Context: The nosologic dichotomy between schizophrenia and bipolar disorder (BD) as formulated by Kraepelin is currently being questioned, stimulated by the finding that schizophrenia and BD partly share a common genetic origin. Although both disorders are characterized by changes in brain structure, family studies suggest more segregating than overlapping neuroanatomical abnormalities in both disorders. Objectives: To investigate whether patients with schizophrenia and patients with BD display overlapping abnormalities in brain volumes and cortical thickness and whether these are caused by shared genetic or environmental influences. Design: Magnetic resonance imaging findings of monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and discordant for BD, and healthy twin pairs were compared using structural equation modeling. Setting: The Netherlands Twin Register and University Medical Center Utrecht. Participants: A total of 310 individuals from 158 (152 complete and 6 incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13MZand 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ discordant), and 83 healthy twin pairs (44MZ and 39 DZ). Main Outcome Measures: Estimates of additive genetic and unique environmental associations between schizophrenia and BD with overlapping and nonoverlapping volumes and cortical thickness. Results: Higher genetic liabilities for schizophrenia and BD were associated with smaller white matter volume, thinner right (and left) parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal and left superior motor cortices; higher environmental liabilities were associated with thinner right medial occipital cortex. Genetic liability for schizophrenia was associated with thicker right parietal cortex; for BD, with larger intracranial volume. Conclusions: Brain structures reflect overlapping and segregating genetic liabilities for schizophrenia and BD. The overlapping smaller white matter volume and common areas of thinner cortex suggest that both disorders share genetic (neurodevelopmental) roots. ©2012 American Medical Association. All rights reserved.