An intriguing line of enquiry in this context has centered on the hypothesis that 5-HTT variation may in part modulate the capacity to cope with stress by shaping the early life development of corticolimbic circuitry (56). In fact, the importance of the 5-HT system in neurodevelopment has long been recognized, and the 5-HTT is known to be critical for the formation of cortical systems in particular (106, 107). Pharmacological inhibition of the 5-HTT during early life mimics the anxiety-like phenotype of 5-HTT knockout (108). Moreover, poor maternal care produces heightened anxiety-like behavior in mice with a partial (heterozygous) 5-HTT null mutation, which are phenotypically normal under conditions of good maternal care (109).
