Understanding Cognitive Disability in Schizophrenia - PowerPoint PPT Presentation

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Understanding Cognitive Disability in Schizophrenia

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Title: Understanding Cognitive Disability in Schizophrenia


1
Understanding Cognitive Disability in
Schizophrenia
Cameron S. Carter MD University of California at
Davis
2
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

3
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

4
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

5
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

6
Alterations in dopamine neurotransmission
  • C11 Racolpride displacement reflects DA release

7
Increased subcortical DA related to psychosis
8
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9
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

10
(No Transcript)
11
CNTRICS
Cognitive Neuroscience Treatment Research to
Improve Cognition in Schizophrenia
http//cntrics.ucdavis.edu
12
(No Transcript)
13
(No Transcript)
14
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
15
Metanalysis of 41 fMRI Studies of Executive
Functions
Schizophrenia
Healthy Controls
16
(No Transcript)
17
Impairment of Top Down Control in Schizophrenia
Functional Connectivity
Yoon, Minzenberg, Ursu, and Carter 2008
American J. Psychiatry
18
Courtesy of David Lewis MD
19
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

20
http//earlypsychosis.ucdavis.edu
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