ژنتیک مولکولی کمرویی و پرخاشگری در کودکان پیش دبستانی
|کد مقاله||سال انتشار||تعداد صفحات مقاله انگلیسی||ترجمه فارسی|
|33203||2002||12 صفحه PDF||سفارش دهید|
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Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Personality and Individual Differences, Volume 33, Issue 2, 19 July 2002, Pages 227–238
Associations between three candidate gene polymorphisms [dopamine D4 receptor (DRD4), serotonin transporter (5-HTT), and serotonin 2C receptor (5-HT2C)] with shy and aggression-related behaviors derived from maternal report and peer play at age four were examined. We noted a significant association of the DRD4 receptor gene with maternal report of problems with aggression at age four. Children with long versus short repeat alleles of the DRD4 gene were reported by their mothers to have significantly more problems with aggression at age four. There were no significant associations of the DRD4 gene with observed behavioral measures of aggression at age four. There were, in addition, no significant associations of either of the serotonin genes with any of the maternal report and observed behavioral measures. The present study extends earlier findings of adults to the preschool years and appears to be the first large scale investigation to examine the molecular genetics of preschoolers’ temperament using behavioral and maternal report measures in normal childhood development.
The notion that there may be a genetic basis to individual differences in temperament is an idea that dates from the time of the early Greeks and extends to contemporary personality research. Much of the scientific support for this concept is derived from three disparate literatures (Eley & Plomin, 1997), two of which have been reliable and convincing sources for years and a third which has emerged only within the last decade. The first literature involves studies of domesticated and laboratory animals in which there is strong evidence in support of a genetic basis to temperament. For example, it has long been noted that inbred strains of animals can be produced that are highly fearful, defensive, aggressive, or subdued (see Plomin, DeFries, McClearn, & Rutter, 1997 for a review). A second body of work concerns findings derived from behavioral genetics studies of human twins. Such studies often find that monozygotic twins, raised either apart or together, appear temperamentally more similar than dizygotic twins and adopted children (see Plomin, 1989 for a review). A third source concerns recent findings from the rapidly emerging field of the molecular genetics of human personality (see Cloninger et al., 1996, Hamer and Copeland, 1998 and Plomin and Rutter, 1998 for reviews). These studies, mostly involving human adults, have found associations between complex human behavioral traits and genes that regulate specific neurochemical systems. Overall, these three sources are beginning to converge to provide the strongest evidence to date that there may be a genetic etiology underlying some complex human personality traits. The purpose of the present study was to explore whether there may be a molecular genetic basis to individual differences in childhood temperament as manifested through shy and aggressive social behaviors. We have been following four separate cohorts of children who have been participating in a larger longitudinal study on socio-emotional development. To date, we have found a number of reliable findings. Individual differences in certain patterns of infant temperament, which appear early in life, are modestly predictive of social interactive behaviors in the preschool years. For example, Fox and his colleagues (Calkins et al., 1996 and Fox et al., 2001) have described two groups of infants who appear to reflect distinct temperamental types. One group of infants are highly reactive and exhibit a high degree of distress to the presentation of novel auditory and visual stimuli at 4 months of age. These infants are likely to display behavioral inhibition at 14 (Calkins et al., 1996) and 24 months (Fox, Calkins, & Bell, 1994) and social reticence to unfamiliar peers at 48 months (Fox et al., 2001), and are reported by their mother as contemporaneously shy at age four (Schmidt et al., 1997). A similar set of findings has been reported by Kagan and his colleagues (Kagan & Snidman, 1991). These infants also exhibit a distinct pattern of psychophysiological activity, including heightened fear-potentiated startle responses at age 9 months (Schmidt & Fox, 1998) and greater right frontal EEG asymmetry at 9 (Calkins et al., 1996), 14, and 48 months of age (Fox et al., 2001) and may be at risk for anxiety-related problems during the early school age years (e.g. Fox et al., 1996, Hirshfeld et al., 1992 and Schmidt et al., 1999). A second group of infants exhibit a high degree of motor arousal and positive affect to novel auditory and visual stimuli at 4 months. These infants display low levels of uncertainty, fear in response to novelty or discrepancy at 14 and 24 months of age, and are socially interactive and engaging as preschool children. Interestingly, they display, as a group, a good deal of continuity across the early childhood years. No children in this group were identified as fearful or inhibited or socially reticent at 4 years of age and few children were in the average range. Most remained high in novelty seeking and low in fear across the 4 years of the longitudinal study. This group, Fox (Fox et al., 2001) calls exuberant, also displayed consistent patterns of left frontal EEG asymmetry at 9, 14, and 48 months of age. Our study of the molecular genetics of child temperament and social behavior focuses on candidate genes involved in signaling by dopamine and serotonin, two key neurotransmitters that have previously been implicated in individual differences in personality in adults. The dopamine D4 receptor gene (D4DR), which contains a functional repeated sequence polymorphism within its coding sequences, was originally studied for its role in personality traits related to novelty seeking. The initial two studies (Benjamin et al., 1996 and Ebstein et al., 1996) found that adults with longer versions (6–8 repeats) self-reported higher novelty seeking scores compared with adults with shorter versions (2–5 repeats) of the coding sequence polymorphism. Dopamine has been implicated as a major neuromodulator of novelty seeking because of the role it plays in inducing euphoria in humans and approach behavior in animals (Cloninger, 1987). The shorter alleles code for a receptor that is apparently more efficient in binding dopamine compared with the larger alleles (see Plomin & Rutter, 1998, for a review). Subsequently, the association between the DRD4 polymorphism and novelty seeking has been replicated in some populations (Ebstein et al., 1997, Noble et al., 1998, Ono et al., 1997, Strobel et al., 1999 and Tomitaka et al., 1999); however, several other studies have found either no association (Gelernter et al., 1997, Goldman et al., 1996, Jonsson et al., 1997, Pogue-Geile et al., 1998, Sander et al., 1997, Sullivan et al., 1998 and Vandenbergh et al., 1997) or association in the “wrong” direction relative to the initial reports (Malhotra, Virkkunen, Rooney, Eggert, Linnoilia, & Goldman, 1996). The serotonin transporter gene was chosen as the second candidate locus for this study because of its role in anxiety-related personality traits in adults. Lesch et al. (1996) reported that adults carrying one or two copies of a short allele of a regulatory DNA sequence polymorphism in the serotonin transporter gene (5-HTTLPR) self-reported higher levels of neuroticism, anxiety, and depression compared with individuals homozygous for the long allele of this polymorphism. In vitro and in vivo expression studies have shown that the short allele leads to less gene transcription and protein production than does the long allele (Greenberg et al., 1999, Heils et al., 1996, Lesch et al., 1996 and Little et al., 1998). Moreover, serotonin has been implicated as a major neurotransmitter of anxiety and withdrawal because of its effects on regulating mood and emotional states (see Westernberg, Murphy, & Den Boer, 1996, for a review). Subsequently, the association between the serotonin transporter gene and anxiety-related states has been replicated in populations in the United States, Europe, Israel, and Japan, (e.g. see Greenberg et al., 1999, and references therein), but other studies have failed to find any association (Ball et al., 1997, Deary et al., 1999 and Kumakiri et al., 1999). We also examined a serotonin receptor gene (5-HT2C; Lappalainen et al., 1995). Ebstein and his colleagues (Ebstein, Segman, Benjamin, Osher, Nemanov, & Belmaker, 1997) found association of a cysteine to serine coding sequence polymorphism in this gene with the personality trait of reward dependence, especially in individuals with a long DRD4 genotype, and this result has been partially replicated (Kuhn, Meyer, Nothen, Gansicke, Papassotiropoulos, & Maier, 1999). The 5-HT2C coding sequence change does not appear to alter the response of the receptor to its ligand (Lappalainen et al., 1995) and thus the mechanism of its postulated role in personality is unclear. All of the studies described earlier were based on personality data derived from self-report measures. To our knowledge, there have been no studies which have examined links between gene markers and social behavior determined by direct, systematic observation. The current study was an attempt to provide those data by utilizing individual differences in observed social behavior. In particular, we collected DNA samples from children from whom we had previously examined behavioral responses during play groups with unfamiliar same-age and-gender peers as well as maternal report of behavioral problems at age four. We examined the association of the DRD4 and two 5-HT-related genes with children’s social behaviors at age four via observed behavior and maternal report. The strongest evidence that exists to date has implicated the DRD4 and 5-HT-related genes as playing some role in complex human traits. We chose to examine approach- (e.g. aggression) and avoidance- (shyness) related behaviors because these two overarching behavioral styles are analogous to those reported in the adult personality literature for which a genetic association has been reported. We predicted that children with long versus short allele repeats of the DRD4 receptor gene would be rated by their mothers as having more problems with aggression and would exhibit more observed disruptive behaviors during peer play at age four; the phenotypic expression of these behaviors at this age is conceptually linked to novelty seeking-related behaviors (i.e. an inability to regulate socially appropriate responses) in adults for which the DRD4 has been implicated. We also predicted that children with short versus long genotypes of the 5-HTT transporter gene and the Ser23 versus Cys23 allele of the 5-HT2C receptor gene would be rated by their mothers as having more problems with social adjustment and would exhibit more observed shyness during peer play at age four; shyness is highly related to anxiety and neuroticism for which the serotonin system and serotonin genes have been implicated.