Page 47 - GPD-4-2

Gene & Protein in Disease Orexin in depression

with the CTQ total score and some CTQ subscale scores, disease. Preclinical studies indicate that the orexin
such as emotional neglect. In the control group, the scores neuropeptide system influences wakefulness and various
for emotional neglect positively correlated with serum behaviors using a network of axons that project from the
orexin levels. Meanwhile, there were no notable differences hypothalamus to multiple, sometimes distant, regions
in serum orexin and cortisol levels between patients and of the brain. Different forms of incoming information
controls, suggesting that orexin levels are associated with are integrated by orexin neurons and transformed into
childhood abuse and not with psychopathology such as the necessary behavioral output in conjunction with
depression or anxiety. appropriate arousal state. 82
Although the orexin system regulates mood and Narcolepsy is caused by the depletion of hypothalamic
stress responses, its role in adolescent depression remains orexin-producing cells. 83 Individuals diagnosed
underexplored. Comprehensive data on age-specific with narcolepsy had undetectable levels of OXA in
orexin expression patterns present a remarkable gap in their cerebrospinal fluid and frequently experienced
the literature, particularly for the developmental changes comorbid depression. 84-87 Patients with depression and
in the orexin system. Additional experiments into targeted narcolepsy have short rapid eye movement sleep latency.
therapeutic strategies for age-related depressive disorders A previous study evaluated OXA levels in 15 individuals
are required to fill this gap. with depression and 14 controls. Under entrained
Furthermore, the impact of sex differences on orexin light–dark circumstances, the cerebrospinal fluid was
signaling and depression has been documented, with continuously extracted from supine participants for 24 h
studies indicating that inherent differences in the orexin using an indwelling intrathecal catheter. Patients with
system may contribute to the higher prevalence of depression were examined before and after receiving the
88
depression in women. Women with depression exhibit antidepressants sertraline and bupropion for 5 weeks.
80
significantly higher levels of orexin-immunoreactivity (ir) Results showed slight changes in OXA levels (10%) in the
than men with depression. Moreover, the daily fluctuation control group; however, the levels remarkably changed
pattern identified in the hypothalamic orexin-ir was throughout the day and night cycle and notably decreased
not detected in individuals with depression. Men with in patients with depression (3%). The levels were the lowest
depression who died by suicide exhibited substantially at noon, which was surprising for a hypothetical peptide
increased OX2R-mRNA expression in the anterior that promotes sobriety. The average level of hypothalamic
cingulate cortex compared with men in control. This secretion was higher in patients with depression than in
finding suggests the need to consider the definite sex- control subjects. After treatment with both drugs, the OXA
related alteration observed in the hypothalamus OXA-ir in level in the sertraline group showed a slight but notable
depression in the development of orexin-targeted therapy decrease (14%), whereas the bupropion group showed no
methods. 81 changes in OXA levels. Sertraline is a selective serotonin
To summarize, the relationship between the orexin reuptake inhibitor that primarily acts on the serotonin
system and depression is an emerging research field. Current system. 89,90 Because an interaction exists between the
studies primarily focus on investigating their correlation, serotonin system and orexin neurons, sertraline may
whereas there is a lack of intervention studies targeting the indirectly affect the release of OXA by regulating serotonin
91
orexin system. Future research could utilize longitudinal levels. Bupropion primarily acts on the noradrenergic
study designs to track changes in orexin levels over time and dopaminergic systems, with minimal direct impact on
92
and evaluate their causal relationship with the onset and the serotonin system. Hence, bupropion and sertraline
progression of depression. In addition, incorporating may affect OXA levels differently. These data are consistent
techniques such as neuroimaging and neurophysiology with physiological findings on depression, indicating that
could provide insights into the relationship from different the diurnal changes in OXA levels are inhibited.
perspectives by tracking changes in the orexin system The states of sleep and wakefulness emerge from the
during the onset, progression, and treatment of depression intricate interactions within the sleep–wake circuitry.
93
and revealing its dynamic mechanisms of action. Drowsiness is caused by long-term signaling abnormalities
5. Orexin- and depression-related in orexin neurons, which are most active when awake and
silent when inactive. Kleine–Levin syndrome (KLS) is a
94
neurological diseases rare recurrent drowsiness disorder. In a clinical evaluation,
The orexin receptor pathway plays a role in the 44 of 57 individuals with recurrent drowsiness fulfilled
pathophysiology of various nervous system disorders, such the behavioral and clinical requirements for KLS. In a
as drug addiction, narcolepsy, depression, and Alzheimer’s subgroup of individuals, the diurnal blood pressure and

Volume 4 Issue 2 (2025) 11 doi: 10.36922/gpd.4210