Causes and origins of Tourette syndrome

Causes and origins of Tourette syndrome have not been fully elucidated. Tourette syndrome (abbreviated as Tourette's or TS) is an inherited neurodevelopmental disorder that begins in childhood or adolescence, characterized by the presence of multiple motor tics and at least one phonic tic, which characteristically wax and wane. Tourette's syndrome occurs along a spectrum of tic disorders, which includes transient tics and chronic tics.^[1][2]

The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved.^[3] The overwhelming majority of cases of Tourette's are inherited, although the exact mode of inheritance is not yet known,^[4] and no gene has been identified.^[5] Tics are believed to result from dysfunction in the thalamus, basal ganglia, and frontal cortex of the brain,^[3] involving abnormal activity of the brain chemical, or neurotransmitter, dopamine. In addition to dopamine, multiple neurotransmitters, like serotonin, GABA, glutamate, and histamine (H3-receptor), are involved.^[6]

Non-genetic factors—while not causing Tourette's—can influence the severity of the disorder. Some forms of Tourette's may be genetically linked to

Genetic factors

The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved.

In some cases, tics may not be inherited; these cases are identified as "sporadic" Tourette syndrome (also known as tourettism) because a genetic link is missing.^[17]

A person with Tourette syndrome has about a 50% chance of passing the gene(s) to one of their children.

The exact mechanism affecting the inherited vulnerability has not been established, and the precise cause of Tourette syndrome is not known. Tics are believed to result from dysfunction in the central nervous system,^[20] in the cortical and subcortical regions, the thalamus, basal ganglia, and frontal cortex of the brain.^[3] Neuroanatomic models implicate failures in circuits connecting the brain's cortex and subcortex,^[5] and imaging techniques implicate the basal ganglia and frontal cortex.^[21][22][23] Research presents considerable evidence that abnormal activity of the brain chemical, or neurotransmitter, dopamine is involved.^[24] Dopamine excess or supersensitivity of the postsynaptic dopamine receptors may be an underlying mechanism of Tourette syndrome.^{[25][26][27][28]}

Multiple neurotransmitters, like histamine (H3R), dopamine, serotonin, GABA and glutamate are involved in the etiology.^[6] After 2010, the central role of histamine (H3-receptor in the basal ganglia) came into focus in the pathophysiology of Tourette syndrome.^[29] The striatum is the main input nucleus of the basal ganglia circuit in the disorder, which is linked to the involvement of the histaminergic H3-receptor.^[30]

Non-genetic influences

Some forms of OCD may be genetically linked to Tourette's,[36] although the genetic factors in OCD with and without tics may differ.^[7] The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established.^[37][38][39] A genetic link between autism and Tourette's has not been established as of 2017.^[40]

Notes