Glutamate, Brain Connectivity and Duration of Untreated Psychosis
Condition: Schizophrenia; Psychosis; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Study type: Observational

Summary: 
      The early stages of schizophrenia are associated with significant decreases in social and
      intellectual abilities, with more declines in chronic disease. Studies have identified
      relationships between duration of untreated psychosis (the duration between the onset of
      positive symptoms and treatment) and worse long term outcomes. However, the neurobiology of
      this phenomenon and its implications for response to antipsychotic medications remain poorly
      understood.

      Glutamatergic excess altering brain connectivity might provide an explanation for why those
      with longer duration of untreated psychosis have worse clinical outcomes. The investigators
      propose to use neuroimaging to study 67 first episode psychosis subjects before and after
      sixteen weeks of treatment with risperidone, a common antipsychotic. We will measure (1)
      glutamate and (2) structural and functional brain connectivity and test the hypotheses that
      glutamatergic abnormalities are present in first episode patients and that longer duration of
      untreated psychosis is associated with greater connectivity abnormalities that set the stage
      for poor response to treatment. 67 demographic-matched controls will also be recruited as a
      comparison group - healthy controls will not receive antipsychotic medication.

      The investigator's previous studies have made progress in the understanding of abnormalities
      in the glutamate system and brain connectivity in unmedicated patients with schizophrenia and
      modulation of these by antipsychotic medication. Two indices of glutamatergic dysfunction
      have been identified. While antipsychotic medications appear to modulate glutamate, the
      disturbance in the relationship between metabolites is not restored with treatment. In
      addition, the investigators found that both structural and functional connectivity
      abnormalities in unmedicated patients with schizophrenia predict patients' response to
      treatment.

      To the investigator's knowledge, no other group has performed a study that uses a combination
      of complementary neuroimaging techniques that will allow generating a broad characterization
      of glutamatergic function and brain connectivity in first episode psychosis and change with
      treatment. The results of the proposed studies could suggest a mechanism by which the
      duration of untreated psychosis is associated with poor treatment response which might lead
      to new interventions to target the illness.
    


Intervention name(s): Risperidone
Intervention type(s): Drug
Intervention description(s): Patients with psychosis will be provided a 16 week regimen of the antipsychotic drug Risperidone in accordance with standard care.
Other intervention name(s): Risperdal
Intervention MeSH terms: Risperidone
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The investigators expect to enroll a total of 67 male and female patients with first
        episode psychosis and 67 demographic matched controls.

        Among patients who participate in research at the University of Alabama at Birmingham (UAB)
        the approximate gender, ethnic and race distribution is 75% male and 25% female; 1%
        Hispanic and 99% Non-Hispanic; 54% White, 44% Black, and 1% Asian/Pacific Islander. The
        gender distribution is consistent with that observed in clinical populations with
        schizophrenia.

        Persons below the age of 17 and above the age of 35 are excluded to minimize the variance
        in cognitive functioning or brain connectivity that might be attributable to development
        rather than diagnosis.
      
Biospecimen description: 
      Genes related to glutamate, n-acetyl-aspartate, dopamine, schizophrenia, and treatment
      response to antipsychotic medication will be collected.
    
Keywords: duration of untreated psychosis; glutamate; functional connectivity; structural connectivity; schizophrenia; psychosis