Transcript Ch03 - Myweb @ CW Post

Genetic and
Environmental
Influences on
Behavior
Chapter 3
Theodore P. Beauchaine and Lisa-Gatzke-Kopp
HISTORICAL CONTEXT
 Early causes of psychopathology focused on
nature versus nurture.
 Due to lack of formal scientific methods and technological
and methodological tools it was difficult to effectively
parse the relative contributions of heritable and
environmental influences on behavior.
 A growing body of research in the last 10 to 15
years indicate that Gene × Environment
interactions may be more important in determining
behavior then either factor alone (Moffitt, Caspi, & Rutter,
2006; Rutter, 2007).
THE DEVELOPMENTAL
PSYCHOPATHOLOGY PERSPECTIVE
 An approach for studying the emergence of
behavior disorders that emerged in the past 30
years.
 Analysis refer to different systems through which a
psychopathological trait is expressed, spanning
genes to behavior to broad cultural factors.
 Integrates the strengths of numerous other
disciplines, including psychiatric genetics, child
clinical psychology, child psychiatry, developmental
psychology, epidemiology, and clinical
neuroscience.
TERMINOLOGICAL AND
CONCEPTUAL ISSUES
 Genotypes, Phenotypes, and Endophenotypes
 Genotype
• Refers to the structural composition of the specific genes within an
individual.
• Some genetic variants give rise to individual differences in the
synthesis, reuptake, and catalysis of neurotransmitters. When
functionally compromised, these neurotransmitter systems may
confer vulnerability to mood disorders, impulse control problems, and
asociality.
• Both genes and environment are implicated in the expression of
almost all forms of psychopathology.
• There are no genes for particular behaviors or disorders.
• Environments can alter gene expression.
• Many people who are genetically vulnerable never develop mental
illness.
TERMINOLOGICAL AND
CONCEPTUAL ISSUES
 Phenotype
• Refers to the observable characteristics—both physical and
behavioral—that result from the interplay between an organism’s
genes and the environment.
• Most forms of psychopatholoy are polygenetic traits and are
influenced by many genes.
• Multiple genetic influences allow for many opportunities for both
gene-gene interactions and environmental regulation of gene
expression.
TERMINOLOGICAL AND
CONCEPTUAL ISSUES
 Endophenotype
• Are a special case of phenotype, as they are measurable physical,
physiological, or behavioral traits; the difference is that they are closer
to the functional output of the gene in question.
• Endophenotypes are valuable to psychiatric geneticists in their
attempts to identify:
• Specific alleles associated with psychopathology
• Genetically vulnerable individuals who have not yet developed
psychopathology
• To qualify an endophenotype, a biomarker must:
•
•
•
•
•
•
Segregate with illness in the general population
Be heritable
Be state independent
Co-segregate with disorder within families
Be present at higher rates in affected families than in the general population
Be measured reliably and specifically
PSYCHIATRIC GENETICS
 Objectives of psychiatric genetics:
 Behavioral genetics research: To parse variability in
behavioral traits within populations into portions
accounted for by (a) heritable mechanisms, (b)
environmental mechanisms, and sometimes (c) Gene ×
Environment (G × E) interactions.
 Molecular genetics research: To identify specific alleles
that confer vulnerability to psychopathology.
PSYCHIATRIC GENETICS
 Behavioral Genetics
 Additive Gene Effects
• Encompass all sources of variance in a behavioral trait that are
accounted for by heritable mechanisms within a population.
• Maternal programming: When genes are activated (“turned on”)
among offspring only when their mothers are exposed to particular
environments, often prenatally (Rutter et al., 2006).
• Such effects may increase risk for or protect against the emergence
of psychopathology. These effects are not purely genetic, yet they
are often subsumed within the additive genetic component in
behavioral genetics studies.
PSYCHIATRIC GENETICS
 Behavioral Genetics
 Shared and Nonshared Environmental Effects
• ACE model
• A is the heritable effects, C is the shared environmental effects,
and nonshared environmental effects are denoted E.
• When squared, each term signifies a proportion of variance in
behavior accounted for. In theory, these sources sum to 1.0,
accounting for all variance in a particular trait (A2 + C2 + E2 =
1.0).
• Research is accomplished through twin, family, and adoption
studies using the ACE model.
Psychiatric Genetics
 Molecular Genetics
 Linkage studies: Scan broad sections of the genome, and
require large samples of families with two or more children
affected by psychopathology. Genetic data are collected from
family members, and searches are conducted for genetic
markers with known chromosomal locations.
 Association studies: Begin with a specific candidate gene that
is suspected of conferring risk for a psychiatric disorder. Allelic
frequencies of this gene are then compared among those with
and without the disorder. Results are expressed as odds
ratios, which compare the likelihood that a person with a
candidate polymorphism has a target disorder with the
likelihood that a person without a candidate polymorphism has
a target disorder.
Psychiatric Genetics
 Heterogeneity of Phenotypes
 Presents obstacles to identifying genetic substrates of
psychopathology:
• Criteria used for symptom assessment and participant selection
often differ across studies.
• Equifinality: The same or similar symptoms can develop through
different etiological pathways.
• Diagnostic syndromes are highly complex and are often defined by
a compilation of symptoms.
PSYCHIATRIC GENETICS
 Gene-Environment Interaction (G × E)
 Refers to situations in which environments moderate the effects of
genes on behavior, or in which genes moderate the effects of
environments on behavior.
 Gene-Environment Correlation (rGE)
 Refers to situations in which heritable traits of parents affect their
child’s exposure to adverse environments or heritable traits of
children affect their own exposure to adverse environments.
• Active rGE occurs when a child’s heritable vulnerabilities influence his or her
selection of environments.
• Evocative rGE occurs when genetically influenced behaviors elicit reactions
from others that interact with and exacerbate existing vulnerabilities.
• Passive rGE occurs when genetic factors that are common to both a parent
and child influence parenting behaviors or home environments more generally.
Psychiatric Genetics
 Epigenetics
 Refers to changes in gene expression that result from
alterations in DNA structure and are mediated primarily
by environmentally triggered methylation processes (i.e.,
conversion of a cytosine to 5-methylcytosine).
 Difficult to research epigrnetic changes in gene
expression humans because it requires random
assignment of groups to different rearing environments
(e.g., impoverished versus enriched) (Rutter, 2007).
 Research on the indirect evidence of epigenetic
processes can be done by measuring methylation of
target genes.
GENETICS OF COMORBIDITY
 Homotypic comorbidity refers to the co-occurrence
of multiple externalizing disorders within an
individual or the co-occurrence of multiple
internalizing disorders within an individual.
 Heterotypic comorbidity refers to the co-
occurrence of at least one externalizing disorder
and at least one internalizing disorder within an
individual (e.g., CD and depression).
GENETICS OF COMORBIDITY
 Behavioral Genetics of Comorbidity
 Homotypic comorbidity: Indicates most disorders within the
externalizing spectrum share a common heritable vulnerability, with
similar findings reported for disorders within the internalizing
spectrum.
 Heterotypic comorbidity: Suggest common heritability across
internalizing and externalizing disorders.
 Molecular Genetics of Comorbidity
 Homotypic comorbidity: Central dopamine (DA) dysfunction may
account for much of the shared vulnerability for externalizing
disorders and vulnerability for internalizing disorders is conferred
largely through trait anxiety, which has been linked closely with
serotonin neurotransmission.
 Heterotypic comorbidity: Deficiencies in DA-mediated reward
circuitry are moderated by other biologically influenced traits to affect
behavior.
Genetics of Comorbidity
Symptom overlap for depression and conduct disorder
Depression
CD
Reward
Dysfunction
High
Inhibition
• anhedonia
• irritability
• low motivation
Low
Inhibition
Genetics of Continuity
 Homotypic continuity: Describes the unfolding of a
single class of behavioral/emotional disturbance
over time (e.g., aggression).
 Heterotypic continuity: Refers to the sequential
development of different internalizing or different
externalizing behaviors or disorders across the
lifespan.
CONCLUSIONS
 Although boundaries between nature and nurture are
dissolving, much work remains toward uncovering
specific mechanisms through which nature and nurture
interact to affect behavior.
 Distance between genotypes and phenotypes, along
with various interdependencies among genotypes,
phenotypes, and environments, can lead to inflated
and misleading estimates of heritability.
 Molecular genetics studies aimed at identifying specific
allelic variations associated with psychological
dysfunction often fail to account for environmental
moderators of genetic vulnerability.