Terrie Moffitt & Avshalom Caspi on Understanding the Causes of Mental Illness
Fast Moving Front Commentary, July 2010
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Article: Opinion - Gene-environment interactions in psychiatry: joining forces with neuroscience
Authors: Caspi, A;Moffitt, TE |
Terrie E. Moffitt & Avshalom Caspi talk with ScienceWatch.com and answer a few questions about this month's Fast Moving Fronts paper in the field of Psychiatry/Psychology.
Why do you think your paper
is highly cited?
This paper appeared in 2006, before the findings from genome-wide association studies (GWAS) research began to emerge, but it is attracting a lot of interest in 2010, perhaps because it offers an evidence-based potential explanation for why the GWAS approach has not generated a trove of disease-genes as expected.
We also suspect this paper has become highly cited because it appeared at just the right moment, when two new subfields were beginning to mature and amalgamate to create a powerful new scientific paradigm to explain genetic effects on mental illness and behavior.
One field is the observational study of gene-environment interactions in the etiology of psychiatric conditions. The second field is the experimental study of genomic neuroscience. Our paper points out that, by joining forces to work on the same problems, these two fields spark a remarkable synergy.
Does it describe a new discovery,
methodology, or synthesis of knowledge?
Coauthor Avshalom Caspi
Experimental neuroscience studies are capable of showing that, when a subject is exposed to an environmental stimulus, the responses of a subject's brain or other physiological systems can vary by their genotype. Since experimental neuroscience cannot establish whether these processes matter, outside the highly controlled confines of the lab, external validity is lacking.
Observational epidemiological studies are capable of showing that when free-living subjects experience an environmental exposure, whether or not they develop mental illness in real life varies by their genotype. But, as observational studies cannot prove cause and effect, internal validity is lacking.
Our paper argues that every hypothesis of gene-environment interaction ought to be tested systematically using both methods—experimental neuroscience, and observational epidemiology. This combination will maximize the validity of discoveries.
Would you summarize the significance of
your paper in layman's terms?
Understanding the causes of mental illness has been making slow progress. This paper shows how two powerful but imperfect approaches to behavioral science can be used in tandem, to provide strong, decisive answers to the question of why people develop mental illnesses. Visit our website to learn more about our research.
How did you become involved in this
research and were any particular problems encountered along the way?
An obvious problem in doing this work was that we needed to master two very complex fields, psychiatric genetics and experimental neuroscience. Luckily, we had clever and generous colleagues who were willing to help us learn.
Where do you see your research leading in
the future?
This year we followed up the "joining forces with neuroscience" paper in a new article, showing how observational and experimental studies have validated the gene-environment interaction between the serotonin transporter genotype and life stress that predicts depression (Caspi, A., et al., "Genetic sensitivity to the environment: The case of the serotonin transporter gene (5-HTT), and its implications for studying complex diseases and traits," American Journal of Psychiatry 167: 509-27, 2010).
Next, we want to look at how the interplay between genes and environments affects the pace of aging. People of the same chronological age vary widely in their biological age; some are remarkably youthful but others have aged prematurely. Unlocking this secret can help enhance the later years for everyone.
Do you foresee any social or political
implications for your research?
Public understanding of gene-environment interaction findings in health is important because it provides concrete examples to show that genes do not determine health and behavior.
Genes' effects on health and behavior often depend on lifestyle choices
that are under humans' control. Public understanding of this should take
genes off the causal pedestal, and once the constraints on genes' effects
are widely understood, an informed public should prevent misuse of genetic
information.
Avshalom Caspi
Edward M. Arnett Professor
Departments of Psychology and Neuroscience, Psychiatry and
Behavioural Sciences
and
Institute for Genome Sciences and Policy
Duke University
Durham, NC, USA
and
Professor of Personality Development
Social, Genetic and Developmental Psychiatry Centre
Institute of Psychiatry
King's College London
London, UK
Terrie E. Moffitt
Knut Schmidt Nielsen Professor
Departments of Psychology and Neuroscience, Psychiatry and
Behavioural Sciences
and
Institute for Genome Sciences and Policy
Duke University
Durham, NC, USA
Professor of Social Behavior and Development
Social, Genetic and Developmental Psychiatry Centre
Institute of Psychiatry King's College London
London, UK
KEYWORDS: DRD4 VNTR POLYMORPHISM; MONOAMINE-OXIDASE-A; SEROTONIN TRANSPORTER GENE; O-METHYLTRANSFERASE GENE; STRESSFUL LIFE EVENTS; MAJOR DEPRESSION; 5-HTTLPR POLYMORPHISM; ANTISOCIAL BEHAVIORS; MALTREATED CHILDREN; ALCOHOL-CONSUMPTION .