As hypocretin can markedly affect neurophysiological and behavioural processes in mood disorders. However, few studies have measured changes in hypocretin levels in patients with mood disorders. We estimated the hypocretin-1 plasma levels in mood disorder patients and controls (CON) using an enzyme-linked immunosorbent assay. Results: (i) The hypocretin-1 plasma level was significantly higher in major depressive disorder (MDD) patients [59.04 (35.78–80.12) pg/ml, P < 0.001] and bipolar disorder (BD) patients [65.50 (58.46–74.57) pg/ml, P < 0.001] patients than in CON [49.25 (28.51–80.40) pg/ml]. Moreover, the plasma hypocretin-1 levels in the BD group were significantly higher than those in the MDD group (P < 0.001). (ii). In the MDD group, patients with higher suicidal ideation had higher hypocretin-1 levels [62.09 (38.23–80.12) pg/ml] than those with lower suicidal ideation [59.63 (35.79–77.37) pg/ml), P = 0.032]. (iii). Plasma hypocretin-1 levels were increased in both female and male mood disorder patients compared to CON [male: MDD 60.51 (35.79–80.12) pg/ml; BD 65.40 (58.76–74.14) pg/ml; CON 45.63 (28.51–62.05) pg/ml; all P < 0.016; female: MDD 57.37 (34.59–80.40) pg/ml; BD 65.61 (58.46–74.57) pg/ml; CON 52.92 (38.23–78.89) pg/ml; all P < 0.015]. (iv). In CON, we found a significant negative correlation between plasma hypocretin-1 levels and age (rho = −0.251, P = 0.032), while this negative correlation was absent in the MDD and BD groups. Limitations may partly arise from the relatively small sample size and the medication history of patients participating in our research. We concluded that the clear changes found in plasma hypocretin-1 levels might be applied in the diagnosis of depression and the differential diagnosis of MDD and BD. The clear suicidal-ideation-related change found in hypocretin-1 levels in depression might be taken into account in the prevention of suicidal behaviour and further study of hypocretin-targeted therapies.
Psychiatric disorders are common, complex, and heritable conditions estimated to be the leading cause of disability worldwide. The last decade of research in genomics of psychiatry, performed by multinational, and multicenter collaborative efforts on hundreds of thousands of mental disorder cases and controls, provided invaluable insight into the genetic risk variants of these conditions. With increasing cohort sizes, more risk variants are predicted to be identified in the near future, but there appears to be a knowledge gap in understanding how these variants contribute to the pathophysiology of psychiatric disorders. Majority of the identified common risk single-nucleotide polymorphisms (SNPs) are non-coding but are enriched in regulatory regions of the genome. It is therefore of great interest to study the impact of identified psychiatric disorders' risk SNPs on DNA methylation, the best studied epigenetic modification, playing a pivotal role in the regulation of transcriptomic processes, brain development, and functioning. This work outlines the mechanisms through which risk SNPs can impact DNA methylation levels and provides a summary of current evidence on the role of DNA methylation in mediating the genetic risk of psychiatric disorders.