The purpose of this case-control genetic association study was to explore potential relationships between polymorphisms in the limbic system-associated membrane protein (LSAMP) gene and mood and anxiety disorders. A total of 21 single-nucleotide polymorphisms (SNPs) from the LSAMP gene were analyzed in 591 unrelated patients with the diagnoses of major depressive disorder (MDD) or panic disorder (PD) and in 384 healthy control subjects. The results showed a strong association between LSAMP SNPs and MDD, and a suggestive association between LSAMP SNPs and PD. This is the first evidence of a possible role of LSAMP gene in mood and anxiety disorders in humans.