Schizophrenia 2.

quickly what is the integrative model of schizophrenia

a combo

of genetic factors plus stress

(cannot be genetic alone as the stress often during brain dev increases risk for the disorder)

how does Neurodevelopment affect Schizophrenia

changes during early in utero brain development play a major role in causing the disorder

this can be causes by poor nutrition during pregnancy

a premature birth, low birth weight

physical and immune stress during pregnancy

(these disruptions create lasting changes in the brain and then subsequent stressors may trigger the disorder)

what part of the brain is enlarged in those with schizophrenia (how does it relevant to efficacy of antipsychotic drugs)

those with schizophrenia have an enlarged cerebral ventricles especially the lateral ones
and can help predict the disorder in adolescents

'larger the ventricles the less likely antipsychotic meds will be as effective

why does having larger ventricles cause schizophrenia

larger ventricles mean you have less white and grey matter, and thus the ventricles grow into that space (brain is smaller than should be meaning there is less neurons and gilal cells)

what happens to ventricles for people with and without schizophrenia when they age?

as you grow older your ventricles will enlargen for everyone as you lose white and grey matter when you age.

in those with the disorder it starts earlier and is much greater

when there is a loss of white and grey matter in those with schizo what areas are affected?

hippocampus and the amygdala

what is wrong with the hippocampus tissue in schizophrenia patients. causes? how does this affect the patient?

they have less pyramidal cells and those cells are more disorganized. usually caused by changes in utero

due to this their pyramidal cells have unusal connections which can lead to memory problems, difficulty in emotional regulation (explains symptoms)

What are the abnormalities in the cortex of people with schizophrenia? what structures

the corpus callosum (connection between hemispheres largest white matter structure) is altered creating problems connecting the hemispheres, causing disorganized thinking

frontal lobe has less grey matter so there is poorer executive functioning, attention (also due to changes in development specially synaptic pruning)

whats synaptic pruning, how is it related to the grey matter of the frontal lobe

we have more synapses when we are younger but hte brain prunes out whtat we don’t need, and it is believed there is more pruning in the frontal lobe for those with schizophrenia leading to less grey matter, or disorganization

does grey matter increase or decrease in people with schizophrenia over time

grey matter decreases over time

what does the brain activation look like on neuropsychlogical tests on those with schizophrenia?

brain activation of the frontal lobes is impaired or reduced on the tests

PET shows reduced metabolic acitivty of the frontal lobe and twin studies (one with disorder and one without) showed this

meaning they have less activation of frontal lobe: explains some negative symptoms (no talking, etc)

what was the original treatment of schizophrenia, 50s what did it help, identify generations of antipsychotics

og treatment was lobotomy (not effective, irreversible)

then in 30s Chlorpromazine originally an anesthetic

was used to minimize positive symptoms only (ex. hallucinations, disorganized thinking)

then antipsychotic drugs were developed had two generations (1. typical, 2. atypical)

typical antipsychotics, what do they do, name two examples

first generation: ex.chlorpromazine

antagonist of dopamine targeting D2 receptors

one targeting D2 receptors are more effective ex. Haloperidol

Dopamine Hypothesis (what is it, what lead to it)

the theory that schizophrenia is cased by having excess dopamine transmission, causing an D2 receptors to be overstimulated

created after medication showed that lessening dopamine treats schizo symptoms

Evidences for the dopamine hypothesis

1. those taking high amts of amphetamine got hallucinations and paranoia like schizophrenics

2. the typical antipsychs targets D2 receptors more, and could do with smaller doses

3. D2 selective drugs, showed d2 receptor hyperactivity is connected to higher dopamine levels

4. increasing dopamine in those with parkinsons (too low) can causes symptoms similar to schizo

what are the limitations of the dopamine hypothesis? (why theres more)

1. antipsychotics are fast at blocking dopamine receptors, but it takes weeks for symptoms to lessen
   (why not immediate)

2. dopamine antagonists do not work on 30% of patients (why)

3. it helps reduce pyschosis but not negative symptoms (theres more)

4. the receptors increase in number when using dopamine blockers overtime, stop taking meds rebound psychosis which is worse than original
   
   5. there are drugs that improve symptoms but struggle blocking D2 receptors (contriduction how do they work if they work on smth besides dopamine)

Tardive dyskinesia

uncontrollable repetitive movements of the face, lips,, tongue

what are the long term effects of antipsychotics. what is the cause?

prolonged use of typical 1 gen: movement disorders

such as

Tardive dyskinesia

condition happens for 1/3 of users, can be constant or irrversible after the drug is discontinued. can be due to upregulation of Dopamine receptors, but signs suggest more

connection between parkinsons and movement disorders and schizophrenia movement disorders from meds

Atypical antipsychotics: (what are they, give an example and what receptors it blocks etc, evidence, side effects)

second-generation antipsychotics: they are different becuase they act on mutliple receptor types (not just D2)

ex. Ciozapine blocks sertonin receptors and D2, while increasing Dopamine in frontal cortex

evidence is mixed as to whether it properly treats negative symptoms

side effects: metabolism: weight gain, immunosupression sometimes

not as high D2 affinity

What are NMDA antagonists, where do they usually strike and what does this cause

antagonists which only blocks NMDA when its channels are open (since inside), thus. it only affects active neurons

it usually targets GABA interneurons of the cortex which mediate the PFC

this interruption / blockage can cause abnormabilies, dysfunction in PFC creating schizophrenia like disorganized thinking

what is interesting about NMDA in relation to schizophrenia?

NMDA antagonists do not target dopamine receptors and yet they create schizophrenia like symptoms

why would having less NMDA receptors be connected to having schizophrenia like symptoms (mice)

they have disorganized behaviour, indicating PFC abnormalities, so schizo like problems if less NDMA receptors, or taking NDMA blockers. this led to proposal of the glutamate hypothesis of schizophrenia

Glutamate Schizophrenia Hypothesis of Schizophrenia what is it, describe study

proposes that NDMA or glutamate signalling is minimal/under-active in schizophrenics

this would account for the problems in the PFC.

studies currently going on: but it can cause seizures, so work being done

schizophrenia is made up the disruption of excitatory and inhibitory signalling (too much dopamine, too little glutamate)

and different symptoms can be traced to certain brain regions

long term treatment of schizophrenia

debate:

medication and therapy is most effective

long term medication does not consistently work well

social reintegration and weening off medication is shown to help fewer replaces

CBT helps too with stress and stress of hallucinations, reactions