Increased Hypocretin (Orexin) Plasma Level in Depression, Bipolar Disorder Patients

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.

Role of Vitamin E and the Orexin System in Neuroprotection

“…Furthermore, and of fundamental importance, they play an important role in neuroprotection by inhibiting oxidative stress and the inflammatory response through their type 1 and 2 receptors (OX1R and OX2R). In particular, some studies show that treatment with orexin A reduces the secretions of IL-1β, IL-6 and IL-8, as well as the production of reactive oxygen species (ROS) [35], which is why hypocretins may play a direct role in neurodegenerative diseases including PD and AD, although these mechanisms are less well known [36]. The functions of orexins prove to be different because of the multiple pathways involved, one of the main functions of orexin is neuroprotection [37].…”

Predictive efficiency of phoenixin, spexin and kisspeptin neuropeptides concentration levels in diagnosis of bipolar disorder in paediatric population

“…Nie jest też wykluczone, że nasilenie lęku w godzinach porannych może mieć związek z okołodobowymi zmianami ekspresji somatostatyny w ciele migdałowatym [8]. W przypadku oreksyn, neuropeptydów podwzgórzowych o szerokim spektrum czynnościowym, wyniki oznaczeń są jednak sprzeczne, zaobserwowano bowiem zarówno spadek, jak i wzrost poziomu oreksyny A w surowicy pacjentów z ChAD [9,10]. Najnowsze badania ujawniły wszakże obniżony poziom oreksyny A, greliny i NPY u pacjentów z ChAD oraz depresją w stosunku do kontroli.…”

Orexin/Hypocretin System Dysfunction in ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations)

“…12,24,46 These include depressive and anxiety disorders, sleep and eating disorders, substance addictions, and posttraumatic stress disorder; whereas changes in orexin levels have been reported in depressive and bipolar disorders, narcolepsy, age-related cognitive decline, anorexia nervosa (AN), ADHD, schizophrenia, and neurodegenerative brain diseases, such as Parkinson's disease, Alzheimer's disease (AD), Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. 12,13,24,25,27,32,38,46,[54][55][56] The Orx-S is also involved in metabolic syndrome, chronic inflammations, and cancers; moreover, orexin has a proposed role on "inverse comorbidity between cancer and neurodegenerative disorders". 32,56 The Orx-S is a potential therapeutic target for several disorders.…”