Understanding Cognitive Disability in Schizophrenia

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Understanding Cognitive Disability in
Schizophrenia
Cameron S. Carter MD University of California at
Davis
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Schizophrenia is common and can lead to lifelong
disability

• 1 of population world wide
• Males and females equally affected but females
  have later onset and better functional outcome
• Onset in late adolescence, early adulthood
• Loss of function, inability to achieve expected
  function

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EtiologyGenetics

• Highly heritable
• Risk increases with relationship e.g. 10 for
  first degree relative or fraternal twin, 50
  concordance for monozygotic twin
• Environmental factors certain but poorly
  characterized (intrauterine malnutrition, viral
  illnesses, perinatal insults, drug exposure)
• Gene environment interactions affect brain
  development and function

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Schizophrenia as a Developmental Disorder

• Most strongly associated risk genes (e.g. NRG,
  DISC1, RGS4) affect early brain development
• People who go on to develop schizophrenia show
  lower school achievement and more behavioral
  problems during childhood
• Onset during early adolescence during massive
  brain development
• Environmental risks factors have their impact
  during critical developmental windows (e.g.
  maternal influenza, early, heavy cannabis use,
  late)
• Some environmental risk factors may be mediated
  through activation of maternal immune system that
  may in turn impact brain development and synaptic
  function

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Symptoms

• At least 4 weeks of 2 of the following
• Hallucinations
• Delusions
• Negative symptoms
• Disorganization
• Minimum duration of 6 months of continuous signs
  of illness

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Alterations in dopamine neurotransmission

• C11 Racolpride displacement reflects DA release

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Increased subcortical DA related to psychosis
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Cognition In Schizophrenia

• Present at onset and throughout the life span
• Impaired cognition is a strong predictor of
  disability in schizophrenia (e.g. Green 1997).
• Currently available treatments have little impact
  on cognitive disability in schizophrenia
• Perhaps the most amenable to investigation using
  modern, non invasive neuroscientific tools
• Promising for biomarker development

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CNTRICS
Cognitive Neuroscience Treatment Research to
Improve Cognition in Schizophrenia
http//cntrics.ucdavis.edu
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Effects of hemodynamic activation on BOLD signal
in the brain a) paramagnetic properties of Hb
and b) overly zealous regulation of perfusion of
the brain
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Metanalysis of 41 fMRI Studies of Executive
Functions
Schizophrenia
Healthy Controls
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Impairment of Top Down Control in Schizophrenia
Functional Connectivity
Yoon, Minzenberg, Ursu, and Carter 2008
American J. Psychiatry
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Courtesy of David Lewis MD
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Improved Management to Improve Functional
Outcomes in Schizophrenia

• Early intervention important for improving
  functional outcome
• Rehabilitative therapies e.g. supportive
  employment and education improve outcomes
• Develop novel medication treatments targeting
  cognition
• Validate neurorehabilitation approaches

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http//earlypsychosis.ucdavis.edu