Major depression, because of its recurring and life-threatening nature, is one of the top 10 diseases for global disease burden. Major depression is still diagnosed on the basis of clinical symptoms in patients. The search for specific biological markers is of great importance to advance the method of diagnosis for depression. We examined the methylation profile of 2 CpG islands (I and IV) at the promoters of the brain-derived neurotrophic factor (BDNF) gene, which is well known to be involved in the pathophysiology of depression. We analyzed genomic DNA from peripheral blood of 20 Japanese patients with major depression and 18 healthy controls to identify an appropriate epigenetic biomarker to aid in the establishment of an objective system for the diagnosis of depression. Methylation rates at each CpG unit was measured using a MassArray® system (SEQUENOM), and 2-dimensional hierarchical clustering analyses were undertaken to determine the validity of these methylation profiles as a diagnostic biomarker. Analyses of the dendrogram from methylation profiles of CpG I, but not IV, demonstrated that classification of healthy controls and patients at the first branch completely matched the clinical diagnosis. Despite the small number of subjects, our results indicate that classification based on the DNA methylation profiles of CpG I of the BDNF gene may be a valuable diagnostic biomarker for major depression.

We examined the utility of DNA methylation profiles at the CpG island of SLC6A4 (DMS) as a diagnostic biomarker for major depression (MD). In addition, the relationship between DMS and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) allele, the severity of symptoms, number of early adversities, and therapeutic responses to antidepressants were examined. Genomic DNA was extracted from peripheral blood of Japanese healthy controls and patients with MD before and after treatment. DMS was analyzed using a MassARRAY Compact System. The severity of depression was evaluated using the Hamilton Rating Scale for Depression, and early adversity was evaluated using the Early Trauma Inventory. We were unable to distinguish between and healthy controls, or between unmedicated patients and medicated patients using DMS. The 5-HTTLPR allele had no significant effect on DMS. The methylation rates for several CpGs differed significantly after treatment. Notably, the methylation rate of CpG 3 in patients with better therapeutic responses was significantly higher than that in patients with poorer responses. Although further studies examining the function of specific CpG units of SLC6A4 are required, these results suggest that the pre-treatment methylation rate of SLC6A4 is associated with therapeutic responses to antidepressants in unmedicated patients with MD.

The literature investigating the relationship between objective and subjective sleep in depressed patients is limited and the results are inconsistent. Furthermore, many factors that influence the aforementioned relationship have not been investigated. The present study was carried out to clarify the characteristics of self-estimation of sleep in depressed patients. Sleep was estimated concurrently using a sleep log and polysomnography for 5 consecutive days to investigate the relationship between subjective sleep estimation and objective sleep estimation in 23 patients with major depression ( Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised; DSM-III-R). Factors related to a discrepancy between both types of estimation were identified. The subjective total sleep time showed a significant, but moderate, positive correlation (correlation coefficient: 0.63) with the objective total sleep time. The degree of discrepancy was significantly correlated with various objective sleep variables and severity of depression. In the underestimation group in which the subjective total sleep time was shorter than the objective total sleep time, the objective total sleep time and slow-wave sleep time were shorter, age was greater and the extroversion score (Maudsley Personality Inventory) was lower than in the overestimation group in which the subjective total sleep time was longer than the objective total sleep time. The data suggest that subjective sleep estimation in depressed patients is influenced by their objective sleep, severity of depression, age and personality.

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