Neural Mechanism Underlying the Beneficial Effect of Theory of Mind Psychotherapy on Early-onset Schizophrenia: A Randomized Controlled Trial.

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. Schizophrenia occurs worldwide, and for decades it was generally believed to have a uniform lifetime morbid risk of 1% across time, geography, and gender. Characteristic, a substantial proportion of patients with schizophrenia experience the onset of their illness by age 18, defined as early-onset schizophrenia (EOS) and were found to be associated with higher rates of premorbid abnormalities, worse cognitive performance and worse functional outcome compared to individuals with adult-onset schizophrenia. Recently, EOS patients have been the focus of substantial interest, since studies of patients with adolescent onset could provide insights into the development of the disorder, in particular the interaction between normal maturational processes and the disorder. Furthermore, EOS is featured as a debilitating form of schizophrenia that has poor prognosis and functional outcomes and that places heavy demands on caregivers.

To the best of investigators' knowledge that enduring cognitive impairment is a core feature of the illness that predict chronicity and contribute to poor functional outcomes. As EOS is potentially a key stage at which early intervention may delay or prevent the poor outcomes, and pharmacological interventions have a limited effect on cognitive impairment in EOS patients, there is a critical need and growing interest in psychosocial interventions for effective treatments for cognitive impairment in young persons with this condition, which are now recognized as an important component of a comprehensive therapeutic approach in schizophrenia. Recent advances in cognitive training, however, may inform strategies to treat EOS. For instance, as cognitive remediation therapy (CRT) uses scientific principles of learning to target cognitive deficits with the ultimate goal of improving functional outcome, there is now a substantial body of evidence in support of its efficacy in adults with schizophrenia. Furthermore, the adult recommendations are adopted in clinical practice for the treatment (referring to group psychotherapy in this study) of children and adolescents with psychosis, as there is a paucity of studies conducted exclusively with EOS patients.

The notion that specific cognitive and social abilities arise from functionally distinct brain regions has been proved by means of multimodal neuroimaging techniques mainly including structural and functional Magnetic Resonance Imaging (MRI). Previous studies of EOS patients have found abnormalities in white matter microstructure, slower white matter growth rates and disrupted functional connectivity in brain networks involved in sensorimotor processing, social cognitions and executive functions. The abovementioned evidence supports the neurodevelopmental and dis-connectivity hypotheses of schizophrenia, but the specific pattern of abnormal brain structural connectivity in EOS remains scarce. Graph-theory analysis, which examines the important properties of complex systems (i.e., centrality, global efficiency, local efficiency and small-world property), is a useful tool to quantify the topology of abnormal brain networks in EOS. To our knowledge, using the graph-based network approach, previous research has mapped structural networks in adult patients with schizophrenia based on across-subject covariance in morphological indexes, such as cortical thickness, gyrification and grey matter volumes. However, in this context, investigators constructed structural connections of brain networks characterized by white matter integrity measured by diffusion tensor imaging (DTI). Moreover, it remains unclear that how brain structural topology is altered in EOS patients after the intervention of group psychotherapy.

In this study, investigators conducted an adaptable randomized controlled trial (RCT) to investigate the effects of group psychotherapy on brain structural connectivity in EOS patients using a graph-based approach of DTI. Investigators hypothesized that adaptable group psychotherapy would help to preserve brain structural network connectivity in addition to better ameliorating clinical symptoms.