The FKBP5 gene variant examined in the present study has not only genetic [27] but also endocrine and neural functional effects, with the T allele being the vulnerability factor [9]. It is likely that insecurity and negative affect, derived from a poor relationship with the parents, are reasons for alcohol misuse in individuals carrying the more stress-sensitive FKBP5 genotype. Indeed, T/TT carriers have been described to have heightened amygdala reactivity to negative emotional stimuli contingent to emotional neglect [54, 55]; increased activation during attention bias towards threat and spatial displacement of the hippocampus in the presence of trauma [56]; lower white matter integrity in the posterior cingulum [57] and in the dorsal anterior and posterior cingulate cortex [58], which connect emotional and cognitive processes; weakened connectivity at rest between left amygdala and caudate, parahippocampal gyrus, inferior and middle frontal gyri, in interaction with negative life events [59]; as well as differential gray matter volumes in brain regions involved in cognitive-affective processing [55, 58, 60], in some cases dependently on experience of adversities [61, 62].
