Causes of Tourette Syndrome
Tourette syndrome is a hereditary neurodevelopmental disorder with a complex genetic basis that is modified by environmental factors, though specific causative genes have not yet been identified. 1
Genetic Factors
- The genetic basis is complex and polygenic, with the disorder clustering strongly within families, indicating substantial heritability 2, 3
- Despite being considered a hereditary disorder, genetic studies have not yet uncovered specific causative genes responsible for Tourette syndrome 1
- Genome-wide association studies have implicated several genes, though these findings are primarily from related conditions like OCD rather than Tourette syndrome specifically 4
- The male-to-female ratio is approximately 4:1, suggesting possible sex-linked genetic factors 3
Environmental Factors
- Both in utero and ex utero environmental factors can modify the phenotypic expression of the disorder, though specific environmental triggers remain incompletely characterized 2
- Environmental factors appear to interact with genetic predisposition to determine disease expression and severity 1
Neurobiological Mechanisms
Neurotransmitter Systems
- The dopaminergic system plays a central role in Tourette syndrome, as evidenced by the therapeutic efficacy of dopamine D2 receptor antagonists 4
- Dopamine has a key role in stereotypic behaviors, including grooming in animal models, which parallels tic behaviors 4
- The serotonergic system may be involved, though evidence for a primary causal role is limited 4
- Glutamatergic neurons originating in the prefrontal cortex and projecting to the striatum are implicated in the cortico-striato-thalamo-cortical (CSTC) circuitry dysfunction 4
Brain Circuit Abnormalities
- Alterations in cortico-striato-thalamo-cortical (CSTC) circuits are central to the pathophysiology, with dysfunction in these networks contributing to tic generation 4
- Recent research has identified alterations in neurophysiology and brain networks that contribute to pathogenesis, though the complete picture remains unclear 5
- Defects in corticostriatal synapses have been demonstrated in animal models of related compulsive behaviors 4
Immune and Inflammatory Factors
- Inflammation related to aberrations in immune activation appears to play a pathogenic role in some cases of Tourette syndrome 2
- The involvement of inflammatory and immune pathways is increasingly recognized, though findings remain preliminary 4
Important Clinical Context
- The underlying pathophysiology remains incompletely elucidated despite advances in neuroimaging and neurophysiological studies 1, 5
- There is currently no animal model that mimics the broad clinical phenomenology of Tourette syndrome, which limits mechanistic research 1
- The heterogeneity of symptoms across patients and the presence of comorbidities make interpretation of pathophysiological studies challenging 1