Brain Activation and Aberrant Effective Connectivity in the Mentalizing Network of Preadolescent Children at Familial High Risk for Schizophrenia or Bipolar Disorder

Abstract

BackgroundSchizophrenia 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 (FHR) for these disorders is associated with neurobiological alterations already present in childhood. MethodsAs part of the VIA 11 (Danish High Risk and Resilience Study), we examined children at FHR for schizophrenia (n = 121, 50% female) or bipolar disorder (n = 75, 47% female) and population-based control participants (PBCs) (n = 128, 48% female). 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. ResultsWe found similar activation of the mentalizing network across groups, including visual area V5, the dorsomedial prefrontal cortex, and the posterior superior temporal sulcus (pSTS). Nonetheless, both FHR groups showed aberrant brain connectivity in the form of increased feedforward connectivity from left V5 to pSTS compared with PBCs. Children at FHR for schizophrenia had reduced intrinsic connectivity in bilateral V5 compared with PBCs, whereas children at FHR for bipolar disorder showed increased reciprocal connectivity between the left dorsomedial prefrontal cortex and the pSTS, increased intrinsic connectivity in the right pSTS, and reduced feedforward connectivity from the right pSTS to the dorsomedial prefrontal cortex compared to PBCs. ConclusionsOur results provide first-time evidence of aberrant brain connectivity in the mentalizing network of children at FHR for schizophrenia or FHR for bipolar disorder. 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.