schizophrenia Flashcards
what are features of schizophrenia
affects most basic human processes of perception, emotion and judgement
heterogeneous sydrome
no single defining symptom or sign
currently cannot be identified with a diagnostic laboratory test, diagnosis is done through psychotic phenomena such as hallucinations and thought disorder, after other causes of psychosis have been excluded
what characterises the positive and negative symptoms of schizo
positive: characterised by abnormal thoughts, perceptions, language and behaviour
negative: characterised by restrictions in range and intensity of emotional expression, communication, body language and interest in normal activities
describe the positive symptoms of schizo
positive symptoms: delusions, hallucinations, disorganised thinking/speech, disorganised behaviour, catatonic behaviour (noticeable decrease in environmental awareness, resulting in unresponsiveness, rigid posture and resistance to movement)
describe the negative symptoms of schizo
negative symptoms: blunted affect (decreased emotional expressiveness, reduced eye contact), alogia (reduced speech, speech may be less fluid), avolition (lack motivation, spontaneity), anhedonia (lacking pleasure or interests in activities that were once enjoyable)
describe cognitive symptoms of schizo
cognitive: impairments in attention, memory, learning, verbal fluency, motor speed and executive functions
poor working memory linked to dysfunction of the dorsolateral pre-frontal cortex, patients with good performance are still inefficient in their use of prefrontal networks
cognitive deficits remain stable and are apparent in first episdoe patients, leads to impairment of skills and diminished functional capacity
relatives of schizo patients also experience related cognitive problems, could be under genetic control
what is diagnosis of schizo based on
diagnosis is non substance induced presentation of over 2 of; hallucinations, delusion, paranoia, loss of motivation, social withdrawal, dysfunction in attention, poor working memory for the duration of 1 month
what is biological basis in schizo
changes in brain volume in scz patients; ventricular enlargement, reduced brain size and weight, small grey matter and cortical volume
changes precede first presentation of disease
changes relatively static post presentation though some subgroups display disease progression
describe changes in brain structure associated w schizo
lateral and third ventricular enlargement
medial temporal lobe volume reduction
no cell death
aberrant neurones in white matter suggestive of disordered cortical neuronal migration
reduction of neuropil, reduced pyramidal neurone cell body size, reduced dendritic arborisations, reduced spine density and synaptic connectivity
reduction in spine density decreases density of synapses, explains how symptoms occur and allows treatment however does not explain why disease is caused
describe overall changes in neurotransmission associated w schizo
both altered dopamine and NMDA transmission are associated w schizo
describe dopamine transmission in schizo
dopamine hypothesis of scz: scz due to hyperactive dopaminergic transduction
D2 receptor blockade is mechanism of anti-psychotics, reduces positive symptoms through mesolimbic dopamine system
extrapyramidal side affects of first generation anti-psychotics include tremor, rigidity, dystonia and dyskinesia (nigrostriatal dopamine system), mimics parkinsons
beneficial effects of D2 receptor antagonists are found in mesolimbic system, negative side affects in nigrostriatal dopamine system
second generation antipsychotics also target 5HT2A receptor
amphetamine or L-Dopa can mimic symptoms of schizophrenia
antipsychotic drugs alleviate symptoms of amphetamine psychosis
excess dopamine release occurs in schizophrenics, as well as increased dopamine receptor binding, specifically in D2 receptors
excess dopamine may explain positive symptoms through mesolimbic system
dopamine overactivity may cause insufficient dopamine in other brain regions which may cause negative symptoms
describe glutamatergic neurotransmission in schizo
NMDA hypofunction associated with schizophrenia
NMDA antagonists can cause psychotic and cognitive abnormalities similar to in scz
NMDA receptor agonists improve symptoms of scz
reduced NMDA receptor expression in mouse model displays scz like symptoms
describe the epidemiology of schizo
incidence of between 7-42/100,000/year
affects roughly 1% of population
age of onset is usually late teens to early 20s
more prevelant in males than females; 1.4:1
urban populations more affected than rural ones
obstetric complications increase incidence of scz; premature birth, low birth weight, pre-eclampsia (pregnancy-induced hypertension), resuscitation at birth and prenatal nutritional deficiency
drug use increases chance
seasonal birth month affects chance; march is highest and september is lowest
describe genetic influence in schizo
identical twins have a 48% chance of getting it if the twin has it
both rare and common genetic variants increase risk;
common disease variants have very small effect size; e.g neuregulin
rare (possibly de novo) variants have large effects; e.g copy number variants or rare point mutations
no mendelian forms of scz identified (rare mutations with deterministic effects)
describe structural variations in the genome and how they relate to schizo
microscopically visable abnormalities are detectable by karyotyping of chromosomes, can be balanced (translocation and inverse mutations) or unblanced (large duplications and deletion mutations), these changes occur in less than 1% of population, e.g DISC1
copy number variations, are submicroscopic variations (1kb to 5Mb), may involve duplications and insertions, present in 100% of population (not specific to schizo)
there are 3.2 million single nucleotide polymorphisms per genome, everyone has them
describe DISC1s influence in schizo
found in all those suffering from scz in the scottish pedigree, translocation between chromosomes 1 and 11
region contained the gene for the previously unknown protein named disc1 (disrupted in schizophrenia 1)
genetic linkage studies indicate DISC1 as a susceptibility factor for schizophrenia
DISC1 expressed in key brain regions; hippocampus, olfactory bulb, cortex, hypothalamus, cerebellum and brain stem
DISC1 expression is developmentally regulated; highest expression during embryonic days and post-natal stages, corresponds with neurodevelopmental nature of scz
DISC1 likely to be an intracellular scaffold protein which interacts with many other proteins affecting; neuronal proliferation, neuronal migration, regulators of key singalling pathways, dendritic spine regulation and synapse maintenace
Disc1 promotes neural progenitor proliferation by modulation of GSK3beta and beta-catenin signalling
