Multi-site Communication Deficits in Schizophrenia
Condition: Schizophrenia; Psychosis
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Study type: Observational

Summary: 
      Multi-site Communication Deficits Underlying Cognitive Dysfunction in the Prodromal Phase and
      First Episode of Schizophrenia
    

Detailed description: 
      Abnormal long-range connectivity between brain areas and corresponding impaired
      synchronization of oscillatory rhythms in neuronal networks represent an important
      pathophysiological mechanism underlying schizophrenia. Although schizophrenia is considered
      as a neurodevelopmental disorder the mechanisms by which the abnormal neural circuitry and
      communication develops before the onset of clinical symptoms are unknown. This project aims
      to investigate the relationship between disturbed neural synchronization and cognitive
      deficits in the prodromal phase of schizophrenia and is intended to identify patients with
      increased risk for developing schizophrenia. Present approaches to describe subjects at risk
      for psychosis based on clinical features have not been completely convincing since
      psychiatric symptoms in the prodromal phase are often too unspecific. Recent studies suggest
      that detecting cognitive deficits might help for a more precise identification of high risk
      subjects. However, the underlying neurophysiological mechanisms have not yet been
      investigated sufficiently. Precise identification of subjects with high risk for switching to
      schizophrenia would be very important since interventional strategies such as medical
      treatment even with second generation antipsychotics are not completely free of risk and
      therefore should be limited to subjects with a maximal benefit. In this project subjects at
      risk for psychosis will be investigated with electroencephalography (EEG),
      magnetoencephalography (MEG) and simultaneous electroencephalography-functional magnetic
      resonance imaging (EEG-fMRI). Follow up investigations will be performed after switching to
      schizophrenia has occurred or not. Neural synchronization between the prefrontal cortex and
      the hippocampal formation will be investigated using a working memory paradigm. Here,
      different levels of memory load will be investigated using the n-back paradigm. Earlier
      studies showed disturbed functional and effective connectivity between the hippocampus and
      the prefrontal cortex both in patients with schizophrenia and subjects at risk. Neural
      synchronization between the prefrontal cortex and sensory areas will be investigated with
      different attentional paradigms. Here, tones will be presented that have to be responded to
      by button press. Earlier studies demonstrated disturbed auditory evoked gamma oscillations in
      patients with schizophrenia and unaffected siblings. Neural oscillations will be recorded
      with 64-channel EEG and localized by means of simultaneous functional magnetic resonance
      imaging (fMRI). Integration of EEG and fMRI will be performed using single-trial coupling in
      order to detect brain regions involved in specific oscillatory rhythms. Using both paradigms,
      neural long-range synchronization will be analyzed. In addition, dynamic causal modelling
      will be used for further characterization of functional relationships among brain regions
      involved. The investigators expect a functional relationship between cognitive deficits in
      subjects with prodromal schizophrenia and subjects with a first episode of schizophrenia with
      regards to long range neural synchronization. In addition, the investigators expect to
      identify subjects at high risk for schizophrenia with the analysis of disturbed long range
      synchronization.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Three groups of subjects will be included: patients with a first episode of schizophrenia,
        subjects at increased risk for schizophrenia, and healthy control subjects.
      
Keywords: Patients with a first episode of schizophrenia; Subjects at risk for psychosis