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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,[1]
associated with creativity in people with high intellectual
and academic performance.[2] 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.[3] 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.[4] This observation is in support
of a previous comparative genomic analysis examining five
species.[5] 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.
[6] While the recently reported link between neuregulin 1 and
creativity[2] 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.[7] ‘Theoretical’ research approaches (similar to
Dr. Keri’s work)[2] based on evolutionary concept advocating
multiple dimensions might facilitate identifying valid
homogeneous subtypes that can advance our understanding
of schizophrenia.[8]
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
DOI: 10.4103/0019-5545.71003
1. Mei L, Xiong WC. Neuregulin 1 in neural development, synaptic plasticity
and schizophrenia. Nat Rev Neurosci 2008;9:437-52.
2. Keri S. Genes for psychosis and creativity: A promoter polymorphism of
the neuregulin 1 gene is related to creativity in people with high intellectual
achievement. Psychol Sci 2009;20:1070-3.
3. Anisimova M, Liberles DA. The quest for natural selection in the age of
comparative genomics. Heredity 2007;99:567-79.
4. Kalmady SV. Adaptive evolutionary studies of genes underlying psychiatric
disorders. Department of Biotechnology. Manipal: Manipal University;
2008. p. 80.
5. Crespi B, Summers K, Dorus S. Adaptive evolution of genes underlying
schizophrenia. Proc Biol Sci 2007;274:2801-10.
6. Seldon HL. Extended neocortical maturation time encompasses speciation,
fatty acid and lateralization theories of the evolution of schizophrenia and
creativity. Med Hypotheses 2007;69:1085-9.
7. Nesse RM, Stearns SC, Omenn GS. Medicine needs evolution. Science
8. Venkatasubramanian G. Evolutionary perspectives on psychoses
and autism: Does genomic imprinting contribute to phenomenological
antithesis? Behav Brain Sci 2008;31:281-2.
Letters to Editor
Psychological support for fathers of articial 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
... (Эфроимсон, 1998). В зарубежной литературе также есть предположение о том, что сохранение гена креативности на достаточно высоком уровне связано с необходимостью эволюционного прогресса (Venkatasubramanian, Kalmady, 2010). Среди отечественных исследователей так же существует мнение, что генетическая природа креативности тесно связана с полем психических расстройств. ...
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В статье рассматривается представление о стилях семейного воспитания, как о факторах, влияющих на проявление креативности у детей младшего школьного возраста. Новизна работы заключается в том, что проведенное эмпирическое исследование является одним из немногих исследований, посвященных изучению взаимосвязи стилей семейного воспитания и проявлений креативности и тревожности детьми младшего школьного возраста. Во Введении автором обозревается актуальность исследования, обусловленная высоким запросом на обеспечение всех сфер общественной жизни кадрами, имеющими нестандартное, творческое мышление, и, вместе с тем, отсутствием понимания того, каким образом отношения в семье влияют на развитие креативности у детей. Приводится анализ различным подходов к проблеме креативности и творческого мышления. В качестве эмпирического объекта исследования выступили 60 детей, в возрасте от 8 до 11 лет и их родители. В разделе «Методы» перечислены статистические методы, а также методический инструментарий: Тест Торренса, Опросник Кетелла, Методика Степанова. Результаты исследования показывают взаимосвязь между стилями родительского воспитания, креативностью и тревожностью у детей. В разделе «Обсуждение результатов» автор отмечает, что в семьях с демократическим стилем воспитания, у детей больше условий для развития их креативности и творческого потенциала, так как здесь родитель осознает важность своей роли, давая при этом ребёнку много пространства для развития. Уровень тревожности в подобных семьях у детей ниже.
... For instance, Kéri (2009) argued that the neuroregulin 1 gene (NRG1) is linked to both increased risk for psychosis (see Mei and Xiong, 2008) and creative achievement, particularly in individuals with high intellectual and academic achievement (see also Venkatasubramanian and Kalmady, 2010). Kéri focused on a particular polymorphism of NRG1, SNP8NRG243177/rs6994992 (C versus T), where the T/T phenotype is associated with an increased risk for psychosis and lower premorbid IQ (Hall et al., 2006), lower working memory capacity (Stefanis et al., 2007), and neurodevelopment and synaptic plasticity (Harrison and Law, 2006). ...
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Why is it that all those who have become eminent in philosophy or politics or poetry or the arts are clearly melancholics? – Aristotle Nothing in biology makes sense except in the light of evolution. – Dobzhansky (1973) Introduction Schizophrenia, a debilitating mental illness affecting roughly 1 percent of the population worldwide, is widely accepted as being highly genetically influenced (Cardno et al., 1999; Gershon et al., 1988; Kendler and Diehl, 1993). Schizophrenia is often marked by distortions of reality, disorganized thought, emotional blunting, and/or social isolation that may interfere with optimal functioning (Cornblatt et al., 2012). Schizophrenia may be associated with creativity, although research findings are mixed (e.g., Andreasen, 2011; Kyaga et al., 2013). Evidence also points to adverse effects on fertility and reproductive success among (particularly) males with schizophrenia (Svensson et al., 2007), in part accounted for by marital status (McCabe et al., 2009), suggesting potential biological and social influences. Collectively, this raises an intriguing potential evolutionary puzzle: How does schizophrenia persist in the population at a stable prevalence rate too high to be explained by simple random mutation? (Doi et al., 2009; see also Del Giudice et al., 2010). Among various hypotheses, including in the context of the emerging field of evolutionary epidemiology, schizophrenia may represent “one extreme of a sexually selected fitness factor” (Shaner et al., 2004).
BACKGROUND: The ability of a person in the process of active activity to adapt to changing environmental conditions is largely related to his creative potential. Creativity, like other physical and mental personality traits, has its own genetic base, which has not been sufficiently studied to date. Certain genes involved in this process are regularly described. The search for an association with new candidate genes for the creative potential of practically healthy, young respondents selected for work in the extreme conditions of the North is extremely important in the selection of people for work and service in difficult conditions. AIM: Search for the correlation of candidate gene polymorphism and the psychological state of the examined. MATERIALS AND METHODS: The psychological block of the pilot study included determining the degree of creativity, as well as the degree of tension of key psychological defense mechanisms. All the techniques used within its framework are part of the standard psychodiagnostic tools that have been tested in domestic conditions. Genotyping was performed by real-time PCR, determining the corresponding alleles of candidate genes, and then the data were compared by the method of analysis of variance. RESULTS: As candidate genes, we selected the angiotensin-converting enzyme gene, the serotonin 2A receptor gene, the neurotrophic factor BDNF, and alpha-actinin-3. According to the literature, all these genes are associated with the ability to adapt and / or psychotic states, which suggests their possible connection with creativity. The most interesting results are associated with the polymorphism of the BDNF gene: respondents with the BDNF Val/Val genotype are characterized by the maximum level of creativity and the minimum level of intensity of basic psychological defenses and coping strategies by types of distancing, as well as seeking social support. On the contrary, their maximum level is associated with the Met/Met genotype. Thus, it has been reliably shown that optimal adaptation to extreme external conditions is most likely to be ensured genetically by the presence of the Val / Val genotype, and psychologically by enhanced use of creative ability. The respondents with the ACTN3 RX genotype (with increased cold resistance) are characterized by a minimum level of creativity, and those with the RR genotype its maximum level. It is also shown that respondents with the ACE DD genotype are characterized by a minimum level of creativity. There were no associations with creativity with the serotonin 2A receptor gene polymorphism. CONCLUSIONS: The totality of the results obtained as a result of this pilot study allows us to consider a systematic study of creative ability and its molecular biological correlates to be correct and constructive for the development of a fundamental problem of the interaction of molecular biological and psychological mechanisms that provide active adaptation, as well as very expedient for solving the complex. scientific and applied tasks for the selection and correction of the state of persons directed to work in special and / or extreme conditions.
Present-day state of the theory of genetic foundations of creative performance, primarily at the level of the dopaminergic, serotoninergic, and noradrenergic systems, as well as neuregulin 1 gene, arginine vasopressin receptor, and angiotensinogene, is briefly reviewed. Basic results of a pilot experiment, focused upon four candidate genes for inclusion into creativity studies, namely neurotrophic factor gene (BDNF), α-actinin-3 protein encoding gene (ACTN3), angiotensin-converting enzyme 1 (ACE1), and serotonin-2A receptor gene (5HTR2A), are presented. Strong correlations between high level of creativity, both verbal and figural, and both Val/Val BDNF genotype, and RR ACTN3 genotype, are demonstrated, along with its somewhat weaker correlation with II ACE genotype. Taking into account levels of activation of basic psychological defense mechanisms and stress coping strategies, proper for 22 practically normal Arctic dwellers, who were examined in the framework of our experiment, allowed to link these correlations to optimal adaptation abilities, and to prolonged life expectancy. Basing upon this result, plausibility of discerning between two facets of creativity, one being adaptive, another being non-adaptive, is discussed, the former concerned with primarily coping with life stress, the latter providing self-actualization. Interrelation between the inherited abilities and the acquired ones, forming subject matter of correspondingly genetic and creativity studies, is regarded as a representation of basic dichotomy between nature and culture.
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The Citation of “Evolution in Action” as Science 's 2005 Breakthrough of the Year confirms that evolution is the vibrant foundation for all biology. Its contributions to understanding infectious disease and genetics are widely recognized, but its full potential for use in medicine has yet to be
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I suggest that the extended maturation time of some regions of the human neocortex is the uniquely human factor which allows the development of language, creativity and madness. The genetic event or events which contribute to the long delay to final maturation occurred at or after the speciation of Homo sapiens sapiens. Neocortical growth may follow the previously detailed "balloon model", which suggests that intra- and subcortical myelin production during development physically stretches each local area of the cortex tangentially to the pial surface, thereby causing neuronal columns to become more disjoint and more functionally independent, thereby increasing the functional capacity of the area [Seldon HL. Does brain white matter growth expand the cortex like a balloon? Hypothesis and consequences. Laterality 2005;10(1):81-95]. This occurs in addition to Hebbian synaptic modeling. Therefore, the size and functional capacity of each cytoarchitectonic area of each individual adult neocortex are the outcomes of partly deterministic (e.g., genetic) and partly statistical growth processes with numerous factors including environmental stimuli and fatty acid content in diets. The possible functional capacity and variation among growth outcomes increase with the length of time allowed to "finalize" synaptic weights, myelination and other plastic processes. For example, acquisition of quite differing linguistic skills becomes possible only in Homo sapiens because of the extended, decades-long plasticity of temporal lobe areas; in contrast, tactile skills vary little among human races and cultures, or even among higher primates, because of the faster maturation of the somatomotor areas. Some of the statistically extreme variations of the neocortical growth processes lead to abnormal cognition and behavior called "madness" or "genius". This maturation hypothesis overcomes some problems with those based purely on fatty acid metabolism or on functional asymmetry (non-human species show functional asymmetry, but no language. Neanderthals had brains comparable in size and shape to ours, but failed to develop language or creativity). This hypothesis implies that the search for genetic factors should include those which influence the temporal regulation of neuronal and myelin growth, but it also allows the development of unusual creativity or madness as a statistical extreme in the absence of any deterministic factors. It has implications about our attitudes toward mental "disorders" and about potential approaches to treating some of them - for example, attempting communication and conditioning via those senses and cortical areas which show less variation and are less affected.
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Schizophrenia poses an evolutionary-genetic paradox because it exhibits strongly negative fitness effects and high heritability, yet it persists at a prevalence of approximately 1% across all human cultures. Recent theory has proposed a resolution: that genetic liability to schizophrenia has evolved as a secondary consequence of selection for human cognitive traits. This hypothesis predicts that genes increasing the risk of this disorder have been subject to positive selection in the evolutionary history of humans and other primates. We evaluated this prediction using tests for recent selective sweeps in human populations and maximum-likelihood tests for selection during primate evolution. Significant evidence for positive selection was evident using one or both methods for 28 of 76 genes demonstrated to mediate liability to schizophrenia, including DISC1, DTNBP1 and NRG1, which exhibit especially strong and well-replicated functional and genetic links to this disorder. Strong evidence of non-neutral, accelerated evolution was found for DISC1, particularly for exon 2, the only coding region within the schizophrenia-associated haplotype. Additionally, genes associated with schizophrenia exhibited a statistically significant enrichment in their signals of positive selection in HapMap and PAML analyses of evolution along the human lineage, when compared with a control set of genes involved in neuronal activities. The selective forces underlying adaptive evolution of these genes remain largely unknown, but these findings provide convergent evidence consistent with the hypothesis that schizophrenia represents, in part, a maladaptive by-product of adaptive changes during human evolution.
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Continued genome sequencing has fueled progress in statistical methods for understanding the action of natural selection at the molecular level. This article reviews various statistical techniques (and their applicability) for detecting adaptation events and the functional divergence of proteins. As large-scale automated studies become more frequent, they provide a useful resource for generating biological null hypotheses for further experimental and statistical testing. Furthermore, they shed light on typical patterns of lineage-specific evolution of organisms, on the functional and structural evolution of protein families and on the interplay between the two. More complex models are being developed to better reflect the underlying biological and chemical processes and to complement simpler statistical models. Linking molecular processes to their statistical signatures in genomes can be demanding, and the proper application of statistical models is discussed.
Why are genetic polymorphisms related to severe mental disorders retained in the gene pool of a population? A possible answer is that these genetic variations may have a positive impact on psychological functions. Here, I show that a biologically relevant polymorphism of the promoter region of the neuregulin 1 gene (SNP8NRG243177/rs6994992) is associated with creativity in people with high intellectual and academic performance. Intriguingly, the highest creative achievements and creative-thinking scores were found in people who carried the T/T genotype, which was previously shown to be related to psychosis risk and altered prefrontal activation.
Schizophrenia is a highly debilitating mental disorder that affects approximately 1% of the general population, yet it continues to be poorly understood. Recent studies have identified variations in several genes that are associated with this disorder in diverse populations, including those that encode neuregulin 1 (NRG1) and its receptor ErbB4. The past few years have witnessed exciting progress in our knowledge of NRG1 and ErbB4 functions and the biological basis of the increased risk for schizophrenia that is potentially conferred by polymorphisms in the two genes. An improved understanding of the mechanisms by which altered function of NRG1 and ErbB4 contributes to schizophrenia might eventually lead to the development of more effective therapeutics.
Crespi & Badcock (C&B) have presented a novel view that the influence of genomic imprinting causes diametrically opposite disorders: namely, psychoses and autism. I propose an extended hypothesis that while genomic imprinting is likely to have an influence on the pathogenesis of psychoses and autism, it might contribute to phenomenological antithesis between as well as within these disorders.
Adaptive evolutionary studies of genes underlying psychiatric disorders
  • S V Kalmady
Kalmady SV. Adaptive evolutionary studies of genes underlying psychiatric disorders. Department of Biotechnology. Manipal: Manipal University; 2008. p. 80