ToM Psychotherapy and Brain Networks in EOS
Condition: Early-onset Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      Background: Presence of a series of typical physical symptoms is an enduring and functionally
      relevant feature of early-onset schizophrenia (EOS). Psychotherapy improves clinical symptoms
      in adults with schizophrenia, although data in adolescents with EOS remain scarce. The
      purpose of this study is to examine the efficacy of the adapted group psychotherapy in
      improving clinical symptoms from a perspective of neuroimaging in a sample of symptomatically
      stable adolescents with EOS.

      Methods: Investigators conducted a double-blind randomized controlled trial using
      multidomain, adaptive, group psychotherapy in 28 EOS patients, who were randomly allocated
      into either training (group psychotherapy) or active control (health education) groups. Data
      of diffusion tensor imaging, and clinical symptoms were obtained at baseline and after an
      average of 2 hours/day, 2 days/week for 4 weeks of intervention.
    

Detailed description: 
      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.
    

Intervention name(s): Theory of Mind psychotherapy; health education
Intervention type(s): Behavioral; Behavioral
Intervention description(s): a semi-structured, multidomain, tailored group psychotherapy; disease-related health knowledge
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment