Inflammation, Obsessive-Compulsive Disorder, and Related Disorders

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) research initially linked brain inflammation to autoimmune responses from infections like Sydenham's Chorea and PANDAS/PANS.
• This autoimmune model, however, only explained a small fraction of OCD cases.
• Translocator protein (TSPO) positron emission tomography (PET) imaging provides a direct measure of gliosis, a key component of brain inflammation, in neuropsychiatric disorders.

Purpose of the Study:

• To investigate the role of brain inflammation, specifically gliosis, in obsessive-compulsive disorder (OCD).
• To explore the utility of peripheral blood serum biomarkers for detecting gliosis in OCD patients.
• To evaluate the potential of anti-inflammatory treatments for OCD.

Main Methods:

• Utilized translocator protein (TSPO) positron emission tomography (PET) imaging to detect gliosis in the brain.
• Examined cortico-striatal-thalamo-cortical circuits in OCD patients using PET imaging.
• Considered blood serum biomarkers as peripheral indicators of microglial and astroglial activation (gliosis).
• Reviewed existing randomized double-blind placebo-controlled trials of anti-inflammatory agents for OCD.

Main Results:

• TSPO-PET imaging revealed increased TSPO binding in the cortico-striatal-thalamo-cortical circuit in OCD patients, indicating elevated gliosis.
• Blood serum biomarkers show promise for identifying OCD cases with significant gliosis in research settings.
• Preliminary clinical trials of anti-inflammatory drugs (celecoxib, minocycline, n-acetylcysteine) suggest a trend toward positive outcomes, though sample sizes were small and drug brain penetration was not optimized.

Conclusions:

• Brain inflammation, particularly gliosis, is a measurable component in a subset of obsessive-compulsive disorder (OCD) cases.
• Peripheral biomarkers could aid in stratifying OCD patients for clinical trials targeting gliosis.
• Future OCD clinical trials should employ larger sample sizes and stratification based on gliosis markers for evaluating anti-inflammatory therapies.