Overlapping phenotypes - a clinical and magnetic resonance imaging investigation of schizotypy and pervasive developmental disorders in adolescents with cognitive impairment
Stanfield, Andrew C.
Introduction: The neurobiological bases of pervasive developmental disorders (PDD) and schizotypy are not well established. In addition there are clinical overlaps between the two which can make diagnostic determination difficult. The primary aim of this thesis was to explore the relationship between PDD and schizotypy by examining their associated clinical and brain structural features in a group of cognitively impaired adolescents. Methods: 138 adolescents receiving special educational assistance and 62 typically developing controls were recruited. Schizotypal features were measured using the Structured Interview for Schizotypy (SIS) and PDD features were measured using the Social Communication Questionnaire (SCQ). Each participant also received a standardised clinical interview and a magnetic resonance imaging (MRI) scan. Whole brain volume, midsagittal corpus callosum area and prefrontal lobe volume and gyrification index (GI) were measured using automated, semi-automated and manual region of interest techniques. The subjects in special education were considered in different groupings in three main analyses. In the first, the SIS was used to divide the subjects into those with and without schizotypal features. In the second, the standard SCQ cut-offs were used to divide the subjects into those with autism, those with non-specific pervasive developmental disorder (PDD-NOS) and those with neither. Finally, both the SIS and the SCQ were used contemporaneously to divide the subjects into 6 groups: schizotypal; autistic; PDD-NOS; comorbid schizotypy and autism; comorbid schizotypy and PDD-NOS; and neither schizotypal nor autistic. In each analysis the groups were compared to each other and to the controls with respect to the clinical features and brain structural measures. Results: The schizotypal subjects showed an increase in right prefrontal volume and changes in the anterior and posterior corpus callosum relative to those without schizotypy and the controls. The autism group had reduced right prefrontal GI relative to the other groups as well as anterior callosal changes. The PDD-NOS group had the highest level of psychiatric symptomatology on the CIS, in particular those who were comorbid for PDD-NOS and schizotypy. This comorbid group, both clinically and structurally resembled the schizotypy group rather than the PDD-NOS group. Conclusions: Distinct neuroanatomical differences can be seen in educationally impaired adolescents with schizotypal features and in those with autistic features. These can be related to the observed clinical impairment and may help to distinguish these disorders in the future. It is possible that adolescents with features of both schizotypy and PDD-NOS suffer from an underlying schizophrenia spectrum disorder rather than an autistic spectrum disorder.