Predictive value of EFHC1 variants for the long-term seizure outcome in juvenile myoclonic epilepsy.

OBJECTIVE: This study aimed to determine the contribution of EFHC1 variants to the phenotypic variability of juvenile myoclonic epilepsy (JME) and to evaluate their diagnostic value regarding previously identified clinical long-term seizure outcome predictors in a consecutive cohort of patients with JME. METHODS: Thirty-eight probands and three family members affected with JME were studied at a tertiary epilepsy center with a review of their medical records and a subsequent face-to-face interview. All coding EFHC1 exons and adjacent exon/intron boundaries were directly sequenced. RESULTS: The previously reported EFHC1 mutation F229L was found in two cases who presented with early generalized tonic-clonic seizure (GTCS) onset and appeared to be associated with milder subtypes of JME. Variant R294H was identified in two further probands who had a subtype of JME developing from childhood absence epilepsy. However, segregation of the phenotype with this variant could not be confirmed in one family. CONCLUSIONS: Our findings corroborate the heterogeneity of JME as an electroclinical epilepsy syndrome and provide evidence that genetic factors may influence and help predict the long-term seizure outcome in patients with JME.

Associations between the oxytocin receptor gene (OXTR) and "mind-reading" in humans--an exploratory study.

BACKGROUND/AIMS: The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. METHODS: 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the "Reading the Mind in the Eyes Test" (RMET). RESULTS: After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). CONCLUSION: This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.

Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects.

Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ.

Alcohol consumption is associated with an interaction between DRD2 exon 8 A/A genotype and self-directedness in males.

BACKGROUND: Both reduced postsynaptic dopamine D(2) receptor function and the character variable self-directedness (SDD) are related to the level of alcohol consumption. We examined for interactions between DRD2 exon 8(rs6276), a polymorphism which has been associated with various alcohol-related phenotypes, SDD and alcohol consumption. METHODS: A total of 144 male and 186 female probands with alcohol dependence or abuse diagnoses and without were included in the study. All subjects were assessed with the alcohol section of the Semi-Structured Assessment for the Genetics of Alcoholism and the Temperament and Character Inventory. RESULTS: Male probands with A/A genotype reported significantly higher alcohol consumption in a typical week (ANOVA; p = 0.024); those with A/A genotype and low SDD showed particularly high consumption levels (interaction DRD2 x SDD: p = 0.019). Alcohol dependence/abuse (DSM-IV) but not nicotine dependence was also relevant for higher alcohol consumption (trend: p = 0.052). In the female group, only alcohol disorders predicted alcohol consumption. CONCLUSIONS: Our findings support a role for a gene-personality interaction of DRD2 exon 8 x SDD in alcohol consumption in males.

Negative perceived paternal parenting is associated with dopamine D2 receptor exon 8 and GABA(A) alpha 6 receptor variants: an explorative study.

Twin studies suggest a genetic influence upon perceived parenting. The D(2) dopaminergic receptor is involved in the modulation of social behaviors, and might influence parenting and its perception. A polymorphism (E8) in exon 8 of the D(2) receptor gene (DRD2) has been previously associated with alcoholism-related phenotypes. Similarly, the Pro385Ser variant of GABRA6, the polymorphic gene for GABA(A) receptor alpha6 subunit, has been associated with alcohol- and depression-related traits; and rat pups maintained a more immature GABAR phenotype after brief separation distress. The relationships among DRD2 (E8) and GABRA6 (Pro385Ser) polymorphisms, and perceived parenting were studied here. The association of DRD2 (E8) and GABRA6 (Pro385Ser) genotypes and perceived parental rearing behavior (short-EMBU; questionnaire concerning own memories concerning upbringing) were determined in 207 unrelated adults using multivariate analysis of variance. Temperaments (Temperament and Character Inventory; TCI) were included as covariates. Probands with DRD2 (E8) A/A genotype showed higher scores for father rejection (P = 0.011), parents overprotection (P = 0.021), and father overprotection (P = 0.016) in the total group. An interaction between DRD2 and GABRA6 genotypes on father rejection (P = 0.010) and parents rejection (P = 0.030) was also observed. Further analyses showed that these associations were restricted to the female subgroup only; however, secondary gender-specific analyses were not corrected for multiple testing. Our findings support a role for DRD2 (E8) and GABRA6 (Pro385Ser) in perceived parenting.