Schizophrenia Basics Flashcards
when does schizophrenia emerge
adolescence and young adults
what is the incidence rate of schizophrenia
1% population
6-17% family history
50% if affected twin
what is the aetiology
genetic predisposition and environmental disturbances affect timing of fine tuning and synaptic stabilisation
what is the pathology
reduced cortical grey matter
in human post mortem there is reduced dendritic length and spine density on pyramidal neurons
positive symptoms
delusions
hallucinations
illusions
thought disorder
abnormal behaviour - aggressive
negative symptoms
social withdrawal
disorganised speech (alogia)
flattened emotions
lack of drive (avolition)
cognitive symptoms
executive function
learning and memory
what is the dopamine hypothesis
DA (mesolimbic) hyperactivity causes positive symptoms of schizophrenia
role of amphetamine
releases DA
induces stereotyped psychotic like symptoms in patients (paranoia/audit/visual hallucinations)
L-DOPA in PD patients
induce psychosis
typical antipsychotics
haloperidol
fluphenazine
chlorpromazine
they are D2 receptor antagonists
affinity for D2 receptors
correlates with clinical potency of drugs
D2 receptor antagonist side effects
sedation (H1 R antagonism)
hypotension (alpha adrenoreceptor antagonism)
anticholinergic side effects: blurred vision, dry mouth, constipation (mAChR antagonism)
what is the mesolimbic pathway
ventral tegmental area (VTA) to limbic area (nucleus accumbent, amygdala, hippocampus)
controls emotions
side effects from D2R blockade by typical antipsychotics
tuberoinfundibulnar pathway - increased prolactin secretion (gynaecomastia)
nigrostriatal pathway - extrapyramidal side effects (EPS): Parkinsonism, tardive dyskinesia
atypical/second generation antipsychotics
clozapine
olanzapine
risperidone
quetiapine
aripiprazole
ziprasidone
atypical antipsychotic receptor affinity
5HT2>D4>D2=D1=a-adrenoreceptor=mACh=H1
blocking D2/4 R in mesolimbic pathway combats positive symptoms
D4 receptor location
mesolimbic pathway
not nigrostriatal
reduces incidence of EPS
what causes negative symptoms
hypoactivity of the mesocortical pathway
5HT2A (Gq GPCR) blockade by atypical antipsychotics increase DA
reduced GABA disinhibits DA release
mesocortical pathway
VTA to PFC
similarities of both typical and atypical antipsychotics
15-30 hours
given orally or I-m 1-2 times a day
chemical lobotomy - too high dose
advantages of atypical antipsychotics
reduces EPS
provides some relief of negative symptoms
disadvantages of atypical antipsychotics
weight gain due to food cravings (5HT2 antagonism)
impairs glycaemic control causing insulin resistance, impaired glucose tolerance and type 2 diabetes
psychosis remains drug-refractory
no cognitive benefit (attention/learning/memory/executive function is still impaired)
