Cognitive changes have been a defining feature of Sz since onset. A lot of research has been done in understanding these changes and its implication in developing novel methods of treatments. This ppt summarises the cognitive changes occurring in the brain.

1. Neurocognition in
Schizophrenia
Dr Parth Goyal
Second Year Resident
Department of Psychiatry

2. History
• Cognitive deficits in schizophrenia have been
identified as early as Kraeplin's original
description of "dementia praecox," meaning
cognitive decline with onset in youth.
• They are widely suggested to be a core feature
of schizophrenia with increasing support for
including impairments in cognition in the
diagnostic criteria of the illness.

3. Reasons why its important ?
• Sz affects various domains of cognition
• Schizophrenics on an average perform 1-2 SD
below healthy controls on tests of cognition
• Adversely impacts day-to-day functioning of
patients

4. Practical Relevance
• Cognitive impairments are associated with poor
functional outcomes in patients
• This includes:
• a) Difficulty in community functioning
• b) Inability to maintain successful employment
• c) Difficulty in problem solving skills.

5. Areas Affected
• Vigilance
• Verbal Memory
• Visual Memory
• Speed Of Processing
• Reasoning & Problem Solving
• Verbal Fluency
• Immediate & Working Memory
• Social Cognition

6. Efforts to understand these
deficits?
• The NIMH undertook a very comprehensive study
titled “MATRICS”, Measurement and Treatment to
Improve Cognition in Schizophrenia, to evaluate
cognition in Sz.
• It evaluated more than 1000 patients on various
cognitive domains in a variety of conditions.
• The “CATIE”, Clinical Anti-Psychotic Trial of
Intervention Effectiveness study was done to assess
the effects of anti psychotics on a variety of domains in
schizophrenia.

7. Finding of MATRICS
• SZ patients perform poorly in all domains of
cognition with a SD of 1-2.
• The impairment in performance is more or less
constant over time
• Most patients have impairment before the onset of
the first episode psychosis
• There is a further decline in cognitive performance
after the first episode of psychotic symptoms.

8. Comparison b/w Various Subjects.

10. Findings of CATIE
• Cognitive decline is present before the initiation of
anti-psychotic treatment
• The AP do little to reverse the changes
• The maximum benefit has been shown with the use
of perfenazine
• Newer AP’s do not provide any sustainable benefit
over the older AP’s in context to cognitive changes.

11. Vigilance
• The first domain to be tested on cognitive
assessment is that of Vigilance:
• Def: Ability to maintain attention over time.
• Test: Continuous Performance Test
• Performance: Perform poorly as compared to
healthy controls

12. Test Procedure (CPT)
• 2-4 digit numbers are shown sequentially @
1/sec
• Patient instructed to press the key/mouse when
he sees an identical number as the one
presented before on the screen.

13. Real Life Difficulties
• Patients unable to maintain vigilance encounter
a number of problems:
• a) Difficulty following social conversation
• b) Inability to follow instructions
• c) Difficulty performing simple activities like
watching tv or reading.

14. Verbal Learning and Memory
• Def: This is the memory a/w a) Learning of new
information b) Retaining new information c)
Recalling new information
• Test: California Verbal Memory Test
• Results: Patients have more difficulty in learning
new things than in recalling.

15. Test Procedure (CVLT)
• Patients are given 15 names and are asked to
recall them afterwards.
• This is true even for more interesting events like
stories.
Trial Number Healthy Controls Schizophrenics
1st 8/15 5/15
5th 13/15 9/15

16. Real Life Difficulties
• Patients experience severe social and
occupational deficits
• Since verbal memory is routinely required in this
ever changing world, deficits on this cognitive
domain severely impair the patients ability to
deal with the changes constantly required at
work place.

17. Visual Learning and Memory
• Def: This is domain a/w learning, retaining and
recalling visual information in its shape, form,
content and position.
• This domain is found to be the least impaired in
schizophrenia than other domains

18. Test Procedure
• Patients are asked to
• a) draw a figure from memory
• b) indicate among an array of figures which was
presented previously.

19. Real life Difficulties
• The impairments in this domain are strongly
correlated with functional outcomes and can
affect patients in all of the ways mentioned
previously.

20. Reasoning & Problem
Solving
• Def: Ability of a person to logically navigate through
problems and take a decision appropriate to the
situation
• Test: Wisconsin Card Sorting Test
• Result: Perform poorly as compared to healthy
controls
• This test also measures vigilance and visual
memory.

21. Test Procedure(WCST)
• The patient is given a deck of cards and is asked to sort the
cards on the basis of three parameters
• 1) Colour
• 2) Form
• 3) Number
• Patients with Sz or with frontal lobe dysfunction exhibit
perseveration on this test.
• This lead to the formulation of the “Frontal hypo function
hypothesis of SZ”

22. Real life Difficulties
• Patients who perform poorly on this test show
impairments in all fronts of life
• Primarily these impairments stem from a
decreased ability to adapt to changes in real life
situations.

23. Speed of Processing
• Def: Ability to automatically and fluently perform
relatively easy cognitive tasks especially when
high mental efficiency is required.
• Test: Wechsler Adult Intelligence Scale Digit
Symbol Test
• Result: Patients perform poorly as compared to
healthy controls.

24. Test Procedure(WAIS-
DST)
• Each number 1-9 is associated with a different
simple symbol
• Subjects are required to copy as many symbols
a/w numerical in 90 secs.
• Patients with SZ show sever deficits on this test
and the performance on this test has accounted
for the maximum variance in the overall
composite score on the CATIE study.

25. Real Life Difficulties
• 1) Reduced ability of patients to keep up with
“Task related Jobs”
• 2) Increased “social latency” which hampers
relationships.

26. Verbal Fluency
• Def: It is a cognitive function that facilitates information
retrieval from memory.
• Successful retrieval requires executive control over
cognitive processes such as selective attention, selective
inhibition, mental set shifting, internal response generation
and self monitoring.
• Tests: There are two different tests, each to test
phonological and semantic fluency
• Results: Patients perform significantly worse than their
healthy counter parts

27. Test Procedure
• Phenomenological Fluency: Name as many
objects starting from a single letter e.g. “a” in 60
seconds.
• Sementic Fluency: Category based. E.g. name
as many animals as you can in 60 seconds
starting with the letter “c”

28. Real life Difficulties
• Hampers social and vocational rehabilitation
• Makes communication difficult and awkward.

29. Immediate/Working Memory
• Def: Immediate memory is the amount of information
that is held online to perform a specific task.
• Working memory: Memory that can be subjected to
some manipulation while being held online
• Also includes the visuo-spatial memory.
• These domains can be tested on routine MSE/MMSE
tests and are severely impaired in patients with SZ.

30. Real life Circumstances
• They are the core components of neuro-cognitive impairment
• Causes impairments in other cognitive domains like:
• attention
• planning
• memory
• intelligence
• IT is also closely related to the “Hypofrontality Hypothesis”

31. Social Cognition
• Refers to how people process social information especially its
encoding, storage, retrieval and application to social
situations.
• This domain of cognition is associated with understanding the
context of conversations based on an accurate interpretation
of facial expression, social cues and eye movements.
• This domain is severely impaired in SZ and the theory
concerning the same is called “Theory of Mind (ToM)”.
• Many studies have been done to measure and objective this
impairment.

32. Course of Cognitive
Impairment
• Significant deficits present in childhood f/b
decline prior to 1st episode.
• Generally stable, not progressive
• Deficits of around 1-2 SD from healthy controls
• Can serve as an early predictor for detecting SZ
in “high risk and ultra high risk” persons.

33. Course of Cognitive Impairment in Sz.

34. Genetics
• Clear Heritable component
• First degree relatives have impaired
performance on a number of tasks.
• Genetic Factors >> Environmental Factors
• A number of genes and SNP’s have been
implicated in the genesis. No single gene has
been identified yet.

35. Deficits in Children and
Follow Back Studies in SZ
• “Follow Back Method” has been used in a number of
studies to assess the temporal relationship and
change in cognition in SZ.
• a) UK National Survey of Health and Development
Study
• b) Swedish Army Study
• c) Iowa Test Study
• d) Israeli Draft Board Registry.

36. Relationship of Neuro cognitive
Changes to Sz Symptoms
• The question of the hours is:
• “Is it possible that the impairments that are seen
on these test could be due to the symptoms of
Sz (positive and negative), rather than them
being an indicator of pure cognitive
dysfunction?”

37. Cognition and Positive
Symptoms.
• If these impairments were due to positive symptoms then they
should reverse when the symptoms are controlled
• Similiar impairments are not seen in patients with other
psychotic illness like Bipolar Mood Disorder.
• In the CATIE study, more than 91% patients were able to
complete the neurocognitive tasks and the over all correlation
b/w positive symptoms and impaired cognition was nearly zero.
• The potential confounds: a) Patients too psychotic to be tested;
b) Low temporal stability and reliability of these symptoms.

38. Cognitive Impairments and
Negative symptoms
• Neuro-cognitive impairments (NCI) are significantly
correlated with negative symptoms
• Motor outcomes strongly related
• A/b/w reduced motivation and poor performance of
tests is complex.
• Increase in pupil size is seen in Sz patients while
performing tests, indicating that patients are engaged
neuro cognitively. However the results on the test are
not convincing

39. Contd.
• There is compelling evidence to suggest that poor
performance on these tests, causes low reward
expectation which in turn enhances low motivation.
• At 1 year interval, both symptoms are a/w poor
performance, but are not predictive of each other. If
negative symptoms were to cause this impairment,
then a longitudinal relationship is to be expected
• Differentially NCI are more strongly a/w poor functional
outcomes and adaptive changes than are negative
symptoms

40. Summary (Correlation with
Negative Symptoms)
• Cross sectional correlation of negative
symptoms and NCI has been “consistently”
reported
• Magnitude: Modest
• Directionality: Not well understood
• Enough evidence for both ends of the spectrum.

41. Treatment of NCI
• Large amount of research is going into
understanding the exact neurobiology, thus giving
us better pharmacological targets in the future.
• Treatment with AP’s (1st Gen) has been shown to
cause lethargy, somnolence and EPS, all of which
impair cognition
• In addition the anti cholinergic given to often
control these symptoms, exacerbate cognitive
impairments by causing confusion.

42. Contd.
• The CATIE study compared the efficacy of 4
different second gen AP in NCI.
• The anti-psychotics studied were olanzapine,
risperdione, ziprasidone and quetiapine.
• These were compared against perfanzine.
• The end result: Effects of AP’s was negligible.

43. Cognitive Remediation.
• Cognitive remediation is an intervention that seeks to enhance the
neuro-cognitive skills in patients relevant to their recovery goals.
• Learning-based behavioural skills designed to enhance neuro and/
or social cognitive skills.
• Based on drills & strategies
• Ultimate goal: generalisation to improve psychosocial outcomes
• Innovations:
-Incorporate new generation of computerised cognitive training
-Integrate CR with skills training,
-Apply techniques to enhance motivation and learning during
CR

44. Compensatory Approach
Two main approaches: Compensatory and
Restorative.
Compensatory approaches utilise environmental
supports and adaptive strategies to bypass
cognitive deficits and improve target behaviours
and functional outcomes in individuals with
schizophrenia

45. Restorative Approach
• Cognitive enhancement therapy (CET) is a multi-
component cognitive remediation approach, is
an e.g. of Restorative Approach.
• CET is designed to provide enriched cognitive
experiences through targeted and integrated
neuro-cognitive and social-cognitive training.

46. Contd.
The focus is on enhancing both "bottom-up" processing of
critical social stimuli, with "top-down" executive control
over distracting information and emotional arousal.
Through the integration of computer-based cognitive
exercises in attention, training, and problem-solving, with
an active social-cognitive group experience designed to
facilitate perspective-taking, gistful processing of
information, and social context appraisal, CET is thought
to provide the requisite experiences needed to enhance
neural processing and achieve adult cognitive milestones.

47. Results
• A/w medium effect sized for cognitive and
functional outcomes
• Better if incorporated with
• a) Psychosocial rehabilitation programs
• b) Incorporate strategy teaching and other
methods.

48. Psychopharmacology
The etiologic and phenomenological complexity of neuro-cognitive
deficits in schizophrenia may be better served by
psychopharmacological agents that
(i) target neurotransmitter systems proximal in the causal chain to
neurocognitive deficits
(ii) enhance distal survival processes in the central nervous
system—neurogenesis, neuronal growth, synaptogenesis, and
connectivity
(iii) counteract the negative effects of aberrant neurodevelopment
in schizophrenia, such as neuroinflammation and oxidative stress.

49. Agents that counteract Neuro
inflammation and Oxidative stress.

50. Results so Far
• Consistent positive improvements in neuro-cognition
have “not” been found with psychopharmacological
treatment in people with schizophrenia.
• Clearly, the neurobiological basis of neuro-cognitive
deficits in schizophrenia is quite complex, not limited to
a single target but several interconnected signalling
systems.
• The variable aetiology and phenomenology of neuro-
cognitive dysfunction in schizophrenia may very well
contribute to the limited efficacy of enhancing drugs.

51. Indian Numbers
• India vs. US- no significant gender differences in Indian
sample vis a vis reproductive indices (n=224 -I and 144-
US) (Bhatia et al 2002)
• New Delhi- 34% lower occupations, + 20% unemployed,
39% drift lower. (Bhatia Chakraborty et al 2008)
• Chennai: Social but not cognitive deficits related to work
dysfunction. (Srinivasan & Tirupati 2005)
• Wandering aimlessly: 22% (Jakhar 2012)
• Cognitive deficits in chronic Sz in India similar to those in
Western studies. N=100 (Srinivasan et al 2005)
• Poor Cognitive test performance related to impaired:
Self-care, occupational role, social role, and family role
Inversely correlated to negative symptoms.

52. Thank You.