8, P = 0.016, CI = 1.1–2.7). No significant gene × gene interaction was detected (Wald 0.54, P = 0.461). Table 2 Logistic regression analysis of the influence of childhood adversity factors and candidate genes on the probability of belonging to

the MDD category. Analysis of CAs With exception of parent divorce and economic adversity, most of the 12 individual CAs were independent predictors of depression as analyzed by logistic regression (Wald statistic range 13–110, P < 0.001; individual data not shown). The psychosocial adversity composite factors: Abuse, neglect, and family dysfunctions Inhibitors,research,lifescience,medical (Wald's 88.2, OR 3.6; CI 2.7–4.6; P < 0.001); parental maladjustment (Wald's 8.2, OR 1.9; CI 1.2–2.9; P < 0.01), parental death (Wald's 6.5, OR 2.0; CI 1.2–3.4; P < 0.01), and to have experienced a life-threatening physical Inhibitors,research,lifescience,medical illness (Wald's 7.0, OR 1.9; CI 1.2–3.1; P < 0.01); were predictors of clinical depression in adolescents. Similar results were observed when data was Inhibitors,research,lifescience,medical analyzed by

gender, except for the cases of parental maladjustment and parental death where the statistical significance was detected only in female subjects or in male subjects, respectively (Table 2). The cumulative number of psychosocial adversities was clearly associated with an increase in the prevalence of depression (Fig. 1A and B). The logistic regression analysis showed that being KU-55933 in vitro exposed to ≥2 CAs during childhood Inhibitors,research,lifescience,medical was an important predictor of MDD as compared with those adolescents that reported none or a single childhood adversity (Wald’s 44.9, OR 4.5; CI 2.9–6.9; P < 0.00). Interestingly, whereas homozygous subjects for the BDNF Val allele displayed an analogous pattern to the whole sample, the possession of at least a copy of

the BDNF Met allele (i.e., Met +) was statistically associated with a “refractory” or resilient phenotype to the mounting influence of CAs (Fig. 1A). In support of the preceding observation, the BDNF genotype × number Inhibitors,research,lifescience,medical of reported CAs interaction nearly analysis showed a protective effect of the Met allele on the risk for MDD (Wald’s 6.5, OR 0.2; CI 0.09–0.7; P < 0.02); this effect was only evident in females (Table 3). No significant differences for the interaction of cumulative number of adversities and SLC6A4 were detected (Fig. 1B). Table 3 Interaction analysis by gender between the cumulative number of childhood adversities (CAs) factors and BDNF on the probability of belonging to the MDD category. Figure 1 Bars represent the percentage of subjects who met DSMIV criteria for Major depression disorder in relation to the cumulative number of CAs experienced during childhood. The specific percentages of affected individuals relative to a particular genotype …