Schizophrenia - Pathophysiology Flashcards
What is Schizophrenia? Why is Schizophrenia the most important psychotic disorder?
is a psychotic disorder
- disorder of thought
= mental state is out of touch, profound alterations in behaviour and abnormal perceptions/ideas/thought
has early onset (aged 18-20) (earlier in men)
is prevalent
is chronically disabling
- responsible for a high percentage of the population morbidity §
What are the classes of schizophrenia?
class are grouped into their predominate symptoms
- positive
- negative
- cognitive
must persist for at least 6 months to be classed a schizophrenia
What are the positive symptoms of schizophrenia?
hallucinations (perceptions without stimuli)
- auditory = voices talking to them/about them/echoing thoughts/commentary
- visual
delusions (fixed/unshakable belief inconsistent with norms)
- often paranoid or persecutory
- passivity of thoughts and actions
movement disorders (motor/volitional/behavioural)
- stereotypies = purposeless, repetitive acts
- bizarre postures, strange mannerisms
- altered facial expressions = grimacing
- catalepsy = waxy flexible (loss of voluntary limbs)
disorganised thought/speech
- catatonia = motionless, mute, expressionless
- impulsive behaviour
- extreme hyperactivity = walk around naked
formal thought disorder
- speech that is difficult to understand and rapidly switches from one subject to another (derailment of speech)
What are the negative symptoms of schizophrenia?
- more prevalent in men
social withdrawal
lack of motivation or initiative
formal thought disorder
- speech is difficult to understand
- poverty of speech = distorted/illogical
- loosening of associations (cannot flow train of thought)
emotional flatness
anhedonia
What are the cognitive symptoms of schizophrenia?
impaired working memory
impaired attention (selective)
impaired cognition
blunted affect - decreased responsiveness to emotional issues
incongruous effect - mismatch between experienced emotion and its expression
insight - lack of understanding of what is wrong (do not accept anything is wrong)
What are the phases of schizophrenia?
The Prodrome
- early onset in late teens/early twenties
= often mistaken for depression or anxiety
- can be triggered by stress
The Active/Acute Phase
- onset of positive symptoms e.g. delusion, hallucinations
Remission
- treatment return to ‘normality’ but schizophrenia is a chronic relapsing disorder (cycle of relapse and remission is common)
Relapse
- schizophreniform = positive symptoms for at least a month, but < 6 months
What is schizophrenia caused by?
genetics
- is not directly inherited but can run in families
- mutation of candidate risk genes increases the likely hood of getting it
= COMT, DISC 1, GRM 3
environmental
- pregnancy/birth complications
= early life stress, e.g. low birth weight, asphyxia during birth, viruses
- stress/early bereavement/loss of job/abuse
- drug abuse
= psychotostimulants (amphetamine, LSD), cannabis
What are the potential pathophysiologies of schizophrenia?
dopamine hypothesis
- hyper DAergic and hypo DAergic
brain structure abnormalities
hypofrontality
- decreased activity in the frontal cortex
NMDA receptor hypofunction
oxidative stress
neuroinflammation
What is the DA hypothesis?
hyperactivity in the mesolimbic DAergic pathway
- VTA to nucleus acccumbens, amygdala and hippocampus
- associated with the positive symptoms
hypoactivity in the mesocorticol DAergic pathway
- VTA to frontal cortex
- associated with negative symptoms
= decreased cognition
What is the pharmacological evidence FOR the DA hypothesis?
amphetamine (psychotostimulant) enhances DA release in schizophrenia
- is associated with psychotic episodes (induces)
reserpine depletes DA
- controls positive symptoms
stimulation of D2 receptors induces stereotyped behaviours
D2 antagonists is an important mechanism of anti-psychotics
What is the pharmacological evidence AGAINST the DA hypothesis?
no clear increase in dopamine levels in cerebrospinal fluid homovanillic acid concentration (CSF HVA)
no change in DA receptors in drug-free patients (but there’s increased D2 receptors in patients taking drug treatment)
What is the evidence for and against brain structure abnormalities?
in schizophrenic patients:
- overall brain size is smaller
- reductions in gray matter (contain neural cell bodies)
- enlarged lateral ventricles and smaller hippocampus
not all patients have such profound structural differences
What is the evidence for and against hypofrontality?
shown by MRI scans
- schizophrenic patients have reduced activity in the frontal cortex
= decreased cognitive functioning
What is the evidence for and against NMDA receptor hypofunctioning?
decreased glutamate and glutamate receptors concentration in the prefrontal cortex of schizophrenic patients
blocking NMDA receptors increases psychotic symptoms
- hallucinations, thought disorder
transgenic mice with reduced NMDA receptor expression have
- stereotyped behaviour, decreased social interaction
What is the evidence for and against 5-HT involvement in schizophrenia?
lysergic acid diethylamide (LSD) is a partial 5HT agonist
- causes hallucinations = positive symptom
many antipsychotics block 5-HT receptors
