Indian Journal of Psychiatry 52(3), Jul-Sep 2010
Creativity, psychosis and human evolution: The exemplar case of
neuregulin 1 gene
The link between creativity and psychosis has derived
more support from a recent demonstration of a biologically
relevant polymorphism of the promoter region of the
neuregulin 1 gene, which is linked with schizophrenia,
associated with creativity in people with high intellectual
and academic performance. In this letter, we summarize
further comparative genomic analyses supporting positive
selection of neuregulin 1 gene that further adds to its
significance in the context of creativity and psychosis from
the perspectives of human evolution.
Comparative genomic analyses examine a fundamental
measure of the relative importance of selection and genetic
drift in causing amino-acid substitutions is the dN/dS ratio
(dN is a measure of the degree to which two homologous
coding Deoxyribonucleic acid (DNA) sequences differ at non-
synonymous sites, dS is a measure of the degree to which
two homologous coding sequences differ with respect
to silent nucleotide substitutions). Analyzing dN and dS
are among the most direct ways to obtain evidence for
positive selection on a protein-coding gene. A comparative
genomic research using sequences from 23 Eutherian species
through phylogenetic analysis by maximum likelihood
demonstrated compelling evidence for positive selection
involving neuregulin 1 gene. This observation is in support
of a previous comparative genomic analysis examining five
species. This adaptive change potentially dates to the
evolution of modern humans i.e. five to seven million years
The intriguing persistence of schizophrenia (approximately 1%
prevalence across all populations), despite adverse fecundity,
argues for a balancing advantage conferred by this disorder
that is shared by all human populations. Schizophrenia,
a heterogeneous construct, is likely to be influenced by
various balancing advantages–creativity being one of them.
 While the recently reported link between neuregulin 1 and
creativity offers important evidence in support of this, other
works (as summarized above) strengthen the evolutionary
significance of neuregulin 1 gene not only for schizophrenia,
perhaps, but also for origins of Homo sapiens.
Dobzhansky’s statement: “Nothing in biology makes sense
except in the light of evolution” emphasizes the need
for evolutionarily-informed approaches to understand
diseases and disorders. Contemporary medicine focuses
predominantly on “proximal-etiology” whereas “distal-
etiology” based evolutionary approach has mostly been
neglected. ‘Theoretical’ research approaches (similar to
Dr. Keri’s work) based on evolutionary concept advocating
multiple dimensions might facilitate identifying valid
homogeneous subtypes that can advance our understanding
Mr. Sunil V. Kalmady is supported by the Innovative Young
Biotechnologist Award of the Department of Biotechnology
(Government of India) awarded to Dr. G. Venkatasubramanian.
Ganesan Venkatasubramanian, Sunil V. Kalmady
The Metabolic Clinic in Psychiatry, Department of
Psychiatry, National Institute of Mental Health and
Neurosciences, Bangalore–560029, India
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4. Kalmady SV. Adaptive evolutionary studies of genes underlying psychiatric
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5. Crespi B, Summers K, Dorus S. Adaptive evolution of genes underlying
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Letters to Editor
Psychological support for fathers of articial insemination donor children
Artificial insemination donor (AID) is pursued by infertile
couples after less investigative procedures have been
exhausted. Although the female goes through the stress
of pregnancy and delivery of the child, the procedure is