Neurobiology of Tourettes Syndrome

Tourette Sydrome is a neuropsychiatric, childhood-onset disorder characterized my motor tics in addition to vocal (phonic) tics.  Original estimates of the prevalence of this condition was that it was very rare.  However, it appears that many individuals with the condition has a relatively mild form of the disorder.  Including these individuals produces a prevalence rate of between .1% and 1% of the population.

Common motor tics presenting on average around ages 5 to 7 years of age include eye blinking, facial twitching, sniffing and shoulder shrugging.  The most common motor tic is throat clearing.  Outbursts of shouting profanities is commonly felt to be common in Tourette Syndrome but actually occurs in only 10% of cases.

Ryan Felling and Harvey Singer recently published an excellent overview of the neurobiology of Tourette Sydnrome in The Journal Neuroscience.  This review includes an introduction to the syndrome before examining brain circuits, animal models, structural and functional brain imaging findings.  

The authors note that brain structural and functional abnormalities in Tourette Syndrome appear diffusely located but do involve the brain stuctures related to motor control including the basal ganglia (See Brain Tutor.  There are several known neuropsychiatric conditions of the basal ganglia that produce motor abnormalities.  

Parkinson's disease is an abnormality of the basal ganglia's substantia nigra producing slowed motor movements with muscle rigidity.  Huntington's disease produces atrophy of the basal ganglia region known as the head of the caudate and is characterized by jerky, uncontrolled movements known as chorea.

The structure and functional brain imaging studies to date in Tourettes Sydrome have demonstrated a variety of effects in the basal ganglia including:

• reduced caudate volume (smaller caudate size linked to greater tic severity)
• enlarged putamen
• activity in putament and caudate (and cortex) correlate with tic activity
• decreased activity in the putamen and caudate with attempts to suppress tic

The review notes that Tourette Syndrome appears to be due to "pathololgic involvement of the cortico-striatal (putamen/caudate)-thalamo-cortico" brain circuits with dysfunction of the neurotransmitter dopamine a key contributor to disorder. 

The authors note that no effective treatment exists for Tourette Syndrome.  Interventions focus on behavioral and drug treatment with an emphasis on treating the common co-occuring disorders: OCD and ADHD.  Thankfully, symptoms often reduce in frequency and severity with age.  

The authors conclude significant additional research is needed using larger samples with better description of specific tic patterns, control for comorbid ADHD and OCD and focus on whether brain changes found in Tourette Sydrome are primary or may result from compensatory mechanism in response to tic motor behaviors. 

Interested readers can learn more about this disorder from a excellent series of discussion by patients with Tourettes Syndrome from the New York Times Patient Voices Multimedia project here. 

Screen Shot of Basal Ganglia Structures from Brain Tutor iPad app.

Felling RJ, & Singer HS (2011). Neurobiology of tourette syndrome: current status and need for further investigation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (35), 12387-95 PMID: 21880899

Common Brain Anatomy Features in Autism and Schizophrenia

Neuropsychiatric disorder classification challenges clinicians and researcher alike.  Classical approaches have used a distinct non-overlapping categories approach.  Increasingly, research suggests that distinct disorders share clinical and neuroanatomical features.  This means that it might be possible for specific genes and environmental effects to produce more than one disorder.

Cheung et al from the University of Hong Kong, China explored brain structural commonalities between autism and schizophrenia.  Using a novel statistical classification strategy, MRI data were compared in a group of 308 subjects with autism, 352 with first-episode schizophrenia and 801 controls.  The strategy group anatomical differences into those found in autism alone, schizophrenia alone and in both autism and schizophrenia (figure).

The authors used a series of imaging data sets to perform their analysis.  The autism group included several clinical groups including autism, Asperger’s and high-functioning autism.  The schizophrenia group were all first-psychotic episode with some being antipsychotic naïve and some with a history of antipsychotic drug exposure.

The figure from the manuscript shows the grouping for various brain regions grouped by frontal/parietal region/temporal lobe-basal ganglia region and cerebellum.   Both diagnostic groups demonstrated gray matter reductions in the right posterior cingulate, the right parahippocampal gyrus, putamen and left thalamus. 

Subjects with schizophrenia demonstrated many more local regions of atrophy not found in autism including the right and left superior and medial frontal gyrus, right and left cingulated and left insula, caudate, temporal gyrus and amygdala.  The only unique site of gray matter atrophy for the autism group was the left putamen.

The authors note that these two disorders are “indicative of overlapping neuroanatomical phenotype” but do not imply that autism and schizophrenia are a “common entity”.  The authors conclude: “Our findings should therefore encourage further exploration of the potential shared etiologies and better understanding of the mechanisms separating the 2 conditions”.

I think you will see increasing research examining commonalities between what have up until now been considered distinct conditions.  Look for more evidence that distinct disorders have significant phenotype overlap.  Examining these shared features may provide a better understanding of the pathophysiology of a variety of mental disorders.

Figure Provided from PloS One Manuscript

Cheung C, Yu K, Fung G, Leung M, Wong C, Li Q, Sham P, Chua S, & McAlonan G (2010). Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation. PloS one, 5 (8) PMID: 20805880