This Project Area focuses on the developmental psychopathology of Autism and other Pervasive Developmental Disorders. Consistent with the mission of the Program Project, this work is strongly interdisciplinary in nature. Four related studies are proposed. The first two studies are concerned with the differentiation of disorders among individuals at the higher functioning end of the spectrum of autism: the validity of Asperger syndrome (AS) relative to Higher-Functioning Autism (HFA). Individuals with a possible diagnosis of AS or HFA will be assessed neuropsychologically and psychiatrically, as will be the first-degree relatives of the patients in order to determine the pattern of familial aggregation of AS and HFA symptoms and neuropsychological profiles. Expression of the syndrome in family members will also be assessed. Preliminary work has suggested distinctive neuropsychological profiles associated with the condition. Other aspects of phenomenology, genetics, and neuropathology will be examined. This work makes use of a large and unique pool of eligible subjects. This work is concerned both with the validity and characterization of the Asperger syndrome concept as well as with the identification of neuropsychological and other factors that differentiate it from autism; a longer-term goal is the extension of this work to the entire range of dysfunction in autism. Several lines of evidence have suggested potential neuroanatomical correlates of AS and HFA. As part of this Project, Magnetic Resonance Image data will be collected on a subsample of (older) subjects to evaluate hypothesized neuropathological correlates. Focused morphological hypotheses will be tested based on the observation that individuals with AS have a high probability of exhibiting the nonverbal learning disability profile which has been hypothesized to particularly reflect aspects of white matter dysfunction. The final study within this Project Area is concerned with evaluating pharmacological treatments for AS and HFA. This work is based on pilot studies that suggest that individuals with these conditions who exhibit high levels of obsessive/ritualistic behavior may respond favorably to a selective-serotonin reuptake inhibitor. Forty individuals will be enrolled in a double-blind, placebo-controlled study of this agent (fluvoxamine); drug response will be related to diagnostic status and measures of serotonergic activity.
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