Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

BACKGROUND: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. METHODS: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. RESULTS: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). CONCLUSION: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

Integration of whole-exome sequencing and structural neuroimaging analysis in major depressive disorder: a joint study.

Major depressive disorder (MDD) is a common mental illness worldwide and is triggered by an intricate interplay between environmental and genetic factors. Although there are several studies on common variants in MDD, studies on rare variants are relatively limited. In addition, few studies have examined the genetic contributions to neurostructural alterations in MDD using whole-exome sequencing (WES). We performed WES in 367 patients with MDD and 161 healthy controls (HCs) to detect germline and copy number variations in the Korean population. Gene-based rare variants were analyzed to investigate the association between the genes and individuals, followed by neuroimaging-genetic analysis to explore the neural mechanisms underlying the genetic impact in 234 patients with MDD and 135 HCs using diffusion tensor imaging data. We identified 40 MDD-related genes and observed 95 recurrent regions of copy number variations. We also discovered a novel gene, FRMPD3, carrying rare variants that influence MDD. In addition, the single nucleotide polymorphism rs771995197 in the MUC6 gene was significantly associated with the integrity of widespread white matter tracts. Moreover, we identified 918 rare exonic missense variants in genes associated with MDD susceptibility. We postulate that rare variants of FRMPD3 may contribute significantly to MDD, with a mild penetration effect.

Association Between White Matter Tract Integrity and Frontal-Executive Function in Non-Geriatric Adult Patients With Major Depressive Disorder.

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

Suicide death and other-cause mortality in psychiatric patients: A South Korean study using nationwide claims data.

INTRODUCTION: It is well-known that suicide and excess mortality are high in patients with psychiatric illnesses and this has long been an important issue in the field of mental health. We aim to investigate suicide and other-cause deaths in patients with psychiatric illnesses. METHODS: This retrospective, population-based cohort was based on the National Health Insurance claims data of the first admission with a principal diagnosis of major psychiatric disorder between 2010 and 2011, and followed up to 2020. A total of 95,855 participants were enrolled. Suicide and other-cause mortality were assessed through Log-rank test and Kaplan-Meier curve. RESULTS: There were 95,855 patients, with an average age of 48.2 years. The number of suicide deaths and other-cause deaths was 2408 (288.1 per 100,000 person-years) and 15,192 (1817.6 per 100,000 person-years), respectively. The rate of healthcare utilization prior to suicide was 95.0 %, and the rate of utilization prior to one week before suicide was 43.5 %. The risk of suicide was highest in patients with depression, followed by alcohol use disorder, schizophrenia, and bipolar disorder. CONCLUSIONS: This study revealed various factors related to healthcare utilization associated with suicide and other-cause deaths in psychiatric patients. Educating frontline healthcare professionals, psychiatrists, emergency department personnel, and general practice doctors using such as Gatekeeper program is important to prevent suicides.

A structural equation modeling approach using behavioral and neuroimaging markers in major depressive disorder.

Major depressive disorder (MDD) has consistently proven to be a multifactorial and highly comorbid disease. Despite recent depression-related research demonstrating causalities between MDD-related factors and a small number of variables, including brain structural changes, a high-statistical power analysis of the various factors is yet to be conducted. We retrospectively analyzed data from 155 participants (84 healthy controls and 71 patients with MDD). We used magnetic resonance imaging and diffusion tensor imaging data, scales assessing childhood trauma, depression severity, cognitive dysfunction, impulsivity, and suicidal ideation. To simultaneously evaluate the causalities between multivariable, we implemented two types of MDD-specified structural equation models (SEM), the behavioral and neurobehavioral models. Behavioral SEM showed significant results in the MDD group: Comparative Fit Index [CFI] = 1.000, Root Mean Square Error of Approximation [RMSEA]) = 0.000), with a strong correlation in the scales for childhood trauma, depression severity, suicidal ideation, impulsivity, and cognitive dysfunction. Based on behavioral SEM, we established neurobehavioral models showing the best-fit in MDD, especially including the right cingulate cortex, central to the posterior corpus callosum, right putamen, pallidum, whole brainstem, and ventral diencephalon, including the thalamus (CFI >0.96, RMSEA <0.05). Our MDD-specific model revealed that the limbic-associated regions are strongly connected with childhood trauma rather than depression severity, and that they independently affect suicidal ideation and cognitive dysfunction. Furthermore, cognitive dysfunction could affect impulsivity.

The effect of inflammation markers on cortical thinning in major depressive disorder: A possible mediator of depression and cortical changes.

BACKGROUND: Major depressive disorder (MDD) is a prevalent mental health condition with significant societal impact. Owing to the intricate biological diversity of MDD, treatment efficacy remains limited. Immune biomarkers have emerged as potential predictors of treatment response, underscoring the interaction between the immune system and the brain. This study investigated the relationship between cytokine levels and cortical thickness in patients with MDD, focusing on the corticolimbic circuit, to elucidate the influence of neuroinflammation on structural brain changes and contribute to a deeper understanding of the pathophysiology of MDD. METHOD: A total of 114 patients with MDD and 101 healthy controls (HC) matched for age, sex, and body mass index (BMI) were recruited. All participants were assessed for depression severity using the Hamilton Depression Rating Scale (HDRS), and 3.0 T T1 weighted brain MRI data were acquired. Additionally, cytokine levels were measured using a highly sensitive bead-based multiplex immunosorbent assay. RESULTS: Patients diagnosed with MDD exhibited notably elevated levels of interleukin-6 (p = 0.005) and interleukin-8 (p = 0.005), alongside significant cortical thinning in the left anterior cingulate gyrus and left superior frontal gyrus, with these findings maintaining significance even after applying Bonferroni correction. Furthermore, increased interleukin-6 and interleukin-8 levels in patients with MDD are associated with alterations in the left frontomarginal gyrus and right anterior cingulate cortex (ACC). CONCLUSIONS: This suggests a potential influence of neuroinflammation on right ACC function in MDD patients, warranting longitudinal research to explore interleukin-6 and interleukin-8 mediated neurotoxicity in MDD vulnerability and brain morphology changes.

Trends in telemedicine utilization for mental illness during the COVID-19 pandemic: an analysis of a nationwide database in Korea.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has worsened mental health and reduced access to mental health services. During the pandemic, the demand for telemedicine has increased and related laws have been enacted. This study aimed to investigate telemedicine use for cases of major mental illnesses during the COVID-19 pandemic and to compare the characteristics of patients who received telemedicine service with those of patients who received in-person care. METHODS: This population-based, cross-sectional, observational study was based on health insurance claims data, and included 2,749,872 patients who received outpatient treatment for mental illness from February 24, 2020 to June 30, 2022. Logistic regression was performed to assess the relationships between patient characteristics and telemedicine service use. Patients who received telemedicine services were analyzed in subgroups of each mental illness. RESULTS: During the study period, 80,157 patients (2.9%), with an average age of 63 years, received at least one telemedicine treatment. There was a predominance of women and medical aid recipients. The lowest proportion of telemedicine treatments was for depression (2.1%), and the highest was for dementia (6.7%). The proportion of patients receiving telemedicine in long-term care hospitals was high (22.6%), with the highest odds ratio (OR) (5.84), compared with that in tertiary or general hospitals, followed by that in psychiatric hospitals and clinics. The proportions were high in the departments of internal medicine, neurology, and psychiatry. Patients aged > 80 years received most telemedicine treatment (OR: 1.23) across all diagnoses. Cases of dementia and other mental disorders had higher ORs (2.60 and 2.36, respectively) compared with cases of depression. Except for dementia and behavioral/emotional disorders, hospitalization increased the probability of telemedicine treatment. Comorbidities were positively associated with telemedicine treatment. CONCLUSIONS: Older people and people with other physical illnesses were more likely to use telemedicine treatments temporarily provided during the pandemic. Telemedicine maintained continuity of treatment for patients with dementia and severe mental illnesses. Telemedicine can be useful for filling the medical gaps for vulnerable populations other than those with mild mental illnesses. This aspect should be considered for the future establishment of telemedicine systems.

COVID-19 Pandemic-Related Job Loss Impacts on Mental Health in South Korea.

OBJECTIVE: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support. METHODS: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire-9, General Anxiety Disorder-7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed. RESULTS: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway. CONCLUSION: COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Correlation between immune-related genes and depression-like features in an animal model and in humans.

A growing body of evidence suggests that immune-related genes play pivotal roles in the pathophysiology of depression. In the present study, we investigated a plausible connection between gene expression, DNA methylation, and brain structural changes in the pathophysiology of depression using a combined approach of murine and human studies. We ranked the immobility behaviors of 30 outbred Crl:CD1 (ICR) mice in the forced swim test (FST) and harvested their prefrontal cortices for RNA sequencing. Of the 24,532 analyzed genes, 141 showed significant correlations with FST immobility time, as determined through linear regression analysis with p ≤ 0.01. The identified genes were mostly involved in immune responses, especially interferon signaling pathways. Moreover, induction of virus-like neuroinflammation in the brains of two separate mouse cohorts (n = 30 each) using intracerebroventricular polyinosinic:polycytidylic acid injection resulted in increased immobility during FST and similar expression of top immobility-correlated genes. In human blood samples, candidate gene (top 5%) expression profiling using DNA methylation analysis found the interferon-related USP18 (cg25484698, p = 7.04 × 10-11, Δß = 1.57 × 10-2; cg02518889, p = 2.92 × 10-3, Δß =  - 8.20 × 10-3) and IFI44 (cg07107453, p = 3.76 × 10-3, Δß =  - 4.94 × 10-3) genes to be differentially methylated between patients with major depressive disorder (n = 350) and healthy controls (n = 161). Furthermore, cortical thickness analyses using T1-weighted images revealed that the DNA methylation scores for USP18 were negatively correlated with the thicknesses of several cortical regions, including the prefrontal cortex. Our results reveal the important role of the interferon pathway in depression and suggest USP18 as a potential candidate target. The results of the correlation analysis between transcriptomic data and animal behavior carried out in this study provide insights that could enhance our understanding of depression in humans.

Decreased cortical gyrification in major depressive disorder.

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.

Gray and white matter abnormalities in major depressive disorder patients and its associations with childhood adversity.

OBJECTIVE: Early life stress of childhood adversity (CA) may result in major depressive disorder (MDD) by sensitizing individuals to proximal stressors in life events. The neurobiological changes that underlie adult depression may result from the absence of proper care and supervision of caregivers. We aimed to find both gray and white matter abnormalities in MDD patients, who reported the experiences of CA. METHODS: The present study examined cortical alterations in 54 patients with MDD and 167 healthy controls (HCs) using voxel-based morphology and fractional anisotropy (FA) tract-based spatial statistics (TBSS). Both patients and HCs were administered the self-questionnaire clinical scale (the Korean translation of the Childhood Trauma Questionnaire CTQK). Pearson's correlation analysis was performed to find the associations between FA and CTQK. RESULTS: The MDD group showed a significant decrease in gray matter (GM) in the left rectus at both the cluster and peak levels after family-wise error correction. The TBSS results showed significantly reduced FA in widespread regions, including the corpus callosum (CC), superior corona radiata, cingulate gyrus, and superior longitudinal fasciculus. The CA was negatively correlated with the FA in CC and crossing pontine tract. CONCLUSION: Our findings demonstrated GM atrophy and white matter (WM) connectivity changes in patients with MDD. The major findings of the widespread FA reduction in WM provided the evidence of brain alterations in MDD. We further propose that the WM would be vulnerable to emotional, physical, and sexual abuse in early childhood during the brain development.

Childhood Sexual Abuse and Cortical Thinning in Adults With Major Depressive Disorder.

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.

Investigating the effectiveness of a smart mental health intervention (inMind) for stress reduction during pharmacological treatment for mild to moderate major depressive disorders: Study protocol for a randomized control trial.

Background: Although psychological interventions for stress relief, such as cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR), have been developed, they have not been widely used in treating depression. The use of mobile devices can increase the possibility of actual use by integrating interventions and reducing the difficulty and cost burden of treatment application. This study aims to determine whether "inMind," an integrated mobile application for stress reduction, developed for the general population, decreases stress for patients with mild to moderate major depressive disorder during the pharmacological treatment period. Methods: This study is a single-blind, multicenter, randomized, controlled crossover trial. The App, developed in Republic of Korea, provides integrated interventions for stress reduction for the general population through three modules based on mindfulness-based stress reduction, cognitive behavior therapy, and relaxation sounds that are known to be effective in stress reduction ("meditation," "cognitive approach," and "relaxation sounds," respectively). Participants (n = 215) recruited via medical practitioner referral will be randomized to an App first group (fAPP) or a wait list crossover group (dAPP). The study will be conducted over 8 weeks; the fAPP group will use the App for the first 4 weeks and the dAPP group for the next 4 weeks. During all study periods, participants will receive their usual pharmacological treatment. The Depression Anxiety Stress Scale-21 is the primary outcome measure. The analysis will employ repeated measurements using a mixed-model approach. Discussion: The App can potentially be an important addition to depression treatment because of its applicability and the comprehensive nature of the interventions that covers diverse stress-relieving models. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT05312203, identifier 2021GR0585.

Changes in mental health service utilization before and during the COVID-19 pandemic: a nationwide database analysis in Korea.

OBJECTIVES: The present study examined the impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health service utilization through a comparative analysis of nationwide data regarding inpatient care users, outpatient visits, emergency department (ED) visits, and admissions via the ED before and during the pandemic. METHODS: Data from approximately 350,000 Koreans diagnosed with mental illness were analyzed in terms of hospitalization, outpatient visits, and ED visits between January 2018 and June 2021. An interrupted time series analysis was conducted to determine the significance of changes in mental health service utilization indicators. RESULTS: The number of hospital admissions per patient decreased by 1.2% at the start of the pandemic and 0.7% afterward. The length of hospital stay increased by 1.8% at the outbreak of the pandemic, and then decreased by 20.2%. Although the number of outpatients increased, the number of outpatient visits per patient decreased; the number of outpatient visits for schizophrenia (3.4%) and bipolar disorder (3.5%) significantly decreased immediately post-outbreak. The number of ED visits per patient decreased both immediately post-outbreak and afterward, and ED visits for schizophrenia (19.2%), bipolar disorder (22.3%), and depression (17.4%) decreased significantly immediately post-outbreak. Admissions via the ED did not show a significant change immediately post-outbreak. CONCLUSIONS: Mental health service utilization increased during the pandemic, but medical service use decreased overall, with a particularly significant decrease in ED utilization. As the pandemic worsened, the decline in outpatient visits became more pronounced among those with severe mental illness.

Childhood abuse and cortical gray matter volume in patients with major depressive disorder.

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.

The Association of White Matter Tracts with Alexithymia among Individuals with Major Depressive Disorder.

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.

Reduced Sulcal Depth in Central Sulcus of Major Depressive Disorder.

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.

Association Between the C4 Binding Protein Level and White Matter Integrity in Major Depressive Disorder.

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.

Shape analysis of the subcortical structures in North Korean refugees with post-traumatic stress disorder and major depressive disorder.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder.

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.