In a study of Lin and colleagues, they investigated a Taiwanese population of 87 anxiety-depression alcohol dependents and 46 pure alcohol dependents, to see whether the TaqIA polymorphism of the DRD2 gene is involved in TPQ novelty seeking and harm avoidance [23]. DRD2 TaqI A1(+) allele (A1/A1 or A1/A2 genotypes) was found to be associated with TPQ novelty seeking in anxiety-depression alcohol dependents [23].

Anxiety-depression alcohol dependence was defined as a genetically specific subtype of alcoholism [24]. Four homogeneous types of alcoholism have been suggested, including the depressed/anxious type, the chronic/severe type, the mildly affected type and the antisocial type [25]. Anxiety disorders represent one of the most common mental illnesses and are complex diseases with both genetic and environmental factors affecting their predisposition [26]. Recent data revealed that the genetic variant of the DRD2 gene was associated with anxiety-depression alcohol dependence [27].

In a Taiwanese population of antisocial personality disorder, 43 with alcoholism and 84 without alcoholism, Wu and colleagues examined the DRD2 gene and the SLC6A4 5-HTTLPR variant on TPQ novelty seeking [28]. They found evidence for an interaction between DRD2 TaqI A1+ (including A1/A1 or A1/A2) and 5-HTTLPR short/short genotype in the novelty seeking scores, and found significant difference in 5-HTTLPR polymorphisms between antisocial alcoholics and antisocial non-alcoholics after stratification of DRD2 TaqIA genotypes [28].

Antisocial personality disorder is a mental disorder defined by a pervasive pattern of deception, manipulation, disregard for the rights of others, and a lack of remorse for their behavior that begins in childhood or early adolescence [29]. Genetic studies showed evidence of genetic influences on personality disorder, such as antisocial personality disorders, borderline personality disorders, schizotypal personality disorders [30-32]. A recent study suggested that the possible interactions between the MAOA and DRD2 genes might be related to antisocial personality disorder with alcoholism among Taiwanese [33]. Future research should further investigate the contributions of the MAOA gene to personality traits in antisocial personality disorder with alcoholism.

Davis and colleagues compared participants with binge eating disorder (n = 56) to normal-weight (n = 59) and obese controls (n = 51) on reward sensitivity and genotyped six markers (TaqIA, −141C Ins/Del, −241A/G, Taq1D, C957T, and rs4648317) of the DRD2 dopamine receptor gene [34]. Two personality measures of reward sensitivity were employed, including the Behavioral Inhibition System/ Behavioral Activation System (BIS/BAS) Scales [35] and the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) [36]. They reported that binge eating disorder and obese participants had greater reward sensitivity than normal-weight controls, but only among those carrying the A1 allele of the TaqIA marker [34].

Binge eating disorder is a provisional eating disorder diagnosis, which core symptom is recurrent binge eating [37,38], and the episode requires consumption of an unusually large amount of food and a sense of being out of control. In addition, individuals with binge eating disorder do not regularly engage in compensatory behaviors. Recent studies suggested that the 5-HTTLPR [39] and ghrelin/obestatin prepropeptide (GHRL) [40] may contribute to the genetic susceptibility to the disorder. Future research should further investigate the contributions of the SLC6A4 and GHRL genes to personality traits in binge eating disorder.

In a study of 73 major depressive disorder and 134 bipolar disorder patients, Serretti and colleagues tested the hypothesis that the exon III variant in the DRD4 gene could influence personality traits in the patients of mood disorders [41]. Genotypes with the long repeat of DRD4 exon III polymorphism were marginally associated with low TCI harm avoidance [41].

Depression and bipolar disorder are the two major types of mood disorders, in which the emotional mood of a patient is distorted or inappropriate to the circumstances [42]. Owing to the fact that personality is itself a complex trait, its use as an endophenotype for genetic studies of bipolar disorder has certain limitations [43]. Newer hypotheses of depression neurobiology suggest an association of major depressive disorder with polymorphisms in the brain-derived neurotrophic factor (BDNF) gene [44]. Future research should further study the contributions of the BDNF gene to personality traits in major depressive disorder.

Based on a Caucasian sample of 111 patients with borderline personality disorder and 287 healthy controls, Ni and colleagues tested the association between the HTR2A gene and personality traits in borderline personality disorder [46]. Among four polymorphisms (rs6313, rs4941573, rs2296972, and rs6314) of the HTR2A gene, the C allele of rs6313 and the A allele of rs4941573 were found to be associated with a higher NEO-PI-R extraversion score, indicating that there were significant associations between the HTR2A gene and personality traits in the patients with borderline personality disorders [46].

Borderline personality disorder, which begins in early adulthood, is a chronic and severe mental disorder characterized by a pervasive pattern of instability in affect regulation, interpersonal relationships, self-image, and impulse control [47]. The SLC6A4 and MAOA genes have been suggested to be involved in the development of it [48]. A recent study demonstrated that there were gender differences in TCI novelty seeking in borderline personality disorder [49]. In future work, the contributions of the MAOA gene to personality traits in borderline personality disorder should be further investigated.

Serretti and colleagues [41] tested the uVNTR variant in the MAOA gene to see if it influences personality traits in the patients of mood disorders or not. The long MAOA allele was found to be associated with decreased TCI persistence scores among female patients [41].

In a study on German alcohol dependents (n = 368), Koller and colleagues [54] hypothesized that the 5-HTTLPR and VNTR variants of the SLC6A4 gene are associated with TCI harm avoidance. An association between short/12-repeat haplotype of SLC6A4 and low level of TCI harm avoidance was found [54]. Furthermore, no significant association was found between TCI harm avoidance and the SLC6A4 5-HTTLPR variant as well as between TCI harm avoidance and the SLC6A4 VNTR variant [54].

Conversely, in a study of 124 subjects seeking inpatient treatment for primary alcohol dependence, Wiesbeck and colleagues reported that the SLC6A4 5-HTTLPR variant was associated with TCI harm avoidance in the group [55]. The conflicting results between this work and the report [54] by Koller and colleagues may be due to the differences in sample sizes, different ethnicities, or different study designs. The studies conducted on small patient populations may also have biased a particular result.

Alcoholism is a chronic disease characterized by alcohol abuse despite recurrent adverse consequences [56]. Recent evidence supports genetic associations with alcoholism of the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene [57] and MAOA genes [27]. In future work, the contributions of the GRIN2A and MAOA genes to personality traits in alcohol dependence should be further tested.

Lin and colleagues [23] assessed whether the SLC6A4 5-HTTLPR variant is involved in TPQ novelty seeking and harm avoidance, and found that the short/short genotype of the SLC6A4 5-HTTLPR variant was associated with TPQ novelty seeking in anxiety-depression alcohol dependents [23].

Pascual and colleagues investigated the association between the SLC6A4 5-HTTLPR and VNTR polymorphisms and personality traits in their study of 65 patients with borderline personality disorder [58]. They reported that patients with long allele (long/short or long/long) in the 5-HTTLPR polymorphism of the SLC6A4 gene showed lower scores on the subscale of the ZKPQ liking of parties and friends [58]. Furthermore, patients with the allele with 10 repeat of the SLC6A4 VNTR polymorphism were found to show lower scores in the ZKPQ impulsivity, sensation seeking and in the subscale liking of parties and friends [58].

Monteleone and colleagues [59] tested whether the 5-HTTLPR polymorphism of the SLC6A4 gene is related to TCI harm avoidance or not. In 125 female Caucasian patients with bulimia nervosa and 94 healthy controls, they found that patients with bulimia nervosa carrying at least one copy of the short allele have significantly higher mean TCI harm avoidance score than those with the long/long genotype [59].

The TPH1 gene codes for tryptophan hydroxylase, the rate-determining enzyme in serotonin biosynthesis [60]. Likewise, Monteleone and colleagues [61] tested whether A218C polymorphism of the TPH1 gene is related to TCI harm avoidance. In their study of 180 female Caucasians (91 patients with bulimia nervosa and 89 healthy controls), they demonstrated that bulimic women with the AA genotype of the TPH1 gene exhibited a more severe binge eating behavior and higher TCI harm avoidance scores than those with CC genotype [61]. Together with the similar study [59] previously discussed, the findings of these two studies support the idea that the SLC6A4 5-HTTLPR polymorphism and the TPH1 A218C polymorphism are involved in predisposing bulimic patients to a more disturbed eating behavior and higher TCI harm avoidance [59,61].

Bulimia nervosa is an eating disorder characterized by recurrent binge eating, which is followed by compensatory behaviors, such as self-induced vomiting, fasting, and over-exercising [38,62]. A recent study revealed that the GHRL gene is associated with susceptibility to bulimia nervosa [63]. In future work, the contributions of the GHRL gene to personality traits in bulimia nervosa should be further assessed.

Internet addiction or excessive internet use is defined as uncontrollable and damaging use of the internet and has been compared to other addictions such as pathological gambling [64]. In a Korean population of 91 male adolescents with excessive internet use and 75 healthy controls, Lee and colleagues conducted group comparisons on the 5-HTTLPR polymorphism of the SLC6A4 gene with respect to TCI novelty seeking and harm avoidance [65]. It was found that participants with excessive internet use with 5-HTTLPR short/short genotype showed higher TCI harm avoidance scores than the ones with the other allele variants [65].

Serretti and colleagues [41] further tested the hypothesis that the variants in the SLC6A4 gene could influence personality traits in the patients of mood disorders. It was observed that the 5-HTTLPR short/short genotype frequency was associated with low TCI novelty seeking scores [41].

Furthermore, based on a sample of 251 participants, another study observed that EPQ neuroticism mediates the association between the SLC6A4 5-HTTLPR polymorphism and lifetime major depression [66].

Nicotine dependence is the physical vulnerability of human body to the chemical nicotine, which is a psychoactive ingredient in tobacco significantly contributing to the harmful tobacco smoking habit [67]. In a study of personality genetics, Kremer and colleagues recruited 244 smokers and examined the association of smoking with the 5-HTTLPR and VNTR polymorphisms of the SLC6A4 gene [68]. It was observed that there was a weak association between TPQ novelty seeking and the VNTR polymorphism as well as between TPQ reward dependence and the 5-HTTLPR polymorphism [68].

Recent studies have reported genetic associations with nicotine dependence of the following genes: BDNF [69,70], cholinergic receptor nicotinic alpha 4 (CHRNA4) [71-73], cannabinoid receptor 1 (CNR1) [74], neurexin 1 (NRXN1) [75], and neurotrophic tyrosine kinase receptor type 2 (NTRK2) [76]. In future work, the contributions of these genes to personality traits in nicotine dependence should be further examined.