Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers

Development of a Suicide Prediction Model for the Elderly Using Health Screening Data

Suicide poses a serious problem globally, especially among the elderly population. To tackle the issue, this study aimed to develop a model for predicting suicide by using machine learning based on the elderly population. To obtain a large sample, the study used the big data health screening cohort provided by the National Health Insurance Sharing Service. By applying a machine learning technique, a predictive model that comprehensively utilized various factors was developed to select the elderly aged > 65 years at risk of suicide. A total of 48,047 subjects were included in the analysis. Individuals who died by suicide were older, and the number of men was significantly greater. The suicide group had a more prominent history of depression, with the use of medicaments significantly higher. Specifically, the prescription of benzodiazepines alone was associated with a high suicide risk. Furthermore, body mass index, waist circumference, total cholesterol, and low-density lipoprotein level were lower in the suicide group. We developed a model for predicting suicide by using machine learning based on the elderly population. This suicide prediction model can satisfy the performance to some extent by employing only the medical service usage behavior without subjective reports

Cortical thickness, cortical and subcortical volume, and white matter integrity in patients with their first episode of major depression

BackgroundThe 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-naïve MDD patients and healthy controls.MethodsSubjects 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.ResultsThe patients with first episode MDD exhibited significantly reduced cortical volume in the caudal anterior cingulate gyrus (

Association between Glucocorticoid Receptor Methylation and Hippocampal Subfields in Major Depressive Disorder

<div><p>Background</p><p>DNA methylation in the promoter region of the glucocorticoid receptor gene (<i>NR3C1</i>) is closely associated with childhood adversity and suicide. However, few studies have examined <i>NR3C1</i> methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between <i>NR3C1</i> methylation and structural brain alterations in MDD in comparison with healthy controls.</p><p>Methods</p><p>We compared the degree of <i>NR3C1</i> promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among <i>NR3C1</i> promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>Lower methylation in the <i>NR3C1</i> 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 <i>NR3C1</i> methylation.</p></div