Cognitive Impairment in Schizophrenia

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Cognitive Impairment in Schizophrenia

• Michael F. Green, PhD
• Department of Psychiatry and Biobehavioral
  Sciences, Geffen School of Medicine at UCLA
• UCLA Semel Institute
• VA Desert Pacific Mental Illness, Research,
  Education and Clinical Center (MIRECC)

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Presidents Commission on Mental
HealthDefinition of Recovery

• Recovery
• refers to the process in which people are able to
  live, work, learn, and participate fully in their
  communities. For some individuals, recovery is
  the ability to live a fulfilling and productive
  life despite a disability. For others, recovery
  implies the reduction or complete remission of
  symptoms. Science has shown that having hope
  plays an integral role in an individuals
  recovery.

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Global Burden of Disease 2000Disease-adjusted
Life Years (DALYs)
Top 10 Causes of DALYs in Adults (15-44 years)
Both Sexes Total Male Total Female Total
HIV/AIDS 13.0 HIV/AIDS 12.1 HIV AIDS 13.9
Depressive disorders 8.6 Road traffic accidents 7.7 Depressive disorders 10.6
Road traffic accidents 4.9 Depressive disorders 6.7 Tuberculosis 3.2
Tuberculosis 3.9 Alcohol Use Disorders 5.1 Iron deficiency anemia 3.2
Alcohol Use Disorders 3.0 Tuberculosis 4.5 Schizophrenia 2.8
Self-inflicted Injuries 2.7 Violence 3.7 Obstructed labor 2.7
Iron-deficiency anemia 2.6 Self-inflicted Injuries 3.0 Bipolar disorder 2.5
Schizophrenia 2.6 Schizophrenia 2.5 Abortion 2.5
Bipolar disorder 2.5 Bipolar disorder 2.4 Self-inflicted injuries 2.4
Violence 2.3 Iron deficiency anemia 2.1 Maternal sepsis 2.1
DALYSum of years of life lost due to premature
mortality and years lost due to disability
WHO. The World Health Report 2001. Available at
http//www.who.int/whr/2001/en/index.html
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Outcome of Schizophrenia in 20th CenturyPercent
Recovered in 306 Follow-up Studies
Hegarty et al. 1994
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Outcome Domains in Schizophrenia
Social Functioning Vocational Functioning Living
Situation Positive Symptoms Negative
Symptoms Self-Esteem Subjective
Distress Satisfaction with Life
Functional Status
Disorder Variables
Subjective Variables
Brekke et al., 1993 Brekke Long 2000
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Cognition in Schizophrenia Core Feature of the
Illness

• Present before onset of clinical symptoms
• Seen in unaffected first-degree relatives
• Relatively stable across clinical state life
  span until late adulthood
• Low cross sectional correlations w/ psychotic
  symptoms
• Discrepancy between clinical and cognitive
  effects of antipsychotic meds
• Schizophrenia profile of deficits (w/ variation)

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Cognitive Impairment Magnitude in Schizophrenia
Meta-Analysis 204 studies, 7420 patients and
5865 controls
Characteristic profile in schizophrenia maximal
impairment in memory, attention, and executive
function relative preservation of old learning
and visual perceptual skills.
SD Units
Heinrichs Zakzanis Neuropsychology 1998
Healthy Comparison Mean
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Alzheimers Dementia compared with Schizophrenia
Neuropsychological Deficit Scores
From Heaton et al. (1994)
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Key Cognitive Domains for Schizophrenia From
NIMH-MATRICS Consensus Process

• 1) Speed of Processing
• 2) Attention / Vigilance
• 3) Working Memory
• 4) Verbal Memory
• 5) Visual Memory
• 6) Reasoning and Problem Solving
• 7) Social Cognition

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Cognitive DomainVerbal Learning
Definition Ability to acquire, store, and
retrieve verbal information for more than a few
minutes
CANARY SHOES EAGLE BLOUSE NAILS CROW BLUEBIRD SCRE
WDRIVER PANTS CHISEL SKIRT WRENCH
Example Hopkins Verbal Learning Test Revised
Activities of daily living remembering
information from a rehabilitation program,
class, vocational setting, clinic visit
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Cognitive DomainWorking memory

• Definition Ability to hold information on line
  in a temporary store and/or to manipulate the
  information

Example Letter Number Span
K3B4 _ _ _ _ R8C3G5 _ _ _ _ _ _
Activities of daily living carrying on a social
conversation switching between different tasks
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Cognitive DomainAttention / Vigilance
Definition Ability to respond to targets, not
respond to non-targets, over a period of time
Example Continuous Performance Test Identical
Pairs
Press when you see the same number twice in a
row
1 second
100 ms
743
Stimuli
254
364
743
Response
hold
hold
hold
press
Time
Activities of daily living identifying relevant
information in a social interaction discussion
with a doctor
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Social Cognition
We mortals cannot read other peoples minds
directly. But we make good guesses from what
they say, what we read between the lines, what
they show in their faces and eyes, and what best
explains their behavior. It is our species most
remarkable talent. Steven Pinker
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Measurement for Social Cognition in Schizophrenia

• 1. Still Faces
• affect perception
• 2. Filmed vignettes
• identifying
• social situations
• or emotions
• 3. Written vignettes
• Theory of Mind,
• social knowledge,
• attributional bias
• emotion management
• 4. Other methods e.g., jumping
• to conclusions, role plays

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Cognition and Functional Outcome in
Schizophrenia

• Cognitive deficits are reliable correlates and
  predictors of functional outcome (disability)
• Functional outcome includes work outcome, social
  outcome, independent living, skills acquisition
• Magnitude of associations medium for specific
  domains large for summary scores
• Relationships are stronger than between psychotic
  symptoms functional outcome
• Cognitive deficits are linked to success in
  psychiatric rehabilitation

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Cognition, Mediating Variables, and Functional
Outcome
Mediating Variables
Functional Outcome Domains
Interventions
Psychopharmacological

• Social
• Occupational
• Independent Living
• Rehabilitation Success

Social Cognition
Basic Cognition
Functional Capacity
Psychosocial
Brekke et al. 2005 2007 Sergi et al. 2006
Bowie et al. 2006
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NIMH MATRICS (Measurement and Treatment
Research to Improve Cognition in Schizophrenia)
Goals and Products

• Create Standardized Measure for use in Clinical
  Trials
• Define Optimal Experimental Designs
• Establish path to FDA Approval
• Attract large pharmaceutical companies to focus
  efforts on this important clinical target
• Success required involvement of NIMH, FDA,
  pharmaceutical industry, and academia

www.matrics.ucla.edu
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Cognition in in Schizophrenia Conclusions

• Functional outcome in schizophrenia is generally
  poor and the level of disability is generally
  high.
• Cognitive impairments are key determinants of
  poor functional outcome in schizophrenia.
• The cognitive impairments of schizophrenia
• Are core features of the illness
• Can be reliably measured
• Are not well-treated by any current medications
• There is considerable activity to develop new
  treatments for cognitive impairment and
  recovery-focused approaches -- but for now,
  outcome remains disappointing.