Obsessive control and challenging tests. Experimental studies on neurobiological mechanisms in the pathogenesis and treatment of obsessive-compulsive disorder

Abstract

In this thesis several neurobiological oriented studies on obsessive-compulsive disorder (OCD) are described. Two pharmacological challenge studies have been performed investigating serotonin-2 and cholecystokinin-B receptor functioning in OCD. No direct relationship between these receptors and OCD symptoms was found. However, an enhanced susceptibility for the panic inducing properties of pentagastrin and an enhanced sensitivity of serotonin-2 receptors could be established in OCD patients compared with healthy controls.

Two other studies were designed to investigate if inhibition processes in OCD are disturbed. In one study, using prepulse inhibition of the acoustic startle reflex and p50 suppression paradigms, no impairments in sensorimotor gating and sensory gating could be established. Thus, it is unlikely that a problem in diffuse gating of irrelevant stimuli is present in OCD. In another study, using a visuospatial priming task, deficits in cognitive inhibition were found in OCD patients. This finding gives support to the hypothesis that disturbances in cognitive inhibition might lead to an increase of intrusive thoughts coming into consciousness, which may cause a more deliberately suppression of these thoughts, with a counterproductive effect.

No association with severity of symptoms was found, so the impairments are probably trait related.

The last study was a randomized placebo-controlled trial, investigating the augmenting effect of D-cycloserine (DCS) added to exposure therapy. DCS has been proven to possess the capability to enhance or accelerate the extinction of conditioned fear in Pavlonian fear paradigms. The group of OCD patients (n=18) using single doses of DCS 1 h before the exposure sessions improved more than the placebo group (n=19), but the difference was not significant. However, the response percentages between the DCS group and the placebo group differed significantly and in the subgroup of ‘cleaning/contamination’ DCS usage led to an enhanced improvement. It was suggested that DCS might be preferably effective in patients with more anxiety related obsessive-compulsive symptoms. Future studies examining DCS in OCD with a greater amount of subjects are warranted.