Association between the Serotonin Transporter Gene (5-HTTLPR) and Anger-Related Traits in Korean Schizophrenic Patients

Department of Neuropsychiatry, Seoul-Paik Hospital, Inje University, Seoul, South Korea.
Neuropsychobiology (Impact Factor: 2.26). 06/2009; 59(3):165-71. DOI: 10.1159/000218079
Source: PubMed


The serotonin transporter-linked polymorphic region (5-HTTLPR) short allele confers a general sensitivity to environmental stimuli, and anger is suspected to have a direct influence on aggressive behavior in schizophrenia. In the present study, we investigated whether the 5-HTTLPR gene was associated with aggression and/or anger-related traits in schizophrenia.
A total of 103 schizophrenic patients, including 46 aggressive and 57 nonaggressive patients, were recruited from psychiatric hospitals in Korea. All of the aggressive patients had committed at least 2 significant violent acts requiring repeated confinement in each of the 2 weeks preceding study inclusion, as well as 2 or more serious assaults on others. Blood samples were collected from all patients for 5-HTTLPR genotyping, and all patients underwent clinical assessments for symptoms of schizophrenia, aggressive behavior and anger-related traits.
There was no significant difference in the distribution of the 5-HTTLPR genotype/alleles between the aggressive and nonaggressive patients. Aggressive patients carrying the s allele exhibited more anger-related traits than those with the l/l homozygotes, but this difference was not significant after correction for multiple testing. Furthermore, there was a dose-dependent relationship between the s allele and high angry temperament subscale scores in the aggressive patients.
These findings seem to support the idea that 5-HTTLPR predisposes aggressive patients to exhibit more anger-related traits, though they do not support the existence of a direct association between 5-HTTLPR and aggressive behavior in schizophrenia in the Korean population; however, larger studies are needed.

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    • "On the other hand, the LL genotype was also significantly associated with suicide attempts in women, but not in men (Gaysina et al., 2006). Ethnic (Noskova et al., 2008) and/or socio-cultural components may also differentially influence the association of 5-HTLLPR polymorphic variations and aggression; for example, no significant correlation was identified in groups of African-Americans (Patkar et al., 2002) or Spanish suicide attempters (Baca-Garcia et al., 2004), and only a marginal association between the s variant and aggressiveness was found in Korean schizophrenia patients (Kim et al., 2009). Additional lines of research suggest that the relevance of 5-HTLLPR with respect to aggression may be related to specific gene  environment interactions; for example, carriers of the short-allele variant were found to exhibit greater proclivity to aggression and suicidal ideation in response to stressful events (Caspi et al., 2003; Verona et al., 2006; Conway et al., 2012). "
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    ABSTRACT: Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the mulifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. After a brief overview of the anatomical distribution of the 5-HT-ergic system in the key brain areas that govern aggression and suicidal behaviours, the implication of 5-HT markers (5-HT receptors, transporter as well as synthetic and metabolic enzymes) in these conditions is discussed. In this regard, particular emphasis is placed on the integration of pharmacological and genetic evidence from animal studies with the findings of human experimental and genetic association studies. Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and find new effective therapies for these conditions.
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    • "In this study, the TPH1 genotype had no effect on anger-related traits in either the aggressive or non-aggressive schizophrenic patients. In our previous study, aggressive behavior was more frequent in schizophrenic patients who were prone to becoming angry.20 Based on our findings, it is suspected that other serotonin-related genes, such as serotonin transporter-related gene,21 or other TPH gene, TPH2, which is considered to control serotonin synthesis in the brain,22 may play a role in aggressive behavior via anger-related traits in schizophrenic patients. On the other hand, as the A218C single nucleotide polymorphism is not considered to be the sole determinant of the functionality of the TPH1 gene,10,23 an analysis of the effect of each haplotype on the expression of the TPH1 gene is also required, in order to clarify the involvement of the TPH gene in aggressive schizophrenia. "
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