did healthy controls with the A allele (p = 0.012). There was no significant difference in the FA value of left PHC for the comparison between the G homozygotes of MDD and healthy control group. Conclusions We observed an association between the risk allele of the SLC6A15 gene rs1545843 and the WM integrity of the PHC in MDD patients, which is known to play an important role in the neural circuit involved in emotion processing.

The tryptophan hydroxylase‐2 (TPH2) gene is considered a promising genetic candidate regarding its association with a predisposition to major depressive disorder (MDD). Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. They aimed to investigate the alterations in the cortical gyrification of the prefrontal cortex and anterior cingulate cortex and their association with the TPH2 rs4570625 polymorphism in patients with MDD. One hundred and thirteen patients with MDD and eighty‐six healthy controls underwent T1‐weighted structural magnetic resonance imaging and genotyping for TPH2 rs4570625. The local gyrification index of 22 cortical regions in the prefrontal cortex and anterior cingulate cortex was analyzed using the FreeSurfer. The patients with MDD showed significant hypergyria in the right rostral anterior cingulate cortex (P = 0.001), medial orbitofrontal cortex (P = 0.003), and frontal pole (P = 0.001). There was a significant genotype‐by‐diagnosis interaction for the local gyrification index in the right rostral anterior cingulate cortex (P = 0.003). Their study revealed significant hypergyria of the anterior cingulate cortex and prefrontal cortex and an interactive effect between the diagnosis of MDD and the genotype in the anterior cingulate cortex. This might be associated with the dysfunction of neural circuits mediating emotion processing, which could contribute to pathophysiology of MDD. Hum Brain Mapp 38:1299–1310, 2017. © 2016 Wiley Periodicals, Inc.

Background Use of mental health services (MHS) by people with suicidal ideation is critical in prevention of suicide, and identification of the factors that influence MHS use may assist in providing efficient interventions and treatments for suicidal individuals. Thus, we investigated the association between socioeconomic factors and use of MHS in people with suicidal ideation. Method We analyzed the data of the Fifth Korea National Health and Nutrition Examination Survey 2010–2012, a nationally representative cross-sectional study of the Korean population. Among the 24,173 people from the national health survey, we investigated the socioeconomic, clinical, and health-related characteristics of 2616 participants aged 19 years and older with suicidal ideation within the previous year. Results In the logistic regression analyses, after adjusting for potentially confounding factors, the odds ratio (OR) for nonuse of MHS was significant in the subjects aged 65 years or older (OR=4.90), aged 50–64 years (OR=2.11), with 10–12 years of education (OR=1.87), widowed (OR=2.75), with economic activity (OR=1.60), with an employment status of paid employee (OR=1.97), without depressive mood (OR=2.73), having not attempted suicide (OR=4.04), and with no reported problems in their usual activities (OR=2.17). Limitations We did not use standardized assessment tools to evaluate suicidal ideation and depressive mood. Conclusions We observed a significant influence of several socioeconomic factors, depressive mood, and suicide attempts on the MHS use of adults with suicidal ideation, based on a nationally representative sample of the Korean population.

Background Hippocampal volume loss is known as the best-replicated finding of structural brain imaging studies on major depressive disorder (MDD). Several evidences suggest localized mechanisms of hippocampal neuroplasticity lead the brain imaging studies on the hippocampus and MDD to perform analyses in the subfield level. The aim of this study was to investigate the differences in total and subfield hippocampal volumes, between medication-naive female MDD patients and healthy controls, through automated segmentation and volumetric methods. Methods Twenty medication-naive female patients diagnosed with MDD and 21 age-matched healthy controls, underwent T1-weighted structural magnetic resonance scanning. Total volumes of both hippocampi and subfield regions were calculated by the automated procedure for volumetric measures implemented in FreeSurfer and automated segmentation method by Van Leemput et al. Results We observed patients to have significantly smaller volumes of the left hippocampus, subiculum, cornu ammonis 2–3, cornu ammonis 4-dentate gyrus, and right subiculum compared to healthy controls. There were no significant predictors for these subfield region volumes among the illness burden-related parameters including duration of illness, number of depressive episodes, severity of depressive symptoms and memory performances. Limitations Our findings relied on the data of only female participants. Conclusions We found significant volume reductions in several hippocampal subfield regions in medication-naive female MDD patients. Our results are consistent with neurobiological evidences on hippocampal neuroplasticity in MDD, and replicate previous findings that suggest morphologic changes of hippocampal subfields in MDD patients.

Considerable evidence suggests a crucial role for the epigenetic regulation of brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD). However, the relationship between BDNF DNA methylation and white matter (WM) integrity in MDD has not yet been investigated. In the current study, we examined the association between the DNA methylation status of the BDNF promoter region and WM integrity in MDD. Sixty patients with MDD and 53 healthy controls underwent T1-weighted structural magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), to assess their WM integrity. BDNF DNA methylation at 4 CpG sites of the promoter region was also measured. As compared to healthy controls, the MDD group demonstrated reduced fractional anisotropy (FA) in the bilateral anterior and posterior corona radiata (ACR and PCR), genu of the corpus callosum, and the bilateral posterior thalamic radiations. We observed a significant inverse correlation between the DNA methylation of the BDNF promoter region and the FA of the right ACR in MDD patients. Our findings demonstrate a relationship between methylation of the BDNF promoter region and the integrity of the ACR, a key structural component of the emotional and cognitive control network involved in the pathophysiology of MDD. This correlation suggests that BDNF DNA methylation may contribute to structural WM changes in MDD patients.

Background DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. Methods We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed. Results In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2–3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas. Conclusions Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.

Background The uncertainty over the true morphological changes in brains with major depressive disorder (MDD) underlines the necessity of comprehensive studies with multimodal structural brain imaging analyses. This study aimed to evaluate the differences in cortical thickness, cortical and subcortical volume, and white matter integrity between first episode, medication-na�ve MDD patients and healthy controls. Methods Subjects with their first episode of MDD whose illness duration had not exceeded 6 months (n=20) were enrolled in this study and were compared to age-, sex-, and education level-matched healthy controls (n=22). All participants were subjected to T1-weighted structural magnetic resonance imaging (MRI). We used an automated procedure of FreeSurfer and Tract-based spatial statistics (TBSS) to analyze differences in cortical thickness, cortical and subcortical volume, and white matter integrity between two groups. Results The patients with first episode MDD exhibited significantly reduced cortical volume in the caudal anterior cingulate gyrus (P

Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed. Thirty-five medication-naive patients with MDD (mean age: 40.34, male/female: 10/25) and age, gender and education level matched 49 healthy controls (mean age: 41.12, male/female: 15/34) underwent DTI. SLC6A4 DNA methylation was also measured at five CpG sites of the promoter region, and the cell type used was whole-blood DNA. Patients with MDD had significantly lower fractional anisotropy (FA) values for the genu of the corpus callosum and body of the corpus callosum than that in healthy controls (family-wise error corrected, Pr=−0.493, P=0.003) and axial diffusivity (CpG3, Pearson's correlation: r=−0.478, P=0.004) values of the body of the corpus callosum in patients with MDD. These results contribute to evidence indicating an association between epigenetic gene regulation and structural brain alterations in depression. Moreover, we believe this is the first report of a correlation between DNA methylation of the SLC6A4 promoter region and white matter integrity in patients with MDD.