Brain activation and aberrant effective connectivity in the mentalizing network of preadolescent children at familial high-risk of schizophrenia or bipolar disorder.

Abstract

Introduction: Schizophrenia and bipolar disorder are characterized by social cognitive impairments and recent research has identified alterations of the social brain. However, it is unknown whether familial high-risk of these disorders is associated with neurobiological alterations already present in childhood.

Methods: As part of The Danish High Risk and Resilience Study - VIA 11, we examined children at familial high-risk of schizophrenia (FHR-SZ, n = 121, 50% females) or bipolar disorder (FHR-BP, n = 75, 47% females) and population-based controls (PBC, n = 128, 48% females). Using functional magnetic resonance imaging and dynamic causal modeling, we investigated brain activation and effective connectivity during the social cognition paradigm from the Human Connectome Project.

Results: We found similar activation of the mentalizing network across groups, including visual area V5, dorsomedial prefrontal cortex (dmPFC), and posterior superior temporal sulcus (pSTS). Nonetheless, both familial high-risk groups showed aberrant brain connectivity in the form of increased feedforward connectivity from left V5 to pSTS compared with PBC. Children at FHR-SZ had reduced intrinsic connectivity in bilateral V5 relative to PBC, whereas children at FHR-BP showed increased reciprocal connectivity between left dmPFC and pSTS, increased intrinsic connectivity in right pSTS, and reduced feedforward connectivity from right pSTS to dmPFC compared with PBC.

Conclusions: Our results provide first-time evidence of aberrant brain connectivity in the mentalizing network of children at FHR-SZ or FHR-BP. Longitudinal research is warranted to clarify whether aberrant brain connectivity during mentalizing constitutes an endophenotype associated with the development of a mental disorder later in life.