Indeed, studies directly linking the short allele of the serotonin transporter to behavior report very small effects, often accounting for only 3–4% of the variance ( Lesch et al., 1996).Įxperts in imaging genetics suggest that a promising approach in bridging the gap between gene variants with small effects and complex disorders is the use of endophenotypes ( Hariri, 2009). Thus, studies attempting to link a candidate gene often require very large sample sizes to detect an effect. It is likely that the effect is further diminished by the fact that the characteristics of many disorders, including psychopathy, exist on a continuum, whereas many commonly studied genetic polymorphisms are biallelic, resulting in only three possible conditions (e.g., ll, ls, ss). However, linking a single genetic polymorphism to a psychological disorder is often less practical, because psychological disorders are complex and are likely influenced by many genetic polymorphisms, as well as environmental factors ( Canli & Lesch, 2007), making the influence of one polymorphism very small. In most studies of psychological disorders, researchers are accustomed to establishing a direct association between the disorder and a particular phenomenon (e.g., depression and increased cortisol responses). Gene Variants, Endophenotypes, and Complex Disorders However, I would hypothesize that the L A version is most likely to be associated with increased risk for psychopathy.Ģ. Since many studies do not yet distinguish between the two versions of the long allele, I will focus only on the long/short distinction. However, recent research suggests that there is an additional A→G single nucleotide polymorphism within the long allele, and that the L G version functions similarly to the short allele ( Hu et al., 2005 Zalsman et al., 2006). Based on the number of parallels between these findings and findings of psychopathy, I propose that the long allele of the serotonin transporter may confer risk for psychopathy.įunctionally, the short allele is associated with reduced transcriptional activity of the serotonin transporter (often termed ‘low-activity’) compared to the long allele ( Lesch et al., 1996). In this article, I reexamine the body of literature regarding the variants of the serotonin transporter, turning the focus to the long allele.

Psychopathy is a disorder characterized by reduced emotionality (e.g., shallow affect, fearlessness, callousness), abnormal interpersonal features (e.g., superficial charm, egocentricity, deceitfulness), and behavioral traits (e.g., impulsivity, risk-taking, aggressiveness) that lead to frequent engagement in antisocial behavior ( Hare, 2003). Many of these findings are very similar to findings observed in psychopathic individuals. Compared to carriers of the short allele (denoted here as ‘ s-carriers’), findings from individuals homozygous for the long allele (denoted here as ‘ l-homozygotes’) tend to reflect reduced stress reactivity and reduced emotional responding. While much attention has been paid to the risks associated with the short allele, findings regarding the long allele are rarely discussed. The presence of one or two short alleles has been linked to a number of intermediate endophenotypes, including increased stress hormone responses ( Way & Taylor, 2010) and increased amygdala responses to threatening stimuli ( Hariri et al., 2002), demonstrating the pathways by which this allele may confer risk. A growing body of research suggests that the short allele is associated with increased psychological sensitivity to stress, thus increasing risk for multiple mental health-related conditions, including depression, anxiety, suicide, and stress-related substance abuse ( Caspi et al., 2010).

A common polymorphism in the promoter region (5-HTTLPR) of this gene results in two variants: a short allele and a long allele. The human serotonin transporter gene ( SLC6A4) is considered the most investigated genetic variant in psychiatry, psychology, and neuroscience ( Caspi et al., 2010).

Parallels transporter