Genetic Correlates

Research has also begun to focus on associations between genetic polymorphisms and personality traits. These polymorphisms may be either functional (i.e., they may encode for a specific protein) or not. Cloninger has developed a theory that explicitly links biogenic amine function with personality traits (Cloninger, 1987). In the first version of this theory, which included only putatively "temperamental" traits, Cloninger hypothesized that a trait called novelty seeking would be related to dopaminergic function, a trait called harm avoidance would be related to serotonergic function, and a trait called reward dependence would be related to noradrenergic function. Cloninger and colleagues also developed a questionnaire to measures these three constructs called the Tridimensional Personality Questionnaire (TPQ). An initial study reporting an association between a polymorphism of the dopamine 4 receptor gene (DRD4) and individual differences in a combination of high NEO-PIR extraversion and low conscientiousness (both purported to index aspects of TPQ novelty seeking) appeared to support this theory (Ebstein et al., 1996). While a meta-analysis of follow-up studies revealed a subsequent failure to replicate this particular association, it did suggest some evidence for an association of a different functional polymorphism in the upstream promoter region of the DRD4 gene (C-521T) with TPQ novelty seeking (Schinka et al., 2002).

Unfortunately, no studies have psychometrically related Cloninger's TPQ traits to those measured by either the NEO-PI-R or to the DAPP-BQ. This may be partially due to the fact that both Cloninger's theory and measures have since undergone at least two major revisions, expanding from three to four and then six traits in the process. However, accumulating evidence does appear to suggest a second set of relationships between NEO-PIR neuroticism as well as possibly disagreeableness and a functional polymorphism of a gene that regulates the expression of the serotonin reuptake mechanism (5-HTTLPR) (Lesch et al., 1996; Murphy et al., 2001).

While these initial findings are intriguing, biogenic amine function is complex and necessarily includes many physiological processes including gene expression, intracel-lular signaling, manufacture and release of neurotransmitters, changes in the number and affinity of postsynaptic receptors, and enzymatic breakdown or reuptake of released neurotransmitter. Different genetic polymorphisms could affect any or all of these steps, and many other polymorphisms remain to be examined. Additionally, currently popular statistical methods primarily deal with single-nucleotide polymorphisms (SNPs) or point mutations and are only beginning to address multivariate interactions such as multiple loci and gene-gene interactions, which must play important roles in generating complex phenotypes such as personality traits (Cloninger et al., 1998). Further, other neural systems besides the biogenic amines (e.g., amino acids, neuropeptides) undoubtedly play important roles in the expression of trait phenotypes. The present gap between heritability estimates for personality traits (~50 percent) and SNP effect sizes (~1 to 3 percent) may seem puzzling but may also indicate that exciting discoveries lie ahead.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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