Figure 5.

RDoC grouping of z-scored data reveals domain-specific differences in the contribution of Tcf4 gene dosage and psychosocial stress to behavioral and cognitive dysfunction. Unsupervised hierarchical clustering of group means of standardized (z-scored) behavioral data clusters primarily by environmental stress. The heatmap highlights changes relative to the healthy control group [wildtype no stress control (wt ns)]. The most prominent effects are seen for the two-hit disease group Tcf4tg mice subjected to social defeat during adolescence (tg sd). Particularly, deficits in the cognitive domain (“C”) are dependent on both genetic and environmental impact, in contrast to more generally stress-dependent abnormalities in the positive (“+”) and negative (“–”) valence as well as the arousal/regulation domain (“A”). The sensorimotor gating system (“S”) clearly separates animals based on Tcf4 gene dosage only. Column blocks are defined by RDoC domains; n = 15/17/15/17.