Genetic and Environmental Influences on Behavior

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Genetic and Environmental Influences on
Behavior

• Chapter 3
• Theodore P. Beauchaine and Lisa-Gatzke-Kopp

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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).

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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.

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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.

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Terminological and Conceptual Issues

• Phenotype
• Refers to the observable characteristicsboth
  physical and behavioralthat result from the
  interplay between an organisms 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.

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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

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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.

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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.

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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.

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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.

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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.

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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 childs exposure to adverse
  environments or heritable traits of children
  affect their own exposure to adverse
  environments.
• Active rGE occurs when a childs 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.

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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.

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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).

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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.

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Genetics of Comorbidity
Symptom overlap for depression and conduct
disorder
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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.

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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.