These findings raise the question of whether the effects of 5-HTT knockout are developmentally driven. It has been hypothesized that the 5-HTTLPR G×E interaction observed in relation to adult stressful life events should selectively affect people already “primed” by childhood adversity (8). This opens up some very interesting avenues for future animal studies. For example, would 5-HTT loss restricted to early life development be sufficient to increase anxiety and impair stress-coping? If so, is there a critical window and what is the corresponding ontogenic period in humans? Researchers could then elucidate the key neural and molecular changes underlying these effects. This could, in turn, “square the circle” by nominating mechanisms to target with novel therapeutic approaches in humans.
