Is there an association between NPY and neuroticism?

Cotton, Colleen; Flint, Jonathan; Campbell, T. G.

doi:10.1038/nature07927

Cited by 14 publications

(11 citation statements)

References 6 publications

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“…21, 22, 23, 24, 25, 26, 27 Candidate studies have reported associations with markers within several genes, 28, 29, 30, 31, 32 but again, replication generally failed. 33, 34, 35 To date, a number of genome-wide association studies (GWAS) for higher-order personality traits have been published. 36, 37, 38, 39, 40 None of them, however, has reported genome-wide significant associations between neuroticism/extraversion and markers.…”

Section: Introductionmentioning

confidence: 99%

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

et al. 2012

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The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<∼2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ∼12 000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e.=0.03) for neuroticism and 0.12 (s.e.=0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ∼45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called ‘missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors.

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Section: Introductionmentioning

confidence: 99%

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

et al. 2012

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“…Indeed, it has been suggested that polymorphisms in the NPY gene predict individual differences in stress response and emotionality. Thus, genetically induced lower NPY expression may result in higher emotion-induced activation of the amygdala (Zhou et al, 2008, but see also Cotton et al, 2009), development of major depression (Mickey et al, 2011), as well as lower NPY plasma levels (Xu et al, 2012, but see also Nishi et al, 2014). Furthermore, a functional NPY variation was suggested to cause lower NPY mRNA expression in the amygdala and reduced cerebrospinal fluid (CSF)-NPY A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 9 levels in higher primates exposed to aversive situations (Lindell et al, 2010).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The role of Neuropeptide Y in fear conditioning and extinction

et al. 2016

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While anxiety disorders are the brain disorders with the highest prevalence and constitute a major burden for society, a considerable number of affected people are still treated insufficiently. Thus, in an attempt to identify potential new anxiolytic drug targets, neuropeptides have gained considerable attention in recent years. Compared to classical neurotransmitters they often have a regionally restricted distribution and may bind to several distinct receptor subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically concentrated in limbic brain areas and signals via at least 5 different G-protein-coupled receptors. It is involved in a variety of physiological processes including the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing property of NPY is supported by many preclinical studies. Whether NPY may also interact with processing of learned fear and fear extinction is comparatively unknown. However, this has considerable relevance since pathological, inappropriate and generalized fear expression and impaired fear extinction are hallmarks of human post-traumatic stress disorder and a major reason for its treatment-resistance. Recent evidence from different laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was also observed in Y1 receptor knockout mice, other Y receptors may be equally important. By acting on Y2 receptors, NPY promotes fear extinction and generates a long-term suppression of fear, two important preconditions that could support cognitive behavioral therapies in human patients. A similar effect has been demonstrated for the closely related pancreatic polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular by activation of Y1 and Y2 receptors in the basolateral and central amygdala, respectively. In the basolateral amygdala, NPY signaling activates inhibitory G protein-coupled inwardly-rectifying potassium channels or suppresses hyperpolarization-induced I(h) currents in a Y1 receptor-dependent fashion, favoring a general suppression of neuronal activity. A more complex situation has been described for the central extended amygdala, where NPY reduces the frequency of inhibitory and excitatory postsynaptic currents. In particular the inhibition of long-range central amygdala output neurons may result in a Y2 receptor-dependent suppression of fear. The role of NPY in processes of learned fear and fear extinction is, however, only beginning to emerge, and multiple questions regarding the relevance of endogenous NPY and different receptor subtypes remain elusive. Y2 receptors may be of particular interest for future studies, since they are the most prominent Y receptor subtype in the human brain and thus among the most promising therapeutic drug targets when translating preclinical evidence to potential new therapies for human anxiety disorders.

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“…In a genome-wide study of US-based and German samples, van den Oord [28] found association between neuroticism and four SNPs in the chr 14 gene MAMDC1 (combined p <10 −6 ). To date, the most recent association study [29] failed to replicate an association between the candidate gene NPY and stress response and emotion (reported by Zhou [30], using instruments other than the EPQ).…”

Section: Introductionmentioning

confidence: 99%

A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

et al. 2010

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Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10−6) and GPC6 showed suggestive evidence for interaction with age (p≈10−7). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.

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Is there an association between NPY and neuroticism?

Cited by 14 publications

References 6 publications

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

The role of Neuropeptide Y in fear conditioning and extinction

A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

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