Despite widespread recognition of the high aggregate prevalence of psychiatric disorders,
their enormous contribution to global disease burden, and vast unmet treatment needs,
therapeutic discovery has languished. What psychiatry lacks is an understanding of
disease mechanisms, without which the nomination of biomarkers and therapeutic targets
remains guesswork. Attempts over decades to derive pathogenic mechanisms by attaining
insight into the healthy and disordered functioning of the human brain have foundered.
The reasons are well known, including brain complexity, inaccessibility of relevant
human brain tissue in life, evolutionary divergences that limit the utility of laboratory
animals as disease models, and the heterogeneity and comorbidity of psychiatric disorders
(
1
). A ray of hope comes from psychiatric genetics, which is providing molecular clues
to pathogenesis in the form of hundreds of genome-wide significant loci associated
with psychiatric disorders (
2
,
3
), a smaller number of rare protein-altering variants, and aggregate risk measures
such as polygenic risk scores. If emerging genetic information can be rigorously and
effectively integrated with neurobiology, clinical investigation, and other disciplines,
we will gain actionable insights into disease mechanisms. Success will not come easily,
however, given the complexity of the emerging genetic picture. Greater investment
and more effective communication across disciplines are needed to build the solid
empirical and methodological foundations required to transform genetic information
into biological insight.To read this article in full you will need to make a payment
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References
- Revolution stalled.Sci Transl Med. 2012; 4: 155cm11
- 10 years of GWAS discovery: Biology, function, and translation.Am J Hum Genet. 2017; 101: 5-22
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Article info
Publication history
Accepted:
August 19,
2020
Received:
August 18,
2020
Identification
Copyright
© 2020 Society of Biological Psychiatry.
