A Study of the Plasma Nociceptin/Orphanin FQ Levels in Children with Tourette Syndrome.
Date Issued
2009
Date
2009
Author(s)
Du, Jung-Chieh
Abstract
Tourette syndrome (TS), a common childhood-onset chronic neuropsychiatric disorder, is among spectrum of tic disorders. The cardinal features of TS are motor and phonic tics that wax and wane in severity. The pattern of inheritance in Tourette syndrome is polygenic with varied penetrance. Some TS patients have other co-morbidities, such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), self-injurious behaviors and sleep disturbances. The pathogenesis of tics or Tourette syndrome is not elucidated clearly so far. Abnormalities in basal ganglia, cortico-striato-thalamo-cortical circuits, dopaminergic systems and hypothalamic-pituitary-adrenal axis (HPA axis) are considered to be possabile mechanisms. Nociceptin/orphanin FQ (N/OFQ) is a kind of heptadecapeptide and its receptor—N/OFQ peptide receptor (NOP receptor)—distributes widely in human organs, especially central nervous system. Most dopominergic neurons express NOP receptors and activation of NOP receptors by N/OFQ reduces dopamine release. N/OFQ also modulates the activity of HPA axis. Based on previous facts, we propose that N/OFQ may play a role in the pathogenesis of tic or Tourette syndrome. Therefore, we conducted a study to investigate the plasma N/OFQ levels in children with TS or transient tic disorders (TTD) and normal children as controls. From Oct, 2007 to Oct, 2008, our study recruited 30 children with TS, 9 children with TTD and 10 children as normal controls. The diagnosis of TS or TTD was based on DSM-IV and patients’ severity of tic symptoms were evaluated by the Chinese edition of Yale Global Tic Severity Scales (YGTSS). We detected plasma N/OFQ levels by radioimmunoassay. Our study revealed that TS chidren had higher plasma N/OFQ levels (137.9±23.6pg/ml) than normal controls (25.6±4.9pg/ml) and TTD children (19.1±4.2pg/ml) with statistical significance (p=0.001).N/OFQ levels in TS children also showed significantly negative correlation with motor YGTSS scores (r=-0.54, p=0.002), especially with motor numbers (r=-0.51, p=0.004).hirteen TS children were also diagnosed with ADHD. Slightly higher plasma N/OFQ levels, though not statistically significantly, were found in pure TS children than those with ADHD (164.7±36.8 v.s. 102.7±23.5pg/ml, p=0.33). The N/OFQ levels of TS children without ADHD were negatively correlated with motor tic numbers (r=-0.50, p=0.04). On the other hand, N/OFQ levels in TS children with ADHD were not only negatively correlated with motor YGTSS scores (r=-0.57, p=0.04), but also positively correlated with phonic complexity scores (r=0.57, p=0.04). Our study demonstrated that TS children have higher plasma N/OFQ levels than normal controls. Due to the fact that N/OFQ negatively regulates dopaminergic system in the central nervous system, it is very likely that the elevation of plasma N/OFQ in TS children is a result of compensation for dopaminergic hyperactivity. Moreover, that N/OFQ levels in TS children were negatively correlated with motor tic symptoms may be explained by the model of tonic-phasic dopamine release. That is, higher N/OFQ level inhibits higher degree of phasic dopamine release and reduce more motor tic symptoms. Our study also revealed that children with pure TS had relatively higher plasma N/OFQ levels than those with ADHD. Both groups showed negative correlation between motor tic symptoms and N/OFQ levels. However, N/OFQ levels in TS children with ADHD were also noted to have positive correlation with phonic tic complexitiy scores. N/OFQ may have affect on ADHD but further study to clarify is necessary. Our study is the first one to investigate the association between clinical symptoms of Tourette syndrome and N/OFQ. It is also the first study to obtain the normal range of N/OFQ levels in normal children. N/OFQ may be applied in animal models of Tourette syndrome for further elucidation of its physiological and pharmacological effect on pathogenesis of tics in the future.
Subjects
Tourette syndrome
tic disorder
attention deficit hyperactivity disorder
Nociceptin/orphanin FQ
dopamine
Yale global tic severity scale
radioimmunoassay
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