Exam 4 Flashcards
Traditional Theory of schizophrenia emphasized the [blank] pathway while newer theories emphasizes the [blank] pathway
Traditional theory: Mesolimbic
New Theory: Nigrostriatial
One type of non-medication apporach to schizophrenia is…
Cognitive behavior therapies
(Dee got points for that answer, but I think you need to list a specific one)
This symptom of schizophrenia is characterized by
maintaining a rigid, inappropriate posture and/or lack of verbal and motor responses
Catatonia
Short Answer:
Describe the neurodevelopmental risk model.
What early riskfactors are associated with Schizophrenia?
What could lawmakers do to prevent risk for development?
Explains the ongoing developmental trajectory and risk factors at different points and how these risk factors accumulate before the individual presents with their first psychotic break.
Underlying genetic risk/predisposition might impair the resiliency of their brain, especially during development. If there are insults that occur during that time, genetic risk really impairs the ability of the brain to repair itself.
Risk factors such as prenatal infections in the mother or perinatal period such as potential hypoxia or nutritional difficult deficiencies might add an additional risk to the genetic risk.
Evidence that children who are born in late winter
or early spring have higher risk of developing schizophrenia due to infections associated with that period.
Stress/early life trauma and dopaminergic dysregulation can make an individual more susceptible to stress and more sensitive and susceptible to later stressors that could occur.
Research in show risk factors are often present early,
specifically, the use a trilogy of markers including speech/motor delays; minor psychotic symptoms; social/behavioral/emotional are present in children around the ages of 9-12 years of age.
Minor psychotic symptoms, cognitive deficits,
exaggerated amygdala response are also associated with schizophrenia.
The neurodevelopmental risk model also explains proximal stressors (additional stressors) in adolescence or late childhood such as a parent’s divorce can add
to the risk factors associated with the individual having their first psychotic episode.
Lawmakers could reduce cannabis use to prevent risk development. Specifically, research has shown that cannabis use is associated with getting over the threshold for the individual’s first psychotic break. Cannabis use during this sensitive time frame can actually increase the risk even further.
Short Answer:
You are a psychiatrist and determined that your patient has Schizophrenia. Answer ALL the following questions:
1) How do you know your patient has Schizophrenia?
2) What is the best treatment approach?
3) How would you determine if they are treatment resistant?
4) What would you do if they are treatment
resistant?
1) There are several symptoms according to the DSM-V the patient must present to establish the patient has schizophrenia. The patient must present with 2 (or more) of the following and each must present for a significant portion of time during a 1-month period (or less if successfully treated), with at least 1 of them being (1), (2), or (3): (1) delusions, (2) hallucinations, (3) disorganized speech, (4) grossly disorganized or catatonic behavior, and (5) negative symptoms. In addition to these symptoms, for a significant portion of the time since the onset of the disturbance, level of functioning in one or more
major areas, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset (or when the onset is in childhood or
adolescence, there is failure to achieve expected level). They have to meet criteria C-F, which explains that the continuous signs of the disturbance persist for at least 6 months. I would make sure that schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out and that disturbance is not attributable to the physiological effects of a substance. I would check to see if the individual has a diagnosis of autism or communication
disorder, if they do I will make sure that there prominent delusions or hallucinations, in addition to the other symptoms of schizophrenia.
2) The best treatment approach will the atypical anti-psychotic medication in addition to psychosocial intervention such as cognitive therapy, psychoeducation, family intervention, and social skills training.
3) An individual is treatment resistant if they don’t respond to at least two trials of antipsychotic medication such as Chlorpromazine or Risperidone of adequate dose and duration.
4) If they are treatment-resistant, the antipsychotic clozapine is initiated. If they don’t respond, ECT might be started.
Short Answer:
Describe important differences between animal models and human models of schizophrenia. In your answer, include symptomatology and neurocircuitry.
Human: Limbic system begins in substantia nigra of ventral tegmental area. Nigrastriatal area is more developed as well as the associative striatum. The nigrastriatal pathway that connects to the substantia nigra to the associative straitum is the key pathway for schizophrenia in humans. Nucleus accumbens is smaller in humans/primates.
Rodent: Limbic system originates in the ventral tegmental area. Mesolimbic area is much more developed compared to humans. Ventral striatum (including nucleus accumbens) is larger part of striatum in rodent.
These neurological findings imply different dopaminergic pathways in rodents than humans when we study schizophrenia.
Alterations in dopamine function in associative striatum likely contribute to misleading attribution of salience to certain stimuli (delusions/psychosis).
Cortico-striatal-thalamic circuit (direct/indirect): not enough filtering to thalamus. Associated with postive symptoms such as hallucinations/delusions.
Primary circuit in psychosis includes thalamus and PFC going to associative striaum. Increased activity in associative striatum and excessive D2 receptor stimulation.
Human: button presses, food/reward, rat level presses, food/reward.
Devaluation: human bias towards food not devalued. (needs PFC and associative striatum, goal directed impairment in schiophrenia is associated with altered caudate function, devluation impairment in schiozphrenia not due to limibic systems)
Locomotion in rats: bad idea to look at this, because uses limbic areas not associative.
Serial reversal learning: two choices, one associated with reward. (OFC and associative stritum when reexposed to previous contingencies (serial reverse learngin), PFC for attentional set-shifting, schizophrenia both imparied).
Name 4 symptoms of schizophrenia.
What is one thing that is NOT a symptom of schizophrenia?
Delusions, hallucinations, disorganized speech, negative symptoms
Multiple personalities (NOT a symptom)
MRI studies of schizophrenia show that individuals tend to have [blank]
larger ventricles
Name processes that occur postnatally that might influence the development of Schizophrenia.
What is NOT one of those processes?
GABA interneuron maturation
Pruning of gluatmate synapses
Maturation of dopaminergic synapses
Oligodendrite differentiation
NOT: 22q11.2 deletion
How do antipsychotics work?
Normalizing excessive D2 signaling
True or False: An individual with schizophrenia does not experience depressive symptoms.
False
Why PTSD? What memories are remembered?
Emotionally arousing ones, positive or negative, mild or intense
Fear conditioning circuitry
What are the ways to ameliorate negative memories?
Fear extinction, reconsolidation interference, memory suppression, erasing memories and future science
Fear conditioning neural circuitry what regions critical? Flow across these regions?
Circuit includes somatosensory cortex, thalamus, lateral and central amygdala.
During conditioning, UCS and CS are paired; although CS only generates small signal, UCS generates large signal that depolarizes the lateral nucleus of amygdala cell, on different spines of the cell.
The neurotransmitter depolarization diffuses from UCS spine to CS spine, strengthening the connection of the spine.
Condition and Extinction paradigm steps and things to know
1) Fear conditioning
2) Extinction
3) Consolidation
4) Extinction
Day 1: both rat groups conditioned
Day 2: extinction in one group
Day 3: extinction recall faster in extinction rats
However, 14 days following extinction, fear response is back. Extinction inhibits, but doesn’t erase memory
Hippocampus provides context
Important stuff about fear extinction:
1) do we erase a memory?
2) If we don’t erase a memory what happens and how?
3) What are relapses and why do they occur?
- Form new memory
- Inhibitory memory competes in context dependent way (retrival of extinction activates inhibitory GABA networks and hippcampus)
- Relapses due to difficulties in extinction memeory recall and/or longlasting transfer beyond therapy context
What happens if we block GABA receptor (PTSD)?
Condition fear is back
Failure to retreive extinction
What is responsible for retrieval of extinction in rats? Humans?
Rats: Infralimibic
Humans: mPFC
Metaanalysis on PTSD shows
1. Region more activity
2. Region less activity
3. Region with consistent lower volume subcortical region?
More activity amygdala (dorsal ACC)
Less activity PFC (vmPFC or inferior PFC)
Hippocampus lower volume
Why is dentate gyrus important in PTSD?
target for memories, subsection of hippocampus.
Use MRI to see subregions. Dentate gyrus lowest volume, most dysfunctional. Other regions small too, but not after multiple comparisons, and not the same in other disorders, this is PTSD specific.
Memory consolidation: define it
Short term to long term memory
Includes LTP (synchronous stimulation incrases signal transmission between two neurons)
Reorganization of brain’s neural circuitry for long-term storage
Rehearsal helps boost consolidation
Describe consolidation on a neuronal level
Could occur during acquistion, or during post-training period to strengthen extinction memory
Structural changes in BLA synapses, GABA receptors upregulated, clustered in synaptic cleft for max inhibition
Infralimbic cortex: high frequency bursting of IL neurons shortly after extinction predicts retrieval or extinction the next day
Hippocampus: MAPk cascade for gene expression/structural changes
What is reconsolidation? How do you disrupt a memory through reconsolidation?
There is synaptic consoliation and reconsolidation, which is the way we intefere with memory via consolidation.
After consolidation, next time you bring memory up, becomes unstable and you can change it. Memory not fixed, constant retrieval, means constant manipulating and changing.
**Reactivated memories vulnerable to interfeneces. Time window in which memory can be altered before stabilizing (minutes to hours) **
What are the maniuplations that cause reconsolidation and how?
Manipulations enrich or deplete neural rsources needed for memory restorage to strengthen or weaken memory
Meds, psychotherapy, cognitive tasks, ECT
In the in class example of reconsolidation, what three things were done to the dog collar for the person scared of dogs?
Updating processes
1. Extinction: see more collars
2. Counterconditioning: learns to associate dog collar with money
3. Interference: plays on phone to ignore dog collar
Can we literally change a human memory with reconsolidation and other techniques?
No, harder in humans. We need psychotherapy and constant teaching of skills
Only moderate clinical evidence. Need to understand what factors destabilize memory. Retrieval may not be enough.
Do Beta Blockers prevent memory consolidation?
No evidence that it works
Review: ways to ameliorate effects of negative memories
- Fear extinction
- Reconsolidation interference
- memory suppression
- Erasing memories and future science
Memory Control and Suppression: Think No Think Paradigm
Brain regions?
Teach association. Then told to think of previously associated picture or not. Better memory when told to think about it.
Lots of mPFC in memory suppression, suppresses hippocampus.
But in PTSD? PTSD and trauma exposed people did not show as much activity in mPFC as controls. PTSD and trauma exposed individuals were nonsuppressors, can’t suppress memories. Controls = more right MFG activation
Significcance: Those exposed to traumatic events have reducedcontrol, activity, and can’t suppress memories. When exposed to trauma, brain more sensitive to negative info.
Trauma = less PFC activity
Current models of PTSD, taking everything into account, link persistence of intrusive memories to a failure of what?
Failure of extinction or uptdating of original memory traces while in safe environment, together with abnormal and exaggerated processing of contextual reminder of trauma in fear circuit.
Optogenetics in PTSD
Foot shock and happy rat example
Genes modifide to express light sensitive opsins (viral vectors). These ion channels/pumps, open and close in response to light. Channelrhodopsins depolrize (activiate) neurons with blue light, halorhodopsins hyperpolarize (inhibit) neurons with yellow light. Expression can be restricted to specific types of neurons/brain regions, allowing researchers to isolate function of particular neural circuits in the complex network of the brain.
Foot shock: LTD after fear conditioning, rat forgets fear memory, then LTP, remember fear memory
Happy rat: simulate when having good time with female rat. Then depress male in isolate, restimulate, he’s happy again.
Creates false memory in hippocampus
First line PTSD treatment
(And what is its goal? success rate?)
Prolonged exposure, congitive processing therapy
Goal: extinguish conditioned fear and provide cognitive framework for change
40-60% patients have suboptimal response
