Advanced Developmental Psychology PSY 620P February 5, 2015.

Advanced Developmental

Psychology

PSY 620PFebruary 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?


• 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


The Epigenetic Explanation of the Stress-Vulnerability 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


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


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?

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 Article1. 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

2. 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



• DNA methylation is a stable covalent modification that persists in post-mitotic cells throughout their lifetime, helping define their cellular identity

Types

1. mCG

2. mCH(where H = A, C, or T)

Key Findings

1. CH methylation accumulates in neurons through early childhood & adolescence – becoming the dominant form of DNA methylation in mature human neurons


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!

Key Findings


2. Inaccessible genomic regions are protected from de novo methylation

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

Key Findings


3. Neurons and glia show cell type-specific DNA methylation patterns

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!

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

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?

3. 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 follow-up

• 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”

Shaffer | Chen et al., 2009

Low SES Stress HPA axis disturbance

Psychiatric & Physical ailments

Vigilance for Threat

Daily Home Chaos

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


SES and Cortisol


SES and Cortisol Moderated by Threat Interpretation

Low SES Higher Threat Interpretation

Greater HPA output


SES and Cortisol Moderated by Chaos

Low SES Higher Home Chaos

Greater HPA output


SES and Cortisol Moderated by Threat Interpretation and Chaos

Low SES

Higher Home Chaos

Greater HPA output

Threat Interpretation


SES and Cortisol Interactions

Low SES HPA axis disturbance

Girls > Boys

Post-Puberty > Pre-Puberty


(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?


Advanced Developmental Psychology PSY 620P February 5, 2015.

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Transcript of Advanced Developmental Psychology PSY 620P February 5, 2015.