Shackman Psyc210 Module12 NatureNurture Part3

Nuts and Bolts Plan for Today Lecture (Bogdan, Meaney, Dias)

No take-home assignment today!

PSYC 210: The nature & nurture of T&P, III

Gene x Environment Interac7ons

(con7nued), Neurogene7cs, & Epigene7cs

AJ Shackman 26 March 2015

Conceptual Roadmap, 1 Individual dierences in T&P reect the brain

e.g., Individuals with higher levels of N/NE show enhanced acTvaTon and slower recovery in the amygdala

Where do dierences in brain acTvaTon come from?

We cant assay Tssue from the living human amygdala but can we use the genome (DNA) to idenTfy candidate mechanisms (that could be mechanisTcally tested in animals)?


e.g., Individuals with higher levels of N/NE show enhanced peak acTvaTon and slower recovery in the amygdala


We cant assay Tssue from the living human amygdala but can we use the genome (DNA) to idenTfy candidate mechanisms (that could be mechanisTcally tested in animals)?



Where do dierences in brain acTvaTon come from? AYer all, we cant assay Tssue from the living human amygdala

Can we use the genome (DNA) to discover candidate molecular mechanisms that could be examined in animal models?



Where do dierences in brain acTvaTon come from? AYer all, we cant assay Tssue from the living human amygdala

Can we use the genome (DNA) to discover candidate molecular mechanisms that could be validated in animal models?

Conceptual Roadmap, 2 Genes interact with the Environment & Experience to produce lasTng changes in T&P

How does early experience (abuse, stress, posi7ve maternal style) get under the skin and reprogram the brain circuits that support key features of T&P?

Can these experien7al modica7ons be inherited by ospring?

Quick Recap from the End of Last Time

Gene-Environment Interac7ons

Maltreatment x MAO-A Gene

Caspi et al Science 2002 monoamine oxidase A (MAOA) gene

Maltreatment x MAO-A Gene

Caspi et al Science 2002 monoamine oxidase A (MAOA) gene

Abused kids with the good allele (grey: thought to confer high levels of MAO-A expression in the brain) showed fewer an7social behaviors protec7ve

Stress x 5-HTT Gene

Caspi et al Science 2003, Amer J Psychiatry 2010; Monroe Psychol Sci 2008

Stress x 5-HTT Gene

Caspi et al Science 2003, Amer J Psychiatry 2010; Monroe Psychol Sci 2008

Short Long

Carriers of the Short allele of the 5-HTT polymorphism (leY) showed a strong posi7ve rela7onship between the number of nega7ve life events and number of depressive episodes Short allele confers risk (or the Long allele confers protec7on)

What about the brain?

The assump7on is that the genotype (MAO-A or 5-HTT gene) is lawfully

related to neurochemistry

Genome Traits (Evildoing, Depression) Intermediate Phenotype

What about the brain?

How might we as scien7sts understand the neuro-molecular

building blocks of traits or disorders?

Genome Traits (Evildoing, Depression) Intermediate Phenotype

Caspis Suggested Strategy: 3 Easy Pieces


Start with solid evidence that MAO-A / Serotonin transporter inuences the emoLonal phenotype in animal models

Use human epidemiological data to address quesLons like: Does the MAO / Serotonin transporter interact with negaLve events to produce deleterious outcomes (e.g., in the Dunedin sample)? Yes!


Test hypothesized mechanisms (serotonin levels in the amygdala?) in animal model or using PET imaging


Building on this framework, other inves7gators have focused on linking genes to imaging measures of brain

structure and func7on

Bogdan (Wash U)

Basic idea - Correlate geneTc variaTon (SNPs) with dierences in brain structure and funcTon (MRI) Goals

- By correlaLng geneLc variaLon with intermediate biological phenotypes (e.g., amygdala acLvaLon), we can discover testable pathways for geneLc inuence on behavior

- Can address quesLons such as, Why is the amygdala hyper-reac3ve in behaviorally inhibited or neuro3c individuals?

PotenTally address the molecular mechanisms linking genes to brain to behavior

- its hard to directly measure neurochemistry (e.g., serotonin levels in the amygdala) in humans

- If we measure a geneLc polymorphism with a known funcLon (e.g., serotonin transporter)

- and we are willing to make some assumpLons (dierences in the poly. have predictable eects on gene expression and ulLmately serotonin levels in the amygdala)

- then we can use noninvasive measures of SNPs (from cheek swabs), as a proxy for individual dierences in neurochemistry (serotonin in the amygdala),

The NeurogeneTc Strategy

Basic idea - Correlate geneTc variaTon (SNPs) with dierences in brain structure and funcTon (MRI) Goals

- By correlaLng geneLc variaLon with intermediate biological phenotypes (e.g., amygdala acLvaLon), we can discover testable pathways for geneLc inuence on behavior

- Can address quesLons such as, Why is the amygdala hyper-reac3ve in behaviorally inhibited or neuro3c individuals?

PotenTally address the molecular mechanisms linking genes to brain to behavior

- its hard to directly measure neurochemistry (e.g., serotonin levels in the amygdala) in humans

- If we measure a geneLc polymorphism with a known funcLon (e.g., serotonin transporter)

- and we are willing to make some assumpLons (dierences in the SNP have predictable eects on gene expression and ulLmately serotonin levels in the amygdala)

- then we can use noninvasive measures of SNPs (from cheek swabs), as a proxy for individual dierences in neurochemistry (serotonin in the amygdala),

The NeurogeneTc Strategy

Drill down into the 5-HTT example

Seminal Example: Amygdala & 5-HTTLPR

- Work by Hariri (prior to Caspi) suggested that amygdala reacLvity is correlated with variaLon in the serotonin-transporter linked polymorphic region (5-HTTLPR)

- S allele is bad: Individuals with the less transcripLonally-ecient short allele (fewer transporter proteins available to clear serotonin from the synapse) show heightened threat-related amygdala reacLvity relaLve to individuals with the long allele

- Gene Amygdala: Meta-analyses suggest that the 5-HTTLPR genotype accounts for 2-5 of the variance in amygdala reacLvity

- Gene Amygdala MDD: Evidence that these geneLcally conferred dierences in amygdala reacLvity mediate some of the associaLon between the 5-HTTLPR polymorphism and depression


- Work by Hariri (prior to Caspi) suggested that amygdala reacLvity is correlated with variaLon in the serotonin-transporter linked polymorphic region (5-HTTLPR)

- S allele is bad: Individuals with the less transcripLonally-ecient short allele (fewer transporter proteins available to clear serotonin from the synapse) show heightened threat-related amygdala reacLvity relaLve to individuals with the long allele

- Gene Amygdala: Meta-analyses suggest that the 5-HTTLPR genotype accounts for 2-5 of the variance in amygdala reacLvity

- Gene Amygdala MDD: Evidence that these geneLcally conferred dierences in amygdala reacLvity mediate some of the associaLon between the 5-HTTLPR polymorphism and depression


S allele Enhanced Amygdala ReacTvity (SensiTzaTon)

These data suggest the following causal chain:

[GENETIC OBSERVATION] Some folks have the 5-HTTLPR S allele [ASSUMPTION] less ecient 5HTT (protein) transcripLon, so fewer transporters [ASSUMPTION] too much 5HT in amygdala synapses (chemistry) [NEURAL OBSERVATION] increased amygdala reacLvity to threat [EPIDEML OBSERVATION] MDD, especially among individuals exposed to stress

Hypothesized Causal Chain

Does the gene actually predict 5-HTT expression in the amygdala

(1st Assump7on)?

Testable hypothesis

No relaTon between polymorphism and amygdalar 5HTT expression when you actually go in and measure the transporter using PET our ndings are in agreement with the majority of human PET studiesthat suggest there is not adetectable relaLonship between in vivo 5-HTT binding and s-allele carrier status our work in the rhesus monkey, and that of others in humans, calls into quesLon whether this increased risk is mediated by changes in the expression of the number of serotonin transporter molecules.

Use PET to test 5-HTT expression

No relaTon between polymorphism and amygdalar 5HTT expression when you actually go in and measure the transporter using PET our ndings are in agreement with the majority of human PET studiesthat suggest there is not adetectable relaLonship between in vivo 5-HTT binding and s-allele carrier status our work in the rhesus monkey, and that of others in humans, calls into quesLon whether this increased risk is mediated by changes in the expression of the number of serotonin transporter molecules.


Kalin (UW)

No relaTon between polymorphism and amygdalar 5HTT expression when you actually go in and measure the transporter using PET our ndings are in agreement with the majority of human PET studiesthat suggest there is not adetectable rela3onship between in vivo 5-HTT binding and s-allele carrier status our work in the rhesus monkey, and that of others in humans, calls into ques3on whether this increased risk [of MDD] is mediated by changes in the expression of the number of serotonin transporter molecules.

Kalin (UW)


Others have quesToned the gene-amygdala link


The alleged associa7on between the serotonin-transporter-linked polymorphic region and amygdala ac7va7on forms a cornerstone of the common view that carrying the short (S) allele of this polymorphism is risk factor for aec7ve disorders [such as depression]

The authors of a recent meta-analysis showed that this associa7on is signicant but warned that es7mates might be distorted because of publica7on bias (not including unpublished failures)

Here, we report a replica7on study of this rela7onship in N=120 par7cipants. We failed to nd the associa7on

Moreover, when we conducted a meta-analysis that included unpublished studies and data from the current study, the pooled meta-analy7c eect size was no longer signicant

These ndings cast doubt on previously reported substan7al eects, sugges7ng that the 5-HTTLPR-amygdala associa7on is either much smaller than previously thought, condi7onal on other factors, or nonexistent.





When we conducted a meta-analysis that included unpublished studies and data from the current study, the pooled meta-analy7c eect size was not signicant

These ndings cast doubt on previously reported substan7al eects, sugges7ng that the 5-HTTLPR-amygdala associa7on is either much smaller than previously thought, condi7onal on other factors, or nonexistent.





When we conducted a meta-analysis that included unpublished studies and data from the current study, the pooled meta-analy7c eect size was not signicant

These ndings cast doubt on previously reported eects, sugges7ng that the 5-HTTLPR-amygdala correla7on is either much smaller than previously thought, condi7onal on other factors (like exposure to stress or trauma), or is simply nonexistent.

Interim Take Home

The NeurogeneTc or Neurogene x Environment strategy is potenTally powerful, but assumpTons need to be tested for each candidate pathway

How might the environment and early experience get Under the Skin and

promote enduring changes in T&P?

Early stress, abuse, or maltreatment Increased stress reac7vity and MDD Risk

Maternal nurturance

Decreased stress reac7vity in adulthood

How might the environment and early experience get Under the Skin and

promote enduring changes in T&P?

Early stress, abuse, or maltreatment Increased stress reac7vity and MDD risk

Maternal nurturance

Decreased stress reac7vity in adulthood

The key mechanis7c ques7on is how such inuences become long

las7ng

Turn to a nonhuman animal model of early Nurture

Michael Meaney

Experimenter handling has enduring consequences for stress reacTvity (N/NE)

Levine Science 1962; see also Weininger Science 1954

Experimenter handling has enduring consequences for stress reacTvity (N/NE)

Levels of the stress-sensiTve hormone corTsol elicited by shock

M Handled N - Not

Levine Science 1962

CorTsol and the HPA Axis

Hypothalamic, Pituitary, Adrenal

CorLsol is released from the adrenals in response to emoLonal and physical stress

Increases glucose availability to the brain

Generates energy from stored reserves

Diverts energy from longer-term prioriLes (such as the immune system and wound healing) in order to survive acute threats


Hypothalamic, Pituitary, Adrenal

CorLsol is released from the adrenals in response to emoLonal and physical stress

Increases glucose availability to the brain

Generates energy from stored reserves

Diverts energy from longer-term prioriLes (such as the immune system and wound healing) to promote survival in the face of acute threat


What mechanisms account for the handling eect on stress reac7vity

(cor7sol)?

Remarkable lifelong changes happen when neonatal rats are removed from mom and placed in a new cage for 15 minutes

Sapolsky Nature Reviews Neuroscience 2004

Tighter regulaLon of the secreLon of a class of stress hormones, glucocorLcoids (lower baseline & poststress levels)

Lifelong increase in the number of glucocorLcoid receptors in the hippocampus, a brain region that plays a key role in regulaLng corLsol release

These changes result in a more exploratory, less fearful , and less stress-reacLve adult

Decreased N/NE, in eect



Tighter regulaLon of corLsol (glucocorLcoids) secreLon: lower baseline & poststress levels*


These changes result in a more exploratory, less fearful , and less stress-reacLve adult

Decreased N/NE, in eect * Bigger early peak; quicker return to baseline; more adapLve



Tighter regulaLon of corLsol (glucocorLcoids) secreLon: lower baseline & poststress levels*


These changes result in a more exploratory, less fearful, and less stress-reacLve adult

Decreased N/NE in ospring * Bigger early peak; quicker return to baseline; more adapLve

What causes enduring changes in the regula7on of

stress hormones in the ospring?

Mothering Style

Sapolsky Nature Reviews Neuroscience 2004; Video @ hops://www.youtube.com/watch?v=nUPmi_dxaPo

Rats show trait-like dierences in mothering style Moms who show high levels of licking, grooming, and arched-back nursing (high

LG-ABN females) cause the handling eect When the handled baby rat is returned to the homecage, mom grooms returned

pup More handling More grooming Less stress reacLvity in adulthood Cross-fostering studies (adopted by Hi or Lo mom) show that this does not reect

an underlying common geneLc cause (Genes Mom Low N/NE prole in ospring);

Remarkably, female pups raised by high-LG-ABN moms become high moms Thereby passing on the trait in a case of mulLgeneraLonal, nongenomic (i.e.

outside of DNA) inheritance

Mothering Style




pup More handling (man) More grooming (mom) less reacLvity in adult ospring Cross-fostering studies (adopted by Hi or Lo mom) show that this does not reect


Remarkably, female pups raised by high-LG-ABN moms become high moms Thereby passing on the trait in a case of mulLgeneraLonal, nongenomic (i.e.

outside of DNA) inheritance

Mothering Style






Remarkably, female pups raised by high-LG-ABN moms become high moms Thereby passing on the trait in a case of mulLgeneraLonal, nongenomic (i.e. outside of DNA) inheritance

Mothering Style






Remarkably, female pups raised by high-LG-ABN moms themselves become high-LG-ABN moms Thereby passing on the trait in a case of mulLgeneraLonal, nongenomic (i.e. outside of DNA) inheritance

LG-ABN also enhances anT-anxiety acTon in the amygdala (CeA)

Caldji et al PNAS 1998; Shackman et al PNAS 2013; Paulus et al AGP 2005



The ospring of High-LG-ABN moms show much higher expression of the benzodiazepine receptor in the central nucleus of the amygdala (CeA)



The ospring of High-LG-ABN moms show much higher expression of the benzodiazepine receptor in the central nucleus of the amygdala (CeA) Correlated with the amount of maternal LG / ABN



The ospring of High-LG-ABN moms show much higher expression of the benzodiazepine receptor in the central nucleus of the amygdala (CeA)



CeA acTvity predicts N/NE in monkeys



CeA acTvity predicts N/NE in monkeys

CeA acTvity is reduced by benzos in a dose-dependent manner in humans

How does maternal behavior lead to mul7-genera7onal transmission of

reduced stress reac7vity?

(we know its not mediated by genes)

Epigene7cs!

Experience and nurtute can re-program

trait-like phenotypes

(e.g., stress reac7vity, N/NE)

1) Non-heritable, but trait-like alteraLons in the transcripLonal (protein-making) potenLal of a cell (such as a neuron)

Dieren3a3on: How come hair cells are dierent than neurons or bone cells?

Development: How come Micah/Hannah are small and Alex is big? DNA is staLc, but cells dierenLate into many dierent types,

which perform dierent funcLons, and respond dierently to the environment at dierent points in life EpigeneLc changes modify the acLvaLon of certain genes

This is why dierenLated cells express only the genes that are funcLonally necessary

2) Heritable changes in gene acLvity that are not caused by changes in DNA

EpigeneTcs: 2 Flavors


Dieren3a3on: How come your hair cells are dierent than neurons or bone cells (despite idenLcal DNA)?







Dieren3a3on: How come your hair cells are dierent than neurons or bone cells (despite idenLcal DNA)?





non-genomic inheritance


How exactly does this work?

2 key mechanisms alter the func7onality of DNA

MethylaTon

Histone ModicaTon

MethylaTon

Do epigene7c mechanisms account for

Handling Maternal Style Ospring Stress Reac7vity

?

Yes! Early emerging epigeneTc changes in pups raised by High LG-ABN moms (own or adopted) Altered translaTon of the glucocorTcoid receptor in the hippocampus Reduced stress reacTvity (corTsol) EpigeneTc and neurochemical changes persist into adulthood

Yes! Early emerging epigeneTc changes in pups raised by High LG-ABN moms (own or adopted) Altered translaTon of the glucocorTcoid receptor in the hippocampus Reduced stress reacTvity (corTsol) Furthermore, epigeneTc marks and neurochemical changes persist into adulthood

Can we benet (or suer) from our parents experience without them teaching (or grooming) us?

Can paternal experience be transmiied to ospring without a behavioral/social intermediary (LG-ABN)?

Can acquired characteris7cs

be inherited, as Lamarck posited in the 18th century?

Kerry Ressler (Emory)

Lamarck

Hughes Nature 2014

Tantalizing armaTve evidence

but sTll early days

Wellberg Nat Rev Neurosci 2014

Details Are Not Important

Dias & Ressler Nature Neuro 2014

IVF

Dad is Fear CondiToned

EpigeneTc marks in sperm



IVF

Dad is Fear CondiToned





IVF

Dad is Fear CondiToned Mom



IVF

Dad is Fear CondiToned Mom

Enhanced Fear to CondiToned Odor in Children and Grandchildren





How are the gametes (sperm) changing???

Begs the ques7on


Key Take Homes

Key Take Homes Individual dierences in T&P reect the brain



We cant assay Tssue from the amygdala (in people), but can we use the genome (DNA) to idenTfy candidate mechanisms (that could be mechanisTcally tested in animals?

Key Take Homes Individual dierences in T&P reect the brain



We cant assay Tssue from the amygdala (in people), but can we use the genome (DNA) to idenTfy candidate mechanisms (that could be mechanisTcally tested in animals?

Traits

Genome Epigenome Environment / Experience G x E or Epi x E

Proteins (e.g., receptors)

Systems / Circuits (e.g., amygdala, hippocampus, HPA axis)

Key Take Homes We cant assay Tssue from the amygdala (in

people), but can we use the genome (DNA) to idenTfy candidate mechanisms (that could be mechanisTcally tested in animals?

SomeTmes. Case by case basis. Individual candidate SNPs account for small % of variance. Need G x E or GWASbut how do you scan 50,000 subjects?

Key Take Homes We cant assay Tssue from the amygdala (in

people), but can we use the genome (DNA) to idenTfy candidate mechanisms (that could be mechanisTcally tested in animals?

Maybe. Test assumpTons, replicate ndings. Individual candidate geneTc variants account for a small % of variance. Need G x E (unmask eects) or GWASbut how do you scan 100,000 subjects with the same paradigm?

Key Take Homes Genes interact with the Environment & Experience to produce lasTng changes in T&P

How does early experience (abuse, stress, posi7ve maternal style) get under the skin and modify the brain circuits that support key features of T&P?

Key Take Homes Genes interact with the Environment & Experience to produce lasTng changes in T&P

How does early experience (abuse, stress, posi7ve maternal style) get under the skin and modify the brain circuits that support key features of T&P?

Traits

Genome Epigenome Environment / Experience G x E or Epi x E

Proteins (e.g., receptors)

Systems / Circuits (e.g., amygdala, hippocampus, HPA axis)

Key Take Homes Can these experien7al modica7ons be inherited by ospring?

Key Take Homes Can these experien7al modica7ons be inherited by ospring? Maybe. Tantalizing preliminary evidence. Requires replicaTon and extension to primates.

The End

Time-Permisng Review QuesTons

The (fear-potenLated or emoLon-modulated) startle reex is

A. Is potenLated (increased) during periods of stress, fear, and anxiety

B. Can be measured using similar techniques in rodents, monkeys, and humans

C. Is a widely used, valence-sensiLve measure of condiLoned and uncondiLoned fear

D. All of the above

Is pote

ntiate

d (increa

sed...

Can b

e measured

using si...

Is a wide

ly used, valence-...

All of the above

0% 0%0%0%

ConvenLonal funcLonal MRI (fMRI) pulse sequences measure

A. Blood oxygenaLon (the hemodynamic BOLD signal); fMRI is an indirect measure of neuronal ring

B. Neuronal ring C. The release of

neurotransmioer-lled vesicles into the synapse (synpapLc cleu)

D. FDG metabolism E. Electrical acLvity generated

by ensembles of neurons, providing exquisite temporal resoluLon

Blood oxygenation (th

e...

Neuro

nal firing

The release

of neuro

tran...

FDG m

etabolism

Electrical activity genera

t..

0% 0% 0%0%0%

Which is true?

A. There is one anxiety disorder

B. There is a whole family of anxiety disorders

There

is one anxiety diso...

There

is a w

hole fam

ily o...

0%0%

The most common family of psychiatric disorders is

A. Anxiety B. Depression C. Schizophrenia D. Somatoform

Anxiety

Depre

ssion

Schizophren

ia

Somatoform

0% 0%0%0%

Anxiety disorders tend to onset

A. Late in life B. Mid life C. Early in life

Late in life

Mid life

Early in life

0% 0%0%

Depression tends to onset

A. Early in life B. Mid life C. Late in life

Early in life

Mid life

Late in life

0% 0%0%

The most burdensome disorder (disability, illnes, death) in the US is

A. Depression B. Heart Disease C. COPD D. Cancer E. Alzheimers

Depression

Heart Disease

COPD

Cancer

Alzheimers

0% 0% 0%0%0%

Elevated N/NE is a risk factor for

A. Anxiety disorders B. Depressive

disorders C. Both

Anxiety disord

ers

Depre

ssive disorde

rsBoth

0% 0%0%

Anxiety and depression symptoms

A. Form a coherent, factor (internalizing)

B. Are categorically disLnct

C. Should be thought of as natural kinds, discrete enLLes that exist in nature waiLng to be discovered Form

a cohere

nt, facto

r (...

Are cate

gorically distinct

Should be thought of as ...

0% 0%0%

Anxiety and depression

A. Are highly co-morbid

B. Rarely co-occur in the same individual

Are highly co-morb

id

Rarely co-o

ccur in

the s...

0%0%

Treatments targeLng one emoLonal disorder

A. Ameliorate (decrease) the symptoms of other emoLonal disorders

B. Decrease raLngs of N/NE

C. Both, suggesLng a common cause

Ameliora

te (de

crease

) the...

Decrease

ratings of N/NE

Both, suggesting a comm

..

0% 0%0%

NegaLve life events & psychological pathogens such as stress tend to

A. Cause individuals to cross the diagnosLc boundary and experience a frank depressive disorder

B. Increase the risk of developing a diagnosable anxiety disorder

C. Increase N/NE D. All of the above

Cause individuals to cross...

Increa

se the

risk of devel...

Increa

se N/NE

All of the above

0% 0%0%0%

Anxiety disorders, depression, and N/NE

A. Reect completely separate genes

B. Are inherited together (shared inheritance), suggesLng a common geneLc underpinning

Reflect comp

letely separ...

Are inherited

togethe

r (...

0%0%

Recent meta-analyses demonstrate that

A. A variety of anxiety disorders, like N/NE, are associated with heightened amygdala acLvaLon to potenLal threat

B. Depression, like N/NE, is associated with increased amygdala reacLvity to aversive cues

C. Both, providing evidence for a common biology

A variety

of anxiety disor...

Depre

ssion, like N/

NE, is ...

Both, providing evide

nce ...

0% 0%0%

Barlow argues that the development of a parLcular Dx (diagnosLc

specicity) reects A. N/NE and a

disorder-specic learned vulnerability (e.g., fear dogs)

B. N/NE and an innate vulnerability

C. N/NE and other non-specic risk factors

N/NE and a disorde

r-speci...

N/NE and an innate

vuln...

N/NE and o

ther non-speci...

0% 0%0%

N/NE is a

A. Cause of emoLonal disorders

B. Symptom of emoLonal disorders

C. IdenLcal to or synonymous with the emoLonal disorders

D. A symptom of too much anxiety

Cause o

f emo

tional disor...

Symp

tom of em

otional d...

Identical to or synonymo

..

A sympto

m of too

much ...

0% 0%0%0%

When confronted by potenLal threat (robot, intruder), children with high levels of behavioral inhibiLon (BI)

A. Exhibit heightened avoidance and freezing

B. Cease playing C. Become quiet D. Withdraw to the

proximity of their caregiver

E. All of the above Exhibit heightened avoid...

Cease playing

Become quiet

Withd

raw to the proximit...

All of the above

0% 0% 0%0%0%

Jenni Blackfords group uses a quesLonnaire to retrospecLvely assess

childhood BI. This is A. Much more pracLcal

than starLng a new longitudinal study (waiLng 20 years)

B. Subject to the usual concerns about mnemonic biases

C. Both Mu

ch more

practical tha

n...

Subject to the

usual co

nc... Bo

th

0% 0%0%

BI in toddlers A. Parallels anxious

temperament (AT) in young monkeys

B. Echoes theoreLcal descripLons of the BIS (Jerey Gray)

C. Is associated with R > L frontal EEG asymmetry, as in studies of monkeys and human adults

D. Is considered a facet of N/NE E. Is somewhat stable (test-

retest) F. Is heritable (inherited) G. All of the above

Parallels anxious tempe...

Echoes theoretical descri...

Is associated with R > L f...

Is considered a facet of ...

Is somewhat stable (test-...

Is heritable (inherited)

All of the above

0% 0% 0% 0%0%0%0%

Most preschoolers with high levels of BI __________

A. SLck with it B. Grow out of it C. Are likely to develop

an anxiety disorder D. Just have an age-

appropriate fear of separaLon or strangers

E. A and C F. B and D

Stick with it

Grow out of it

Are likely to develop an ...

Just have an age-ap

propr...

A and C

B and D

0% 0% 0%0%0%0%

Kids with _____ & ______ are at risk for developing ___________

A. Consistent, high levels of BI, substance and emoLonal disorders

B. Stable, high levels of BI, schizophrenia and personality disorders

Consistent, h

igh levels o

f ...

Stable

, high

levels o

f BI, ...

0%0%

Social anxiety disorder can be characterized by

A. Heightened anxiety about people and performance

B. Pervasive worries about being judged

C. Avoidance D. Hyper-arousal E. A disconnect between

what paLents know to be raLonal vs what they feel

F. All of the above Heighten

ed anxiety abou...

Pervasive w

orries about ...

Avoidance

Hyper-arou

sal

A disconnect between w

...

All of the above

0% 0% 0%0%0%0%

BI is associated with A. Less eecLve ways of

interacLng with others B. Worse social outcomes C. Lower quality peer

relaLons D. A loss of opportunity to

acquire criLcal social skills E. Challenges forging strong

relaLons with new peers and schoolmates

F. All of the above

Less effective ways of int...

Worse social outcomes

Lower quality peer relations

A loss of opportunity to ...

Challenges forg

ing stron

g...

All of the above

0% 0% 0%0%0%0%

Over Lme, the repeated experience of social failure among individuals with

high levels of BI may A. Train them to interpret

ambiguous social situaLons as threatening

B. Cause them to believe that poor social outcomes are their fault

C. Promote excessive anxiety about social situaLons and public performance

D. All of the above Tra

in the

m to interp

ret ...

Cause them to believe th..

Promo

te excessive anxiet...

All of the above

0% 0%0%0%

BI is a strong (candidate) _________ for ______________; but we sLll need

to establish ______ . A. Intermediate

phenotype, dysthmia, causaLon

B. Endophenotype, social anx disorder, causaLon

C. Biomarker, emoLonal disorders, heritability

D. Marker, overacLve insula, heritability

Interm

ediate phenotyp

e,...

Endophenoty

pe, so

cial a..

Biomarke

r, emo

tional dis...

Marke

r, overactive insula...

0% 0%0%0%

T&P reect

A. Nature B. Nurture C. Both

Nature

Nurture

Both

0% 0%0%

Genes (nature) can inuence

A. Environments and experience

B. Neither. Nature and nurture are disLnct and independent forces

Environments and experi...

Neither. Na

ture and nurtu..

0%0%

Nature (heritability) is

A. Fixed and immutable

B. PlasLc and can change in response to growing autonomy or due to cumulaLve impact

Fixed and imm

utable

Plastic and can change in...

0%0%

Heritability is

A. The proporLon of variaLon in a trait, such as C/SC, that is accounted for by the pedigree (family tree)

B. GV / Total PV = GV / GV + EV

C. A and B The prop

ortion

of variati..

GV / T

otal PV = GV

/ GV..

A and B

0% 0%0%

EsLmates of heritability A. Are xed B. Can be inuenced by

social and environmental inuences (e.g., living in a conservaLve religious community) that increase or decrease the amount of variaLon in the trait (e.g., disinhibiLon, partying, smoking) Are

fixed

Can b

e influenced by soci..

0%0%

Heritability

A. Is the % of variaLon in a trait, such as E/PE, that is passed down from your parents

B. Reects the inheritance of genes, not phenotypes or traits

Is the % of va

riation in a

t...

Reflects the inheritan

ce o...

0%0%

Heritability describes A. The % of my trait that

is inherited (nature) vs. environmental (nurture)

B. The % of phenotypic variaLon across a group of individuals that is inuenced by geneLc factors

C. Individuals within a populaLon (e.g., Alex)

The %

of my trait th

at is ...

The %

of phenoty

pic vari...

Individuals within a popu...

0% 0%0%

Highly heritable traits, such as height

A. Are our desLny B. Can potenLally be

powerfully inuenced by intervenLons (environment)

Are our destiny

Can pote

ntially be powerf...

0%0%

Ryan Bogdan: The neurogeneLc strategy

A. Involves correlaLng variaLon in geneLc polymorphisms (SNPs) with variaLon in intermediate phenotypes, such as dierences in amygdala acLvaLon

B. Promises to address WHY individuals dier in brain acLvaLon (e.g., why do individuals high in N/NE show heightened amygdala reacLvity)

C. Opens the door to discovering testable mechanisms for geneLc inuence on behavior

D. All of the above Involves correlating varia...

Promises to addre

ss WH

...

Opens the door to discov...

All of the above

0% 0%0%0%

Which is false about the serotonin transporter geneLc polymorphism

A. Amygdala reacLvity is correlated with variaLon in the serotonin-transporter linked polymorphic region (5-HTTLPR) on the SLC6A4 gene

B. The L allele is bad: Individuals with the more transcripLonally-ecient long allele (more transporter proteins available to clear serotonin from the synapse) show heightened threat-related amygdala reacLvity relaLve to individuals with the short allele

C. Meta-analyses suggest that this allele accounts for 20-50% of the variance in amygdala reacLvity

D. B and C

Amygdala rea

ctivity is cor...

The L allele is b

ad: Ind...

Meta-analyses suggest th..

B and C

0% 0%0%0%

Which is false? A. Some have suggested that the neurogeneLcs

strategy can address the molecular mechanisms linking genes to brain to traits, such as N/NE

B. Some have suggested that if we measure a geneLc polymorphism with a known funcLon (e.g., serotonin transporter) and we are willing to make some assumpLons, then we can use SNPs as a proxy for individual dierences in brain chemistry (serotonin in the amygdala). Which is awesome because we usually cannot measure neurochemistry in living human brains.

C. In relaLon to the serotonin transporter allele, a key assumpLon of this strategy is that dierences in the allele are actually associated with dierences in the expression of the serotonin transporter in the brain

D. Several groups (e.g., Kalin) have used PET to show that there is in fact an associaLon between the allele transporter expression in the amygdala, conrming this key assumpLon

Some

have suggested tha...

Some

have suggested that...

In relation to the sero

toni...

Several groups (e.g., Ka

lin...

0% 0%0%0%

Which is true A. The HPA axis is involved in

the release of corLsol, epinephrine/adrenaline, and norepinephrine/noradrenaline in response to physical and psychological stress, which increases the availability of energy for the brain as well as defensive behaviors (ght/ight)

B. HPA = hippocampal, pituitary, amygdala

The H

PA axis is in

volved i...

HPA = hippocampal, pitui...

0%0%

Which is false A. Remarkable life-long changes

happen to stress-reacLvity when neonatal rats are exposed to experimenter handling, providing a nonhuman animal model of early experience & temperament

B. Handling leads to Lghter, more precise regulaLon of corLsol

C. Handling leads to increased expression of the glucocorLsoid receptor in the hippocampus in adulthood

D. As adults, rats who were handled as pups are less exploratory, more fearful, and more stress reacLve (N/NE)

Remarka

ble life-long cha...

Handling leads to tighte

r...

Handling leads to increa

...

As adults, rats who were

...

0% 0%0%0%

Which is false: Michael Meaneys group has provided evidence that the impact of handling on

temperament (N/NE or stress reacLvity) is

A. Related to increased expression of benzodiazepine receptors in the amygdala

B. Mediated by a social factor, namely, maternal style (LG-ABN: licking, grooming, and arched-back nursing)

C. Mediated by genes that increase maternal LG-ABN and decrease ospring reacLvity

D. Not geneLcally transmioed (i.e., moms can alter adopted/cross-fostered pups)

Related to increase

d expr...

Mediated

by a social facto..

Mediated

by genes that i...

Not genetically transm

itte...

0% 0%0%0%

Which is false about epigeneLcs A. Refers to trait-like alteraLons in the

transcripLonal (protein-making) potenLal of a cell (such as a neuron) that are not due to changes in the genome (DNA); turning certain genes on/o, without changing the genes themselves

B. Ouen reects methylaLon or histone modicaLon of the DNA

C. Explains cell dierenLaLon (liver vs brain cell) & developmentally appropriate changes in the brain and body

D. Can never be heritable (transmioed to subsequent generaLons)

E. Can be heritable, violaLng a key tenet of modern biology (inherited traits, such as T&P, reect the intergeneraLonal transmission of DNA)

Refers to trait-like alterat...

Often

reflects meth

ylatio...

Expla

ins cell diffe

rentiatio...

Can n

ever be he

ritable (...

Can b

e heritab

le, violatin...

0% 0% 0%0%0%

Which is false: How does maternal behavior produce lasLng changes in

(rodent) temperament (N/NE) A. Meaneys team showed that

maternal behavior (LG-ABN) produces epigeneLc changes

B. EpigeneLc changes lead to increased expression of glucocorLcoid receptors in the hippocampus, supporLng enduring changes in stress reacLvity

C. EpigeneLc changes induced by maternal behavior only persist during the neonatal period

Meaneys team showed t...

Epigenetic changes lead t...

Epigenetic changes in

duc..

0% 0%0%

Can paternal experience be transmioed to ospring without a behavioral/social intermediary? Can we benet (or suer) from our parents experience without them teaching (or grooming) us? Can acquired characterisLcs be inherited, as Lamarck posited in the 18th century? A. Yes! B. No! C. Ressler and others have

provided tantalizing evidence suggesLng that this is possible, but much remains unclear (e.g., how fear learning in the brain inuences epigeneLcs in the sperm/gametes)

Yes! No

!

Ressler and othe

rs have ...

0% 0%0%

Which is false: Trait-like dierences in T&P reect the brain. Dierences in brain structure and funcLon

reect the inuence of A. Genome/DNA B. Epigenome C. Experience/

Environment D. Experience

interacLng with the genome and epigenome

E. None of the above Genome/D

NA

Epigenome

Experience/Environment

Experience interacting w

i..

None of the above

0% 0% 0%0%0%

Which is false: Trait-like dierences in T&P reect the brain. Nature (genome/DNA, epigenome) and nurture (experience)

interact to change

A. Protein expression B. DNA methylaLon C. Neurochemical

receptor expression and binding

D. Hippocampal structure and funcLon

E. Histone status F. None of the above

Protein expression

DNA m

ethylation

Neuro

chemical recepto

r ...

Hippocam

pal structure a..

Histon

e status

None of the above

0% 0% 0%0%0%0%

How does early experience (abuse, stress, caregiver behavior) get into

the brain A. Changes in the

geneLc code B. Changes in the

epigenome that alter the expression of genes, leading to changes in protein synthesis and, ulLmately, acLvity

Changes in

the genetic code

Changes in

the epigeno..

0%0%

GWAS pretends that

A. Alleles (i.e., geneLc variants) do not interact with or inuence one another (only independent eects are considered)

B. Alleles do interact with one another

Alleles (i.e., genetic varia...

Alleles do inte

ract w

ith o..

0%0%

* Taylors ques7on in class

GWAS genome-wide associaLon study

A. Brute force approach to idenLfying correlaLons between alleles and phenotypes, such as N/NE

B. Ouen relies on SNP chips C. Suers from low staLsLcal

sensiLvity, because of the very large number of tests performed

D. Opens the door to discovering new and potenLally important molecular pathways

E. All of the above

Brute force appro

ach to ...

Often

relies on SNP chips

Suffers from low

statistica...

Opens the door to discov...

All of the above

0% 0% 0%0%0%

Showing that a trait, such as E/PE, is heritable indicates

A. A single, coherent or unied biological cause

B. Nothing whatsoever with regard to the number or kind of substrates

A single, coheren

t or unif...

Nothing whatso

ever with...

0%0%

Kagans model of BI A. Shows a number of

parallels with N/NE and Grays BIS, reinforcing the idea that childhood temperament and adult personality are closely related

B. Shows a number of important dierences from N/NE and Grays BIS, reinforcing the idea that childhood temperament and adult personality are disLnct kinds

Shows a number of paralle..

Shows a number of impo...

0%0%

An allele is

A. A geneLc polymorphism

B. A geneLc variant C. The thing; that gives

rise to geneLcally-determined individual dierences in trait-like phenotypes

D. All of the above A g

enetic polymo

rphism

A genetic variant

The thing; th

at gives rise...

All of the above

0% 0%0%0%

Family, twin, and adopLon studies (aka behavioral geneLcs) are

A. CorrelaLonal B. MechanisLc C. Provide a tool for

discovering the molecular substrates of T&P

Correlation

al

Mechanistic

Provide a tool for disco

ve...

0% 0%0%

Family, twin, and adopLon studies (aka behavioral geneLcs) teach us

that A. Psychiatric disorders,

like T&P, aggregate in families

B. Are heritable C. Things that blood

relaLves share (e.g., SES, toxin exposure, stress, habits) are important determinants of psychopathology

Psych

iatric disor

ders, like...

Are h

eritab

le

Things that bloo

d relative...

0% 0%0%

Which is true A. In humans, DNA is organized

into 23 pairs of chromosomes, one descended from Mom and one from Dad

B. Chromosomes are organized into genes, regions of DNA corresponding to the instrucLons for a protein

C. These proteins form neurons, axons, the myelin sheath covering axons, neurochemicals, synapses and every other component of our brains, the wetware that gives rise to our T&P

D. All of the above

In humans, DNA is org

ani...

Chrom

osom

es are

organiz..

These

prote

ins form neu...

All of the above

0% 0%0%0%

Developing a mechanisTc understanding of the molecular neurobiology of T&P and associated psychiatric disorders promises to

A. Redene diagnosLc categories and T&P traits in terms of quanLable eLology (root causes)

B. Accelerate the development of novel treatments or prevenLon eorts targeLng links in the eLological chain

C. IdenLfy at-risk individuals early (e.g., carriers of a parLcular polymorphism)

D. Predict treatment response or more quickly pick the best treatment (e.g., carriers of a parLcular polymorphism)

E. Enhance prognosis: You have 3 months to live

F. Provide a novel discovery tool for addressing some of the most fundamental quesLon about the nature of T&P

G. All of the above

Redefine diagnostic cate

...

Accelera

te the

develop

me..

Identify at-risk individual...

Predict treatment resp

o...

Enhance p

rognosis: You...

Provide a no

vel discover...

All of the above

0% 0% 0% 0%0%0%0%

Children with elevated behavioral inhibiLon (BI)

A. Are more likely to develop anxiety, mood, and co-morbid substance abuse disorders later in life

B. Are more likely to develop psychopathology if they show stable, high levels of BI across development

C. Are shy and reLcent in the face of novelty and potenLal threat (e.g., scary robot, human intruder)

D. May show elevated levels of the stress hormone corLsol

E. Show a R > L paoern of frontal EEG F. Show heightened amygdala

reacLvity to novel faces in adulthood

G. All of the above Are m

ore likely to devel..

Are m

ore likely to develo...

Are shy and reticen

t in th...

May show elevated levels...

Show a R > L p

attern

of f...

Show heighten

ed am

ygda..

All of the above

0% 0% 0% 0%0%0%0%

If a trait is highly heritable, this means that group dierences at one point in

history will always be that way A. Yes B. No

Yes No

0%0%

What are the long-term prospects for linking genes to intermediate neural phenotypes to traits, such as C/SC?

A. Awesome! B. Terrible! What a waste of

taxpayer money! C. It depends on the nature

of the linkages, which we do not yet know

D. Current evidence suggests somewhere in between awesome and terrible, but we do not yet know

E. C and D Awesome!

Terrible! W

hat a waste of...

It depends on the natu

re ..

Current evidence sugges..

C and D

0% 0% 0%0%0%

Which is true A. Common geneLc polymorphisms

(the SNPs measured by SNP chips) have, at most, weak eects on brain funcLon and behavior (e.g., 2-5%)

B. Such small eects are small and hard to reliably detect without using very large and expensive samples

C. Such small eects have led to many non-replicaLons

D. Such small eects have led many to wonder whether this research strategy is worth the money

E. All of the above

Comm

on genetic polym

o...

Such sm

all effects are

sma..

Such sm

all effects have le...

Such sm

all effects have l..

All of the above

0% 0% 0%0%0%

Which is true

A. Hannah is a 6 y.o. boy

B. Micah is an 18 m.o. girl

C. Both of Dr. Ss kids are cute as all get out

D. All of the above Hannah is a 6 y.o. boy

Micah is an 18 m

.o. girl

Both of Dr. Ss kids are cu..

All of the above

0% 0%0%0%

The Big 3 superfactors are about

A. 10% heritable B. 45% heritable C. 90% heritable

10% heritable

45% heritable

90% heritable

0% 0%0%

In class, we discussed several arguments for why even these small eects are potenLally important

A. Small is mis-leading; a limited number (on the order of a few tens) of SNPs, each accounLng for a small % of the variance, can add up to meaningful dierences (as in the height example)

B. The expense to date of this research is modest compared to military expenditures or even large-scale physics projects (colliders)

C. The discoveries are truly novel, opening the door to models and treatments that we probably never would have predicted or developed based on our exisLng knowledge and intuiLons

Small is mis-leadin

g; a lim...

The expense to date of th..

The discoveries are

truly ...

0% 0%0%

Which is inherited (heritable)?

A. Genes B. Trait-like

phenotypes, such as E/PE

C. All of the above

Genes

Trait-like ph

enoty

pes, s

...

All of the above

0% 0%0%

Heritability reects

A. The % of between-individual variaLon predictable from pedigree

B. The % of a trait within an individual (you!) that is inherited from your forebears

The %

of be

tween-individ...

The %

of a trait w

ithin an...

0%0%

A wide variety of environmental factors can

A. Trigger geneLc predisposiLons (e.g., to high levels of N/NE)

B. Compensate for or regulate the expression of geneLc predisposiLons

C. Enhance or accentuate geneLc predisposiLons

D. All of the above

Trigger genetic predispos...

Comp

ensate for or regula..

Enhance or acce

ntuate

g...

All of the above

0% 0%0%0%

Heritability A. Is probabilisLc and

predicLve of average outcomes

B. Is determinisLc if you know the parents, you know exactly what to expect of the ospring regardless of environment or experience

Is prob

abilistic and p

redic...

Is dete

rministic if you ...

0%0%

Anxiety disorders, such as GAD, and major depression are

A. Categorically dierent

B. Ouen co-morbid and show a number of other similariLes, in terms of therapeuLc response, heritability, and do on, suggesLng that they are closely related to one another and form a spectrum Categ

orically different

Often

co-morb

id and sho...

0%0%

Treatments targeLng anxiety disorders

A. Tend to inuence N/NE as well as depression

B. SelecLvely inuence the targeted disorder

C. Only help some paLents

D. A and C E. B and C

Tend to influence N/NE a...

Selectively influence the ...

Only help some patients

A and C

B and C

0% 0% 0%0%0%

Anxiety disorders, depression, and N/NE appear to share

A. Genes B. Neural substrates

(e.g., amygdala hyper-reacLvity)

C. Both

Genes

Neura

l substrates (e.g.,... Bo

th

0% 0%0%

Lesion studies in rodents, monkeys, and humans demonstrate that the

amygdala A. Is required for the

normal acquisiLon of new fear learning (condiLoned emoLonal response)

B. Not required C. Is required for the

retenLon of already learned fears

Is required for the norma...

Not required

Is required for the reten

t...

0% 0%0%

Elevated N/NE

A. Is common among anxiety paLents

B. Is common among depression paLents

C. Both

Is com

mon amo

ng anxiet...

Is com

mon amo

ng depre

... Both

0% 0%0%

Psychological pathogens, such as stress and family conict

A. Exert similar eects on depression, anxiety disorders, and N/NE, suggesLng a common substrate

B. Have disLnct eects on T&P vs. depression vs. anxiety disorders

Exert sim

ilar effects on

...

Have distinct effects on

...

0%0%

In a widely cited paper published in Science in 2003, Caspi and colleagues provided evidence that Individual dierences in the serotonin transporter

SNP

A. predicted depression B. interacted with life stress

to predict depression, providing evidence of a G x E interacLon and suggesLng a neurochemical substrate for psychiatric risk

C. Was completely and uoerly unrelated to depression

predicted

depre

ssion

interacted w

ith life stress...

Was completely and utte...

0% 0%0%

Amygdala lesions in monkeys block

A. The acquisiLon of new condiLoned fears

B. Innate anxiety about snakes

C. Both

The acquisitio

n of new c...

Innate

anxiety about snakes

0%0%

Height is A. Trait-like B. Among the most

heritable traits, although ospring will show considerable variaLon

C. Can be markedly aected by intervenLons (diet, nutriLon, and healthcare access)

Trait-like

Among the most heritab

le...

Can be m

arkedly affected

..

0% 0%0%

Jerry Kagan argues that the root cause of childhood behavioral inhibiLon (BI)

is A. An over-reacLve

amygdala B. MaladapLve

cogniLve coping mechanisms

C. Worry D. Disress E. Social reLcence F. Shyness

An over-reactive am

ygdala

Maladaptive cognitive co...

Worry

Disress

Social reticence

Shyness

0% 0% 0%0%0%0%

The administraLon of a benzodiazepine (anL-anxiety

medicaLon) A. Causes a dose-

dependent reducLon in amygdala acLvaLon

B. Causes a dose-dependent increase in amygdala acLvaLon

Causes a dose-d

ependent...

Causes a dose-d

ependent...

0%0%

Why do some individuals develop parLcular disorders, such as specic phobia of dogs? A. Learning and experience B. Core vulnerability

(heightened neuroLcism, hyper-reacLve amygdala, inadequate regulaLon of the amygdala)

C. Both, neither is sucient to explain the development of specic emoLonal disorders Learn

ing an

d experience

Core vulne

rability (heigh...

Both, ne

ither is s

ufficient...

0% 0%0%

The RoboGator Experiment: Amygdala lesions in rodents aoenuate

A. ReLcence to get the food pellet in the presence of the remote-control robogator, suggesLng a substrate for the reLcence demonstrated by BI kids, consistent with lesioned monkeys and the human intruder

B. The amount of Lme hiding in the nest area (outside the arena containing the Rgator)

C. All of the above Reticence to get th

e food...

The amo

unt of time

hidin...

All of the above

0% 0%0%

Heritability

A. Is informaLve about the nature and plasLcity of group dierences (men/women, black/white) in traits

B. Is not informaLve about such mean dierences

Is info

rmative about th

e ...

Is not inform

ative about...

0%0%

Amygdala damage

A. Increases raLngs of trust and approachability to faces that are normally deemed untrustworthy

B. Has no consequence of social interacLons or social cogniLon

Increa

ses ratings of tru

st...

Has no conseq

uence o

f so...

0%0%

N/NE is

A. A specic risk factor for anxiety disorders

B. A nonspecic risk factor for a broad range of psychiatric disease

A specific risk facto

r for a...

A nonspecific risk factor f..

0%0%

PaLent SM has circumscribed bilateral destrucLon of her amygdalae. She

A. Picks up snakes and spiders, despite professing anxiety

B. Shows no fear in the haunted house

C. Is unable to acquire new condiLoned fears in the lab

D. Quickly returned to the park where she was assaulted

Picks up snakes and spide...

Shows no fear in

the hau...

Is unable to acquire new...

Quickly return

ed to the ...

0% 0%0%0%

Is BI a viable intermediate phenotype for social anxiety disorder

A. Yes B. No

Yes No

0%0%

EmoLonal disorders and N/NE

A. Are fundamentally dierent

B. Reect a common cause

C. Are categorically disLnct

Are fundame

ntally differen

t

Reflect a com

mon cause

Are cate

gorically distinct

0% 0%0%

Exam Review:

Material Covered During the First Third of Course

How can we idenLfy the cause(s) of T&P (e.g., low C/SC)?

A. Forge a link between individual dierences in a trait and variaLon in a relevant behavioral or biological measure

B. Correlate traits and fMRI acLvaLon

C. Compute a regression (correlaLon) between task performance (e.g., BART) and traits of interest

D. Directly manipulate the hypothesized cause.

E. All of the above

Forge a link betw

een indi...

Correlate traits and fMR

I ...

Compute

a regression (co...

Directly manipulate the ...

All of the above

0% 0% 0%0%0%

What's the problem with reducing a complex, broad-band trait to a single

number? A. Mixes disLnct

processes B. Hinders our ability

to clearly resolve the underlying substrates

C. Too simplisLc D. All of the above

Mixes distinct processes

Hinders our ability to cle

a...

Too simplistic

All of the above

0% 0%0%0%

One strategy for discovering the cause of phenomenologically complex traits

(and mental disorders) is to A. Decompose them

into simpler, more manageable intermediate phenotypes

B. Give up C. Search for

endophenotypes D. A and C

Decompose them into si...

Give up

Search for endophenoty

pes

A and C

0% 0%0%0%

Which of the following can we plausibly model in nonhuman animal models (where we can perform mechanisLc

experiments to determine causaLon)

A. AnL-social behavior B. C/SC C. Delay of graLcaLon D. Turn-taking and

emoLonal irritability E. Hyper-sensiLvity to

reward-related cues F. C and E

Anti-social behavior

C/SC

Delay of gratification

Turn-taking and emotiona...

Hyper-sensitivity to rew

a...

C and E

0% 0% 0%0%0%0%

With respect to neurological sou signs (trait), elevated lead levels in the hair

are A. Noncausal symptom/

marker of the process that causes the trait or phenotype

B. Marker or scar of the trait or the organisms response to the trait

C. Endophenotype

Noncausal symp

tom/mar...

Marke

r or scar o

f the tra..

Endophenoty

pe

0% 0%0%

We discussed 2 kinds of intermediate phenotypes. Both kinds are

A. Causal B. Heritable C. Aggregate in

families D. Co-segregate in

families

Causal

Heritable

Aggregate in fam

ilies

Co-segregate in fam

ilies

0% 0%0%0%

Endophenotypes are

A. Simpler than the trait one seeks to understand

B. Causal C. A bridge between

the genotype and phenotype

D. Heritable E. All of the above

Simpler than the tra

it on...

Causal

A bridge between the ge...

Heritable

All of the above

0% 0% 0%0%0%

Which is true A. Intermediate

phenotypes cause traits, markers do not

B. Markers cause traits, intermediate phenotypes do not

C. Endophenotypes cause traits, biomarkers do not

D. A and C E. B and C

Interm

ediate phenotypes...

Markers cau

se traits, in...

Endophenoty

pes cause tr...

A and C

B and C

0% 0% 0%0%0%

Remarkably A. We know quite a bit

about the mechanisms linking genes to endophenotypes

B. We know quite a bit about the mechanisms linking endophenotypes to traits (and disorders)

C. We know next to nothing about either mechanism for any established endophenotype

We know quite a bit abou...

We know quite a bit abo..

We know next to nothin...

0% 0%0%

EEG/ERP aords

A. Exquisite spaLal resoluLon

B. Exquisite temporal resoluLon

C. Neither D. Both

Exquisite spatial resolution

Exquisite temporal resol...

Neither

Both

0% 0%0%0%

ConvenLonal fMRI signals reect

A. Blood oxygenaLon levels

B. Neuronal ring

Blood oxygenation levels

Neuro

nal firing

0%0%

Conceptually, acLvaLon in both ERPs and event-related fMRI is

esLmated by A. CompuLng the

average response evoked by a parLcular condiLon or kind of event

B. CompuLng the cross-correlaLon among sensors

Comp

uting the averag

e ...

Comp

uting the cross-corr...

0%0%

Which is true A. EEG is relaLvely cheap,

tolerant of moLon, and reects neuronal electrical acLvity (EPSPs)

B. fMRI is relaLvely expensive, sensiLve to moLon arLfacts, and does not directly measure neuronal acLvity

C. Both EEG is relatively cheap, t...

fMRI is relatively expensiv.. Bo

th

0% 0%0%

EEG and fMRI are

A. Causal (like lesion studies)

B. MechanisLc (like manipulaLng brain acLvity in rodents with drug infusions)

C. CorrelaLonal (like longitudinal studies of behavior)

Causal (like lesion studies)

Mechanistic (like m

anipu

...

Correlation

al (like longit...

0% 0%0%

In his 1968 book Personality and Assessment, Walt Mischel argued that the primary determinant of moods, thoughts, and behavior is

A. The situaLon, because T&P at most predict outcomes r = .30 (9% variance)

B. T&P C. Both

The situation, beca

use ... T&

PBoth

0% 0%0%

But contemporary science suggests that moods, thoughts, and behavior are determined by

A. The situaLon B. T&P C. Both

The situation T&

PBoth

0% 0%0%

Trait-like individual dierences in T&P are strongly predicLve of

A. Academic performance (above & beyond IQ)

B. Marital stability & saLsfacLon

Shackman Psyc210 Module12 NatureNurture Part3

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