Abstract
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.
Highlights
Depression is characterised by depressed mood and/or a loss of interest or pleasure that may adversely affect one’s daily work, hobbies and general health, and it is a worldwide mental health disorder
Brundin et al found that hypocretin levels in the cerebrospinal fluid (CSF) from suicidal patients with major depressive disorder (MDD) were reduced compared with patients suffering from adjustment disorder or dysthymia with suicide attempts [13]
We observed a significant difference (K-W: P < 0.001, Figure 1A), in that plasma hypocretin-1 levels were significantly higher in MDD [59.04 (35.78–80.12) pg/ml] and bipolar disorder (BD) [65.50 (58.46–74.57) pg/ml] patients than in controls [49.25 (28.51–80.40) pg/ml]
Summary
Depression is characterised by depressed mood and/or a loss of interest or pleasure that may adversely affect one’s daily work, hobbies and general health, and it is a worldwide mental health disorder. Hypocretin studies were focused on the regulation of sleep-wake function and narcolepsy [4,5,6], but recent studies have suggested that hypocretin plays a further role in depression, emotion processing, energy homeostasis, reward-seeking behaviour, and the regulation of endocrine functions [7,8,9]. It is interesting to note that the functions mentioned above are severely affected in depressed patients, and hypocretinexpressing neuron or hypocretin level changes seem to vary widely among experimental studies in rodents and humans [10]. Our postmortem study showed that hypocretin1-expressing neurons were increased in depression patients compared with controls [11]. A recent plasma study reported lower hypocretin-1 levels in bipolar disorder (BD) patients than in controls, but no association was detected between plasma hypocretin-1 levels and any clinical symptoms, depression severity, or medication doses [12]. Brundin et al found that hypocretin levels in the cerebrospinal fluid (CSF) from suicidal patients with major depressive disorder (MDD) were reduced compared with patients suffering from adjustment disorder or dysthymia with suicide attempts [13]
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