Hungarian Brain Research Program(KTIA_NAP_13-2-2015-0001)
(TKP2021-EGA-25)
(K 143391)
(PD 146014)
János Bolyai Research Scholarship of the Hungarian Academy of Sciences
(ÚNKP-23-4-I-SE-31)
(EKÖP-2025-624)
(ÚNKP-22-4-II-SE-1)
(ÚNKP-23-3-I-SE-73)
(EKÖP-2024-68)
Szakterületek:
Pszichiátria
A recent study demonstrated that rodents exposed to early life stress (ELS) showed
changes in fat tissue composition and exhibited depression-like phenotype. Decreased
Sirt1 expression in the reward-related nucleus accumbens (NAc) was a key component
of this alteration. Our aim was to translate these findings into humans using a population
genetic approach and brain imaging data. We tested the interaction of genetic risk
of NAD + /SIRT1 pathway and ELS on depression and investigated whether body fat mediates
this interaction effect. We also investigated the effect of the genetic risk and ELS
interaction on functional connectivity of the NAc. Our findings suggest that interaction
between NAD + /SIRT1 pathway risk and ELS contributes to depression in males (beta
= 2.9275, p = 0.0002). Additionally, this interaction influences sex-dependent functional
connectivity of the NAc with the middle frontal gyrus and triangular part of the inferior
frontal gyrus (p = 0.0139). The observed interaction effect is independent of body
fat percentage in adults, indicating that these depressogenic genetic effects are
not mediated through adiposity. Overall, these results pave the way for potential
therapeutic interventions in depressed male patients with NAD + /SIRT1 risk variants
who experienced ELS, regardless of their body fat percentage.
