Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder

Abstract

Functional and structural imaging studies suggest that obsessive-compulsive disorder (OCD) symptoms arise from dysfunction in cortico-striato-thalamo-cortical circuits. It has therefore been hypothesized that neurophysiological tasks subserved by these circuits should be abnormal in OCD patients. One neurocognitive probe associated with this circuitry is prepulse inhibition (PPI) of the acoustic startle response. PPI deficits are thought to reflect abnormalities in processing and integration of sensory and motor information. Two prior studies found that OCD patients had PPI deficits at single prepulse (PP) intensities. However, most patients in these studies were taking psychotropic medications at the time of PPI testing, and preclinical studies have demonstrated effects of psychotropic medications on PPI. We examined PPI in 22 unmedicated OCD patients and 22 matched healthy controls at three different PP intensities (74, 78, and 86 dB). OCD patients had significantly less PPI across all three PP intensities compared with controls. Exploratory analyses indicated that OCD patients with a history of tics had lower levels of PPI. Our results demonstrate that unmedicated OCD patients have impaired sensorimotor gating as measured by PPI. This indicates that PPI deficits are present in OCD patients and are not the result of medication effects. Our findings also suggest that OCD patients with a history of tics may have greater impairment in sensorimotor gating than the general OCD population. Future studies should be designed to examine whether PPI deficits characterize tic-related OCD.

Figure 1

Percent PPI is significantly lower in OCD subjects. Bar graph demonstrates percent PPI (mean±SEM) at 74, 78, and 86 dB PP intensities. Mean±SEM of the mean are as follows: HC: 74 dB=29.9 (5.1); 78 dB=45.4 (5.0); 86 dB=60.9 (4.0). OCD: 74 dB=13.4 (4.5); 78 dB=29.5 (5.5); 86 dB=47.5 (4.8). HC: healthy control subjects; OCD: OCD subjects. ^*Indicates significance at p<0.02 (74 dB), p<0.04 (78 dB), and p<0.04 (86 dB).

Figure 2

Percent PPI for each individual subject demonstrates inter-subject variation. Scatter-plot indicates percent PPI for each individual subject at PP intensities of 74, 78, and 86 dB. Closed circles indicate healthy controls (n=22) and open circles indicate OCD subjects (n=22). Black bars indicate the mean percent PPI at each PP intensity. The three individuals with tics are highlighted with arrows; each individual subject is assigned a different arrowhead (filled, open, or double) that can be tracked across all three PP intensities.