schizophrenia

Question 1

what is schizophrenia

Answer 1

neurodevelopmental disorder of thought characterised by positive and negative symptoms

Marked by extreme heterogeneity in psychopathology, treatment response and outcome both within and between people.
Treatment resistance is common

Question 2

what is the diagnostic critieria for schziophreni

Answer 2

2+ symptoms in the last month, with at least one of these positive

positive symptoms: delusions, hallucinatins, disorder of speech, catatonic movement

negative symptoms: alogia, avolition, flat affect

Question 3

what are the stages of development of schizophrenia

Answer 3

premorbid: abnormal brain development between birth and puberty
prodomal: early symptoms and signs concentration and memory problems, unusual behaviour and ideas, withdrawl

onset/deterioration: acute episode of hallucinations and delusions causing agitation and distress

residual: attenuation of positive symptoms with persistent negative symptoms

due to neurochemical dysregulation such that there is sensitisation by dopamine and excitatory neurotoxicity of glutamate

potentially neurdegenerative

Question 4

what are the issues with the definition of schizophrenia

Answer 4

there is extreme heterogeneity within and between people in psychopathology, treatment response and outcome

better conceptualised as part of the same spectrum syndrome

distinct genetic brain disease which is not seen in other psychosis disorders so it is seen as somewhat separate

Question 5

what is the content of hallucinations

Answer 5

hearing voices, lights changing, feeling spiders etc

auditory, visual, touch

Question 6

what is the nature of delusions

Answer 6

thoughts are broadcasted internally
there is a withdrawal from thought
feeling of external tampering with thought,
delusions of control (an external force moved me etc)
delusions of persecution (something being after you)
delusions of gradneur
delusions of reference (e.g facebook status contains a secret message for me to decipher)

Question 7

what is the epidemiology of schizophrenia

Answer 7

associated with substantial morbidity and with personal and societal costs
the typical age of onset is in adolescene and early adulthood but can be later
more common in ubran, socially disadvataged and BAME groups
more common in winter and early spring (leading to the idea of flu during pregnancy as a contributing factor)
equally common in men and women

Question 8

what are the outcomes for schizophrenia patients

Answer 8

sustained recovery occurs in less than 14% within the first 5 years following a psychotic episode (Robinson et al., 2004)

an additional 16% show late-phase recovery (Harrison et al., 2001)

less than 20% in Europe with schizophrenia are employed

20% are homeless within a year

3x more likely to end up in criminal justice system than hospital in USA

more likely to be victims of violent attacks than purportrators

Question 9

what are the levels of explanation for schizophrenia

Answer 9

behaviour: signs and symptoms
cognition: endophenotypes
biological: brain structure and dynamics - neurotransmitter function, blood flow, metabolism

genes x environment interaction

Question 10

what are the genetic explanations for schizophrenia

Answer 10

the average risk of schizophrenia increases with increasing closeness to a biological relative with schizophrenia proband

MZ twins: 48%
offspring of two parents: 46%

still not entirely genetic

non-shared environmental factors

being raised by parents with schizophrenia will introduce key environmental influences

Question 11

why is schizophrenia described as polygenic

Answer 11

studies have found small effects for 150 common variants

however only a small proportion of these have obvious functional effects

DRD2 encodes the D2 subtype of DA receptor

also genes involved in glutamatergic neurotransmission

Question 12

what is the social defeat hypothesis of schizophrenia (Selten et al., 2005)

Answer 12

common denominator of four key environmental influences
urban upbringing
migration - higher risk for 2nd gen migrants, not about ethnicity
low IQ
drug use

common and long-term experience of social defeat may lead to long-term neurophysiological changes

sensitisation of mesolimbic dopamine system

Question 13

how do most risk factors for schizophrenia show similar associations with psychotic experiences

Answer 13

parental: genes, pregnancy and birth complications e.g early birth, low weight, illness, trauma
childhood: social cognition, neurodevelopment
adolescence: trauma and victimisation, social environment, cannabis use

impact on adulthood

developmental view - timing of when things are occurrig

Question 14

are there early cognitive deficits associated with schizophrenia

Answer 14

children show no obvious impairment

late onset measn we should of this as a neurodevelopmental condition

Question 15

what is the relationship between the environment and schizophrenia

Answer 15

individuals with genetic vulnerabilities may be more sensitive to particular environments

a disorder of adaptation to social context

degrees of relatedness

Question 16

what evidence is there for vulnerable subgroups and gene-environment interactions using proxy measures of genetic risk

Answer 16

with low genetic risk you do not see the same elevated risk due to environmental factors

consistent with cognitive fitness

Question 17

what is the dopamine hypothesis

Answer 17

schizophrenia arises as a consequence of hyperactivity of the dopamine system - this explains the positive symptoms through a mechanism of aberrant salience

antipsychotic drugs have a common mechanism on DA release targeting D2 receptors

drugs that limit DA result in psychosis like experiences e.g amphetamine and cocaine

Griffith et al., (1972): experienced amphetamine users received 10mg d-amphetamine every hour for five days. All 7 volunteers became psychotic within 2-5 days.

Post-mortem studies show abnormalities in the metabolites of dopamine

Question 18

what did Howes et al., 2007 find about dopamine in schizophrenic’s brains

Answer 18

radio labelled L-dopa
track DA release across synaptic cleft
scz patients have elevated presynaptic striatal DA synthesis capacity
suggests patients produce more DA than controls

elevated dopamine synthesis capacity is seen in the nigral origin of dopamine neurons as well as their striatal terminals in schizophrenia, and is linked to symptom severity in patients.

Question 19

what is abnormal about presynaptic dopamine in patients with dementia

Answer 19

Review of 44 PET studies found the locus of the largest dopaminergic abnormality in scz is presynaptic
Affects DA synthesis capacity , baseline synaptic DA, DA release
No evidence of alterations in DA transporter availability
Small elevation in D2/3 receptor availability but not evidence in drug-naive patients
All current drug treatment act on receptors failing to target abnormalities

Question 20

how do abnormalities of DA transmission cause schizophrenia symptoms

Answer 20

DA: incentive/motivational salience and reward prediction
DAergic abnormalities may lead to aberrant assignment of salience to external objects/internal representations
Hallucinations = abnormal salience attributed to internal representations
Delusions = cognitive explanation for these bizarre experiences
Filtered through patient’s existing cognitive and sociocultural schemas
Way they are rationalised will vary from patient to patient

Question 21

what is the idea of dopamine as the final common pathway

Answer 21

multiple hits interact to result in striatal dopamine dysregulation to alter the appraisal of stimuli and resulting in psychosis

Question 22

do patients with schizophrenia have cognitive impairments

Answer 22

1.5SD below normative sample

composite score of processing speed, attention, working memory, verbal learning, visual learning, reasoning and social cognition

however cannot reliably be used to diagnose schziohrenia

need to have a focus on individual change pre and post onset - it is less hlepful as a between group identifier

Question 23

what is the course of cognitive impairments over time

Answer 23

Pre-morbid - small differences
Sudden decline before onset
Antipsychotics do not improve cognitive decline (argument that they may slow down this decline)
Argument that they may contribute - ‘dampening’ / slow down side effects

Question 24

what information processing biases are seen in schizophrenia

Answer 24

interpretation and reasoning are impaired, and this extends to memory and attention

there is a tendency for the information processing system to consistently favour stimuli material of a particular type or content

interpretation biases could be external attributions

Question 25

what is Morrison’s 1998 interpretation of triggers

Answer 25

in those most vulnerable, internal and external triggers such as stress, sleep deprivation and isolation can result in auditory hallucinations

these cause safety behaviours to prevent these things happening again however stress is not attributed as the cause

instead there is worry that there is a perceptual abnormality to blame which subsequently affects mood and physiology

this results in a cycle of worsening sleep and increasing stress

Question 26

what is the bias of jumping to conclusions (Fine et al., 2007)

Answer 26

rather than just being a consequence of the symptoms of schizophrenia, the tendency to jump to a conclusion without full evidence may contribute to schizophrenia patients accepting hypotheses that other people reject as implausible

BUT
No evidence that scz patients have a bias against disconfirmatory evidence
Unsupported delusion maintenance
Limited number of typical scz delusions
Role of insight into experience and condition

Question 27

how is schizophrenia treated

Answer 27

antipsychotics/ neuroleptics
these dampen down the system but have a limited impact on negative symptoms
appear better to doctors in terms of compliance
often see weight gain, eye twitch, strange movements, increased risk of cardiovascular problems

compliance in taking medication is poor, some people do not respond in the first place and some symptoms persevere

can also use family or cognitive therapy

Question 28

how can CBT be used to treat psychosis

Answer 28

need to challenge the origins of delusions
highlight irrational and inconsistent features
offer alternative perspectives (such as making friends with the voice)
reduce feelings of persecution and paranoia
focus on personal impact
suggest behavioural tests

Question 29

how effect is CBT for positive symptoms (Zimmermann et al., 2005)

Answer 29

effective with antipsychotics

most so for acute episodes over chronic conditions

Question 30

summary

Answer 30

Neurodevelopmental syndrome over one psychotic illness
Can explain scz in terms of genetic risk factors in combination with environment
And dopamine striatal release
Neurocognitive and neuropathological conditions
Antipsychotics treat downstream effects
CBT may be important factor