P.0516 Genotype rs25531 polymorphisms and quality in peer relationships adjust the neural response of the anterior prefrontal cortex to cry

Major theories in developmental psychobiology have demonstrated that emotional regulation depends on social experiences (i.e., confidence, seeking attention, discomfort with closeness) and on genetic characteristics that modulate the sensitivity to contextual social cues [1]. Amidst numerous genes, a targeted allelic variation of the serotonin transporter gene, namely 5HTT rs25531, could be linked to expectations and needs in social interactions [2]. The elaboration of social cues occurs in the brain's prefrontal area, integrating information from the limbic system, deputed to emotion processes, and the premotor cortex, involved in planning a behavioural response [3]. However, there is a lack of evidence for gene-by-environment mechanisms related to 5HTT rs25531. With this study, we hypothesized different oxygenated haemoglobin (HbO) concentrations in the prefrontal cortex to stressors between genetic carriers with different susceptibility to social environments. 98 Singaporean undergraduate students (63 females, 35 males) were involved in an auditory task. Three 15-seconds vocalizations (3-months baby cry, woman cry, cat cry) were presented ten times, while the prefrontal activity of six Broadmann Areas (BA08, BA09, BA10, BA45, BA46, BA47) was recorded by Near-Infrared Spectroscopy's (NIRS) 20 channels. We adopted the same NIRS data acquisition and pre-processing used previously [3]. Information about quality in social relationships was assessed by the self-report Attachment Style Questionnaire [4] across the five dimensions Trust, Fear of Intimacy, Relationship as Secondary (RaS), Need for Approval, and Worry with Relationship. Buccal mucosa samples were collected to evaluate genetic features of rs25531 (TT = 67; T/C = 31). An averaged HbO response to each cry stimulus was calculated. Data distributions of continuous variables were inspected for normality; 125 outliers, defined as values 3 SDs above/below the mean, were removed. This exploratory quasi-experimental study applied a 2 × 3 × 5 factorial design. For each NIRS channel, one mixed repeated-measures ANCOVA was executed with the HbO level (Beta) as the dependent variable, the genotype rs25531 as a between-subjects factor, cry stimulus as within-subjects factor, and the dimensions as covariates (corrected α = 0.0025). Participants' sex was included as a between-subjects factor only in the models for which preliminary analysis showed an effect of sex (channels 7, 9, 14). Given our research aim, we considered only the effects of higher-order interactions with genotype, which survived the family-wise error rate. The analysis highlighted one three-way interaction on the neural response. Genotype, RaS dimension and cry type emerged for HbO mean levels of channel 12 (BA10) (F(2, 96) = 8.11, p < 0.001, ηp² = 0.10, power = 0.96). Correlational analysis (corrected α = 0.008) revealed that RaS, a measure of insecure and avoidant relationship with peers, was significantly and positively associated with prefrontal activity to baby cry for C-carriers ({t = 3.15, df = 29, r = 0.51, p = 0.003) but not for T/T homozygous (t = 1.01, df = 53, r = 0.14, ns). These results suggest the involvement of the anterior prefrontal cortex in affective regulation and promptness to action and stressors as a function of gene-by-environment determinants in non-parent adults [5].