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Abstract 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.

Abstract 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.

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.

BackgroundAlthough 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.MethodsThis 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.DiscussionThe 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 registrationhttps://clinicaltrials.gov/ct2/show/NCT05312203, identifier 2021GR0585.

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.

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.

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.