Bipolar disorder (BD) is a neuropsychiatric disorder that is characterized by afluctuation between depressive and manic phases. In previous studies of a multigenerational
family with bipolar disorder, a variant was identified in NTRK1 which codes
for TrkA. The variant, rs144901788, causes an amino acid change from glutamate to
lysine at position 492. This is located in close proximity to the SHC/Frs2 binding site at
tyrosine 490, through which TrkA is known to play a role in cell survival and neurite
growth. iPSCs have been generated from lymphoblast cell lines taken from members of
the family, both with and without the mutation. These are further differentiated into
neural stem cells (NSCs). NSCs derived from the affected patients exhibited differences
in gene expression and neurite outgrowth. Downstream signaling of TrkA binding was
also evaluated. NTRK1 appeared to be downregulated in the affected neural stem
cells. Additionally, NTRK1, as well as it’s ligand nerve growth factor (NGF), have been
found to be associated with bipolar disorder in genome wide association studies.
Understanding the role of NTRK1 in bipolar disorder may allow for establishing distinct
sub-forms of illness that operate through different pathways, yet ultimately culminating
in a final disease presentation.