Neural Correlates of the Risk for Schizophrenia and Bipolar Disorder: A Meta-analysis of Structural and Functional...

Clinical features and genetics overlap in schizophrenia (SCZ) and bipolar disorder (BD). Identifying brain alterations associated with genetic vulnerability for SCZ and BD could help to discover intermediate phenotypes, quantifiable biological traits with greater prevalence in unaffected relatives (RELs), and early recognition biomarkers in ultrahigh risk populations. However, a comprehensive meta-analysis of structural and functional magnetic resonance imaging (MRI) studies examining relatives of patients with SCZ and BD has not been performed yet.

We systematically searched PubMed, Scopus, and Web of Science for structural and functional MRI studies investigating relatives and healthy control subjects. A total of 230 eligible neuroimaging studies (6274 SCZ-RELs, 1900 BD-RELs, 10,789 healthy control subjects) were identified. We conducted coordinate-based activation likelihood estimation meta-analyses on 26 structural MRI and 81 functional MRI investigations, including stratification by task type. We also meta-analyzed regional and global volumetric changes. Finally, we performed a meta-analysis of all MRI studies combined.

Reduced thalamic volume was present in both SCZ and BD RELs. Moreover, SCZ-RELs showed alterations in corticostriatal-thalamic networks, spanning the dorsolateral prefrontal cortex and temporal regions, while BD-RELs showed altered thalamocortical and limbic regions, including the ventrolateral prefrontal, superior parietal, and medial temporal cortices, with frontoparietal alterations in RELs of BD type I.

Familiarity for SCZ and BD is associated with alterations in the thalamocortical circuits, which may be the expression of the shared genetic mechanism underlying both disorders. Furthermore, the involvement of different prefrontocortical and temporal nodes may be associated with a differential symptom expression in the two disorders.