Abstract
Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p<0.001). CSF orexin A concentration showed a correlation with Mini-Mental State Examination scores, drug assumption, history of compulsive behaviour and extrapyramidal signs. Moreover, we found a relationship between CSF markers of neurodegeneration, total tau and Aβ1–42 and CSF orexin A concentrations. Our study provides evidence of an orexinergic dysfunction in bvFTD, correlating with several clinical symptoms. Further larger studies are needed to confirm our data.
Highlights
Behavioural variant frontotemporal dementia is the most common clinical variant within the spectrum of Fausto Roveta, Andrea Marcinnò, Alessandro Mauro and Innocenzo Rainero contributed to this work.Orexins are two neuropeptides synthesized by hypothalamic neurons with widespread projections throughout the central nervous system
We found increased cerebrospinal fluid (CSF) orexin A concentrations in Behavioural variant frontotemporal dementia (bvFTD) patients compared to controls, and this resulted statistically significant (p < 0.001) (Fig. 1), when adjusted for age and sex (p < 0.001)
Several clinical and demographic variables emerged as significantly linked to CSF orexin A concentrations in the bvFTD group (Table 1)
Summary
Behavioural variant frontotemporal dementia (bvFTD) is the most common clinical variant within the spectrum of Fausto Roveta, Andrea Marcinnò, Alessandro Mauro and Innocenzo Rainero contributed to this work. Orexins (orexin A and orexin B) are two neuropeptides synthesized by hypothalamic neurons with widespread projections throughout the central nervous system. Orexins regulate several physiological functions, like appetite, arousal, cognition, stress, sleep and metabolism. Several studies suggested a role for orexins in psychiatric disorders, including addiction, depression and anxiety [2]. The modulation of the orexinergic system may have a role in sleep disorders as well as rehabilitation of traumatic brain injury [3]. Some studies evaluated cerebrospinal fluid (CSF) orexin levels in Alzheimer’s disease (AD), finding a high level of orexin A that correlates with AD progression, sleep fragmentation and neuropsychiatric symptoms [4]
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