The investigation of the biological bases of personality has been an object of study for a long time. Specifically, inter-individual variations in personality traits have been considered highly heritable and therefore associated with the action of specific neurotransmitters which are, in turn, regulated by a biological constellation of genes and their polymorphic variants (Cloninger et al. Reference Cloninger, Przybeck, Svrakic and Wetzel1994). Although there is a variety of questionnaires used for exploring the personality's profile of individuals, the Temperament and Character Inventory (Cloninger et al. Reference Cloninger, Przybeck, Svrakic and Wetzel1994) is the most widely used and validated scale employed for identifying the biological underpinning of personality (Comings et al. Reference Comings, Gade-Andavolu, Gonzalez, Wu, Muhleman and Blake2000; Brändström et al. Reference Brändström, Richter and Przybeck2001). This psychobiological model of personality identified seven clusters that can be subdivided in four dimensions of temperament – Harm Avoidance, Novelty Seeking, Reward Dependence and Persistence – and three dimensions of character – Self-Directedness, Cooperativeness and Self-Transcendence. Cloninger's theory of the inter-relation between neurotransmitters and personality traits has opened a new field of investigation exploring the impact of specific genetic polymorphisms on personality and therefore on human behaviour. So far, the research in this field explored the effect of the (1) dopamine, linked to Novelty Seeking and with the ‘system of behavioural activation’; (2) serotonin, related to Harm Avoidance and with the ‘system of behavioural inhibition’; and (3) noradrenalin, associated with Reward Dependence (Comings et al. Reference Comings, Gade-Andavolu, Gonzalez, Wu, Muhleman and Blake2000). The majority of personality genetics studies based their investigation on the impact of genetic polymorphisms known to regulate the action of serotonin transporter (5-HTT) and dopamine's receptors (DRD2 and DRD4) in both patients and healthy subjects. Therefore, we here specifically focus on serotonin and dopamine.

The 5-HTT is a functional polymorphism within the promoter sequence of the serotonin transporter gene and it is involved in a variety of processes, including impulsivity, suicidal ideation, mood and anxiety. Moreover, the presence of the short allele of this polymorphism (s-allele) was associated with major depression, anxiety and schizophrenia (Kuzelova et al. Reference Kuzelova, Ptacek and Macek2010). Similarly, the DRD2 and DRD4 are functional polymorphisms that regulate the expression of the dopamine D2 and D4 receptors, which are important in modulating reward, locomotion and learning. The low-frequent alleles within these polymorphisms are also linked to schizophrenia, depression and drug addiction (Missale et al. Reference Missale, Nash, Robinson, Jaber and Caron1998). However, although the effects of these genes on psychopathology have been explored, there is not a general consensus about the strength and nature of the relationship between the serotonin and dopamine activity and personality traits in healthy subjects.

The importance of studying the role of genetic variants on human personality is evident especially because it might inform us on the traits that are more predictive of risk of psychiatric illnesses. With regard to the 5-HTT polymorphism, the majority of the studies on healthy subjects found significant associations with anxiety-traits, such as Harm Avoidance (Van Gestel & Van Broeckhoven, Reference Van Gestel and Van Broeckhoven2003). These findings are in line with the neurobiological basis of depression and anxiety which has been linked to the mechanism of action of serotonergic antidepressant medications. The first study that paved the way for the identification of the association between serotonin and personality traits was published in 1996 by Lesch et al. showing that carriers of the short allele of the 5-HTT polymorphism had higher Harm Avoidance. On the other hand, the DRD2 and DRD4 polymorphisms have been found to be associated with Novelty Seeking, which is linked with exploratory excitability and impulsivity (Ebstein et al. Reference Ebstein, Novick, Umansky, Priel, Osher and Blaine1996; Noble et al. Reference Noble, Ozkaragoz, Ritchie, Zhang, Belin and Sparkes1998) (see Table 1 for a selection of studies exploring the association between the serotonin and dopamine neurotransmitters and personality). This association is consistent with previous findings which reported the role of the dopamine in mediating exploratory behaviours in animal models as well as in emotion and cognition (Benjamin et al. Reference Benjamin, Li, Patterson, Greenberg, Murphy and Hamer1996). Interestingly, a recent review also reported a significant association between dopamine and the schizophrenia spectrum, including the schizotypal personality disorder (Mohr & Ettinger, Reference Mohr and Ettinger2014). This evidence further supports the importance of exploring the neurobiological bases not only of severe chronic disorders, but also of psychiatric spectra which include personality disorders as well as subjects with increased genetic and clinical risk for a specific illness. However, it is important to highlight the existence of some negative studies which found no association with these personality dimensions (Herbst et al. Reference Herbst, Zonderman, McCrae and Costa2000; Gebhardt et al. Reference Gebhardt, Leisch, Schüssler, Fuchs, Stompe, Sieghart, Hornik, Kasper and Aschauer2004) as well as studies reporting contrasting results, with the same genetic variant associated with higher and lower scores in the same personality scale (van Gestel & Van Broeckhoven, Reference Van Gestel and Van Broeckhoven2003). In addition, there is increase evidence of the association between the 5-HTT and DRD2/DRD4 polymorphisms with character dimensions which, according to Cloninger's Theory, are acquired during the development through socio-cultural learning and not as genetically determined as the temperament dimensions (Cloninger et al. Reference Cloninger, Przybeck, Svrakic and Wetzel1994). Studies from different cultural populations reported that healthy subjects carriers of the short allele within the 5-HTT showed lower scores in all the Cloninger's character dimensions, including Self-Transcendence (Ham et al. Reference Ham, Kim, Choi, Cha, Choi and Lee2004), Self-Directedness (Gonda et al. Reference Gonda, Fountoulakis, Juhasz, Rihmer, Lazary, Laszik, Akiskal and Bagdy2009; Saiz et al. Reference Saiz, Garcia-Portilla, Herrero, Arango, Corcoran, Morales, Bascarán, Alvarez, Coto, Paredes, Fernández and Bobes2010; Calati et al. Reference Calati, Signorelli, Gressier, Bianchini, Porcelli, Comings, De Girolamo, Aguglia, MacMurray and Serretti2014) and Cooperativeness (Pełka-Wysiecka et al. Reference Pełka-Wysiecka, Ziętek, Grzywacz, Kucharska-Mazur, Bienkowski and Samochowiec2012). Similarly, for the DRD2 polymorphism, Tsuchimine et al. (Reference Tsuchimine, Yasui-Furukori, Sasaki, Kaneda, Sugawara, Yoshida and Kaneko2012) found that the less frequent allele was associated with significant lower scores in the Self-Directedness scale (Table 1). This biological evidence further supports the findings from independent twin studies, which supported a similar heritability for temperament and character dimensions (Al-Halabí et al. Reference Al-Halabí, Herrero, Sáiz, García-Portilla, Errasti and Corcoran2011; Brambilla et al. Reference Brambilla, Fagnani, Cecchetto, Medda, Bellani, Salemi, Picardi and Stazi2014; Picardi et al. Reference Picardi, Fagnani, Medda, Toccaceli, Brambilla and Stazi2015).

Table 1. Selection of studies investigating the association between serotonin and dopamine neurotransmitters and personality in healthy subjects

In conclusion, these findings point to two new avenues of enquiry in relation to personality traits. First, the results from the personality genetics studies, together with previous evidence from family and twin studies reporting heritability estimates of personality traits, further suggest that genes play a greater role in shaping all aspects of personality, including both character and temperament dimensions. Second, although the study of specific candidate genes brought compelling findings, the lack of consistency underscores the need for a more detailed examination of the role of genetic variants on personality traits. Indeed, the success of the future genetics personality research in identifying genetic factors might be linked to (a) the employment of larger sample size which may overcome the limitations of the current studies characterised by small sample size and therefore with low explanatory power; (b) the investigation of multiple genetic variants, especially because complex traits are characterised by pleiotropy and polygeneity (Plomin et al. & Deary, Reference Plomin and Deary2015); and (c) the differentiation of the sample according to the age and sex of the participants which have been reported to significantly influence personality scales (Fresán et al. Reference Fresán, Robles-García, López-Avila and Cloninger2011).