W1.1
CHAPTER 24 (KESSELS, ELING, PONDS, SPIKMAN & VAN ZANDVOORT) –
SCHIZOPHRENIA
HISTORY OF SCHIZOPHRENIA
Kraepelin: Referred to schizophrenia as dementia praecox (= ‘premature dementia’)
- Particularly focused on the progressive course – Thought this would eventually result
in a terminal type of dementia
- Hallucinations: Sensory perceptions that resemble an actual perception, yet without
the stimulation of the sense involved
- Delusions: Beliefs that do not correspond to reality and which are not shared by others
in the patient’s culture or subculture
Bleuler: Introduced the term schizophrenia
- Pessimistic about the course of the disorder and emphasised its progressive nature
- Bleuler’s four A’s: Four symptoms which Bleuler considered to be the most
distinctive aspects of schizophrenia:
1. Ambivalence: Not being able to make choices
2. Blunted affect: A decreased expression of emotions
3. Autism: Decreased participation in social interactions
4. Loosening of association: Not being able to make proper logical connections
SYMPTOMOLOGY
Subdivision:
1. Positive symptoms: Delusions and hallucinations – The increase in certain functions or
thoughts
2. Negative symptoms: Blunted affect, ambivalence and autism – The decrease in certain
behaviours or functions
3. Disorganisation: Loosening of association
Criteria for a diagnosis of schizophrenia:
- There must be a deterioration in social functioning
- The symptoms must last at least 6 months
- At least two symptoms, of which at least one positive symptom, must be present
70-80% of people with schizophrenia suffer from cognitive impairments – Cognitive
impairments are also commonly seen in relatives of people with schizophrenia, which is why
these impairments are considered to be an indicator of genetic predisposition to schizophrenia
– Endo-phenotype: More stable phenotypes with a strong genetic connection – Not in DSM-5
Onset is usually between the ages of 18 and 25 years in men and 3-4 years later in women
The incidence is higher among migrants and in urban regions
More men than women are affected by schizophrenia
,NEUROPATHOLOGY
Decreased volume of grey matter, especially in the superior temporal gyrus and medial
temporal and limbic structures – Already apparent around the time of the first psychotic
episode, and possibly even 1 or 2 years earlier than this
The normal asymmetry of the cerebral hemispheres is absent – Changes in the white matter
that forms the pathways for communication between the two cerebral hemispheres
The volume of certain structures decreases as the disorder progresses – Complicating factor =
Effect of antipsychotic drugs on brain volume
- Widening of the ventricles
- Reduction in volume of the hippocampus
Changes in activation of the DL-PFC during tasks that use executive functions – If there is a
low task load the patient reaches the activation peak sooner (hyper-frontality), but if there is a
high task load the patient’s capacity is exceeded sooner, causing them to quit (hypo-frontality)
Functional deviations in the hippocampus during the capture and retrieval of information –
Patients with schizophrenia typically not show an increase in activation of the hippocampus
during a recognition task
Increased activation in the amygdala during the processing of neutral stimuli – Might explain
why patients with schizophrenia tend to provide neutral events with an incorrect and
emotional interpretation
MEDICATION
Agonist: A medication that mimics the action of the signal ligand by binding to and activating
a receptor – Enhanced cellular activity
Antagonist: A medication that typically binds to a receptor without activating them, but
instead, decreases the receptor’s ability to be activated by another agonist – Blocked cellular
activity
First-generation/classic antipsychotic drugs: Have a dopamine-antagonist function and a
sedating effect – Extrapyramidal side effects (E.g.: an inability to sit still, involuntary muscle
contraction, tremors, stiff muscles and involuntary facial movements)
Second-generation/atypical antipsychotic drugs: Target the positive symptoms of
schizophrenia – Involve the serotonin and glutamate receptors to a greater extent and the
dopamine receptors to a lesser extent than the first-generation antipsychotic drugs – Fewer
side effects
Third-generation antipsychotic drugs: Consist of partial dopamine agonists – Balancing
dopamine levels
Cognitive impairments in schizophrenia are not undesirable side effects of antipsychotic
drugs! Antipsychotic drugs have even been shown to have a modest positive effect on
cognitive functioning
,COGNITIVE IMPAIRMENTS
Patients with schizophrenia perform less well on all aspects of most neuropsychological tests
compared with healthy controls
↓ However
There is no single cognitive domain in which test performances by patients do not partly
overlap with those of healthy controls, so neuropsychological tests cannot be used to
distinguish schizophrenia patients from healthy volunteers
MATRICS: A group of American neuropsychologists has recently attempted to create an
overview of the cognitive impairments
1. Speed of information processing – Especially coding tasks
2. Attention and vigilance
3. Working memory – Some researchers believe that dysfunction of the working memory
is at the core of cognitive impairments in schizophrenia
- Remembering information (E.g.: Forward Digit Span task, in which series of
digits need to be repeated)
- Processing information (E.g.: Backward Digit Span, in which series of digits
need to be repeated but in reverse) – The severity of the anomaly increases
considerably
- Vigilance tasks (E.g.: Continuous Performance Test (CPT), in which a long
series of numbers is presented in rapid succession; the task of the participant is
to respond to a certain combination of digits, such as a 3 followed by a 7) –
Measures sustained attention
4. Learning and memory:
- Declarative memory is especially affected
- In particular the encoding of information is impaired
- Capture and retrieval of information are also affected, but to a lesser extent
- Immediate memory (= a type of memory in which an individual recalls
information recently presented) is highly affected, in particular for verbal
information, and to a lesser extent for non-verbal information
- The active retrieval of information is more severely affected than the
recognition of information, which may indicate a prefrontal component in
addition to the involvement of the temporal cortex
5. Executive functions – Decreased initiative and social insight
Impairments in social cognition:
1. Lower-order processes: Basic emotion perception
2. Complex/higher-order processes: Related to the interpretation of social information,
such as social perception, social knowledge, ToM and attribution style
There is evidence of minor abnormalities in cognitive functioning before the first psychotic
episode occurs:
- Dunedin cohort: Individuals who were diagnosed with schizophrenia at the age of 32
years already exhibited impairments in verbal reasoning by the age of 7-13 years
, - Especially intelligence and language seems to be underdeveloped before the onset of
schizophrenia – For other cognitive functions, almost no differences between children
with a genetic predisposition to schizophrenia and controls have been found
For a long time it was assumed that hallucinations and delusions were the consequence of
cognitive impairments – Most studies show that there is only a weak relationship between
positive symptoms and cognitive impairments
↓ However
There are a few specific cognitive processes that are related to positive symptoms:
- Impairments in social cognition:
- Impairments in Theory of Mind (ToM) (= the ability to ascribe mental states to
other persons) in particular are believed to contribute to the development of
delusions – Individuals who are unable to understand emotions from someone
else’s perspective might ascribe negative intentions to others and thus become
suspicious of them
- Impairments in meta-cognitive processes (= processes that involve the capacity to
reflect on one’s own cognitive functions) are related to the development and
maintenance of psychosis
- Source-monitoring bias: A type of memory error where the source of a
memory is incorrectly attributed to some specific recollected experience (E.g.:
people who hallucinate have more difficulty than others in distinguishing
between their own thoughts and those of other people) – Associated with
current psychotic symptoms! Problems with source monitoring do not occur in
people who have suffered from hallucinations in the past
- Difficulty distinguishing between own written thoughts and those
written by others
- Inclination to attribute one’s own voice to another person
- Jumping to conclusions: The inclination to draw conclusions when there is insufficient
evidence available – Cognitive style – May contribute to delusions – Beads task
- Attentional bias: More attention is devoted to stimuli that involve delusional
conviction
- Memory bias: Stimuli that involve delusional convictions are remembered better
Rate-limiting-factors: Cognitive dysfunctions will limit the options that an individual has to
be competent in daily life
↓
Green: Provided an overview of the links between cognitive dysfunctions and various aspects
of social functioning
1. Social functioning – Verbal memory is the strongest predictor of problems
2. Social problem solving
3. Skill acquisition – Correlated with level of vigilance
CHAPTER 24 (KESSELS, ELING, PONDS, SPIKMAN & VAN ZANDVOORT) –
SCHIZOPHRENIA
HISTORY OF SCHIZOPHRENIA
Kraepelin: Referred to schizophrenia as dementia praecox (= ‘premature dementia’)
- Particularly focused on the progressive course – Thought this would eventually result
in a terminal type of dementia
- Hallucinations: Sensory perceptions that resemble an actual perception, yet without
the stimulation of the sense involved
- Delusions: Beliefs that do not correspond to reality and which are not shared by others
in the patient’s culture or subculture
Bleuler: Introduced the term schizophrenia
- Pessimistic about the course of the disorder and emphasised its progressive nature
- Bleuler’s four A’s: Four symptoms which Bleuler considered to be the most
distinctive aspects of schizophrenia:
1. Ambivalence: Not being able to make choices
2. Blunted affect: A decreased expression of emotions
3. Autism: Decreased participation in social interactions
4. Loosening of association: Not being able to make proper logical connections
SYMPTOMOLOGY
Subdivision:
1. Positive symptoms: Delusions and hallucinations – The increase in certain functions or
thoughts
2. Negative symptoms: Blunted affect, ambivalence and autism – The decrease in certain
behaviours or functions
3. Disorganisation: Loosening of association
Criteria for a diagnosis of schizophrenia:
- There must be a deterioration in social functioning
- The symptoms must last at least 6 months
- At least two symptoms, of which at least one positive symptom, must be present
70-80% of people with schizophrenia suffer from cognitive impairments – Cognitive
impairments are also commonly seen in relatives of people with schizophrenia, which is why
these impairments are considered to be an indicator of genetic predisposition to schizophrenia
– Endo-phenotype: More stable phenotypes with a strong genetic connection – Not in DSM-5
Onset is usually between the ages of 18 and 25 years in men and 3-4 years later in women
The incidence is higher among migrants and in urban regions
More men than women are affected by schizophrenia
,NEUROPATHOLOGY
Decreased volume of grey matter, especially in the superior temporal gyrus and medial
temporal and limbic structures – Already apparent around the time of the first psychotic
episode, and possibly even 1 or 2 years earlier than this
The normal asymmetry of the cerebral hemispheres is absent – Changes in the white matter
that forms the pathways for communication between the two cerebral hemispheres
The volume of certain structures decreases as the disorder progresses – Complicating factor =
Effect of antipsychotic drugs on brain volume
- Widening of the ventricles
- Reduction in volume of the hippocampus
Changes in activation of the DL-PFC during tasks that use executive functions – If there is a
low task load the patient reaches the activation peak sooner (hyper-frontality), but if there is a
high task load the patient’s capacity is exceeded sooner, causing them to quit (hypo-frontality)
Functional deviations in the hippocampus during the capture and retrieval of information –
Patients with schizophrenia typically not show an increase in activation of the hippocampus
during a recognition task
Increased activation in the amygdala during the processing of neutral stimuli – Might explain
why patients with schizophrenia tend to provide neutral events with an incorrect and
emotional interpretation
MEDICATION
Agonist: A medication that mimics the action of the signal ligand by binding to and activating
a receptor – Enhanced cellular activity
Antagonist: A medication that typically binds to a receptor without activating them, but
instead, decreases the receptor’s ability to be activated by another agonist – Blocked cellular
activity
First-generation/classic antipsychotic drugs: Have a dopamine-antagonist function and a
sedating effect – Extrapyramidal side effects (E.g.: an inability to sit still, involuntary muscle
contraction, tremors, stiff muscles and involuntary facial movements)
Second-generation/atypical antipsychotic drugs: Target the positive symptoms of
schizophrenia – Involve the serotonin and glutamate receptors to a greater extent and the
dopamine receptors to a lesser extent than the first-generation antipsychotic drugs – Fewer
side effects
Third-generation antipsychotic drugs: Consist of partial dopamine agonists – Balancing
dopamine levels
Cognitive impairments in schizophrenia are not undesirable side effects of antipsychotic
drugs! Antipsychotic drugs have even been shown to have a modest positive effect on
cognitive functioning
,COGNITIVE IMPAIRMENTS
Patients with schizophrenia perform less well on all aspects of most neuropsychological tests
compared with healthy controls
↓ However
There is no single cognitive domain in which test performances by patients do not partly
overlap with those of healthy controls, so neuropsychological tests cannot be used to
distinguish schizophrenia patients from healthy volunteers
MATRICS: A group of American neuropsychologists has recently attempted to create an
overview of the cognitive impairments
1. Speed of information processing – Especially coding tasks
2. Attention and vigilance
3. Working memory – Some researchers believe that dysfunction of the working memory
is at the core of cognitive impairments in schizophrenia
- Remembering information (E.g.: Forward Digit Span task, in which series of
digits need to be repeated)
- Processing information (E.g.: Backward Digit Span, in which series of digits
need to be repeated but in reverse) – The severity of the anomaly increases
considerably
- Vigilance tasks (E.g.: Continuous Performance Test (CPT), in which a long
series of numbers is presented in rapid succession; the task of the participant is
to respond to a certain combination of digits, such as a 3 followed by a 7) –
Measures sustained attention
4. Learning and memory:
- Declarative memory is especially affected
- In particular the encoding of information is impaired
- Capture and retrieval of information are also affected, but to a lesser extent
- Immediate memory (= a type of memory in which an individual recalls
information recently presented) is highly affected, in particular for verbal
information, and to a lesser extent for non-verbal information
- The active retrieval of information is more severely affected than the
recognition of information, which may indicate a prefrontal component in
addition to the involvement of the temporal cortex
5. Executive functions – Decreased initiative and social insight
Impairments in social cognition:
1. Lower-order processes: Basic emotion perception
2. Complex/higher-order processes: Related to the interpretation of social information,
such as social perception, social knowledge, ToM and attribution style
There is evidence of minor abnormalities in cognitive functioning before the first psychotic
episode occurs:
- Dunedin cohort: Individuals who were diagnosed with schizophrenia at the age of 32
years already exhibited impairments in verbal reasoning by the age of 7-13 years
, - Especially intelligence and language seems to be underdeveloped before the onset of
schizophrenia – For other cognitive functions, almost no differences between children
with a genetic predisposition to schizophrenia and controls have been found
For a long time it was assumed that hallucinations and delusions were the consequence of
cognitive impairments – Most studies show that there is only a weak relationship between
positive symptoms and cognitive impairments
↓ However
There are a few specific cognitive processes that are related to positive symptoms:
- Impairments in social cognition:
- Impairments in Theory of Mind (ToM) (= the ability to ascribe mental states to
other persons) in particular are believed to contribute to the development of
delusions – Individuals who are unable to understand emotions from someone
else’s perspective might ascribe negative intentions to others and thus become
suspicious of them
- Impairments in meta-cognitive processes (= processes that involve the capacity to
reflect on one’s own cognitive functions) are related to the development and
maintenance of psychosis
- Source-monitoring bias: A type of memory error where the source of a
memory is incorrectly attributed to some specific recollected experience (E.g.:
people who hallucinate have more difficulty than others in distinguishing
between their own thoughts and those of other people) – Associated with
current psychotic symptoms! Problems with source monitoring do not occur in
people who have suffered from hallucinations in the past
- Difficulty distinguishing between own written thoughts and those
written by others
- Inclination to attribute one’s own voice to another person
- Jumping to conclusions: The inclination to draw conclusions when there is insufficient
evidence available – Cognitive style – May contribute to delusions – Beads task
- Attentional bias: More attention is devoted to stimuli that involve delusional
conviction
- Memory bias: Stimuli that involve delusional convictions are remembered better
Rate-limiting-factors: Cognitive dysfunctions will limit the options that an individual has to
be competent in daily life
↓
Green: Provided an overview of the links between cognitive dysfunctions and various aspects
of social functioning
1. Social functioning – Verbal memory is the strongest predictor of problems
2. Social problem solving
3. Skill acquisition – Correlated with level of vigilance
