Abstract
Neuroanatomical endophenotypes may reveal insights into the processes by which genetic factors increase the risk of developing schizophrenia. To determine whether patterns of neuroanatomical asymmetries may be useful as schizophrenia-related endophenotypes, we compared patterns of structural asymmetries in patients with schizophrenia, healthy controls, and their respective siblings. The surfaces of the left and right amygdala, hippocampus, thalamus, caudate nucleus, putamen, globus pallidus, and nucleus accumbens were assessed in 40 pairs of healthy comparison controls (CON) and their siblings (CON-SIB) and 25 pairs of patients with schizophrenia (SCZ) and their siblings (SCZ-SIB) in magnetic resonance (MR) images using large deformation diffeomorphic metric mapping (LDDMM) and parallel transport techniques. The within-subject asymmetry deformation of each structure was first measured via LDDMM, and then translated to a global template via parallel transport for evaluation of the patterns of asymmetry both within and across siblings. Our results revealed that asymmetries observed in CON subjects occurred in the amygdala and the anterior segment of the hippocampus with more pronounced expansion deformation in the right-sided structures (R>L asymmetry) but not in the basal ganglia and thalamus. Disturbance in this pattern of asymmetries was observed in both SCZ and SCZ-SIB subjects. More specifically, exaggerations and reductions in the normative pattern of asymmetries were observed in the amygdala-hippocampus formation, basal ganglia, and thalamus. These altered patterns of asymmetries are present in subjects with schizophrenia and their siblings, and therefore may represent a schizophrenia-related endophenotype.