Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and childhood-onset mood disorders.
OBJECTIVE
Genome scans have revealed significant evidence for linkage of depression to chromosome 15q25.3-q26.2. The gene for neurotrophic tyrosine kinase receptor 3 (NTRK3), the receptor for neurotrophin-3 (trkC) and a key gene in neurotrophin signaling, is located within this region and, given evidence for synaptic plasticity as a mechanism in mood disorders, was considered a prime candidate. The authors investigated NTRK3 as a susceptibility gene for childhood-onset mood disorders.


METHODS
The study sample consisted of 603 families with 723 affected children and adolescents diagnosed with a mood disorder with onset of the first episode by age 15. The authors genotyped 18 polymorphic markers across the NTRK3 gene in this sample and tested for association.


RESULTS
Results identified significant evidence for association for five of the markers using the transmission disequilibrium test. Four of the five markers were located in a region of strong linkage disequilibrium and were highly correlated. Haplotype results provided significant evidence for association to haplotypes composed of markers located in two haplotype blocks.


CONCLUSIONS
The results for NTRK3 as well as the authors' previous finding for association to brain-derived neurotrophic factor in this sample support synaptic plasticity as a mechanism contributing to mood disorders that begin during childhood and adolescence and specifically implicate the NTRK3 gene as a contributing factor in the 15q-linked region.
Feng
Yu
Y
Toronto Western Research Institute, University Health Network, Toronto, Ont., Canada M5T 2S8.
Vetró
Agnes
A
Kiss
Eniko
E
Kapornai
Krisztina
K
Daróczi
Gabriella
G
Mayer
László
L
Tamás
Zsuzsanna
Z
Baji
Ildikó
I
Gádoros
Júlia
J
King
Nicole
N
Kennedy
James L
JL
Wigg
Karen
K
Kovacs
Maria
M
Barr
Cathy L
CL
D000293:Adolescent; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D019964:Mood Disorders / Q000175:diagnosis / Q000235:genetics*; D020812:Receptor, trkC / Q000235:genetics*; D012307:Risk Factors
D005819:Genetic Markers; D020812:Receptor, trkC