Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

Abstract

Tourette syndrome (TS) is a common, chronic neuropsychiatric disorder characterized by the presence of fluctuating motor and phonic tics. The typical age of onset is ϳ5-7 years, and the majority of children improve by their late teens or early adulthood. Affected individuals are at increased risk for the development of various comorbid conditions, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder, school problems, depression, and anxiety. There is no cure for tics, and symptomatic therapy includes behavioral and pharmacological approaches. Evidence supports TS being an inherited disorder; however, the precise genetic abnormality remains unknown. Pathologic involvement of cortico-striatal-thalamo-cortical (CSTC) pathways is supported by neurophysiological, brain imaging, and postmortem studies, but results are often confounded by small numbers, age differences, severity of symptoms, comorbidity, use of pharmacotherapy, and other factors. The primary site of abnormality remains controversial. Although numerous neurotransmitters participate in the transmission of messages through CSTC circuits, a dopaminergic dysfunction is considered a leading candidate. Several animal models have been used to study behaviors similar to tics as well as to pursue potential pathophysiological deficits. TS is a complex disorder with features overlapping a variety of scientific fields. Despite description of this syndrome in the late 19th century, there remain numerous unanswered neurobiological questions.In the 1880's, Georges Gilles de la Tourette published a two-part article in which he emphasized differences between tics and chorea. Although many of the descriptions about the disorder, which now bears his name [Tourette syndrome (TS)], have been revised, his belief that tics are a neurological movement disorder and not a psychiatric condition persists to the present (Goetz and Klawans, 1982). Nevertheless, despite multiple advances and widespread acceptance of TS being a biological disorder, the precise etiology and underlying pathophysiological mechanisms remain unknown. The goals of the present review are to briefly describe the clinical phenomenology of TS and related tic disorders, to review current information on genetic and neurobiological mechanisms, and to identify areas in need of further investigation.

Deep brain stimulation for psychiatric disorders: where we are now

“…203,206 Individuals with TS have demonstrated structural and functional abnormalities within the corticostriatothalamocortical loop, 261,302 although the primary site of abnormality remains controversial. 65 In fact, imaging studies in individuals with TS reveal widespread abnormalities in the size, connectivity, and microstructure of the caudate nucleus, 158,222 thalamus, 174 sensorimotor and prefrontal cortex, 268 cerebellum, 277 corpus callosum, 41 amygdala and hippocampus, 221 and limbic structures such as the amygdalae and NAcc. 207 Electrophysiological studies implicate overexcitability and dysregulation of frontal-subcortical circuitry resulting in deficiencies in processing of stimuli.…”

Histaminergic modulation in Tourette syndrome

“…The exact pathophysiological mechanisms underlying TS are unknown, however converging lines of evidence point to abnormally increased dopamine neurotransmission, particularly at the level of the basal ganglia and fronto-striatal circuitries [2,[28][29][30]. This hypothesis is in line with evidence of altered structural connectivity within the cortico-striato-pallidothalamic circuitry [31].…”

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

“…[1][2][3][4][5][6] Compulsive, repetitive and tic/TD-like behaviors in rodent models have been associated with variants in single genes such as Sapap3 and Slitrk5. [7][8][9][10] Recently, single-nucleotide polymorphisms (SNPs) within the canine neuronal cadherin gene (CDH2) were shown to confer a significant risk for canine compulsive disorder (CCD).…”