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Gene & Protein in Disease Orexin in depression

OXA levels in the cerebrospinal fluid were evaluated in concentrations in patients with BD, schizophrenia, or
relapse versus remission. The heart rate and blood pressure MDD differ from those in the healthy control group.
fluctuated during the symptomatic phase and were lower Moreover, a potential relationship between plasma
during remission, suggesting an involvement of orexin OXA levels and clinical characteristics was investigated
dysregulation in KLS pathogenesis. To investigate the in a study of 80 healthy controls, 80 patients with
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correlation between OXA and sleep in obese patients, schizophrenia, 80 patients with MDD, and 40 patients with
orexin content and sleep were evaluated in 26 participants BD. Plasma OXA levels were measured using an enzyme-
with obesity, 40 participants who were pathologically linked immunosorbent assay, showing that the mean
obese, and 32 normal weight participants. Structural OXA levels of the four diagnostic groups considerably
equation modeling revealed that plasma OXA levels were varied. Specifically, patients with BD had far lower levels
associated with decreased overall sleep quality. The results of OXA than controls. The study found no correlation
support a link between high plasma OXA concentrations between plasma OXA levels and pharmaceutical dosages,
and insufficient sleep, which may exacerbate depression. 96 depression severity, or any clinical symptoms, implying
An increasing body of research link orexin disturbances that patients with BD had lower plasma OXA levels. 99,100
to a number of neuropsychiatric conditions, such as According to research, the symptoms of Parkinson’s
addiction, anxiety, and depression. Several psychiatric disease frequently include sadness, hallucinations,
conditions share similarities with the behavioral variant sleeplessness at night, daytime sleep episodes, and rapid eye
frontotemporal dementia (bvFTD) syndrome. A study movement sleep behavior disorder. Narcolepsy presents
evaluated the OXA concentrations in the cerebrospinal various symptoms related to a specific depletion of orexin
fluid of 40 patients with bvFTD and 32 non-demented neurons. A previous study investigated the functionality of
individuals and correlated them with various clinical the orexin system in individuals with Parkinson’s disease
features. There was a remarkable elevation in OXA to determine any potential dysfunction in orexin cells. The
concentrations among patients with bvFTD compared hypothalamus of 11 patients with Parkinson’s disease and
with those in the control. OXA concentrations in the 5 normal controls was examined, revealing that the loss of
cerebrospinal fluid correlated with the Mini-Mental State hypothalamic secretin cells increased with the progression
Examination scale score, medication hypothesis, history of of the disease. Similarly, the loss of MCH cells increased
compulsive behavior, and extrapyramidal signs. These data as the illness worsened. The entire anterior to posterior
provide evidence of orexin dysfunction in patients with region of the hypothalamus distribution showed a loss of
bvFTD associated with depression. 97 orexin and MCH cells. A significant loss of orexin neurons

Orexin exerts considerable effects on the is a hallmark of Parkinson’s disease. Therefore, therapies
neurophysiological and behavioral aspects of emotional targeted at correcting orexin deficiencies can mitigate
illnesses. However, there is limited research on alterations in depression, which may be caused by the loss of orexin
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orexin levels among individuals with emotional problems. cells.
In one study, the plasma level of OXA was measured in To summarize, dysfunction of the orexin system is
individuals with mood disorders and a control group using manifested in various neurological disorders, providing a
the enzyme-linked immunosorbent assay. Patients with scientific basis for the development of treatments targeting
bipolar disorder (BD) and MDD showed considerably depression and related neurological diseases. Considering
higher plasma levels of OXA. Moreover, plasma OXA levels the overlap between the inflammatory processes of
of the BD group were remarkably higher than those of the depression and neurodegenerative disorders, the current
MDD group. Individuals in the MDD group who thought research lacks exploration into the bidirectional relationship
about suicide more often had higher OXA levels than those between orexin signaling and neuroinflammation.
who thought about suicide less frequently. Thus, the
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distinct variations in plasma OXA levels might differentiate 6. Regulatory process of depression
between MDD and BD and diagnose depression. The mediated by orexin
distinct alterations in OXA levels associated with suicidal The orexin/receptor system is essential for regulating
ideation in depression may prevent suicidal behavior and various physiological functions such as sleep–wake
is considerable in the ongoing research on orexin-targeted cycles, reward processing, feeding behavior, addiction,
therapeutics. 98 and energy balance. The regulation of energy expenditure
The pathophysiology of mental illnesses has been is related to the active hypothalamic nerve mechanism
associated with changes in the orexin system. There that controls adaptive stimulation. Extensive research
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have been attempts to determine whether plasma orexin has demonstrated the participation of orexin/receptor

Volume 4 Issue 2 (2025) 12 doi: 10.36922/gpd.4210