What is a stressor?

Anything that throws body out of allostatic

balance

What is allostasis?
Allostasis is the process of achieving stability, or homeostasis, through physiological or
behavioral change
What are the 3 stages of a stress response?
1. Alarm: SNS activation
2. Resistance: decreased SNS activity; increased HPA
activity cortisol & other hormones for maintaining
prolonged alertness & increased immune function (to
fight infections & to heal wounds)
3. Exhaustion: NS and Immune system are spentperson
is tired, inactive, and vulnerable to illness

What is the role of the sympathetic NS in the stress response?
sympathetic nervous system (SNS) is one of the three parts of the autonomic nervous
system, along with the enteric and parasympathetic systems. Its general action is to
mobilize the body's nervous system fight-or-flight response. It is, however, constantly
active at a basal level to maintain homeostasis.
[1]

What is the HPA and what is its role in the stress response?
Hypothalamus, pituitary gland, adrenal cortex
Hypothalamus makes CRH Pituitary makes ACTH
adrenal secretes cortisol increase in blood sugar &
metabolism
Activated w/ prolonged stressors
Beneficial in the short-term; detrimental in the long-
term
Negative consequences of stress (like effects on
learning and memory) can be induces by stress
itself, or by an injection of cortisol!

Why do you feel terrible during finals week?
Acute activation boosts the immune system,
even improves memory
Useful for escaping a predator
*but* Powerful, inescapable, temporary stress body
reacts like illness, w/ increased immune activity
Like exam week!
body increases production of natural killer cells (a type of
white blood cell for fighting infections) and cytokines.
Cytokines help fight infections, but they are also the bodys
way of telling the brain you are sick, so you have sickness
syndrome (fever, exhaustion, decreased appetite)

What are some factors that affect the stress response?
Individuals perception of their own ability to cope
with stress
Intensity of the stressor (novel environment vs. life-
threatening situation)
Individuals control over the stressor
Duration of stressor
Personality traits (individuals with high anxiety) are
more likely to show impaired memory after stressor)
Gender (males more affected than (young)
femalessome measures improve in females!)
Age (older more vulnerable to deleterious effects
of stress than younger; early stress might not
show cognitive effect until later in life)

What are some effects of long-term stress?
Hippocampal damage (b/c increased cortisol makes
hippo. neurons more vulnerable)
Chronic infant stress leads to deceased hippo
plasticity & impaired spatial memory in adulthood
(rats)
Explicit memories (consolidated by hippocampus)
are esp. vulnerable to stress; implicit memories are
not (sometimes opposite effect!)interesting b/c
amygdala increases branches and other brain
regions that do implicit learning (like cerebellum)
are not as affected by stress.
Reproductive effects:
Decreased libido in women
Can inhibit menstrual cycle, ovulation in women
Decreased sexual performance in men
Decreased immune function, Prolonged sickness
syndrome??
Prolonged increase in cortisol decreases protein
synthesis, including proteins for the immune
systemso lots of either feeling sick or being sick.
Increased blood sugar (b/c stress (cortisol?) causes
pancreas to release glucagon)is this bad if happens
for too long??
Chronic hyperglycemia can lead to kidney damage,
neurological damage, cardiovascular disease!!

How does stress affect the hippocampus and amygdala?
Hippocampus and amygdala are 2 brain regions w/ lots of receptors for
cortisol.
PFC has many as well.
So do hypothalamus and pituitarythese serve as substrates for negative
feedback to turn off cortisol production.

PTSD: what are the symptoms? What types of events can precipitate it?
Why doesnt everyone who is exposed to such a stressor develop PTSD?
In people who:
Severe injury or threat
Witness others harmed or killed
Soldiers, victims of rape, kidnapping or torture, car
crash survivors, sudden loss of loved one
Symptoms (lasting >1 mo):
Flashbacks and nightmares about event
Avoidance of reminders of event
Exaggerated arousal in response to noises, other
stimuli
Why doesnt everyone in such situations develop
PTSD?
PTSD victims have smaller hippocampuschicken
or egg??
PTSD patients w/ identical twin & no trauma or
PTSDtwin had smaller hippocampus
toosuggests small hippocampus came before
PTSD and is not result of PTSD.
PTSD victims have lower than ave. cortisol levels at
time of event and 2 wk later
Maybe people w/ low cortisol are ill-equipped
to handle extreme stress
Vietnam vets w/ brain damage & PTSD: those w/
damage to amygdala NEVER had PTSD!


What is an engram, and what were Lashleys critical mistakes in looking for the
engram?
A physical representation of a memory
Lashley: trained rats, then cut* or lesioned^ certain areas of
cortex *no significant effect on performance; ^the bigger the
lesion, the greater the impairment (location didnt matter)
2 false assumptions:
(1) memory is in cortex
(2) all memories are physiologically the same

What are implicit memory and explicit memory? What brain regions are important for
each?


What are some differences b/t short-term memory (working memory) and long-term
memory? What brain region is important for working memory?
Short Term Memory
Small capacity
CYZUAUF
Fades quickly unless rehearsed
Once forgotten, it is gone
Working memory is alternate way of thinking of
STM:
lasts hours to days w/o rehearsal: where car
is parked, when/where lunch date is
Time needed for consolidation varies,
especially depending on familiarity of topic &
emotional content
Long Term Memory
Infinite capacity
Lasts indefinitely
Could be forgotten and then later remembered w/
appropriate cues.
Phone # vs. names of grade school teachers
Working memory
Delayed response task
Dorsolateral prefrontal cortex

What were some of HMs impairments; what could he still do?
HM: anterograde amnesia
Lost declarative (explicit)
memory & spatial memory
Intact procedural memory
(a type of implicit) and
working memory

With regard to memory, what are some functions of the hippocampus?
Active during formation of memories & during
recall
Consolidation (STM LTM)
Declarative/explicit memory
Spatial memory
Increased activity in hippocampus
when doing spatial task (ex:
imagining best route; fMRI)
Damage impairment of spatial
tasks
London taxi drivers: hippo active
during spatial tasks; larger posterior hippo
& positive correlation to time being a taxi
driver
Birds that live at high altitude and bury seeds
= larger hippocampus
Place neurons

What other brain regions are important in learning and memory, and what type of
learning do they subserve?
Cerebellum: for learning a conditioned response
Also for motor learning (skills) & cognitive
stuff too.
Parietal lobe: if damage, dont spontaneously
elaborate on memories
Temporal lobe (ant./inf.): damage causes
semantic dementia
SD: loss of factual knowledge
Probably b/c this region is a hub for retrieving
info; not the location of storage.
Prefrontal cortex: learning reward and
punishment
Also working memory of course

What is a Hebbian synapse?
Hebbian synapse: a synapse that
increases in effectiveness b/c of
simulataneous activity in pre- and
postsynaptic neurons

What is LTP? What receptors are necessary?
Long Term Potentiation: a burst of stimulation
from axons, e.g., 100 excitations per second for
1-4 seconds onto dendrites, results in
potentiated (strengthened) synapses for minutes,
days or weeks
Necessitates glutamate receptors: AMPA and
NMDA receptors

What are some presynaptic changes that occur in LTP? What are some postsynaptic
changes that happen in LTP?
Presynaptic changes during LTP
Retrograde transmitter from dendrite to
axon terminal, usually nitric oxide (NO)
Decreased threshold for producing APs
Increased release of neurotransmitter
Expansion of axon (seen in prev. slide along
w/ increase in spine number
Release of NT from more sites along axon

What is evidence that there is a functional connection between LTP and actual
learning?
Neurons change early in training, a
preliminary step before behavioral change
Research with mice
abnormal NMDA receptors impair learning
drugs that block LTP block retention of
learned material
drugs that facilitate LTP facilitate learning
LTP increases certain proteins, & blocking
those proteins weakens memories
LTP increases GAP-43 & over
production of GAP-43 enhances
learning and problem solving
following training, LTP seen in hippocampus
quickly and in cerebral cortex 90-180 minutes
later (this might have been in rats)

What are some cognitive and non-cognitive symptoms of dementia? What are the 4
As of demenita?
The diseases of aging
Different causes; similar presentations
Impairment in memory & cognition, accompanied by
decreased ability to relate/function at home/work/social
settings
Noncognitive symptoms: delusions, suspicions,
hallucinations, agitation, depression
Up to 2/3 of AD patients develop delusions & hallucinations
Depression & dementia are often comorbidhave to distinguish b/t
the two
Also have to distinguish b/t dementia and psychosis
Amnesia
Loss of memory (working memory goes first)
Agnosia
Loss of ability to recognize objects
Apraxia
Loss of knowledge about how to do
things
Aphasia
Loss of speech

What are some symptoms of Alzheimers Disease (AD)?
Deficits in explicit and implicit memory
Better procedural than declarative memory
First symptoms can be mild anterograde amnesia
Gradual progression to more serious memory loss and
Language problems (loss of vocabulary)
Confusion
Depression
Restlessness
Hallucinations
Delusions
Sleeplessness
Loss of appetite
Sundowning
End stage is usually coma; death usually caused by an
infection
Very early cognitive symptoms (difficulty committing new things to
memory) can be noticed up to 8 yrs before symptoms progress enough
to meet criteria for AD.
In early stages of Alzheimer's disease, there is a steady decline.
Symptoms include: loss of recent memory, language skills and motor
skills. The person may become hostile and agitated due to the losses
that are occurring. Visual-spatial skills are impaired. There is an inability
to orient in an unfamiliar environment. Depression may also be present.
What is the difference b/t early-onset and late-onset AD? Which one has a stronger
genetic contribution?
Early onset
People <40 yr old
Only about 1% (or up to 10%) of people w/ AD
Gene on chromosome 21 (for APPdont want 3 copies of
this)
Gene for ApoE4 which breaks down beta-amyloid (this
version isnt very good at it)
Mutations in presinilin (part of family of enzymes that chop
APP into beta amyloid) can increase risk
Other genes on other chromosomes linked to more of these
cases
Take-home message on genes: less contribution in
late-onset vs early-onset.
People w/ Downs Syndrome get AD if they
survive to middle age. So looked on chromosome
21found gene linked to many cases of early
onset AD

Late onset:
Over 60 yr old
5% of people b/t 65-74 yr old
50% of people over 85 yr old
Some genes that increase risk, but only account for small
percentage of cases
Half of patients have no known relative with A.D.
Yoruba people (Nigeria): lots of A.D. genes; very little
A.D.

What do the neurons and the brain of an AD patient look like?
Brain atrophy
Loss of neurons
Loss of spines & synapses
Loss of connections between neurons
Proteins fold abnormally, clump, and interfere w/
neuronal activity

Plaques and tangles: Where are they (inside or outside of cells) and what forms them?
Amyloid precursor protein
Normally important in neuron growth,
survival and post-injury repair (?)

cleaved to A
40


in AD, cleaved to A
42


A
42
accumulates (usually prior to behavioral symptoms)
widespread atrophy of cortex, hippocampus, etc amyloid
plaques (formed from degenerating axons & dendrites, in
the places b/t neurons)
Tau
Normally part of intracellular support structure of neurons;
involved in transporting things w/in the cell
Abnormal form in AD (hyperphorphorylated; aggregates w/
other strands of tau)
Produces tangles, from degenerating structures w/in
neuronal cell bodies

What are some treatment options for Alzheimers Disease?
Drugs to stimulate Acetylcholine receptors or prolong Ach release
Ach system is first to go
Aricept
One area damaged (basal forebrain) is important in Ach system & for
arousal
NMDA receptor antagonists to block excitotoxicity
Anti-inflammatory drugs (inflammation may be caused by plaques and lead to
neuronal dysfunction)
Drugs to stimulate cannabinoid receptors
Limits overstimulation by glutamate
Looks good in rat model of AD
Antioxidants to block -amyloid
Aged mice: curcumin (in yellow dye and tumeric) reduces amyloid and
plaques
Immunization
to produce antibodies against -amyloid
Researched in mice & humans (a few life-threatening side effect in
humans though, so research stopped)
Worth mentioning: Memory books, respite for caregivers

Know causes, symptoms, and (when applicable) treatment options of Korsakoffs
Syndrome, Parkinsons Disease, Huntingtons disease and CJD.
Korsakoffs Syndrome
Aka. Wernicke-Korsakoff Syndrome
Brain damage caused by prolonged thiamine (vitamin B1)
deficiency
Usually in alcoholics: poor diet: lots of carbs; no vitamins
Thiamine needed to metabolize glucose (fuel for the brain)
Shrinkage of neurons, esp. in mammillary bodies & dorsomedial
nucleus of thalamus, which sends axons to prefrontal cortex
Damage of axons & myelin
Can also involve other brain areas
Symptoms of Korsakoffs
Syndrome
Like damage to prefrontal ctx
Apathy
Confusion
Retrograde & anterograde amnesia
Better implicit than explicit memory
Difficulty reasoning thru memories (ex. what event happened
first?)
Confabulation: person takes a guess to fill in blanks of memory
Learning becomes difficult b/c confabulate answers and then
remember the confabulation instead of the correct answer
Eye abnormalities (nystagmus, oculomotor paralysis, paralysis of
conjugate gaze)
Ataxia of stance and gait
Parkinsons Disease
Loss of dopaminergic cells in
substantia nigra that project to
striatum less excitation of cortex
Rigidity, muscle tremors, slow
movement, difficulty initiating movement (or cognitive
activity)
Dementia can be similar to AD, but movement problems are
first and predominant sign in PD
Depression
Deficits in memory and reason
Mix of causes
Genetics? Yes for early-onset
Toxins? MPTP MPP, which is toxic to SN neurons
Exposure to MPTP or similar chemical in
pesticides and herbicides
Drugs: cigarettes & coffee decrease vulnerability;
marijuana increases vulnerability
Virus? PD symptomS
Huntingtons Disease
Loss of cells in caudate & putamen
Arm jerks & facial twitches, later tremors and
writhing
Cognitive changes and psychiatric symptoms, which often
develop prior to movement disorders
Depression & anxiety
sleep disorders
memory impairment
Hallucinations & delusions
Poor judgement
Alcoholism & drug abuse
Sexual disorders
Genetic (autosomal dominant)
95% penetrance
Chromosome 4
Trinucleotide repeate (C-A-G)
Normal gene makes protein huntingtin
More repeats get it earlier
Earlier it begins quicker it progresses
Abnormal huntingtin harms neurons by:increasing NT release,
decrease BDNF release, impairs mitochondria
Creutzfeldt-Jakob Disease
Familial (Inherited) or sporadic (spontaneous)
New variant CJD (nvCJD): these are known as transmissible
spongiform encephalopathies
BSE or Mad cow disease
nvCJD resulting from contaminated instruments or transplants

For PD, HD and Korsakoffs, what brain regions are involved?
What are prions?
Prions (protein-based infectious agent);
Misfolded proteins that promote refolding of native
proteins into diseased states
There is a normal prion protein which is a membrane-
bound protein that is implicated in LTP and long-term
memory. This is what becomes abnormal and affects
other prion proteins.
Infectious (acquired), spontaneous (sporadic) or
inherited (familial)
Pruisner won Nobel Prize in 1997
Symptoms:
rapidly progressing dementia, confusion, blurred vision,
hallucinations, incoordination, changes in gait, muscle twitching and
stiffness, seizures, personality changes, nervousness, speech
impairment, sleepiness


What kind of language do other species have? What do we learn from studying how
other species communicate or from their potential for language?
Chimps: attempted to teach chimps ASL or other visual
systems.
Chimps didnt use symbols in new original combinations
Used symbols to request, not describe
Produced requests more then they understood
Bonobos: very human-like; what Kanzi learned:
250 human words; language of 2-2 yr old
Understand more than they can produce
Use symbols to name/describe
Request items they dont see
Use symbols to describe past
events
Original, creative requests
Why so much better than chimps?
More language potential?
Started younger?
Method of training (observation/
imitation)
Elephants imitate the sounds they hear,
including vocalizations of other elephants
Dolphins learn to respond to
gestures and sounds
Alex, the African gray parrot
Learned to give spoken answers to
spoken questions (What color is
the key? What object is gray? How
many blue keys are there?)
What do we learn from this?
How to teach language to people
who do not easily learn it
Our concept of language is
ambiguous

What are the hypothesis on how humans evolved language?
How did humans evolve language?
Hypothesis 1: a by-product of overall brain
development:
But some people w/ normal sized brain dont have normal
language; language requires specialization, not just
expansion
Family w/ normal intelligence and normal activity in
language centers but poor language skills (dominant gene)
Another problem: Williams syndrome:
Deletion of many genes on chromosome 7; decreased gray
matter
mental retardation, but skillful use of language
How did humans evolve language?
Hypothesis 2: an extra brain module, aka, a
new specialization
Language acquisition device
Built-in mechanism (instinct) for acquiring language
that is uniquely human
Can be explained by evolution
Steven Pinkers The Language Instinct (also Noam
Chomsky)
Ease w/ which children learn language
Even if no one teaches them, they invent their own
Applies to deaf and hearing children
Certain brain areas necessary for language, but
language isnt their only job
Probably not a totally separate brain module

Is there a critical period for learning language? If so, when is it? Is there a critical
period for learning a second language?
The younger the betterprobably a critical
period but no sharp cut-off age
No exposure to any language in infancy and
young childhood never develop much skill at
any language
Learn foreign language before puberty to speak
w/o an accent

Where is language? Generally (L hemisphere, with a role for the right as well) and
specifically? Are a persons first and second languages in the same location?
Left hemisphere
95% of strongly right handed people have
language on L side
60% of left-handed and ambidextrous
have language on L
Child w/ L hemispherectomy before puberty can acquire
language on R
R hemisphere is important for some aspects of language,
like prosody.


If acquire 2
nd
language later, 2 separate areas,
1 for each
If acquire early, more overlap
w/ aphasia, can lose 1 language and preserve
other

Emotionality can make 2
nd
language tougher

What is aphasia? What causes it and who does it affect?
Impairment of language
Due to brain injury
Can be very mild to very severe
Can affect any symbol system (language, music, math)
Around 1 million people in US
Can happen to anyone
Can be transient

What are Brocas aphasia and Wernikes aphasia? What are the symptoms of each
and what brain regions are involved?
BROCAS APHASIA
Non-fluent aphasia
Caused by damage to Brocas area & surrounding area
Part of frontal lobe of L cortex near motor cortex
Difficulty with motor production of words
speak slowly and inarticulately
Omit prepositions and conjunctions, and have difficulty
understanding them
Trouble saying no ifs ands or buts
Trouble reading to be or not to be but can read two bee oar
knot two bee
So problem w/ language, not just vocal muscles
Trouble with writing and gestures
Comprehension deficits w/ complicated sentence structure

WENIKES APHASIA
Fluent aphasia
Impaired ability to remember names of objects
Impaired language comprehension
Articulate speech (speak smoothly) but
nonsense
Difficulty finding the right word
Are Brocas area and Wernikes area the only brain areas important for
language?

Need connection b/t Wernikes area and motor
cortex/Brocas area for understanding and forming
words.
Lose connection b/t WA and BA conduction aphasia: speak
like WA but good comprehension
Get activation of motor cortex w/ any action word
(kick activates foot part of motor cortex)
Alexia w/o agraphia: damage to particular part of
parietal lobe


What are mood disorders?
Affective disorders
Illnesses that effect the emotional
coloring with which we see the world

What are some common myths about suicide? What should you do if you fear
someone you know is contemplating suicide?
Thoughts of suicide are considered a medical
emergency
Myths:
people who talk about it never do it
you can precipitate someone into doing it by asking
them about it.
If you think someone might be depressed and
considering suicide:
Discuss your concern with simple straightforward
questions
Encourage person to seek medical treatment
Keep weapons away from depressed person
All attempts should be taken seriously, even if they
appear to be an obvious cry for help
especially worrisome in adolescents who might
not understand how easy it is to actually
complete the task
Risk is especially high for people who have expressed
suicidal thoughts or have attempted suicide in the past

Be able to recognize the symptoms of major depression, atypical depression,
dysthymia and bipolar disorder. Be able to recognize the symptoms of mania.
Atypical depression
Responds to positive and negative experiences, but
especially sensitive to negative experiences
Often have many partners, frequent break-ups
Weight gain, hypersomnia, increased appetite
Respond best to SSRIs with psychotherapy
Dysthymia
Mild and persistant (chronically miserable)
Tend toward the emotional and cognitive
symptoms
Sometimes worsen into major depression
double depression
Can be brought on by specific life events
Bipolar Disorder
Used to be called manic-depressive disorder
Can cycle over different periods of time
Rapid cycler b/t extremes in days or hours
Symptoms of mania
Restless activity (goal-directed or psychomotor
agitation)
Decreased need for sleepenormous surge of
energy
Excitement (elevated, expansive or irritable
mood)
Laughter
Self-confidence (inflated self-esteem or
grandiosity)
Rambling speech
Flight of ideas or subjective experience that
thoughts are racing
Loss of inhibitions (excessive
involvement in pleasurable activities
that have high potential for painful
consequences)
Distractibility
Impairments in verbal memory

Is there a role for hormones in depression? What is the evidence?
Stress can elevate cortisol weak immune system,
impairment of sleep stage set for depression
Females vs. males
Equal in boys and girls
More common in women than men (in all cultures,
not due to who seeks treatment)
Sex hormones:
Emotional distress after giving birth
Baby blues
Postpartum depression
Drug-induced drop in estrogen and progesterone
cause depression in women who already suffered
from PPD
Estrogen relieves depression during menopause
Prolonged cortisol: weakens immune system, impairs sleep, therefore
sets stage for depression
Females vs males: equally uncommon in boys and girls, more common
in girls/women then boys/men after puberty (for all cultures for which
data exist and not due to women being more likely to seek treatment)
What is the difference b/t bipolar I and bipolar II?
Bipolar I: full manic episodes
Lifetime prevalence ~2%
Equally common in men & women, found
in all cultures
Bipolar II: mild manic episodes, mostly
w/ agitation or anxiety

What do adoption studies and twin studies tell us about the heritability of mood
disorders?
Identical twins: 50% chance
Fraternal twins, siblings, children: 5-10%
chance of developing it
Adoptive children w/ bipolar disorder likely
to have biological relative with mood
disorder
Several genes more common in people w/
bipolar, but these only increase risk.
Having a relative with a mood
disorder increases your likelihood of
developing a mood disorder (but not
necessarily the same one)
Identical twins: 65% chance
Fraternal twins: 14% chance
Most genes that may be involved are
related to dopamine or serotonin
transmission (particularly, their
receptors)


What neurotransmitter systems are most genes involved in mood disorders related to?
Most genes that may be involved are
related to dopamine or serotonin
transmission (particularly, their
receptors)

Understand the graph on slide 6 (really you should always understand all of the graphs
and figures from lectures!).

What are treatment options for depression? Compare/contrast SSRIs, MAOIs, atypical
antidepressants.
Psychotherapy produces metabolic changes similar to drugs
and person is less likely to relapse after treatment
67% improve with drugs or psychotherapy or both, 33%
improve with no treatment
Sleep deprivation works for certain patients
depressed people enter REM sleep early, have
trouble staying asleep and awaken early
one night of total sleep deprivation or rescheduling
sleep pattern relieves depression
like drugs, reduces REM
Tricyclics block the reuptake of dopamine,
norepinephrine, or serotonin. SSRIs specifically
block the reuptake of serotonin. MAOIs block
the enzyme MAO, which converts dopamine,
norepinephrine, or serotonin into inactive
chemicals. Atypical antidepressants have
varying effects.


Be able to recognize the symptoms of schizophrenia. Understand what those
symptoms are.
Split or fragmented mind
A disorder characterized by deteriorating
ability to function in everyday life and by
some combination of hallucinations,
delusions, thought disorder, movement
disorder, and inappropriate emotional
expressions
Symptoms vary between people (H and D for
some; TDs predominate for others)
Some have brain damage, others dont
Acute: quick onset, high likelihood of
recovery
Chronic: gradual onset, long-term course

What does it mean that some symptoms are positive symptoms and others are
negative symptoms?
Positive Behavioral
Symptoms
Behaviors that are present that shouldnt be
Psychotic:
Delusions: unfounded beliefs
Hallucinations: abnormal sensory experiences
Increased activity in thalamus, hippocampus, cortex
Disorganized:
Inappropriate emotional displays
Bizarre behavior
Incoherent speech
Thought disorder: difficulty understanding and using
abstract concepts
Negative Behavioral Symptoms
Negative: behaviors that are absent that should be
present, including weak:
Social interactions
Emotional expressions
Speech
Working memory
Stable and hard to treat

What do twin studies and adoption studies tell us about the heritability of schizophrenia?
Twin studies:
MZ > DZ> siblings
MZ still have just 48% concordancewhy?
Maybe a gene is activated in one and suppressed in another.
Also, note DZ>siblings.
Share same amt of DNAso whats going on? Maybe more
similar prenatal/neonatal environment for DZ twins than
siblings.
Adoptions studies:
More resemblance to biological parents than adoptive
parents
One study showed that home (adoptive) environment must be
somehow dysfunctional for effect from biological parents to
manifest
Especially increased if bio mom is schizophreniccould
represent poor prenatal environment

What are some prenatal and neonatal risk factors for schizophrenia?
Poor nutrition of mom during pregnancy
Extreme stress early in pregnancy
Premature birth
Low birth weight
Complications during delivery
Head injuries in childhood (cause or
effect?)
Rh-incompatibility
Season-of-birth effectmaybe due to
virus
Other infections in mom too: rubella,
herpes, etc.
Childhood infection w/ toxoplasmosis

What are some mild brain abnormalities sometimes seen in schizophrenia?
Small, variable
Thinner cortex, but same cell number, so what
is lacking?
Fig summarizes 15 studies, 390 people
Most of cortex, depending on study
Left prefrontal and temporal
Increased ventricle size
Smaller thalamus
Smaller cell bodies, esp. in hippo. & prefrontal
Larger sulci

What is cognitive dysmetria?
Cognitive dysmetria: a disruption
of the fluid coordination of mental
activity
What is the neurodevelopmental hypothesis of schizophrenia? .
Neurodevelopmental Hypothesis: S is based
on abnormalities of the prenatal or neonatal nervous system development
which can lead to abnormalities of brain anatomy & behavior

What neurotransmitters are likely involved in schizophrenia, and how are they
involved (is there too much transmission or too little)? What is the evidence for the
dopamine hypothesis of schizophrenia?
Dopamine: too much! This is the dopamine
hypothesis of schizophrenia.
Antipsychotic drugs block dopamine receptor
Repeated doses of drugs of abuse that increase
dopamine induce substance-induced psychotic
disorder (H&D)
Glutamate: too little! This is called
hypofrontility.
Especially in prefrontal cortex
PCP (phencyclidine; angel dust) inhibits NMDA
receptors Positive & negative symptoms of
schizophrenia at high doses (again, substance-
induced psychotic disorder)
Serotonin
Atypical antipsychotic drugs block serotonin
receptors

What drugs are used to treat schizophrenia?

Older ones (Thorazine and more)
Only helped positive symptoms
Extrapyramidal side effects
(involuntary movements)
D2 R antagonists
Second-generation: atypical
antipsychotics
Clozapine, Risperidone, etc.
Help positive & negative symptoms
Fewer extrapyramidal side effects
Side effects: increased appetite,
weight gain, diabetes, effect on
prolactin leading to breast formation,
decreased immune function

Also block D2 R, but maybe with
shorter timecourse than 1
st
gen.
drugs.
Also block serotonin 2A receptors
Efficacy and lack of side effects may
be due to balance b/t action on
dopamine and serotonin systems.
One study showed that these drugs
decrease positive & negative
symptoms but do not improve quality
of life.