The
orexins (
hypocretins) are
neuropeptides deriving from the lateral hypothalamus and may be of importance within the context of drug craving, withdrawal, and relapse. Therefore, the
orexin A expression and promoter methylation in peripheral blood cells of 68 patients (41 male and 27 female patients at three different time points during withdrawal and 27 patients during stationary dehabituation
therapy) suffering from
alcohol dependence were assessed by quantitative reverse transcription-polymerase chain reaction and
bisulfite sequencing. There was a statistically significant difference of
orexin A expression between the three time points of withdrawal and long-term (LT) abstinence (F=4.16, P=.011). This difference was most prominent in comparison with LT abstinence (t=-3.08, P=.0032). Expression was significantly associated with the severity of
withdrawal symptoms measured with the Withdrawal Syndrome Scale for Alcohol and Related
Psychoactive Drugs (WSA) (t=2.17, P=.0356). The stronger the
withdrawal symptoms, the lower the
orexin A expression (F=4.69, P=.036). Body mass index (t=2.15, P=.041), the severity of withdrawal measured with the WSA (t=2.595, P=.0133), craving measured either by the Obsessive Compulsive Drinking Scale (t=2.77, P=.0085) or the Lübecker Craving Questionnaire (t=-2.23, P=.0314) had a significant influence on
orexin A expression taking into account mean methylation of the CpG island of the
orexin A promoter during withdrawal.
Orexin A may be a possible candidate to further elucidate mechanisms of alcohol withdrawal taking into account energy homoeostasis in the circuit of reward and motivation.