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Oxytonergic circuitry sustains and enables creative cognition in humans.

ABSTRACT: Creativity enables humans to adapt flexibly to changing circumstances, to manage complex social relations and to survive and prosper through social, technological and medical innovations. In humans, chronic, trait-based as well as temporary, state-based approach orientation has been linked to increased capacity for divergent rather than convergent thinking, to more global and holistic processing styles and to more original ideation and creative problem solving. Here, we link creative cognition to oxytocin, a hypothalamic neuropeptide known to up-regulate approach orientation in both animals and humans. Study 1 (N = 492) showed that plasma oxytocin predicts novelty-seeking temperament. Study 2 (N = 110) revealed that genotype differences in a polymorphism in the oxytocin receptor gene rs1042778 predicted creative ideation, with GG/GT-carriers being more original than TT-carriers. Using double-blind placebo-controlled between-subjects designs, Studies 3-6 (N = 191) finally showed that intranasal oxytocin (vs matching placebo) reduced analytical reasoning, and increased holistic processing, divergent thinking and creative performance. We conclude that the oxytonergic circuitry sustains and enables the day-to-day creativity humans need for survival and prosperity and discuss implications.

SUBMITTER: De Dreu CK

PROVIDER: S-EPMC4127019 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Oxytonergic circuitry sustains and enables creative cognition in humans.

De Dreu Carsten K W CK Baas Matthijs M Roskes Marieke M Sligte Daniel J DJ Ebstein Richard P RP Chew Soo Hong SH Tong Terry T Jiang Yushi Y Mayseless Naama N Shamay-Tsoory Simone G SG

Social cognitive and affective neuroscience 20130716 8

Creativity enables humans to adapt flexibly to changing circumstances, to manage complex social relations and to survive and prosper through social, technological and medical innovations. In humans, chronic, trait-based as well as temporary, state-based approach orientation has been linked to increased capacity for divergent rather than convergent thinking, to more global and holistic processing styles and to more original ideation and creative problem solving. Here, we link creative cognition t ...[more]

PMID: 23863476

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Project description:BackgroundGenomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive.MethodsWe examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR-Cas9 genome editing in samples from patients.ResultsOur data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR-Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7.ConclusionsOur results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects. (Funded by the German Research Center for Environmental Health and others.).

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Oxytonergic circuitry sustains and enables creative cognition in humans.

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Oxytonergic circuitry sustains and enables creative cognition in humans.

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