Neuropsychology of Schizophrenia: Implications for Treatment

1
Neuropsychology of Schizophrenia Implications
for Treatment

• Bernice A. Marcopulos, Ph.D., ABPP-Cn
• Neuropsychology Lab
• Western State Hospital

2
Talk Overview

• Provide an overview of the main
  neuropsychological findings in persons with
  schizophrenia (PWS) and functional implications

3
Talk overview

• Provide evidence that schizophrenia is a
  neurodevelopmental disorder that affects brain
  functions
• Review neuropsychological test findings
• Review neuropsychological interventions

4
History

• Over the past 15 years, there has been a steady
  increase in interest in the cognitive deficits
  associated with schizophrenia (Goldstein, 1987
  Heinrichs, 1993 Keefe, 1995)
• Cognitive deficits were observed early in the
  study of the disease

5
Schizophrenia is a Brain Disease

• Kraeplin (1907) dementia praecox - gradual
  cognitive deterioration
• "the fact is decisive that the morbid anatomy has
  disclosed not simple inadequacy of the nervous
  constitution but destructive processes in the
  background of the clinical picture."

6
History

• However, during the middle of this century, the
  neurological basis of schizophrenia was not
  appreciated
• Psychosocial etiologies were favored
• schizophreno-genic mother

7
History

• Efficacy of neuroleptic drugs which block
  dopamine in the brain prompted researchers to
  look for biochemical imbalance

8
Schizophrenia is a neurodevelopmental disorder

• Weinberger (1987)
• high probability that schizophrenia will manifest
  itself in late adolescence or early adulthood
• the role of stress in onset and relapse
• the therapeutic efficacy of neuroleptics

9
Schizophrenia is a neurodevelopmental disorder

• if a lesion affects a brain structure or region
  that has yet to mature functionally, the effects
  of the lesion may remain silent until that
  structure or system matures. (Weinberger, 1987,
  p. 662)

10
Pre- and perinatal environmental risk factors of
schizophrenia

• Place or time of birth
• Winter
• Urban
• Prenatal infection
• Maternal malnutrition
• Prenatal stress
• Obstetric complications

11
Evidence for neurodevelopmental encephalopathy

• Increased association with prenatal viral
  exposure
• Mednick et al.(1988) large epidemiological study
  in Finland. Influenza epidemic in 1957. Those at
  risk during the 2nd trimester had significantly
  more hospitalizations for schizophrenia

12
Evidence for CNS Abnormality

• Physical Abnormalities
• more abnormalities than controls
• not associated with cognitive deficits (Green et
  al., 1989)
• evident in early development (Walker - home
  movies)

13
Evidence for neurodevelopmental encephalopathy

• Increased frequency of minor physical anomalies
• enlarged ventricles
• head circumference
• hair whorls
• very fine hair
• covered epicanthus
• low seated ears
• furrowed tongue
• curved 5th finger
• single palmar crease
• webbed toes
• 3rd toe longer than 2nd

14
Evidence for CNS Abnormality

• Neurological Soft Signs
• Abnormalities comprising deficits in sensory
  integration, motor coordination, and sequencing
  of complex motor acts
• More prevalent in schizophrenia (Dazzan Murray,
  2002)
• Can decrease with stabilization of symptoms
• Associated with outcome

15
Evidence for neurodevelopmental encephalopathy

• Increased frequency of obstetric complications
• Abnormal fetal development associated with
  abnormal delivery (Gunther-Genta, Bovet,
  Hohlfield (1994)

16
Evidence for CNS Abnormality

• Detectable at or near onset of illness
• Meta-analysis of 58 MRI studies (Wright et al.,
  2000)
• Enlarged lateral and 3rd ventricles
• Mild reduction (2) in global cerebral volume
• Prefrontal, hippocampus, amygdala,
  parahippocampal gyrus, superior temporal gyrus,
  cingulated gyrus, thalamus insula
• Increased volume of basal ganglia
• Due to antipsychotics
• Also seen in unaffected relatives to a lesser
  degree
• No further volume reduction (Whitworth et al.,
  2005)

17
Evidence for CNS Abnormality

• Abnormalities have been found in frontal (i.e.,
  frontal-striatal-thalamic-cerebellar axis),
  temporolimbic, dopaminergic, and glutaminergic
  systems (Keshavan et al., 2004)

18
Evidence for CNS Abnormality

• fMRI of high risk children
• Offspring of parent with schizophrenia
• 10-16 risk of developing schizophrenia-related
  illness compared with 1 of general population
  (Gottesman et al., 1982)
• Reduced activation in frontal and parietal areas
• Abnormalities in frontal and parietal heteromodal
  association cortex may precede illness (Keshavan
  et al., 2002)

19
Premorbid cognitive functioning

• Children from 1946 birth cohort who later
  developed schizophrenia had lower mean scores on
  educational tests at ages 8, 11, 15 (Jones et
  al., 1994)
• Children seen at child guidance clinic those
  who developed schizophrenia had lower IQs and
  impaired speech, language and reading (Ambleas,
  1992)
• Premorbid language dysfunction - 12 fold increase
  (Bearden et al., 2000)

20
Premorbid cognitive functioning

• Children who later developed schizophrenia fell
  below state norms on the Iowa Tests of Basic
  Skills for every category for grades 4, 8 11
  (Fuller et al., 2002)
• Linear decline in language across time
• Statistically significant difference at grade 11

21
Premorbid behavioral abnormalities

• Elaine Walker and colleagues (1993, 1994) study
  of home movies
• Children who later developed schizophrenia show
  less joy and more negative facial expressions of
  emotion when compared with healthy siblings

22
Early detection of high risk children

• Unusual movements and coordination problems in
  mid-childhood significantly associated with adult
  schizophrenia (Rosso, et al., 2000)
• More likely to have delayed milestones (Jones et
  al, 1994)

23
Neurocognitive Deficits

• Heinrichs (2005) has cogently argued for the
  primacy of cognition in characterizing
  schizophrenia, stating,
• Cognitive differences between schizophrenia
  patients and healthy people have emerged
  systematically as the most powerful findings
  across hundreds of studies and two decades of
  neuroscience-based research (p. 238).

24
Neurocognitive Deficits

• Neurocognitive deficits are a core, stable trait
  of the schizophrenic illness that accounts for
  much of the functional impairment observed
  (Green, 1996 Green, Kern, Braff, Mintz, 2000
  Green Nuechterlein, 1999)

25
Neuropsychological Deficits in Schizophrenia

• Heterogeneous cognitive deficits in up to
  61-78(Heinrichs Zakzanis, 1998)
• Memory deficits, esp. verbal
• Lower intelligence
• Poor attention

26
Neuropsychological Deficits in Schizophrenia

• A large proportion of this patient population is
  impaired on standard neurocognitive tests
• Meta-analysis suggests that any selective
  deficits in functions like verbal memory are
  relative and exist against a background of
  general dysfunction (Heinrichs Zakzanis, 1998,
  p. 437)

27
Cognitive Functions

• Intelligence
• 3 trajectories (Weickert Goldberg, 2000)
• Widespread impairment early in development Low
  premorbid scores on children who later develop
  Schizophrenia (Seidman et al., 2006)
• Low IQ as risk factor (Reichenberg, et al., 2006)
• Cognitive deficits at onset of psychosis
• Little or no decline
• Working Memory factor most susceptible

28
Decline in IQ?

• IQ decline observed during adolescence for
  children with schizophrenia
• Due to inability to acquire new information and
  abilities rather than cognitive deterioration
  (Bedwell, et al., 1999)

29
Cognitive Functions

• Executive Functions
• WCST
• fewer categories
• increased perseverations

30
Cognitive Functions

• Language
• schizophasia - thought disorder affects speech
• neologisms
• paraphasias
• perseverations

31
Memory Functions

• Impaired memory is most common in schizophrenia,
  but also occurs in other psychiatric disorders,
  esp. depression (Egeland et al., 2003)
• Both patients with depression and schizophrenia
  show working memory problems
• Schizophrenia shows acquisition failure
• Depression shows primarily retrieval problems

32
Memory Impairment in Schizophrenia

• Aleman, Hijman, de Haan, Kahn (1999)
  meta-analysis in Am J Psych
• Memory impairment disproportionate to overall
  level of intellectual impairment
• Compared with normals, impairments on
• Long term recall
• Short term recall

33
Memory Impairment in Schizophrenia

• Meta-analysis
• Moderator variables which did NOT have an effect
  on memory
• Medication status
• Duration of illness
• Severity of psychopathology
• Positive symptoms
• Age

34
Memory Impairment in Schizophrenia

• Meta-analysis
• Moderator variables which did have an effect on
  memory
• Negative symptoms

35
Summary on Cognitive Dysfunction in Schizophrenia

• All cognitive deficits most associated with
  negative symptoms
• -implies more severe disease, more neurological
  involvement

36
Cognitive effects from typical antipsychotics
(Blyler Gold, 2000)

• Possible improvement
• Wechsler Memory Scale
• No effect
• WAIS
• Verbal fluency
• Stroop
• Mazes

37
Cognitive effects from typical antipsychotics
(Blyler Gold, 2000)

• Possible improvement
• attention on CPT sx reduction effect?
• No effect or possibly worsen
• WCST
• Trails
• Simple reaction time
• manual motor tests
• Some side effect medications (anti-Ach) can make
  cognitive functioning worse

38
New antipsychotics may improve cognition

• Risperidone associated with greater gains in
  learning acquisition, recall consistency, and
  recognition on the CVLT (Kern et al., 1999)
• Risperidone treated patients improved by 1 SD
  from baseline
• Haloperidol by 0.25 SD

39
New antipsychotics may improve cognition

• Pharmacological mechanism for improvement as yet
  unknown, but believed to be mediated by cortical
  dopaminergic transmission

40
New antipsychotics may improve cognition

• Meta-analysis by Woodward, Purdon, Meltzer Zald
  (2005)
• Atypicals (Clozapine, Olanzapine, Quetiapine,
  Risperidone) have a mild cognitive remediation
  effect and are superior to typicals in improving
  cognition
• Improvements noted in Learning and Processing
  Speed

41
Neurocognitive deficits predict adaptive
functioning

• Verbal memory related to community outcome
• Vigilance predicts social effectiveness
• Executive function related to work/productivity,
  independence in ADLs, social competence and
  global measures of functioning (Velligan et al.,
  2000)

42
Vocational Outcome

• Only 16 to 30 of patients with schizophrenia are
  employed
• effective med tx has little impact
• no correlation with BPRS or SANS
• cognitive variables most predictive
• processing speed
• working memory
• reasoning

43
Clinical Implications of Neuropsychological
deficits

• Cognitive deficits underlie adaptive behavior
  deficits which medications cannot improve
• Improvement in cognition may improve social
  skills, work skills, etc
• Cognitive domains of executive functioning,
  verbal fluency and verbal working memory
  correlate with recovery from schizophrenia
  (Kopelowicz et al., 2005)

44
Rationale for Developing Cognitive Rehabilitation

• Neuropsychological studies of PWS show deficits
  believed to be part of primary symptom complex
• Deficits have functional implications re
  successful discharge
• Many patients referred for Neuropsychological
  testing show deficits

45
Effects of cognitive deficits

• Cognitive deficits are related to insight
  insight related to treatment compliance
• Cognitive deficits related to social perception
• Interferes with learning so that patients cannot
  benefit from traditional rehab approaches

46
Definition of Cognitive Rehabilitation(Sohlberg
Mateer, 1989)

• Cognitive Rehabilitation has been defined as the
  therapeutic process of increasing or improving an
  individuals capacity to process and use incoming
  information so as to allow increased functioning
  in everyday life. This includes both methods to
  restore cognitive function and compensatory
  techniques

47
Effects of Cognitive Remediation

• Patients on atypicals benefit more from Cog Rehab
• Cognitive performance improvement indirectly
  related to changes in social functioning (Wykes
  et al., 1999 Spaulding et al., 1998)
• Cog Rehab improved self-esteem (Wykes et al.,
  1999)

48
Does Cog Rehab work?

• Mueser, Bond Drake (2001) Critical review of
  community based treatment outcomes
• Promising results suggesting cog rehab has impact
  and other areas of functioning
• but too few studies, rehab methods and outcome
  variables differ, to draw specific conclusions
• More research needed

49
Recommendations

• Understand neurocognitive status when designing
  interventions
• All patients on atypicals few, if any on
  anticholinergics
• Error-free learning, reinforcement, feedback
• Encourage/enhance empowerment and recovery

50
Case Presentation