Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder

Area of Science:

• Neuroscience
• Psychiatry
• Neurophysiology

Background:

• Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, potentially due to impaired inhibitory mechanisms.
• Cortical gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptor systems are implicated in OCD pathophysiology.

Purpose of the Study:

• To investigate neurophysiological indices of GABAergic and NMDAergic neurotransmission in patients with OCD using transcranial magnetic stimulation (TMS).
• To compare inhibitory and facilitatory neurotransmission between individuals with OCD and healthy controls.

Main Methods:

• Utilized TMS to measure short-interval cortical inhibition (SICI), cortical silent period (CSP), and intracortical facilitation (ICF) in 34 OCD patients and 34 healthy controls.
• Assessed both unmedicated and medicated OCD patients, and analyzed results excluding those with comorbid major depressive disorder (MDD).

Main Results:

• Patients with OCD showed significantly shortened CSP (indicating impaired GABAergic inhibition) and increased ICF (suggesting enhanced NMDAergic facilitation) compared to controls.
• No significant differences in SICI were observed between the groups.
• Findings remained significant after excluding patients with comorbid MDD.

Conclusions:

• OCD is associated with dysregulation in cortical inhibitory and facilitatory neurotransmission, specifically implicating GABA(B) and NMDA receptor systems.
• These neurophysiological findings align with genetic studies linking GABA and NMDA genes to OCD.
• Aberrant neurotransmission may contribute to the generation and persistence of intrusive thoughts in OCD.