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.
