Williams syndrome (WS) is a rare genetic disorder (1 in 25, 000 to 50,000 births) characterized by a relative preservation of linguistic and social-affective skills in the face of profound impairment of visual-spatial abilities and numeric processing. Obsessive-compulsive disorder (OCD) is a chronic, debilitating neuropsychiatric syndrome which encompasses a broad spectrum of cognitive, behavioral, and neurophysiological abnormalities. In this paper, we observe some striking parallels in the clinical presentation and neuropsychological test performance of these distinct syndromes which may illustrate the adaptive function of the frontal lobes, albeit a gross exaggeration of the normal function of this cortical region.
Functional neuroimaging studies have demonstrated significant elevations in baseline glucose metabolism in orbitofrontal cortex among OCD patients (Baxter et al., 1987; Baxter et al., 1988; Nordahl et al., 1989; Swedo et al., 1989). Moreover, functional imaging studies have
documented increased glucose utilization and regional cerebral blood flow (rCBF) in the orbitofrontal region during exposure to OC-relevant stimuli among OCD subjects in comparison
to controls (Breiter et al., 1996; Cottraux et al., 1996; McGuire et al., 1994; Rauch et al., 1994). Neuropsychological testing has revealed a pattern of neurocognitive impairment among OCD subjects which clearly implicates the orbitofrontal region (Abbruzzese, Bellodi, Ferri, & Scarone, 1995; Abbruzzese, Ferri, & Scarone, 1995, 1997; Cavedini, Ferri, Scarone, & Bellodi, 1998; Dinn & Harris, 1998). The neural labeling of environmental stimuli as threatening is one of the primary functions of the orbitofrontal system. Hypermetabolism of this circuit generates intense anxiety which, in turn, engenders compensatory mechanisms for reducing anxiety, such as compulsive rituals and checking behaviors. Orbitofrontal hypermetabolism represents the physiological substrate of the OCD patientÕs exaggerated sensitivity to noxious stimuli.
The threshold for stimulation is dramatically lowered, resulting in a hypersensitivity to cues which signify potential harm. These patients adapt to this hypersensitivity through a variety of strategies which constitute OCD. They attend to threat with great vigilance (obsessional phenomena) and go to considerable lengths to avoid harm (i.e., compulsive checking, cleaning, ordering, and so forth). We suggest that the symptoms of OCD represent adaptations to orbitofrontal dysfunction. Obsessive-compulsive phenomena can be best understood as attempts to achieve equilibrium gone awry (Dinn & Harris, 1999).
Individuals with Williams syndrome exhibit reduced overall cerebral volume and decreased myelination (Bellugi et al., 1990; Jernigan & Bellugi, 1990), while frontal neocortical volume is normal generating what Deacon (1997) described as a comparative prefrontalization or exaggerated prefrontal predominance. Recently, Grachev et al. (1998) found that ten OCD patients exhibited greater total neocortical volume in comparison to control subjects matched for age, gender, educational level, and handedness. Moreover, they reported that OCD subjects demonstrated volumetric abnormalities (significantly greater volume) in several frontal subregions. Volumetric abnormalities in two of these subregions, the right inferior frontal pars triangularis and right mid-frontal cortex, were associated with performance deficits on a measure of non-verbal memory (the Rey-Osterrieth Complex Figure). That is, greater right frontal volumes were associated with impaired non-verbal memory. However, they also found that OCD patients did not demonstrate volumetric abnormalities in the orbitofrontal region in comparison to matched control subjects. Neuropsychological test performance of WS subjects demonstrates a relative preservation of linguistic skills, while visual-spatial abilities are profoundly impaired. Interestingly, OCD patients display a similar, albeit much less pronounced, performance pattern. OCD subjects exhibit impaired performance on visual-spatial and non-verbal memory tasks (Aronowitz et al., 1994; Grachev et al., 1998; Purcell, Maruff, Kyrios, & Pantelis, 1998), while performing equal to or better than controls on many verbal tasks (Zielinski, Taylor, & Juzwin, 1991).
A number of authors have observed the relationship between the selective preservation of frontal structures and the relative sparing of linguistic skills and social-affective behavior among WS children and adults. Indeed, individuals with WS demonstrate a hypersensitivity to social cues. WS children have also been shown to be unusually empathic, in comparison to age-matched Down syndrome subjects. The orbitofrontal system does not simply process noxious information and mediate avoidance behavior. We suggest that the orbitofrontal system represents a social cognition module. This system may play a vital role in regulating oneÕs relation to the group. Consider our patient populations: Rachman (1976, 1993) observed that much OC phenomena stem from a fear of criticism and a heightened sense of personal responsibility. He suggested that compulsive checking behavior may represent an attempt to forestall criticism. Obsessional themes typically focus on behaviors and impulses which, if acted on, will evoke considerable criticism (e.g., concern with aggressive and sexual behavior, rigid adherence to social rules and standards of behavior). This hypersensitivity to criticism and excessive conscientiousness may reflect a heightened concern for oneÕs position in the social hierarchy. OCD appears to represent a gross distortion of adaptive behaviors which serve to integrate the individual into the group (e.g., adherence to group rules, regulations, grooming rituals and moral standards) (Dinn & Harris, 1998). Indeed, the term scrupulosity was used by authorities in the middle ages to describe obsessive-compulsive phenomena. Similarly, children and adults with WS display a heightened sensitivity to social cues and relationships (Deacon, 1997). In addition, they exhibit a high incidence of behavioral disturbance including intense anxiety and obsessions (Bradley & Udwin, 1989; Davies, Udwin, & Howlin, 1998; Einfeld, Tonge, & Florio, 1997; Udwin & Yule, 1991).
OCD and WS are discrete syndromes possessing separate etiologies. Nevertheless, they may represent disorders of frontal predominance.
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