Non-linear development of brain morphometry in child and adolescent offspring of individuals with bipolar disorder or schizophrenia.

Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at increased risk of developing psychopathology. Structural brain alterations have been found in child and adolescent offspring of patients with bipolar disorder and schizophrenia, but the developmental trajectories of brain anatomy in this high-familial-risk population are still unclear. 300 T1-weighted scans were obtained of 187 offspring of at least one parent diagnosed with bipolar disorder (n=80) or schizophrenia (n=53) and offspring of parents without severe mental illness (n=54). The age range was 8 to 23 years old; 113 offspring underwent two scans. Global brain measures and regional cortical thickness and surface area were computed. A generalized additive mixed model was used to capture non-linear age trajectories. Offspring of parents with schizophrenia had smaller total brain volume than offspring of parents with bipolar disorder (d=-0.20, p=0.004) and control offspring (d=-0.22, p=0.005) and lower mean cortical thickness than control offspring (d=-0.23, p<0.001). Offspring of parents with schizophrenia showed differential age trajectories of mean cortical thickness and cerebral white matter volume compared with control offspring (both p's=0.003). Regionally, offspring of parents with schizophrenia had a significantly different trajectory of cortical thickness in the middle temporal gyrus versus control offspring (p<0.001) and bipolar disorder offspring (p=0.001), which was no longer significant after correcting for mean cortical thickness. These findings suggest that particularly familial high risk of schizophrenia is related to reductions and deviating developmental trajectories of global brain structure measures, which were not driven by specific regions.

Age Trajectories of the Structural Connectome in Child and Adolescent Offspring of Individuals With Bipolar Disorder or Schizophrenia.

Background: Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at elevated risk of developing psychiatric illness owing to both genetic predisposition and increased burden of environmental stress. Emerging evidence indicates a disruption of brain network connectivity in young offspring of patients with bipolar disorder and schizophrenia, but the age trajectories of these brain networks in this high-familial-risk population remain to be elucidated. Methods: A total of 271 T1-weighted and diffusion-weighted scans were obtained from 174 offspring of at least 1 parent diagnosed with bipolar disorder (n = 74) or schizophrenia (n = 51) and offspring of parents without severe mental illness (n = 49). The age range was 8 to 23 years; 97 offspring underwent 2 scans. Anatomical brain networks were reconstructed into structural connectivity matrices. Network analysis was performed to investigate anatomical brain connectivity. Results: Offspring of parents with schizophrenia had differential trajectories of connectivity strength and clustering compared with offspring of parents with bipolar disorder and parents without severe mental illness, of global efficiency compared with offspring of parents without severe mental illness, and of local connectivity compared with offspring of parents with bipolar disorder. Conclusions: The findings of this study suggest that familial high risk of schizophrenia is related to deviations in age trajectories of global structural connectome properties and local connectivity strength.

In this article, we show that child and adolescent offspring of parents with schizophrenia had different patterns in the development of their brain's structural connections compared with offspring of parents with bipolar disorder and offspring of parents without these conditions. The findings of this long-term study indicate that having a family history of schizophrenia is associated with changes over time during adolescence in the overall organization of the brain's structural network.