Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia

Correlational approaches that examine the relation between neuropsychological measures and brain morphology or physiology in schizophrenia have yielded inconsistent results. This may be due in part to difficulties in ascertaining precisely to what degree each measure deviates from its genetically and enviromentally determined potential level. We attempted to surmount this problem in a paradigm involving monozygotic twin pairs discordant for schizophrenia. In this paradigm, the difference score between the unaffected member and affected member of a twin pair should represent the degree of pathologic involvement irrespective of actual level. In correlating intrapair difference scores of anatomic structures measured from magnetic resonance imaging (n = 15) and prefrontal regional cerebral blood flow (rCBF) (n = 10) with cognitive abilities (after partialing IQ), we found strong associations between (1) the left hippocampus and a parameter of verbal memory and (2) prefrontal rCBF with symptom scores and perseveration on the Wisconsin Card Sorting Test. These results support other research implicating medial temporal and prefrontal regions as important in the symptomatic expression and cognitive failures of schizophrenia. Overall, however, there was a relative paucity of significant associations between neuroanatomic and neurocognitive variables. This may have been due to the relatively restricted ranges of hippocampal size or cognitive ability found in this sample.