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5 (r = 0.16, p = 0.01), and more weakly so at 5 (r = 0.10, ns). Family socio-economic status (SES, indicated by mothers�� report on the family��s income relative to the given national average, where 1 = much below national average, 3 = around average, and 5 = much above average) did not Alisertib significantly correlate with affective knowledge at age 3.5 (r = -0.12, ns), but was significantly related to better performance at age 5 (r = 0.25, p = 0.01). We therefore examined a covariate-adjusted model, controlling for within-age group age differences and SES. Importantly, the genotype �� sex interaction remained significant when controlling for these variables, at both age 3.5, [Wald ��2(1, N = 236) = 5.00 p = 0.025], and age 5 [Wald ��2(1, N = 210) = 3.92, p = 0.048], attesting to the robustness of the findings. Discussion We examined the association between the DRD4-III polymorphism and affective knowledge among children 3.5 and 5 years of age. The findings demonstrate that the association between DRD4-III and affective knowledge is contingent on sex. In both age groups, in the presence of the 7R allele boys scored significantly higher than girls, whereas in the absence of the 7R there was no significant sex effect on affective knowledge. Due to the fact that socio-cognitive abilities, and especially cognitive empathy, develop dramatically during the preschool period (Lennon and Eisenberg, 1990), this consistent replication across two age groups is of special value. In other words, although children mature and change in these critical years, the interaction effect remains consistent, reflecting its robustness. The results of the current study can be interpreted in the context of brain mechanisms underlying socio-cognitive abilities. The DRD4 is widely expressed in the brain, particularly in the prefrontal cortex, hippocampus, hypothalamus, amygdala, and mesolimbic pathways (Matsumoto et al., 1995; Oak et al., 2000). These regions are considered to be a part of the ��social brain�� (Skuse and Gallagher, 2009), that includes the amygdala as one of the central parts of the reward system. DRD4 is an integral part of the dopamine system, a system that is considered to be involved in making social interactions rewarding. The importance of the dopaminergic reward circuits in the regulation of social cognition is presented in the model of Skuse and Gallagher (2009, 2011). This model suggests that genetic variation in the receptors associated with OT, AVP, and dopamine may explain individual differences, as well as, deficits, in socio-cognitive processes and behaviors (Skuse and Gallagher, 2009, 2011). For example, the negative symptoms of schizophrenia (impairments in emotional processing, social perception and knowledge, ToM, and attributional bias) may be associated with abnormalities in OT and dopamine signaling in the amygdala (Rosenfeld et al., 2011).