Neurobiological basis of serotonin-dopamine antagonists in the treatment of Gilles de la Tourette syndrome.
Tourette syndrome (TS) is a heritable neuropsychiatric disorder that presents in childhood with a constellation of motor and non-motor symptoms. The defining feature of the disorder is the presence of brief, stereotyped, motor or vocal behaviours called tics. Although tics are themselves voluntary, they are typically performed secondary to involuntary sensory symptoms or irresistible urges. TS is therefore said to be a disorder of human volition that likely represents a general failure of inhibition. It shares many features with obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD) and impulse control disorder with which it is also commonly associated. Much of the anatomic substrate for TS probably lies in the circuits that connect multiple areas of cortex with the basal ganglia and thalamus to subserve motivation, inhibition of behaviour, planning of motor acts and detection of threats. To date, pathological studies of TS have been very few and the number of subjects evaluated too small to reliably elucidate the nature and significance of several reported abnormalities. However, evidence derived from both pharmacological trials and selected functional imaging studies suggests that disturbances of the dopaminergic and serotonergic neurotransmitter systems play a key role in the pathogenesis of TS. At the same time, multiple studies have demonstrated reciprocal interactions between the serotonin and dopamine systems of the brain. This information, when placed in the context of the observed functional imaging abnormalities, may generate further insights into the pathophysiology of TS.
Steeves
Thomas D L
TD
Division of Neurology, University of Toronto, Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Ontario, Canada.
Fox
Susan H
SH
D001479:Basal Ganglia / Q000502:physiology / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000502:physiology; D005879:Tourette Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D012701:Serotonin; D004298:Dopamine