Evidence for a possible association of neurotrophin receptor (NTRK-3) gene polymorphisms with hippocampal function and schizophrenia

Mona K Otnaess, Srdjan Djurovic, Lars M Rimol, Bettina Kulle, Anna K Kähler, Erik G Jönsson, Ingrid Agartz, Kjetil Sundet, Håkan Hall, Sally Timm, Thomas Hansen, Joseph H Callicott, Ingrid Melle, Thomas Werge, Ole A Andreassen

38 Citations (Scopus)

Abstract

Altered neurodevelopment and plasticity are implicated in schizophrenia pathology. Based on the important role of neurotrophic factors in brain development and plasticity as well as their extensive expression in hippocampal areas, we hypothesized that a variation in the neurotrophin receptor 3 gene (NTRK-3) is associated to hippocampal function and schizophrenia. Thirty-three tagging NTRK-3 single nucleotide polymorphisms (SNPs) were genotyped in 839 schizophrenia patients and 1473 healthy controls. SNPs that were significantly associated with schizophrenia were evaluated in subgroups of the sample with neuropsychological test battery (n=104 patients and 175 controls) and functional magnetic resonance imaging tests of hippocampal function (n=36 controls). rs999905 was nominally significantly associated with schizophrenia and the haplotype block that included markers rs999905 and rs4887348 remained significant after permutation tests. These gene variants are also related to in vivo brain function in healthy control subjects, shown by a significant association with hippocampal activation during an encoding task. The present results, although not robust, suggest that the NTRK-3 gene influences hippocampal function and may modify the risk for schizophrenia.
Original languageEnglish
JournalNeurobiology of Disease
Volume34
Issue number3
Pages (from-to)518-24
Number of pages6
ISSN0969-9961
DOIs
Publication statusPublished - 2009

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