Review article
Toward a molecular architecture of personality

https://doi.org/10.1016/S0166-4328(02)00267-XGet rights and content

Abstract

Epidemiological studies provided a large body of evidence that personality dimensions are influenced by genetic factors and that the genetic component is highly complex, polygenic, and epistatic. However, consistent findings on the genetic basis of personality have yet remained sparse. In recent years, molecular genetics has begun to identify specific genes coding in particular for components of the serotonergic and dopaminergic neurotransmitter systems representing quantitative trait loci (QTLs) for behavioral traits. The QTL concept suggests that complex traits are not attributable to single genes. According to this polygenic model, the genetic basis of personality and behavior and its pathological variations thus results from additive or nonadditive interactions of various genes. As the number of suitable candidate genes constantly increases, the QTL model provides a reasonable explanation for the genetic basis of personality and its disorders. In this review, the current knowledge on the impact of a large number of candidate gene polymorphisms (e.g. variations in serotonin and dopamine receptor and serotonin transporter genes) on personality and temperament is summarized. Additionally, investigations of gene–gene and gene–environment interactions in humans and animals, which currently intensify the identification of genes that underlie behavioral variations, are examined. The findings converge on the notion that a probabilistic rather than deterministic impact of genes on the expression of behavior will contribute to the demystification of behavioral disorders.

Introduction

Personality is generally defined as the characteristic manner and style of an individual's behavior and encompasses vigor, temper, and persistence of the resulting behavior [12]. Several models of human personality do exist, especially with respect to the ‘basic variables’ or behavioral dimensions which shape personality traits. Examples are the seminal models proposed by Eysenck (measured by Eysenck's Personality Questionnaire EPQ), Cloninger (which involves three basic dimensions, measured by the Tridimensional Personality Questionnaire TPQ; [31]) and McCosta and Crae; the latter concept involves five basic dimensions dubbed the ‘Big Five’ and is quantified using the NEO-PI-R questionnaire [42]. Several other rating scales and models do exist, with varying importance and impact; however, there is considerable agreement between different personality measurements used [51].

Human personality is shaped by both genetic factors as well as environmental influences, and the proportion between both varies for different traits, with some traits having a substantial genetic impact, whilst others are influenced more by environment [146]. The apparent heterogeneity of both genetic and environmental determinants predicts the ineffectiveness of searching for unitary causes, so that dimensional and quantitative approaches to personality and behavioral genetics were increasingly applied in the recent years. While quantitative genetics has focused on complex, quantitatively distributed traits caused by multiple genetic and environmental factors, molecular genetics has begun to identify specific genes for quantitative traits, called quantitative trait loci (QTLs) [63]. In this polygenic model, behavior and personality are dissected into several dimensional traits determined by various genes which interact either additively or nonadditively.

This review discusses the current knowledge on the molecular basis of personality, its variations and disorders and focuses on topics undergoing particularly rapid progress. Since they play a critical role in the appraisal of empirical findings in behavioral genetics, conceptual and methodological issues related to the search for candidate genes will also be considered.

Section snippets

Personality disorders: distinct categories or dimensions of human behavior?

‘Personality disorder’ (PD) is an umbrella term covering various conditions characterized by a persistent pattern of abnormal behavior, social dysfunctioning, and suffering of either the individual and/or the environment. Despite problems of classification, epidemiological research involving family, twin, and adoptee studies has accrued persuasive evidence that several categories of PD are influenced by genetic factors and that the genetic component is highly complex, polygenic, and epistatic

The genetic dissection of personality

Human personality, apart from environmental influences, is a multi-gene product. Behavioral traits are polygenic, so that classical genome-wide linkage analyses fail to detect the genes accounting for personality traits. Accordingly, there are only a few studies employing this technique in personality genetics, and they were conducted in alcoholics which restricts the findings. A study derived from the Collaborative Study on the Genetics of Alcoholism data set indicated that the TPQ trait NS

Candidate genes for personality

A hypothesis-driven and hence powerful complementary approach to quantitative genetic studies are investigations whether certain candidate genes are involved in the manifestation of a specific phenotype. Psychobiology meanwhile has accrued thorough knowledge of neurotransmitter networks, and consequently the first candidate genes investigated were components of the monoamine neurotransmitter pathways. Almost no information is yet available on the role of constituents of messenger pathways or

Gene–gene interaction

Since human behavior is influenced by additive and nonadditive interactions of many different genes, the dissection of gene–gene interaction (i.e. epistasis) is a pertinent and exciting avenue of behavioral research. As it seems to be essential to control for environmental factors, recent studies have focussed on the neonatal period, when environmental influences may be minimal. Ebstein et al. investigated the behavioral effects of the DRD4-nR and of 5HTTLPR in 2 week-old neonates [57]. In

Outlook

The integration of novel genetic tools and technologies will further empower gene identification and functional studies in behavioral genetics. Several refined concepts and caveats should be adopted to ensure meaningful findings. First, future studies will require extended, homogeneous, and ethnically matched samples in conjunction with family-based designs with controlled genomic background [7], [149]. Second, more functionally relevant polymorphisms need to be identified and investigated in

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