Association between the Serotonin Transporter Gene (5-HTTLPR) and Anger-Related Traits in Korean Schizophrenic Patients
ABSTRACT 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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ABSTRACT: Antipsychotic drugs are the neuroleptics currently used in the treatment of schizophrenia (SCZ) and psychotic disorders. SCZ has a heritability estimated at 70%-90%; and pharmacogenomics accounts for 60%-90% variability in the pharmacokinetics and pharmacodynamics of psychotropic drugs. Personalized therapeutics based on individual genomic profiles in SCZ entails the characterization of 5 types of gene clusters and their related metabolomic profiles: 1) genes associated with disease pathogenesis; 2) genes associated with the mechanism of action of drugs; 3) genes associated with drug metabolism (phase I and II reactions); 4) genes associated with drug transporters; and 5) pleiotropic genes involved in multifaceted cascades and metabolic reactions. Genetic studies in SCZ have revealed the presence of chromosome anomalies, copy number variants, multiple single-nucleotide polymorphisms of susceptibility distributed across the human genome, aberrant single-nucleotide polymorphisms in microRNA genes, mitochondrial DNA mutations, and epigenetic phenomena. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Approximately 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4. About 10% - 20% of Western populations are defective in genes of the CYP superfamily. Only 26% of Southern Europeans are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6 + CYP2C19 + CYP2C9 genes. Efficacy and safety issues in the pharmacological treatment of SCZ are directly linked to genetic clusters involved in the pharmacogenomics of antipsychotic drugs and also to environmental factors. Consequently, the incorporation of Pharmacogenomic procedures both to drugs under development and drugs on the market would help to optimize therapeutics in SCZ and other central nervous system disorders.Open Journal of Psychiatry 01/2013; 3(01):46-139. DOI:10.4236/ojpsych.2013.31008
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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.Neuroscience 02/2013; 236:160-185. DOI:10.1016/j.neuroscience.2013.01.015 · 3.33 Impact Factor
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ABSTRACT: Studies on violence in schizophrenia use two different approaches: use of epidemiological data, and clinical studies recording direct patient data after gaining informed consent. With regard to informed consent requiring agreement and cooperation, the question arises as to what extent participants represent patients with schizophrenia and violent behaviour (external validity). We conducted a systematic literature research. In most of the studies, aggression or violence, respectively, were poorly defined. Only 5 (15.2%) studies used a cut-off score on an aggression scale. Only 6 studies (18.2%) reported the number of patients who refused to participate, and 16 (48.5%) reported the number of drop-outs. Only 3 studies (9.1%) reported a systematic comparison of participants and non-participants. We found that data which allow for the assessment of representativeness of the investigated samples are poorly reported. For most studies, doubts regarding external validity seem justified and generalisability is questionable due to possible selection bias.Clinical Practice and Epidemiology in Mental Health 08/2012; 8(1):74-80. DOI:10.2174/1745017901208010074