Neuropsychological performance and regional cerebral blood flow in obsessive–compulsive disorder

Abstract

Convergent findings from neuropsychological and neuroimaging studies have suggested that neural dysfunction in frontal–subcortical circuits may play a central role in the pathophysiology of obsessive–compulsive disorder (OCD). To further examine the relationship between these two sets of findings we investigated both neuropsychological functions and regional cerebral blood flow (rCBF) in a combined study. Fourteen unmedicated patients fulfilling DSM-IV criteria for OCD and 14 healthy controls matched for age, gender, handedness, and education were assessed on neuropsychological tests that included Trail Making Test (TMT), Rey Complex Figure Test (RCF) (copy and 5-min recall), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST). rCBF was studied with ^{99 m}Tc-hexamethyl-propyleneamine-oxime (HMPAO) single photon emission computed tomography (SPECT). Patients performed more poorly than controls (P<.05) on RCF (copy), VFT, and WCST (perseverative errors). Spearman's correlations indicated that severity of OCD correlated inversely with performance on the RCF (copy and recall scores) and positively with rCBF in the right thalamus. Positive correlations were observed between nonperseverative errors (WCST) and rCBF in frontal areas and anterior cingulate. Perseverative errors (WCST) correlated negatively with rCBF in the right thalamus. These findings are consistent with most previously published studies and suggest neural dysfunctions in the frontal–subcortical circuits probably more pronounced in the right hemisphere. They also extend the existing research, showing associations between deficits in cortical–subcortical circuitry and performance on neuropsychological tests of controlled attention and visuospatial functions.

Introduction

Obsessive–compulsive disorder (OCD) is a chronic, disabling anxiety disorder that affects about 2% of the population. Clinically, OCD is characterized by the presence of recurrent and persistent thoughts that cause marked anxiety or distress (obsessions) and/or repetitive behaviors or mental acts that are performed to prevent or reduce distress (compulsions). Both obsessions and compulsions are recognized as excessive or unreasonable by the patients, who frequently attempt to ignore or suppress them (American Psychiatric Association, 1994). This clinical presentation resembles some features of organic mental disorders, specifically those related to the so-called “frontal syndrome,” which is characterized by deficits in executive abilities, including the ability to flexibly shift cognitive sets, along with cognitive rigidity in problem solving, anxiety, depression, and poor impulse control as important features Dolan et al., 1993, Grafman et al., 1996, Robinson et al., 1984.

As early as 1838, Esquirol anticipated that some neurological dysfunctions would be found to underlie OCD symptomatology; as to its pathophysiology, Ball in 1892, emphasized possible cerebral blood flow abnormalities (from Berrios, 1989). Recently, various lines of evidence supporting the neurobiological basis of OCD have been reported (Insel, 1992): a high prevalence of OCD in some neurological diseases such as Tourette syndrome, postencephalitic Parkinson, Sydenham chorea, and temporal lobe epilepsy Bihari et al., 1991, Hollander et al., 1990, Jenike, 1984, Malloy et al., 1989, Rapoport, 1990; favorable response to biological treatments such as selective serotonin reuptake inhibitors and psychosurgery Baer et al., 1995, Humble et al., 2001, Insel et al., 1985, Jenike et al., 1991, Mindus and Jenike, 1992; a high prevalence of neurological soft signs and abnormal evoked potential Bihari et al., 1991, Hollander et al., 1990, Lieberman, 1984; structural and functional abnormalities detectable by neuroimaging techniques Robinson et al., 1995, Rosenberg et al., 2000, Saxena et al., 1998; specific neuropsychological deficits Okasha et al., 2000, Schmidtke et al., 1998; and evidence of genetic transmission in at least some patterns of OCD (Pauls and Alsobrook, 1999).

Performance of different cognitive tasks has been assessed in OCD patients. Previous neuropsychological studies, albeit with some contradictory findings, have pointed to impairment in at least four domains: “frontal lobe” and visuospatial functions, memory, and lateralization of assumed cognitive dysfunction (Schmidtke et al., 1998). According to these authors, the apparent contradictions may be due, in part, to methodological differences in the selection, matching, and testing of the subjects studied. Hence, such factors as evaluation of patients on medication, inclusion of subjects with mild forms of OCD or with subtle central nervous system insults, as well as failure to adequately match healthy controls to OCD subjects could be important sources of variance in the findings across studies (Schmidtke et al., 1998). Neuroimaging studies examining OCD patients have consistently described abnormalities in frontal lobes, cingulate, basal ganglia, and thalami (Saxena et al., 1998). Taken together, neuroimaging and neuropsychological findings have provided considerable evidence pointing to dysfunction of prefrontal–subcortical circuits in OCD Abbruzzese et al., 1995a, Baxter, 1990, Baxter et al., 1987, Martinot et al., 1990, Okasha et al., 2000, Saxena et al., 1998, Schmidtke et al., 1998.

In the present study, the authors examined the neuropsychological performance of 14 unmedicated OCD patients and 14 comparison subjects matched for age, gender, handedness, and level of education. Four tests, addressing different cognitive functions such as verbal fluency, visuospatial orientation, set shifting, and memory, were applied. Patients were also investigated with single photon emission computed tomography (SPECT). Bearing in mind the findings of previous studies, we hypothesized that OCD patients would have an impaired performance on neuropsychological tests evaluating frontal and visuospatial functions and that scores on the same tests as well as severity of symptoms would be associated to regional cerebral blood flow (rCBF) measurements in structures involved in prefrontal–subcortical circuits.