Schizophrenia Flashcards
What is schizophrenia?
State of distorted perception, not limited to visual info.
Why is schizophrenia the most important psychotic disordeR?
Early in onset
Prevalent
Disabling and chronic
What are the 4 phases of Schizophrenia?
1.The Prodrome
Late teens/early twenties: often mistaken for depression or anxiety
Can be triggered by stress
- The Active/Acute Phase
Onset of positive symptoms
Differentiation of what is and isn’t real becomes difficult - Remission
Treatment –> return to ‘normality’ - Relapse
What are the 3 classes into which schizophrenia can be grouped?
POSITIVE (an increase in abnormal behaviours):
- Hallucinations (e.g. visual, auditory)
- Delusions
- Disorganised thought/speech
- Movement disorders
NEGATIVE (an absence of normal behaviours):
- Social withdrawal
- Anhedonia (inability to feel pleasure at pleasurable activities)
- Lack of motivation
- Poverty of speech
- Emotional flatness
COGNITIVE (problems with thought processes):
- Impaired working memory
- Impaired attention
- Impaired comprehension
Two or more of these symptoms must persist for at
least 6 months to be classed as schizophrenia.
What are hallucinations?
Perception experienced without stimulus
What are delusions?
A fixed/unshakable belief, not consistent with cultural/social norms.
What are motor, volitional and behavioural disorders?
Peculiar forms of motility, stupor, mutism, stereotypy, mannerism, negativism, spontaneous automatism, impulsivity
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).
What is 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 them.
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.
What is insight?
An understanding of what is wrong.
Insight lacking in schizophrenia.
Patients usually do not accept that any thing is wrong or that treatment is necessary.
What is the aetiology of schizophrenia?
There are genetic factors:
- SCZ isn’t directly inherited, but can ‘run in families’
- ‘Candidate’ risk genes: gene deletions, gene mutations
There are environmental factors:
- Pregnancy/birth complications
- Stress
- Drug use
It is due to both nature and nurture that schizophrenia develops.
What are some of the candidate genes for schizophrenia?
Examples of some of these genes is:
- COMT
- DISC1
- GRM3
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 can pregnancy/birth complications cause schizophrenia?
A Finnish study reported a spike in schizophrenia for people who were foetuses during the 1957 influenza epidemic. Thus, pregnant women in the UK are advised to be vaccinated against seasonal flu.
Low birth weight, premature birth, and asphyxia during birth are all causes of early-life stress (stemming from birth complications).
Give some examples of stress that can cause schizophrenia.
- MOVING COUNTRY: Swedish cohort 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 can drug abuse lead to schizophrenia?
Continued cannibas use during early life for ~15 years has been shown to increase the risk of schizophrenia development.
Other drugs that could are:
- amphetamine
- cocaine
- LSD
What are the hypotheses for the pathophysiology of schizophrenia?
There is the:
- dopamine hypothesis
- glutamate hypothesis
There are many other hypotheses:
- Brain structure differences
- Hypofrontality
- Inhibitory interneuron dysfunction
- Kynurenic Acid
- Oxidative Stress
- Immune System Abnormalities
What are the main dopamine pathways?
MESOCORTICAL PATHWAY: cognitive control and motivation and emotion
MESOLIMBIC PATHWAY: reward
NIGROSTRIATAL PATHWAY: movement
TUBEROHYPOPHYSEAL PATHWAY: prolactin release
Describe the dopamine hypothesis.
Schizophrenia is associated with abnormally high dopaminergic transmission from mesolimbic pathways.
However, there is no conclusive evidence that dopamine levels are increased in schizophrenia.
What are some theories regarding dopamine and the symptoms of schizophrenia?
Positive symptoms – hyperDAergic in mesolimbic system (increase D2 )-but D2 antagonists do the same
Negative symptoms – hypoDAergic activity in mesocortical system (decrease D1 )=>decrease cognition
D4 involved? But selective D4 antagonists not effective
What is the pharmocological evidence for dopamine hypothesis?
DA release (amphetamine) produces ‘schizophrenia’
DA release only in mesolimbic, mesocortical NOT nigrostriatal
D2 agonists produce stereotyped behaviour (not D1)
Reserpine depletes DA – controls positive symptoms
Strong correlation D2 blocking activity & antipsychotic action
Amphetamine enhances DA release in schizophrenics more than controls which makes the disease worse
What is some evidence against the dopamine hypothesis?
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 are some brain structural differences in schizophrenic brains vs normal brains?
Overall brain size slightly smaller
Reductions in grey matter
Enlarged lateral ventricles – smaller hippocampus
*Not all people with schizophrenia have such profound structural brain differences
What is hypofrontality?
Reduced blood flow to the frontal cortex
Reduced activity in frontal cortex?
What does the prefrontal cortex do?
This brain region has been implicated in planning complex cognitive behavior, personality expression, decision making, and moderating social behaviour
What is some evidence for the glutamate hypothesis?
Glutamate hypothesis states that the low levels of glutamate and glutamate receptor in prefrontal cortex induces negative symptoms of schizophrenia
decreased [glutamate] and glutamate receptor density in prefrontal cortex
NMDA hypofunction
1- NMDA antagonists (ketamine / phencyclidine)
- – Psychotic symptoms – hallucinations & thought disorder
- ketamine blocks NMDA receptor
2 - Transgenic mice with low NMDA receptor expression showed stereotyped behaviour & low social interaction, responsive to antipsychotics
What activity is enhanced/reduced with NMDA hypofunction?
NMDA hypofunction enhances mesolimbic DAegic activity
NMDA hypofunction reduces GABAergic striatal neuron activity
Project to the thalamus / sensory gate (GABA inhibitory)
Glutamate excitatory on GABAergic neurons
DA inhibitory on GABAergic neurons
Too little glutamate, too much DA – uninhibited sensory input to limbic regions (NAc, Hi, Amy)
Explain the symptoms of schizophrenia using NMDA hypofunction?
increased DA mesolimbic (positive symptoms), decreased DA mesocortical (negative symptoms),
decreased glutamate (NMDA) (negative symptoms)
Explain the serotonin evidence for schizophrenia
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 for schizophrenia?
Over stimulation of mesolimbic D2 receptors
Hypoactivity of frontal cortical D1 receptors
Reduced prefrontal glutaminergic activity
5HT involved
What are the types of antipsychotics taken for schizophrenia?
There are two types: TYPICALS: - Also known as ‘first generation’ - First developed in the 1950s - Mainly antagonise D2 receptors
ATYPICALS:
- Also known as ‘second generation’
- First developed in the 1980s
- Mainly antagonise D2 and 5-HT2A receptors
What are some general side effects of antipsychotics?
- Extra-pyramidal side effects
- Increased prolactin secretion
- Weight gain
- Sedation
- Hypotension
- Anticholinergic effects
The typical antipsychotics tend to induce these side-effects to a greater extent than the atypicals.
Describe the effects of prolactin secretion as a side effect.
Prolactin (hormone) promotes milk production. Normally, dopamine negatively regulates it’s secretion. In schizophrenia, there is no blockade of the tuberohypophyseal pathway (where a lot of the dopamine receptors are), so prolactin is secreted.
Symptoms:
- Breast swelling (yes, even in men)
- Milk secretion (yes, even in men)
- Period cessation
Describe the effects of weight gain as a side effect.
This is an ‘off-target’ side effect.
Antipsychotics can antagonise histamine H1 receptors.
Central H1 receptor antagonism can cause:
- increased appetite via stimulating the production of AMP- activated protein kinase (AMPK)
- decreased lipolysis
- decreased thermogenesis
An overall effect of stimulating appetite and fat accumulation and reducing energy expenditure.
How can sedation occur as a result of taking antipsychotics?
It can occur via two different mechanisms:
- D2 receptor antagonism
- central H1 receptor antagonism
