A single nucleotide polymorphism at the LHPP gene (rs35936514) has been reported to be associated with major depressive disorder (MDD) in genome-wide association studies. We conducted a neuroimaging analysis to explore whether and which brain neural systems are affected by LHPP variation. Since LHPP variants seem to be associated with the hippocampus, we assessed the relationship between rs35936514 variation and structural-functional connectivity within a hippocampal-corticolimbic neural system implicated in MDD. A total of 122 Chinese subjects were divided into a CC homozygous group (CC genotype, n = 60) and a T allele-carrier group (CT/TT genotypes, n = 62). All subjects participated in resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) scans. Structural and functional connectivity data analyses were then performed. Compared to the CC group, the T allele-carrier group showed significantly higher fractional anisotropy (FA) values in the fornix as well as increased functional connectivity from the hippocampus to the rostral part of the anterior cingulate cortex (rACC). Moreover, a significant negative correlation between fornix FA value and hippocampus-rACC functional connectivity was identified (P < 0.05). These findings suggest that there is a relationship between rs35936514 variation and both structural and functional hippocampal-corticolimbic neural system involvement in MDD. LHPP may play an important role in the neuropathophysiology of MDD.
Keywords: Functional connectivity; Hippocampal–corticolimbic neural circuitry; LHPP gene; Major depressive disorder; Structural connectivity; rs35936514.