Less is known about the neurobiological mechanisms by which the 5-HTTLPR mediates the effects of recent life events and acute stressors in increasing the risk of the development of psychopathology.27 It has been suggested that presence of the s allele increases stress sensitivity by biasing those neurobiological systems that underlie threat reactivity and arousal.27 An association between processing images of fearful and negative expressions, but not positive expressions, and increased amygdala reactivity and 5-HTTLPR genotype has been found in several studies.28, 29 Furthermore, during acute stress exposure, ss carriers preferentially modulate their attention towards threat, perseverate on the emotional salience of threat, and exhibit a tendency for preferential engagement of fear- and arousal-enhancing neural systems due to an enhanced activation of a neural network including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, nucleus caudatus, precuneus, anterior cingulate cortex, and the medial prefrontal cortex.27 A recent meta-analysis also found a small but significant association between 5-HTTLPR genotype and hypothalamic-pituitary-adrenal-axis reactivity during acute psychosocial stress, with a higher cortisol response in those carrying the s allele, potentially contributing to a heightened risk for the development of stress-related disorders.30
