title: Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder.
abstract: Several lines of evidence suggest that obsessive-compulsive disorder (OCD) is associated with an inability to inhibit unwanted intrusive thoughts. The neurophysiological mechanisms mediating such inhibitory deficits include abnormalities in cortical γ-aminobutyric acid (GABA) inhibitory as well as N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms. Molecular evidence suggests that both these neurotransmitter systems are involved in OCD. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to ascertain neurophysiological indices of inhibitory GABA and facilitatory NMDA receptor-mediated mechanisms. In this study, both mechanisms were indexed in 34 patients with OCD (23 unmedicated and 11 medicated) and compared with 34 healthy subjects. Cortical inhibitory and facilitatory neurotransmission was measured using TMS paradigms known as short-interval cortical inhibition (SICI), cortical silent period (CSP), and intracortical facilitation (ICF). Patients with OCD demonstrated significantly shortened CSP (p<0.001, Cohen's d=0.91) and increased ICF (p<0.009, Cohen's d=0.71) compared with healthy subjects. By contrast, there were no significant deficits in SICI. After excluding patients with OCD and comorbid major depressive disorder (MDD) from the analysis, these differences remained significant. Our findings suggest that OCD is associated with dysregulation in cortical inhibitory and facilitatory neurotransmission. Specifically, these findings suggest impairments in GABA(B) receptor-mediated and NMDA receptor-mediated neurotransmission. These findings are consistent with previously published genetic studies implicating GABA(B), and NMDA transporter and receptor genes in OCD. It is posited that dysregulation of such mechanisms may lead to the generation and persistence of intrusive thoughts that form the basis for this disorder.
authors.affiliation: Director of OCD and Related Disorders, Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Richter
authors.forename: Danilo R
authors.initials: DR
authors.lastname: de Jesus
authors.forename: Sylco
authors.initials: S
authors.lastname: Hoppenbrouwers
authors.forename: Melissa
authors.initials: M
authors.lastname: Daigle
authors.forename: Jasna
authors.initials: J
authors.lastname: Deluce
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Ravindran
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D013181:Cortical Spreading Depression / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009771:Obsessive-Compulsive Disorder / Q000473:pathology*; D010555:Personality Inventory; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation