Pharmacogenetics of antiepileptic drugs: A brief review.

The goal of pharmacogenetic research is to assist clinicians in predicting patient response to medications when genetic variations are identified. The pharmacogenetic variation of antiepileptic drug response and side effects has yielded findings that have been included in drug labeling and guidelines. The goal of this review is to provide a brief overview of the pharmacogenetic research on antiepileptic drugs. It will focus on findings that have been included in drug labeling, guidelines, and candidate pharmacogenetic variation. Overall, several genes have been included in guidelines by national and international organizations; however, much work is needed to implement and evaluate their use in clinical settings.

The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia.

The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT-s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F(2, 84)=5.78, P=0.0044) and site 2 (F(2, 84),=3.79, P=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.

The influence of the brain-derived neurotropic factor Val66Met genotype and HMG-CoA reductase inhibitors on insulin resistance in the schizophrenia and bipolar populations.

INTRODUCTION: The brain-derived neurotrophic factor (BDNF) Val66Met variant and HMG-COA reductase inhibitors (statins) have been implicated in insulin resistance with a possible increased risk of diabetes. We sought to determine the effect of the BDNF Met variant and statin medication use on insulin resistance in schizophrenia and bipolar disorder using the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: A cross-sectional design was used and patients with diabetes or on any medications affecting glucose regulation were -excluded. Associations between insulin resistance and genotype were then analyzed by ANOVA and regression analysis. Subjects were grouped by BDNF genotype as well as presence of statin. RESULTS: Two hundred fifty-two subjects with a mean age of 44 years were included. The group was 53% male and 41% had a diagnosis of bipolar disorder; 78% and 19% were receiving atypical antipsychotics (AAPs) and statin medications, respectively. Analysis showed schizophrenia subjects with the BDNF met allele as well as schizophrenia subjects with both the BDNF met allele and were receiving a statin had significantly higher HOMA-IR values compared to the other groups (p= 0.046 and p= 0.016, respectively). CONCLUSIONS: Our results suggest that in the metabolically high-risk population of schizophrenia the BDNF met allele alone and in combination with statin medications is associated with higher insulin resistance values. This was not seen in the bipolar population. Further validation of these associations remains necessary.

Traumatic responses among battered women who kill.

This study compared levels of violence, social support, and post-traumatic stress between battered women charged with a violent crime against an abusive partner and those seeking help from a mental health clinic. Results indicated that forensic battered women were more likely than clinical battered women to report experiencing severe violence, including sexual abuse, in their relationships. Women in the forensic sample also reported less social support and greater post-traumatic stress than women in the clinical sample. However, when social support and level of violence were accounted for, levels of general post-traumatic stress indicators (MMPI-PTSD, CR-PTSD, GSI) were no longer different between groups, although levels of specific post-traumatic stress indicators (intrusion, avoidance) remained higher for battered women in the forensic sample. Implications for understanding battered women's response to violence and their post-traumatic reactions to it are discussed.

Battered women's cognitive schemata.

This study examined battered women's cognitive schema in relation to their cognitions about violence (i.e., the "meaning" attached to the violence), post-traumatic reactions to violence, and sexual victimization histories. Seventy-two battered women seeking help from an outpatient family violence clinic were subjects. The meaning of the violence (e.g., expectations of recurrent violence and of severe/lethal violence, causal attribution) was found to explain variance in cognitive schemata about SAFETY, SELF, AND OTHER (McCann and Pearlman, 1990a). All measures of cognitive schemata were significantly related to various global and specific measures of posttraumatic stress (GSI, MMPI-PTSD, IES). No differences were found for cognitive schemata based on histories of sexual victimization. Results point to the importance of assessing the impact of traumatic experiences on core cognitive beliefs as a component in the constellation of post-traumatic sequelae.