Transcript Advanced Developmental Psychology

Advanced
Developmental
Psychology
PSY 620P
February 5, 2015
Culture and Neuroscience in
Developmental Psychology (Miller &
Kinsbourne, in press)
• Possible influences of culture on neural maturation
• Structural differences between cultures
• Cultural differences in patterns of utilization that mirror behavioral differences
• Cultural differences in patterns of utilization not reflected in behavioral
differences
• Reviews of recent findings
• Genetics as potential and influences of environment determine which of the
potentials will be realized
Imagine you’re in a
library…
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
• 1 DNA Sequence = 1 Book
• DNA Transcription: the process of DNA being read
by an enzyme called RNA polymerase > leading to
the production of mRNA > which is then translated
into a protein
• Epigenetic influences: determine the expression of
DNA without altering the sequence of DNA
• DNA methylation: one type of epigenetic
mechanism; reduces the accessibility of DNA and
can lead to “silencing” of the gene
• Why are some read and others not?
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
• Epigenetic processes can be
altered by an individual’s
experiences during development
• Rats bred to be “maze-dull” or
“maze-bright” exhibited different
levels of cognitive abilities
•“Maze-dull” reared in enriched environment
>improved learning ability
•“Maze-bright” reared in impoverished environment >
significant decline in performance
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
The Epigenetic Explanation of the StressVulnerability Model
• Humans have genetic variations that lead to either high or low levels
of the serotonin transporter
• Dunedin study: risk of depression was predicted by the interaction of
the serotonin transporter genotype and the number of stressful life
events experienced
• If few stressful life events, no risk difference by genotype
• If many stressful life events, genotype effects
• Individuals with the low-serotonin-transporter-level gene variant were at
greater risk of depression
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
Implications of Epigenetic X Environment
Interplay for Psychology
• Elevated levels of methylation in ribosomal RNA genes among suicide
victims, specific to the hippocampus
• In monozygotic twins, increased discordance in patterns of gene
expression among older twins
• Suggests increasing differences in DNA methylation, which could account for
differences in risk of mental illness between MZ twins
• Changes in methylation may be subsequently passed on to later
generations through the germ line, or there may be a behavioral
transmission of individual differences > It is possible that nurture
changes nature
(Champagne & Mashoodh, 2009; Syzf & Bick, 2012)
Questions
• How can epigenetics inform our understanding of the impact of
technology on different cultures?
• Can you see the effects of epigenetics in your own research?
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Background
• Early postnatal burst of synaptogeneis  activity-dependent pruning of
excess synapses during adolescence
 This process forms the basis for experience-dependent plasticity
 Disruption leads to behavioral alterations & neuropsychiatric disorders
• Epigenome: Network of chemical compounds surrounding DNA that modify
genomic expression without altering DNA sequences
 Dynamic epigenetic changes occur during brain development,
maturation, & learning
 DNA METHYLATION PLAYS KEY ROLE:
Major transcriptional changes  adult electrophysiological
characteristics in neocortical neurons
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Goals of the Article
1.
Better understand the unique role of DNA methylation in brain development and
function  Unravel the genetic program and experience-dependent epigenetic
modifications leading to a fully differentiated nervous system
1.
Offer framework for testing the role of epigenome in:
Healthy function vs. Pathological disruptions of neural circuitry
Methods: Integrate empirical data of genome-wide composition, patterning,
cell specificity, and dynamics of DNA methylation at single-base resolution in
human & mouse frontal cortex at different developmental stages
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Types
1. mCG
2. mCH
(where H = A, C, or T)
• DNA methylation is a stable covalent modification that
persists in post-mitotic cells throughout their lifetime,
helping define their cellular identity
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Key Findings
1. CH methylation accumulates in neurons through early
childhood & adolescence – becoming the dominant form of
DNA methylation in mature human neurons
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Key Findings
1. CH methylation accumulates in neurons through early
childhood & adolescence – becoming the dominant form of
DNA methylation in mature human neurons
Q1: What’s so cool about that?
A1: Demonstrates large-scale reconfiguration of
neuronal epigenome!
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Key Findings
2. Inaccessible genomic regions are protected from de novo methylation
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Key Findings
2. Inaccessible genomic regions are protected from de novo methylation
Q2: Why is that important?
A2: Timing matters!
Example: Central nervous system deletion of Dnmt3a
If during late gestation  Motor deficits, premature death 
If during second postnatal week  Plays critical role in establishing normal
brain methylation profile and allowing healthy brain development 
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Key Findings
3. Neurons and glia show cell type-specific DNA methylation patterns
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Key Findings
3. Neurons and glia show cell type-specific DNA methylation patterns
Q3: What are the implications of this association?
A3: Suggests a role for DNA methylation in
distinguishing these 2 broad classes of cortical cells!
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Other Key Findings:
4.
The mCH position is highly conserved:
Precise positioning of mCG and mCH marks (which are conserved
between individuals and across humans and mice) is consistent with a
functional role
5.
X chromosome shows gender-specific DNA methylation patterns
Global Epigenomic Reconfiguration During Mammalian
Brain Development (Lister et al., 2013)
Discussion Qs
1. What’s the bigger picture?
2. What are the benefits of such experience-dependent
epigenetic modifications contributing to the development of
a fully differentiated nervous system? Any potential
drawbacks?
1. Are we any closer to a framework for testing the role of
epigenome in healthy function vs. pathological disruptions
of neural circuitry?
Cognitive ability changes and dynamics of cortical thickness
(Burgaleta et al., 2014)
• Background:
• IQ has been found to be associated with changes in cortical thickness (Ramsden et al.,
2011)
• Higher IQ associated with greater fluctuations in cortical thickness ; See declines in cortical thickness
during late adolescence (Shaw et al., 2006)
• Goal of the study:
• To better understand structural correlates of changes in IQ for healthy youth over time
• And are these changes in cognitive ability or measurement error?
• Hypotheses:
• Structural change in the brain (e.g., cortical thickness/surface area) would be positively
associated with Verbal IQ, Performance IQ, and Full Scale IQ for children/adolescents
over time
• Associations would appear in sensorimotor areas
• Why do you think these are important questions to study?
Methods
(Burgaleta et al., 2014)
• Sample
• Multi-site (6 sites), longitudinal study
• N= 188, Ages 6-20, Mean age at Time 1: 11.59 + 3.46; assessed at 2 year followup
• Measures
• Cognitive Measures:
• WASI (VIQ, PIQ, and FSIQ)
• MRI and MRI processing system
• Used corticometric methods to represent gray matter change: cortical thickness (CTh) and
cortical surface area (CSA)
Methods
(Burgaleta et al., 2014)
• Analysis
• As part of pre-post design, computed difference scores for CTh, CSA, and IQ
• Change scores represent relative change compared to same-aged peers (not absolute change)
• Then, analyzed change by IQ change group (using 90% CI):
• Reliable IQ increases
• Reliable IQ decreases
• No reliable IQ changes
Results
(Burgaleta et al., 2014)
• ΔFSIQ associated with Δ CTh, but not Δ CSA
• ΔPIQ associated with changes in CTh; trend for ΔVIQ
Results
(Burgaleta et al., 2014)
• ΔCTh over time
• Increase IQ group: non-significant
•
•
increase in CTh
Decrease IQ group: steepest rates of reduction in CTh
Stable IQ group: smaller decreases in CTh
Conclusions
(Burgaleta et al., 2014)
• Consistent with previous literature, individual
differences in rate of change in cortical thickness appears to
be related to changes in 3 parts of IQ
• Results of this study support that relationship over time
• CSA does not seem to be associated with changes in
IQ
• How can we explain these changes in FSIQ/brain
structure? Ideas for future directions?
Reconceptualizing functional
brain connectivity in autism
from a developmental
perspective
Uddin, Supekar & Menon, 2013
Functional Connectivity
• Functional connectivity- “temporal correlations between remote
neurophysiological events”
• Analyzing data: 1) seed region of interest
2) correlating multiple regions
3) mapping areas with shared profiles
• Resting State fMRI – reflects history of task-dependent activation
• Development and functional connectivity:
•
•
Adults have more high level connections
Networks are more diffuse in adult brain
Autism and Connectivity
• ASD: social and communication deficits, repetitive and restricted
behaviors
• Hypo VS. Hyper connectivity theories
• Methodology? Conceptual questions? Development?!?!?!
Hypo-Connectivity
 Language
 Working Memory
 Executive
Functioning
 Visuomotor
coordination
 Cognitive Control
Hyper-Connectivity
 Language
 Memory
 Emotion Processing
 Visual search
 Visuomotor
coordination
Functional Connectivity and ASD
• Pattern of hypo-activity in adults
• Hyper-activity in children
• Found in children aged 7-12
• Possible hormonal role?
Possible Issues and Roadblocks
• Concerns you have with this theory?
• Lack of study
• Little understanding of a typical trajectory
• No connection between functional connectivity and behavioral outcomes
• What would we need to do to test it?
•
•
•
•
Longitudinal research
Assess pubertal stage of participants (not just age)
Find participants with heterogeneous outcomes
Look at region-specific patterns of activation
Kelly Shaffer
Background
• “Health disparities are a pressing reality of our society”
Vigilance for
Threat
Low SES
Daily Home
Chaos
Shaffer | Chen et al., 2009
Stress
HPA axis
disturbance
Psychiatric
& Physical
ailments
Methods
• 54 healthy children  50 included in analyses
• IV: SES
• Family savings
• Home ownership
• Mediators:
• Children’s perception of threat – Cognitive Appraisal and Understanding of
Social Events videos
• Household chaos – Parent report on Confusion, Hubbub, and Order Scale
• DV: Salivary cortisol – total cortisol output
Shaffer | Chen et al., 2009
SES and
Cortisol
Shaffer | Chen et al., 2009
SES and Cortisol Moderated by Threat
Interpretation
Low SES
Shaffer | Chen et al., 2009
Higher Threat
Interpretation
Greater HPA
output
SES and Cortisol Moderated by Chaos
Low SES
Shaffer | Chen et al., 2009
Higher
Home Chaos
Greater HPA
output
SES and Cortisol Moderated by Threat
Interpretation and Chaos
Higher
Home Chaos
Low SES
Threat
Interpretation
Shaffer | Chen et al., 2009
Greater HPA
output
SES and Cortisol Interactions
Girls > Boys
Low SES
HPA axis
disturbance
Post-Puberty >
Pre-Puberty
Shaffer | Chen et al., 2009
(Possible) Limitations
• Ethnic composition & setting
• Attrition: those lost < family savings
• Parent rating of chaos
• SES did not relate to cortisol pattern, only cortisol amount
Your recommendations for:
Interventions?
Future Research?
Shaffer | Chen et al., 2009