Molecular Genetic Research

Molecular Genetic Research

Molecular biology studies have reported, replicated, or failed to replicate various associations between several specific genes or gene markers and mood disorders (Sevy et al., 1995; Reus and Freimer, 1997; Sherman et al., 1997; Kendler, 1998; Dubovsky and Buzan, 1999; Kelsoe, 2000; Berrettini, 2000; Craddock and Jones, 2001; Johansson et al., 2001).

Why have no genetic associations been consistently repli-cated? Reasons include: 1) complexity of the phenotype; 2) the like-lihood that multiple genes and gene combinations contribute to the phenotypes; 3) gene–environment effects; 4) the complexity of the environment; and 5) the low power of sample sizes studied to date (Dubovsky and Buzan, 1999; Kelsoe, 2000; Mann et al., 2001). A major problem of studies in psychiatric genetics is that psychiatric diagnoses are not known to be biologically homogeneous entities. Syndromal psychiatric diagnostic categories such as depression or anxiety disorders potentially include etiologically, pathologically and prognostically heterogeneous disorders (Charlton, 1997; Sher, 2000a). However, behavioral geneticists remain cautiously opti-mistic and hope that genetic studies promise a new era of under-standing and treatment of mood disorders. There is confidence in the existence of genetic factors in mood disorders without having as yet succeeded in identifying the responsible genes.