(Open access funding provided by Semmelweis University)
(2017-1.2.1-NKP-2017-00002.)
(National Brain Programme 3.0(NAP2022-I-4/2022))
(2019-2.1.7-ERA-NET-2020-00005) Támogató: Nemzeti Kutatási, Fejlesztési és Innovációs
Hivatal
(ÚNKP-22-3-II-SE-27)
(ÚNKP-22-4-II-SE-1)
(2020-4.1.1.-TKP2020)
(TKP2021-EGA-25)
(139330)
Szakterületek:
Gyógyszerészet, farmakogenomika, gyógyszerkutatás és tervezés, gyógyszeres kezelés
Manipulation of intake of serotonin precursor tryptophan has been exploited to rapidly
induce and alleviate depression symptoms. While studies show that this latter effect
is dependent on genetic vulnerability to depression, the effect of habitual tryptophan
intake in the context of predisposing genetic factors has not been explored. Our aim
was to investigate the effect of habitual tryptophan intake on mood symptoms and to
determine the effect of risk variants on depression in those with high and low tryptophan
intake in the whole genome and specifically in serotonin and kynurenine pathways.
63,277 individuals in the UK Biobank with data on depressive symptoms and tryptophan
intake were included. We compared two subpopulations defined by their habitual diet
of a low versus a high ratio of tryptophan to other large amino acids (TLR). A modest
protective effect of high dietary TLR against depression was found. NPBWR1 among serotonin
genes and POLI in kynurenine pathway genes were significantly associated with depression
in the low but not in the high TLR group. Pathway-level analyses identified significant
associations for both serotonin and kynurenine pathways only in the low TLR group.
In addition, significant association was found in the low TLR group between depressive
symptoms and biological process related to adult neurogenesis. Our findings demonstrate
a markedly distinct genetic risk profile for depression in groups with low and high
dietary TLR, with association with serotonin and kynurenine pathway variants only
in case of habitual food intake leading to low TLR. Our results confirm the relevance
of the serotonin hypothesis in understanding the neurobiological background of depression
and highlight the importance of understanding its differential role in the context
of environmental variables such as complexity of diet in influencing mental health,
pointing towards emerging possibilities of personalised prevention and intervention
in mood disorders in those who are genetically vulnerable.