schizophrenia and depression Flashcards
what percentage of the population has schizophrenia?
1-2% worldwide
what percentage of the population has depression?
13-20%
how are mental disorders diagnosed?
based on how the patient appears to the clinician or how the condition is descrobed, i.e signs and symptoms rather than aetiology
- same diagnosis may arise from different underlying pathologies
mortality and schizophrenia
schizophrenia patients die 15-20 years earlier than non-schizophrenics
complications associated with schizophrenia and depression
- increased alcohol and drug use
- poor diet
- suicde risk of 5-8%
neurodevelopmental schizophrenia
- diagnosed around late teens however has a prodromal phase much younger
kraepelin’s diagnosis of schizophrenia
- called schizophrenia dementia praecox (1887)
symptoms: paranoia, grandiose delusions, auditory hallucinations, abnormal emotional reg., bizarre thoughts. - noted potential genetic linkage
bleuler’s diagnosis of schizophrenia
emphasised the core symptoms of the disorder – difficulties in thinking straight, flattened affect, loss of
goal-directed behaviour, ambivalence due to conflicting
impulses, and retreat into an inner world (autism)
positive symptoms of schizophrenia
- hallucinations (most often auditory)
- delusions of granduer, persecution etc
- disordered thought processes
- bizarre behvaiours
negtaive symptoms of schizophrenia
- social withdrawal- leads to catatonia
- flat effect (blunted emotional responses)
- anhedonia (loss of pleasure)
- reduced motivation, poor focus
- alogia (rediced speech output)
- catatonia
cognitive symptoms of schizophrenia
- attention, working memory, verbal memory and fluency
- processing speed
- executive functions
symptoms of schizophrenia background
detectable before onset of psychosis
detectable in healthy relatives
good predictors of treatment success
start with +ve (acute) into -ve symptoms (chronic)
schizophrenia: experimental example of memory deficits
- presents on a computer a stimulus that patient has to remember its location or remember the object
- after delay the object has either changed location/image
- asked if there is a change
- patients show visuospatial deficits
what are the 2 hypotheses of neurochemical dysfunction of schizophrenics?
the dopamine hypothesis
the glutamate hypothesis
biological basis of schizophrenia examples
- neurochemical dysfunction
- genetic risk factors
- structural changes in the brain
what does the hyper-dopaminergic hypothesis state?
abnormally high levels of dopamine receptor
stimulation (mesolimbic) results in the symptoms of
schizophrenia
evidence for the hyper-dopaminergic hypothesis
- neuroleptics which ameliorate the positive
symptoms of schizophrenia block DA receptors – specifically D2 receptors - dopamine-releasing drugs e.g. amphetamine,
produce symptoms similar to positive symptoms of schizophrenia – also produce schizophrenic
episodes in patients in remission - antipsychotic medication reverses
amphetamine psychosis in humans
mesolimibic and mesocortical pathways and the dopaminergic hypothesis
ventral tegmental area (VTA) to nucleus accumbens, amygdala,
hippocampus and prefrontal cortex (limbic)
- memory
- motivation and emotional response
- reward and desire
- addiction
seaman (1980) neuroleptic research
- almost perfect correlation between the dosage effective for controlling schizophrenia and their ability to bind to D2
receptors - some patients given antipsychotic medication develop
parkinsonian symptoms – dyskinesia. - if they develop
slowly=tardive dyskinesia - motor impairments especially involve the face (mouth, tongue, lips). some patients show jerking/twisting
movement of arms and legs
what does the glutamate hypothesis state?
schizophrenia arises from the underactivity of glutamate (reflects diminshed activity of NMDA receptors in the brain)
evidence for the glutamate hypothesis
- NMDA receptor antagonists (e.g. the channel blockers
phencyclidine (PCP) and ketamine induce psychosis (i.e are psychomimetic) in healthy volunteers and
exacerbate symptoms in patients - some in vivo and post-mortem studies show decreased NMDA receptor number in brain tissue from patients
- levels of amino acids N-acethylaspartate (NAA) and nacetylaspartylglutamate (NAAG) are altered in the CSF and PM tissue of schizophrenic patients
- many genes implicated as risk factors in schizophrenia
are associated with the glutamatergic system
evidence of heritability in schizophrenia
- associated gene loci
e.g identical twins share 48% risk of schizophrenia
fratenal twins=17%
evidence of environemnetal influence in schizophrenia
- obsteric complciations
- immigration
- city living
- drug abuse
(early life adveristy is particularly damaging as schizophrenia is neurodevelopmental)
generalised structural changes of schizophrenia
- cortical tissue loss
- lateral ventricular enlargment
- third ventricle enlargement
regional structural changes of schizophrenia
- smaller thalamus
- enlarged caudate nucleus
- smaller temporal lobes
- reversed cerebral asymmetries
most pronounces structural deficits in schizophrenia
global deficits, ventricular enlargment and frontotemporal deficits
classes of depression:
- unipolar
- bipolar
- postnatal
- seasonal effective disorder
what is unipolar depression?
sustained low mood
what is bipolar depression?
periods of low mood are punctuated by bouts of mania
what is postnatal depression>
development of depression in mothers following birth
what is SAD?
form of depression that has a seasonal pattern (winter)
GxE environments in depression
evidence of genetic influence on depression+ DNA linkage anaylsis revealse depressed brain regions and twin/adaoption heritability studies
bipolar= 95% heritability, depression= 37%
s/s genotype (depression)= more likely to get disorder of they have more stressful life events
what does the monoaminergic theory of depression state?
depression results from functionally deficient monoaminergic (noradrenaline and/or 5-HT) transmission in the synaptic cleft
important brain regions include: raphe nucleus, nucleus accumbens, VTA, hippocampus, striatum and frontal cortex
evidence for the monoaminergic theory of depression
- indications that reserpine (which blocks transport of monoamines into vesicles) causes depression
- Iisoniazid (used to treat TB) can elevate mood subsequently found to block monoamine oxidase and thereby reduce monoamine breakdown
- subsequent development of antidepressant drugs (tricyclic antidepressants TCA and MAO inhibitors) to
facilitate monoaminergic transmission - CSF of patients shows low levels of 5HIAA (5-hydroxyindoleacetic acid main metabolite of 5-HT)
- PM studies show n that in the prefrontal cortex in brains from depressed patients there are above average numbers of 5HT & NA receptors (→upregulation of receptors in response to low basal levels)
what are the problems with the monoamine hypothesis?
- recent biochemical studies on depressed patients do not support the monoamine hypothesis, except that
consistently low concentrations of 5-HIAA in the CSF are found
*2. fails to explain why the clinical response to all antidepressant drugs is very slow (3-4 weeks)
*3. oher drugs that increase NA at the synapse (e.g. cocaine and amphetamine) or 5-HT are NOT effective
antidepressants- although will produce euphoria in normal subjects - antidepressants have some clinical efficacy in panic disorder, OCD and bulimia
what is the most successful theraputic approach to depression?
pharamacological manipulation of monoamone transmission (despite evidence issues)
state 3 antidepressants
MAO inhibitor
tricyclics
SSRIs
role of MAO inhibitor
Inhibits the enzyme MAO, which breaks down 5-HT, NA and dopamine
role of tricyclics
inhibit the reuptake of 5-HT, NA and dopamine
role of SSRIs (e.g fluoxetine)
block the reuptake of 5-HT, has little effect on NA, or DA synapses
name 3 non-pharmacological treatments of depression
electroconvulsive therapy (ECT)
physotherapy (CBT)
deep brain stimulation
what is ECT? (localised electrical stimulation)
- unknown mechanism in relieving depression
- affects temporal lobe
- advantage: quick relief of depression, mania
- adverse effect: loss of prior memories, impaired storage of new information
what is CBT?
- help patients overcome negative views
- effective for mild to moderate depression
what is deep brain stimulation?
- when severe depression fails to respond to other treatment
- electrode implanted deep in the brain
- electrical stimulation → decrease activity in brain circuits that are chronically overactive
