week 3 Flashcards
(123 cards)
1
Q
PTSD Exposure
A
traumatic event = experience or witnessed
response = intense fear, helplessness, horror
2
Q
PTSD symptoms
A
re-experiencing
avoidance
autonomic arousal
3
Q
CNS regions involved in PTSD
A
amygdala = increased activation
hippocampus = decreased activation during memory tasks and decreased size
medial prefrontal cortex = decreased activation and decreased size
HPA = increased activation (more cortisol)
4
Q
functions of brain areas affected by PTSD
A
amygdala hippocampus medial prefrontal cortex accumbens HPA
5
Q
amygdala
A
fear recognition & fear memory (& HPA regulation = increases HPA )
- social behaviors
- influences autonomic and endocrine functions & stress/disease = cortisol release
6
Q
hippocampus
A
declarative (episodic) memory
HPA regulation = inhibition of HPA axis = decreased cortisol
7
Q
medial prefrontal cortex
A
inhibitory control (amygdala etc)
8
Q
HPA
A
stress response = cortisol release
9
Q
amygdala role in social behaviors
A
aggression fear (activated during fear) - bilateral damage = fearless mouse anger face recognition social hierarchy
10
Q
amygdala influence on autonomic and endocrine functions
A
increases BP, HR and cortisol levels
11
Q
amygdala dependent associative learning
A
pairs sounds, smells, environments with emotional value judgments fear, pleasure
12
Q
amygdala in fear, anger and aggression
A
fight or flight response
drives hypothalamus, brainstem
13
Q
hippocampus and medial temporal lobe functions
A
formation of new memories
spatial navigation
stress response and feedback regulation of GC secretion
14
Q
regulation of HPA axis
A
amygdala = stimulatory hippocampus = inhibitory (stimulated by cortisol = negative feedback loop)
15
Q
PTSD affects on HPA axis
A
increases stimulation from amygdala
hippocampus = decreased inhibitory output to HPA (and decreased size)
ALTERED STRESS RESPONSE = increased
16
Q
medial prefrontal cortex
A
inhibitory effects on amygdala
inhibitory regulation diminished in PTSD
17
Q
Result of HPA dysregulation in PTSD
A
increased amygdala
decreased prefrontal cortex
increased HPA = increased BP, HR, etc.
18
Q
interoceptive stimuli
A
derive from inside body = gut, heart etc
19
Q
exteroceptive stimuli
A
derive from outside body = sounds, sights etc
20
Q
PTSD modifies responses to interoceptive & exteroceptive stimuli
A
Neural models for awareness of emotional feelings
involve sensations associated with interoceptive and exteroceptive stimuli
21
Q
neurochemical changes in PTSD
A
NE increased in (BP, HR etc); periphery & in CNS
5HT dysregulated
22
Q
memory recall
A
require reconsolidation every time they are recalled
can be modified during reconsolidation and this modification can be influenced by
Behavioral therapy or Pharmacological manipulation or both
23
Q
PTSD situations (examples)
A
post war
Rape Burns Motor vehicle accidents Observing disaster (e.g. Challenger disaster) Heart attack Cancer diagnosis and treatment
24
Q
PTSD DSM IV criteria
A
Predicted by a person’s physical and emotional reaction to the traumatic event more than by the absolute magnitude of the event
Reactions which predicted PTSD were extreme fear, horror, or helplessness (elevated heart rate)
Preexisting anxiety contributed to the reaction, and to the likelihood of PTSD
Occurring at least one month after the event
25
Complex PTSD
Seemed to be different symptoms if the traumatic event was a single event, like an assault, compared to ongoing trauma, like child abuse
Early traumatic events increased vulnerability to genetic risk for substance abuse, depression
Prolonged traumatic events in childhood interfere with development of emotional regulation, and symptoms may look like personality disorders
26
result of chronic trauma
bodies develops other compensatory reactions - can't deal with constant heightened level of arousal
- become immune to events or disconnected
OR interfere with emotional regulation development
27
PTSD symptoms
Re-experiencing =Nightmares, Flashbacks
Avoidance = Avoid reminders, Emotional numbing
Autonomic arousal = Exaggerated startle, Hypervigilance
28
Acute stress disorder
Seen in the first 30 days after an acute stressor
Dissociation is a key component (loosing track of time, self and/or usual thought processes and memories)
Thought to predict PTSD
Key: it can’t really be called PTSD until a month after the event
29
reminders / triggers (PTSD)
Aspects of the event (sound, smell, visual)
Trigger emotions, memories, or flashbacks
Are avoided as much as possible
Trigger sympathetic autonomic response
E.g. sounds of helicopters, sight of white coats, smell of chemo
30
risk factors for developing PTSD
heart rate immediately after event = INCREASED RISK
increased pain level = INCREASED RISK
early interventions to reduce arousal might reduce the intensity of memory consolidation about the traumatic event
31
Pharmacological Treatment PTSD
Mostly symptomatic at this point
Beta blockers = decrease baseline arousal or reactivity to reminders
SRIs
Benzodiazepines = acutely
32
PTSD Psychotherapies
Trauma focused CBT is the most tested
- reduce autonomic arousal with relaxation or meditation training
confront reminders
rework trama narrative = recall event to change memory
redefine safety standards
33
Intraaxial Brain Tumor
glioblastoma = most common
malignant
glial and neuronal tumors
34
extra axial brain tumor
meningioma most common
often benign
outside of brain parenchyma
35
keratin positive brain tumors
carcinomas
36
glial fibrillary acidic protein (GFAP) positive brain tumors
glioblastomas
37
MGMT biomarker
O6-methylguanine methyltransferase = DNA repair enzyme
low levels = tumor responds to Temodar
high levels MGMT = resistant
38
IDH1 mutation
isocitrate dehydrogenase 1 - common in low grade gliomas
- astrocytoma
- oligodendroglioma
- oligo-astrocytoma
common in secondary glioblastoma (rare in primary GBMs)
39
common metastatic tumors to the brain
```
LUNG = #1
breast
melanoma
renal
GI (colon)
meningeal or intraaxial
```
40
glioblastoma brain tumors
astrocytic tumors with pseudopalisading necrosis
butterfly glioma - intraaxial involvement of both hemispheres
high grade - atypical mitosis, giant cells
vascular proliferation
GFAP positive (astrocytes)
41
meningioma brain tumors
neurofibromatosis type 2 associated
| histo = whorls, psammoma bodies, nuclear pseudo inclusions
42
MERLIN gene
membrane-cytoskeleton scaffolding protein on chromosome 22
bilateral bestibular schwannomas
neurofibromatosis Type 2
43
clinical presentation meningiomas
neurological deficits
headaches
seizures
44
neurofibromatosis type 2
meningioma (psammoma bodies)
schwannoma (verocay bodies)
ependymoma (perivascular pseudorosettes)
45
common primary adult brain tumors
meningioma (extraaxial)
glioblastoma (intraaxial)
metastases (intra or extraaxial)
pituitary adenoma
46
most common childhood brain tumors
medullobalstoma
pilocytic astrocytoma
= cerebellum/posterior fossa
47
bilateral schwannomas
diagnostic for neurofibromatosis 2
48
psychosis signs
hallucinations
delusions
disorganized speech
49
hallucinations
perceptions in the absence of external stimuli (seeing a light that isn't there)
50
delusions
false beliefs about oneself or others that persist despite the facts (thinking the CIA is spying on you)
51
disorganized speech
words and ideas are strung together based on sounds, puns, or loss associations
52
most common type of hallucination
auditory (verbal) = hearing voices
- other peoples voices, one's own thoughts heard aloud
- voices commenting (2nd or 3rd person)
- multiple voices talking to each other
- command hallucinations
53
cause of auditory hallucinations
abnormal generation of internal verbal experience coupled with delaterized processing errors--> perceptions of non-volitional, external and auditory speech
54
errors in processing for auditory hallucinations
1. non-volitional = feel unable to control the voice (involuntary)
2. non-self = defect in source monitoring (internally generated experiences feel as if they are external sources)
3. auditory = brain becomes confused with stimuli that aren’t noises
4. external
55
verbal thinking
normal thoughts, inner speech
56
self, but “ego-dystonic” thoughts
in conflict with one’s desires, feelings and goals
• ruminations = seen in depression
• obsessions
57
not- self thoughts
```
thought insertion (not a sensory experience)
illusions
```
58
Illusion
Misperception or misinterpretation of a real external sensory stimulus
often occurs in relation to substance intoxication (ex: hearing a whisper and thinking the person said they want to kill you)
59
Delusions
A fixed, false belief
false belief based on incorrect inference about external reality that is firmly sustained despite what almost everyone else believes and despite what constitutes incontrovertible and obvious proof or evidence to the contrary.
60
Delusions are culturally relevant with common themes
Persecution/paranoia (with ideas of reference) = people watching/out to get you
• Grandiosity (e.g. special powers, spiritual, erotomania) = ex: think famous people are in love with you
• Somatic (e.g. control, hypochondriacal, infection, infestation)
• Misidentification
61
Misidentification
Caogras delusions
Fregoli delusions
Cotard delusions
62
Coagras delusions
disorder in areas normally associated with facial recognition (ex: believe friend or family member is actually an imposter)
belief that others have been replaced by imposters
63
Fregoli delusions
believe that different people are actually the same person in a disguise
(persecutor with many faces)
64
Cotard delusions
(nihilistic/negation) = belief that they are dead
65
“Cognitive” features of delusions
Unwarranted and excessive conviction: problem with reasoning process
Creative explanations for anomalous experiences
evaluations based on not enough evidence (impulsivity)
Evaluations based on poorly selected evidence (↓ filtering)
Difficulties distinguishing coincidence vs. causality
Few opportunities for “social” reality testing due to social isolation
preoccupation
affective valence- distress, worry fear - tied to emotions
66
Dopamine and psychosis
Psychosis as state of aberrant “salience” mediated by dopamine
Excess mesolimbic DA results in heightened “salience” (neutral/cold stimuli → relevant/hot stimuli)
Neutral stimuli becomes more important (more prominent)
DA agonists and stimulants result in psychosis
67
Abnormal salience of external stimuli
→ delusional thinking
68
Abnormal salience of internal stimuli
→ hallucinations
69
mechanism of antipsychotics
block DA transmission
| Salience ↓ = become less distracted by voices in head
70
DDx psychosis
1. No mental illness (hearing voices can occur in up to 40% normal individuals)
2. Malingering = making up psychosis for external gain (ex: to be released for criminal charges)
3. Mania
4. Major depressive episode
5. Dementia (blame external factors for loss of memory)
6. Delirium = loose ability to differentiate reality
7. Non-psychiatric brain disorder = seizure, tumor, infection, endocrine, etc
71
Drug-Induced Psychosis
Hallucinogens (visual distortions and hallucinations)
• Psychostimulants (paranoia, illusions, hallucinations)
• Alcohol withdrawal (VH)
• Glutamatergic drugs (AVH, delusions)
• Solvents (VH)
• Cannabis (mild paranoia) – increase risk of schizophrenia in young adults
• Medications (e.g. DA agonists, steroids, etc.)
72
Schizophrenia
Chronic disorder with periods of psychosis, disturbed behavior and thought, and decline in functioning that lasts > 6 months
Associated with increased dopaminergic activity, decreased dendritic branching
73
Schizophrenia DSM IV Criterion A
Two or more of the following 5 symptoms:
1. Delusions = positive symptom
2. Hallucinations = positive symptom
3. Disorganized speech = disorganized thinking
4. Grossly disorganized or catatonic behavior = disorganized thinking
5. Negative symptoms
> 6 months
74
positive symptoms
extra abnormal behaviors
a. Hallucinations
b. delusions
75
negative symptoms
```
lack normal behaviors
affective flattening
alogia
avolition-apathy
anhedonia-asociality
```
76
Affective flattening
poor eye contact, ↓ spontaneity, emotional withdrawal
77
Alogia
impoverished thinking, speech latency, thought blocking,↓ abstract thought (little going on in head)
78
Avolition-apathy
↓ motivation, anergia, passivity
79
Anhedonia-asociality
↓ pleasure (anticipatory > consummatory), ↓ social drive
May be found in other conditions (ex: depression)
Patients with schizophrenia who have negative symptoms are not depressed
80
primary negative symptoms
core features of schizophrenia
don't respond well to antipychotic therapy
"deficit syndrom" = associated with poored social/occupational fan, QOL and overall outcome
81
secondary negative symptoms
due to positive symptoms exacerbation, depression, medical illness, medication, side effects, psychosocial/environmental factors
82
disorganized symptoms
lack normal linear, logical, goal-directed thinking (A → B)
| feature of schizophrenia “thought disorder”
83
tangental thinking
(A → C) = completely deviate from desired topic
84
Circumstantial
non-linear thought process, deviation to irrelevant topics but eventually returns to desired point
85
thought disorder
may reflect diminished hemispheric lateralization of language and disruption of somatic networks:
o stilted, overly formal speech
o loosening of associations, illogically, incoherence = (schizophrenina disruption of associations = associate things abnormal)
• neologism = make up words
• paranoid themes
o neologism = “dramatic”, “schizophenzyism”
o concreteness/lack of abstractions
86
stilted speech
inappropriately pompous, legalistic, philosophical or quaint
| symptom exhibited through a person's communication of thought disorder in schizophrenia
87
loosening of associations
illogically, incoherence = (schizophrenina disruption of associations = associate things abnormal)
- neologism
- paranoid themes
88
neologism
make up words
89
concreteness thinking
lack of abstractions
90
schizophreniform subtypes
1. paranoid (delusions)
2. disorganized = regard to speech, behavior, and affect
3. catatonic = automatisms
4. undifferentiated = elements of all types
5. residual
91
schizophrenia epidemiology
< 1% rate (7/1000 lifetime risk)
risk = urban, migration, winter births, birth complications, 1st/2nd trimester maternal infections, advanced paternal age, cannabis use
Male = Female (approx. male 1.4X)
92
age of onset schizophrenia
```
male = 20-24 yrs
female = 25-29 yrs
```
93
neurobiology schizophrenia
reduced grey matter volume = excessive synaptic pruning
enlarged ventricles
increased striated dopamine receptor density
decreased N-acetyl aspartate
decreased glutamate receptors
94
schizophrenia disease course
```
risk = genetic, environmental, social
prodrome = non-specific symptoms, functional decline (several years prior)
diagnosis = positive symptoms, chronicity (meets DSM criteria)
```
95
favorable predictors of schizophrenia = decreased severity
```
acute or later onset
precipitating event
good premorbid fxn
lack of negative and cognitive symptoms
female gender
psychosocial support
```
96
mortality in schizophrenia
increased suicide (10% complete)
accidents
medical morbidity
lifespan 10-15 yrs shorter
97
cognitive symptoms of schizophrenia
```
Vigilance/sustained attention
Processing speed
Memory
• Immediate and “working” memory
• Secondary memory
• Verbal memory
Verbal fluency (word generation)
Executive function (volition, planning, set-shifting)
Social cognition (emotional processing, theory of mind, etc.)
```
98
cognitive symptoms tx
only modernly respond to drugs
99
non-affected first degree relatives
can show mild cognitive symptoms ass. w/ schizophrenia
100
initial workup for schizophrenia
hx & PE, labs, urine drug screen
| neuroimaging for first episode psychosis, children, elderly
101
treatment schizophrenia
antipsychotics D2 receptor antagonists
| lifetime treatment
102
clozapine
2nd generation antipsychotic = atypical
gold standard for refractory schizophrenia
many SEs = agranulocytosis (check CBC weekly), seizures, myocarditis
103
results of pharmacotherapy tx for schizophrenia
```
20% reduction in symptoms
30% don't respond
clozapine = best for non-responders
non-compliance common
positive symptoms respond best to tx
```
104
antipsychotic drugs
dopamine D2 antagonists
clinical potency of most drugs proportional to ability to bind DA D2 receptors
higher binding affinity = greater efficacy of drug
105
duration of effect of antipsychotics
```
lag time (3-6 weeks) before antipsychotic effects
but blockade of D2 receptors occurs immediately
```
106
serotonin hypothesis of schizophrenia
5-HT acting at 5-HT 2A receptors (esp locus ceruleus and the cerebral cortex) ==> enhancement of glutamatergic transmission
107
glutamate hypothesis of schoizophrenia
hypo function of glutamatergic signaling via NMDA receptors
| physchotomimetic properties of antagonists of the NMDA subtype of glutamate receptors (phencyclidine and ketamine)
108
treatment of early onset neurologic (extrapyramidal) symptoms from antipsychotic drugs
```
stop drug OR
antimuscarinic drugs (Parkinsonian tx)
-Benztropine
Trihexyphenidyl
diphenhudramine (antihistamine with antimuscarinic activity)
```
109
neuroleptic malignant syndrome
rare idiosyncratic response = akinesia, rigidity, mutism, hyperthermia
can follow large parenteral dose of dopamine-antagonist drug or rapid withdrawal of dopaminergic medications
110
treatment of NMS
```
stop antipsychotic medication
cooling
rehydration
administer dopamine agonist = bromocriptine
direct muscle relaxant = dantrolene
```
111
aripiprazole
partial agonist of dopamine and serotonin receptors
| atypical antipsychotic used for schizophrenia treatment
112
atypical antipsychotic drug activity
high affinity for 5-HT2 receptors (vs. D2 receptors in typical antipsychotics)
olanzepine
resperidone
clozapine
113
typical antipsychotics
higher D2 antagonist affinity
| Haloperidol
114
SEs of atypical antipsychotics
much lower risk of extrapyramidal symptoms
greater risk weight gain (esp. olanzapine and clozapine)
Q-T interval lengthening (esp. Ziprasidone) = ventricular tachycardia, torsades de pointes and sudden death
115
neurocutaneous disorders = disordered growth of ectodermal tissue
Neurofibromatosis Type 1
Tuberous sclerosis
Sturge-Weber syndrome
Neurofibromatosis Type 2
116
Neurofibromatosis type 1
```
neurocutaneous disorder
cafe-au-lait spots
lisch nodules = pigmented iris hamartomas)
neurofibromas in skin
optic gliomas
pheochromocytomas
autosomal dominant - 100% penetrance, variable expression
muted NF1 gene on chr 17 (neurofibromin)
```
117
tuberous sclerosis
```
hamartomas in CNS and skin
adenoma sebaceum (cutaneous angiofibromas)
mitral regurgitation
ash-leaf spots
cardiac rhabdomyoma
mental retardation
renal angiomyolipoma
seizures
autosomal dominant
```
118
hamartomas
benign focal malformations of normal tissue type growing in disorganized mass
grow at same rate of tissue
non-neoplastic
119
sturge-Weber syndrome
congenital disorder
port-wine stains (nevus flames) - V1 ophthalmic distribution
ipsilateral leptomeningeal angiomas
pheochromocytomas
can cause glaucoma, seizures, hemiparesis and mental retardation
occurs sporadically
120
von hippel-Lindau disease
autosomal dominant - mutated tumor suppressor VHL gene on chromosome 3
cavernous hemangiomas in skin, mucosa, organs
bilateral renal cell carcinoma
hemangioblastoma in retina, brain stem, cerebellum, pheochromocytomas
121
hemangiomas
benign tumor of epithelial cells lining blood vessels
122
hemangioblastoma
tumor originating from vasculature
123
neurofibromatosis Type 2
chromosome 22 mutation - merlin gene, schwannomin, or neurofibromin 2
associated with BILATERAL SCHWANNOMAS, meningiomas and ependymomas
