Inhibition of Gamma Oscillations as a Neurophysiological Endophenotype of Schizophrenia

Abstract Background The pathophysiology of schizophrenia (SCZ) has not been fully elucidated. Studies have demonstrated that SCZ patients have impairments in the dorsolateral prefrontal cortex (DLPFC). Two findings have been shown in the DLPFC: deficits in GABAergic inhibitiory neurotransmission and abnormal inhibition of cortical oscillations. Thus, we aimed to assess frontal inhibition as a potential endophenotype of SCZ. Objectives The first objective was to quantitatively assess transcranial magnetic stimulation (TMS) motor cortex measures of inhibition and excitation in obsessive-compulsive disorder (OCD), major depressive disorder (MDD) and SCZ, as a meta-analysis. The second objective was to evaluate the inhibition of overall and gamma oscillations in the DLPFC and motor cortex using TMS and EEG in SCZ and OCD. The final objective was to evaluate the inhibition of overall and gamma oscillations in SCZ patients, OCD patients, and their unaffected first-degree relatives with TMS and EEG. Hypotheses First, we hypothesized that motor cortex inhibitory deficits would be a ubiquitous finding across OCD, MDD and SCZ patients. Second, we hypothesized that patients with SCZ would show deficits in overall and gamma inhibition in the DLPFC compared to healthy subjects and patients with OCD. Lastly, it was hypothesized that frontal inhibition in first-degree relatives of SCZ would be intermediate of healthy subjects and their related probands. Results The first study showed that motor inhibitory deficits were a ubiquitous finding across OCD, MDD, and SCZ. The second paper found that SCZ patients demonstrated inhibitory deficits in the DLPFC (overall and gamma inhibition), not observed in OCD patients. This was found to be independent of illness severity and medication. The final study demonstrated deficits in frontal inhibition in SCZ patients, which were significantly less than their unaffected first-degree relatives. No differences were found between first-degree relatives of SCZ and healthy controls. First-degree relatives were intermediate of their related probands and healthy controls. We did not show inhibition deficits in OCD patients and their first-degree relatives. Conclusions Frontal inhibition (measured via TMS and EEG) may be an essential neurophysiological process that is impaired in SCZ. Multi-site trials are needed to investigate inhibition as a potential endophenotype for SCZ.

Department dc:contributor.department

Medical Science

Year dc:date.issued

2015

Author dc:creator

• Radhu, Natasha

Advisor dc:contributor.advisor

• Daskalakis, Zafiris J

• Cortical Inhibition
• Electroencephalography
• Endophenotype
• Obsessive-Compulsive Disorder
• Schizophrenia
• Transcranial Magnetic Stimulation

Handle dc:identifier.uri

http://hdl.handle.net/1807/71603

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/71603