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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. 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. 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 = 0.361; = 1.78 × 10 ). 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. These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.

Abstract Study Objectives To investigate the association between weekend catch-up sleep (WCS) and the levels of high-sensitivity C-reactive protein (hsCRP)—a serum inflammatory maker—in adults Methods Data 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. Results The 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. Conclusions Our 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.

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.

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.

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. 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. 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. 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.

Suicide is a major challenge in public health and is strongly associated with major depressive disorder (MDD). Despite recent neuroimaging developments, the neural correlates of suicide behavior in patients with MDD remain unclear. Independent component analysis (ICA) for neuroimaging data allows the identification of functional brain networks without prior regions of interest and may help to identify neurobiological markers of specific disorders. Using ICA, we investigated the differences in resting-state brain networks in patients with MDD who had or did not have a history of suicide attempts and in healthy controls (HCs). Suicidal depressed (SD) patients, non-suicidal depressed (NSD) patients, and HCs significantly differed from each other in the pattern of connectivity of multiple functional networks, network synchronization, and functional network connectivity (FNC). The patient groups had a decreased network synchronization in the insular, cerebellum, basal ganglia, thalamus, operculum, frontoparietal cortices, and sensory cortices relative to the HCs. The decreased FNC between these networks (insular–default mode network and insular–cerebellum) was found in the SD group compared to the NSD and HC groups. These differences were not related to illness duration and medication status differences between SD and NSD. Furthermore, the degree of FNC in these networks was associated with the suicide ideation and stress level. Our results demonstrated that widespread but discrete network changes in brain networks and their interconnectivity was associated with suicide attempts in patients with MDD. Our results suggest that the neural basis underlying the psychopathology of attempted suicide in patients with MDD involves multiple brain networks and their interaction.

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.

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. 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. 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 ( , , , , , and ). 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.

This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18–65 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy.

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. 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. 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. 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.