Dysregulated maturation of the functional connectome in antipsychotic-naïve, first-episode patients with adolescent-onset schizophrenia

Abstract

Background: Schizophrenia has been conceptualized as a brain network disorder rooted in dysregulated neurodevelopmental processes. Recent neuroimaging studies revealed disrupted brain connectomic organization in adult schizophrenia patients. However, altered developmental trajectories of the functional connectome during the adolescent maturational stage have not been examined. Methods: The present study combined functional MRI with a graph theoretical approach to examine functional network topology and its age-related development in 39 medication naïve, first-episode patients with adolescent-onset schizophrenia and 31 matched controls (age range: 12-18 years). Results: Patients demonstrated impaired large-scale integration as reflected by reduced global efficiency as well as decreased regional nodal efficiency in highly integrative network hubs, most consistently the hippocampal formation and the precuneus. Furthermore, the left hippocampus showed opposite age-efficiency associations in healthy controls and patients, indicating dysregulated maturational trajectories in adolescent schizophrenia and a particular vulnerability of this region during early pathological attack. Conclusions: The findings allow an integrative perspective on network and neurodevelopmental perspectives on schizophrenia, suggesting that dysregulated maturation of the functional connectome during adolescence might reflect an early marker for the disorder.