Neuromorphometric Measures as Endophenotypes of Schizophrenia Spectrum Disorders

Abstract

Abnormal size of cortical and subcortical brain structures is strongly associated with schizophrenia, and has also been reported in unaffected relatives of patients, and in those with associated diagnoses such as schizotypal personality disorder. Such volumetric measures have been considered as potential candidates for schizophrenia endophenotypes as they are heritable, co-segregate with the broadly defined neurocognitive and behavioral phenotypes within first degree relatives, and are frequently present in unaffected family members. In recent years, shape analyses have become of increasing interest due to their potential to precisely locate surface defects and their increased sensitivity for subtle volume changes. Statistical analysis of shape variables have recently been shown to improve the discrimination of individuals with schizophrenia from healthy controls, when included with overall volume. Computerized methods of shape analysis have been used to detect systematic differences in regional cortical thickness and gyral patterns between individuals. Methods such as large-deformation high-dimensional brain mapping and spherical harmonics have identified localized abnormalities within the hippocampus, thalamus and basal ganglia in schizophrenia, which were similar to those observed in unaffected siblings. The chapter reviews the status of current research involving both shape and volume of brain structures that applies to schizophrenia, and discusses future research directions required to establish these measures as endophenotypes.