Schizophrenia Flashcards
What is a psychotic disorder?
Major psychoses (‘madness - cancer of mental illness’)
Name examples of psychotic disorders
- Schizophrenia
- Schizoaffective disorder = schizophrenia and bipolar
disorder - Delusional disorder
- Some depressive and manic illnesses
Why is schizophrenia the most important psychotic disorder?
Early in onset
Prevalent ~1%
Disabling and chronic
Describe the characteristics of schizophrenia
Mental state that is out of touch with reality
Abnormalities of perception, thought & ideas
Profound alterations in behaviour (bizarre and disturbing alienation)
Outline the prevalence of schizophrenia
Affects up to 1% of the population
No significant influence of culture, ethnicity, background, socioeconomic groups
Increased in urban areas
How does gender influence schizophrenia
No difference between sexes:
Men: 15-25yrs (poorer response to therapy)
Women: 20-30yrs
What are the 4 phases of schizophrenia?
- Prodome
- Active/Acute phase
- Remission
- Relapse
Describe the prodome phase
The Prodrome (wks - yrs)
Early onset of symptoms in late teens/early twenties: often mistaken for depression or anxiety
Can be triggered by stress
What occurs during the active phase of schizophrenia?
The Active/Acute Phase (4-6wks SCZ diagnosed)
Onset of positive symptoms (hallucinations/delusions)
Differentiation of what is and isn’t real becomes difficult
What is remission?
Remission when treatment 🡪 return to ‘normality’
What happens in relapse?
Cycles between remission and relapse common – patients can tell when relapse is coming
What is schizophreniform?
Schizophreniform disorder is a type of psychotic illness with symptoms similar to those of schizophrenia, but lasting for less than 6 months.
What are the 3 classes of schizophrenia symptoms?
- Positive
- Negative
- Cognitive
What are the positive symptoms of schizophrenia
- Hallucinations (visual/auditory)
- Delusions
- Disorganised thought/speech
- Movement disorders
What are the negative symptoms of schizophrenia?
- social withdrawal
- anhedonia
- lack of motivation
- poverty of speech
- emotional flatness
Outline the cognitive symptoms of schizophrenia
- impaired working memory
- impaired attention
- impaired comprehension
Which symptoms must persist for a patient to be classed as schizophrenic
2 or more of these symptoms must persist for >6months to be classed as schizophrenia
What are hallucinations?
Perception experienced without stimulus. (Functional Hallucination)
Most commonly auditory
What do SCZ patients commonly hear during auditory hallucinations
Patients hears
Voices talking about them (3rd person)
Voices talking to them
Voices giving a running commentary
Voices echoing their thoughts (thought echo)
Patients may engage in a dialogue with the voices or obey their commands.
What are delusions?
A fixed/ unshakable belief. Not consistent with cultural/ social norms
Often paranoid or persecutory
E.g. under control of an external influence, thoughts known to other people because they are transmitted by radio and TV
Passivity of thoughts and actions
What are motor, volitional and behavioural disorders?
Peculiar forms of motility, stupor, mutism, stereotypy, mannerism, negativism, spontaneous automatism, impulsivity
Give examples of motor, volitional and behaviour disorders
Stereotypies: purposeless, repetitive acts
Bizarre postures, strange mannerisms
Altered facial expression – grimacing
State of catatonia – motionless, mute, expressionless, uncomfortable or contorted postures
State of catalepsy – waxy flexible
Bouts of extreme hyperactivity (destructiveness; walk around naked)
Impulsive behaviour – violent acts; murder w/o reason
What is formal thought disorder
A disorder of conceptual thinking, reflected in speech that is difficult to understand and rapid shifts from one subject to another. New words are invented (neologisms).
Give examples of formal thought disorder
Disturbances in thinking → unintelligible speech
Derailment of speech
Loosening of associations; failure to follow train of thought to its conclusion
Poverty of speech (speech fails to convey sense/information)
- Manifests as distorted or illogical speech
What is meant by social withdrawal?
Patients withdraw from their families and friends and spend a lot of time on their own.
Lack of initiative or motivation
Do not want to do anything.
No longer interested in things that used to interest
What are cognitive deficits?
Deficits in SELECTIVE attention, problem solving and memory
Blunted affect
Decreased responsiveness to emotional issues.
Incongruous affect. Expression of affect inappropriate to circumstances.
Describe SCZ patients ‘insight’
An understanding of what is wrong.
Insight lacking in schizophrenia.
Patients usually do not accept that anything is wrong or that treatment is necessary.
What genetic factors lead to SCZ?
SCZ not directly inherited but can ‘run’ in families
there are candidate risk genes
- gene deletions
- gene mutations
What environmental factors contribute to schizophrenia?
- seasonal
- maternal influenza
- early-life stress
- drug use (cannabis esp.)
What role does nature and nurture have in developing SCZ?
A person may not develop SCZ if they have only the genetic risk factors or experience of the environmental factors. It is current thinking that a person needs to have both in order for the disease to manifest
What results have twin studies shown regarding SCZ?
> study a monozygotic twin to see what the chances are of the other twin developing SCZ
50% chance of developing schizophrenia if one twin diagnosed
~14% chance of developing schizophrenia if one twin diagnosed - dizygotic
What are the candidate genes seen in schizophrenic patients?
Some of the ‘risk’ or ‘candidate’ genes for schizophrenia
- COMT (enzyme metabolising L-DOPA)
- DISC1
- GRM3 (glutamate metabolism)
Possessing these abnormal genes does not mean you will definitely get schizophrenia – similarly, some people who have schizophrenia do not have these genetic abnormalities
How does maternal influenza lead to schizophrenic patients?
Season of birth: influenza Pregnant women in the UK are advised to be vaccinated against seasonal flu - Low birth weight - Premature birth - Asphyxia during birth
These are all causes of early-life stress
Outline the stresses previously seen to cause SCZ
- Moving country
- Early-Life Bereavement; Cohort under 18 (Denmark & Sweden)
- Loss of >1 first-degree relative further increased risk
- Loss of job/home/relationship
- Physical/emotional/sexual abuse
> The mechanism by which stress may trigger schizophrenia is unknown
How is drug use related to SCZ?
Cannabis use in early life (~15 years)
- Amphetamine
- Cocaine
- LSD
What are the different pathophysiologies of schizophrenia?
Dopamine hypothesis Brain structure differences Hypofrontality NMDA receptor hypofunction Oxidative Stress Neuroinflammation
What is the importance of DA pathways?
Involved in:
- Movement
- Cognition
- Emotions
- Motivation
- Reward
How does DA lead to schizophrenia?
Schizophrenia – overactivity of DAergic, mesolimbic pathways
What causes positive symptoms of SCZ?
Positive symptoms – hyperDAergic in mesolimbic system (↑ D2 )-but D2 antagonists do the same
What causes the negative SCZ symptoms?
Negative symptoms – hypoDAergic activity in mesocortical system (↓ D1 )=>decrease cognition
D4 involved? But selective D4 antagonists not effective
how can we combat the SCZ symptoms?
So we need to increase DAergic transmission in mesocortical regions, decrease DAergic transmission on mesolimbic regions
What is the evidence against DA theory of schizphrenia?
No clear change in CSF HVA concentration
No change in DA receptors in drug-free patients (Increased D2 receptors in p-m samples attributed to drug treatment)
What brain structure abnormalities are linked to SCZ?
- Overall brain size is slightly smaller
- Reductions in grey matter
- Enlarged lateral ventricles - smaller hippocampus
*Not all people with schizophrenia have such profound structural brain differences
How is hypofrontality linked to SCZ?
Reduced blood flow to the frontal cortex
Functional MRI find hypofunctioning in frontal cortex - affects decision making
What role does glutamate play in schizophrenia?
↓ [glutamate] and glutamate NMDA receptor density in the prefrontal cortex associated with negative symptoms
What is the evidence supporting the glutamate theory of SCZ?
Transgenic mice with ↓ NMDA receptor expression showed:
Stereotyped behaviour & ↓ social interaction, responsive to antipsychotics
How do NMDA antagonists also cause psychosis symptoms?
NMDA antagonists (ketamine / phencyclidine) Block NMDA receptors producing psychotic symptoms – hallucinations & thought disorder
How does serotonin affect SCZ?
Serotonin hyperactivity (5-HT) evidence: Lysergic acid diethylamide (LSD): partial 5HT agonist– hallucinations
Many antipsychotics antagonise 5-HT receptors
5-HT activates DA pathways
- 5-HT2A antagonism – may contribute to antipsychotic effect
- 5-HT2A antagonism – may reduce movement disorder side effects
What is the main current theory of schizophrenia?
Main current theory
- Over stimulation of mesolimbic D2 receptors
- Hypoactivity of frontal cortical D1 receptors
- Reduced prefrontal glutaminergic activity
- 5HT involved
What are the treatments used to stabilise SCZ patients?
Antipsychotics – many also antagonise 5-HT receptors (esp 5-HT2A).
What are the 2 types of antipsychotics used to treat SCZ patients?
Typicals
Atypicals
Describe the typical antipsychotics used
Typicals
- Also known as ‘first generation’
- First developed in the 1950s
- Mainly antagonise D2 receptors
What are atypical antipsychotics?
Atypicals
- Also known as ‘second generation’
- First developed in the 1980s
- Mainly antagonise D2 and 5-HT2A receptors
What are the different dopaminergic pathways involved in SCZ?
Nigrostriatal pathway
Reward pathway
Mesolimbic pathway
Tubero-hypophyseal pathway
What is the nigrostriatal pathway?
dopaminergic neurons project onto substantia nigra to the striatum where DA is released ⇒ movement (seen in PD)
Outline the reward pathway
Reward pathway: Dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens
What is the mesolimbic pathway?
Mesolimbic Pathway: neurons projecting from the amygdala to the hippocampus
Hyperactivity of this pathway is associated with positive SCZ symptoms
Blocking this D2 receptors produces antipsychotic effects
What is the role of the tubero-hypophyseal pathway?
Tubero-hypophyseal pathway: DA released from hypothalamus as neurohormone to act on D2 receptors on the pituitary ⇒ decreased PL
