Serotonergic gene polymorphisms (5-HTTLPR, 5HTR1A, 5HTR2A), and population differences in aggression: traditional (Hadza and Datoga) and industrial (Russians) populations compared

Abstract Background Current knowledge on genetic basis of aggressive behavior is still contradictory. This may be due to the fact that the majority of studies targeting associations between candidate genes and aggression are conducted on industrial societies and mainly dealing with various types of psychopathology and disorders. Because of that, our study was carried on healthy adult individuals of both sex (n = 853). Methods Three populations were examined: two traditional (Hadza and Datoga) and one industrial (Russians), and the association of aggression with the following polymorphisms 5-HTTLPR, rs6295 (5HTR1A gene), and rs6311 (5HTR2A gene) were tested. Aggression was measured as total self-ratings on Buss-Perry Aggression Questionnaire. Results Distributions of allelic frequencies of 5-HTTLPR and 5HTR1A polymorphisms were significantly different among the three populations. Consequently, the association analyses for these two candidate genes were carried out separately for each population, while for the 5HTR2A polymorphism, it was conducted on the pooled data that made possible to introduce ethnic factor in the ANOVA model. The traditional biometrical approach revealed no sex differences in total aggression in all three samples. The three-way ANOVA (μ + 5-HTTLPR + 5HTR1A + 5HTR2A +ε) with measures of self-reported total aggression as dependent variable revealed significant effect of the second serotonin receptor gene polymorphism for the Hadza sample. For the Datoga, the interaction effect between 5-HTTLPR and 5HTR1A was significant. No significant effects of the used polymorphisms were obtained for Russians. The results of two-way ANOVA with ethnicity and the 5HTR2A polymorphism as main effects and their interactions revealed the highly significant effect of ethnicity, 5HTR2A polymorphism, and their interaction on total aggression. Conclusions Our data provided obvious confirmation for the necessity to consider the population origin, as well as cultural background of tested individuals, while searching for associations between genes and behavior, and demonstrated the role of cultural attitudes towards the use of in-group aggression. Our data partly explained the reasons for disagreement in results of different teams, searching for candidate-gene associations with behavior without considerations of culturally desirable norms. Previous studies suggested that the 5HTR2A gene polymorphism associates with aggression and criminality. Our data extended these findings, demonstrating the role of rs6311 (5HTR2A gene) in aggression in adult healthy men and women from our samples. We found that G-allele carriers were rated higher on total aggression

Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells

Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

<div><p>The androgen receptor (<i>AR</i>) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between <i>AR</i> gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the <i>AR</i> gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between <i>AR</i> gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer <i>AR</i> CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born.</p></div

Goodness of model fit.

<p>CMIN/DF—chi square/degree of freedom ratio; CFI–Confirmatory Fit Index; RMSEA–the Root Mean Square Error of Approximation; PCLOSE—the p-value for a test of close fit.</p><p>Goodness of model fit.</p

Sample sizes of age groups and mean number of children (± <i>SE</i>) per age group in Hadza and Datoga men.

<p>Note: * these are probability values obtained in <i>post hoc</i> test using Scheffe’s modification as the most conservative among all others. Age group: 1 = 17–19 years; 2 = 20–29; 3 = 30–39; 4 = 40–49; 5 = 50–60+ years</p><p>Sample sizes of age groups and mean number of children (± <i>SE</i>) per age group in Hadza and Datoga men.</p

The association between the number of children and fathers’ age in Hadza and Datoga separately represented by five age groups (1 –fathers younger than 20 years of age; 2 –fathers from 20 to younger than 30 years of age; 3 –fathers from 30 to younger than 40 years of age; 4 –fathers from 40 to younger than 50 years of age; 5 –fathers from 50 years of age and older).

<p>The association between the number of children and fathers’ age in Hadza and Datoga separately represented by five age groups (1 –fathers younger than 20 years of age; 2 –fathers from 20 to younger than 30 years of age; 3 –fathers from 30 to younger than 40 years of age; 4 –fathers from 40 to younger than 50 years of age; 5 –fathers from 50 years of age and older).</p

The associations between age group (Age, manifested exogenous variable), number of CAG repeats of <i>AR</i> gene (CAGn, manifested exogenous variable), ethnic group (Ethnicity, manifested exogenous variable) and number of children (NC, dependent variable), mediated by total aggression (TA, endogenous mediating variable) scores based on structural equation modeling; asterisks designate significance level: *- 0.01

<p>The associations between age group (Age, manifested exogenous variable), number of CAG repeats of <i>AR</i> gene (CAGn, manifested exogenous variable), ethnic group (Ethnicity, manifested exogenous variable) and number of children (NC, dependent variable), mediated by total aggression (TA, endogenous mediating variable) scores based on structural equation modeling; asterisks designate significance level: *- 0.01</p

Standardized regression weights according to the model with lower and upper limits of the 95% confidence interval.

<p>S.E.–standard error of regression weights, C.R.–critical ratio, P–probability value.</p><p>Standardized regression weights according to the model with lower and upper limits of the 95% confidence interval.</p