ReviewThe Genetics of Depression: A Review
Section snippets
MDD
The lifetime prevalence of unipolar MDD is at least 10%, with the risk in women twice that in men (Moldin et al 1991, Tsuang et al 1994, Weissman et al 1996). Heritability based on twin studies is 40% to 50% (Bierut et al 1999, Kendler et al 1993a, Kendler et al 2001, McGuffin et al 1991, McGuffin et al 1996, Sullivan et al 2000, Torgersen 1986) and perhaps higher when measurement error is modeled based on repeated assessments (Kendler et al 1993a). Adoption studies provide some support for a
Monoaminergic Candidate Genes and Gene-Environment Interactions
Most of the published genetic association studies of mood disorders have focused on functional polymorphisms (DNA sequence variations that alter the expression and/or functioning of the gene product) in the loci encoding the serotonin transporter (SLC6A4), serotonin 2A receptor (5HTR2A), tyrosine hydroxylase (TH) (the limiting enzyme for dopamine synthesis), tryptophan hydroxylase 1 (TPH1) (serotonin synthesis), and catechol-o-methyltransferase (COMT) (dopamine catabolism). There are one or
Genetic Linkage Studies
An alternative to the study of mechanism-based candidate genes is the positional cloning strategy–the systematic study of the genome, either with genetic linkage studies of informative pedigrees followed by association studies of candidate regions (e.g., using very dense maps of single nucleotide polymorphisms) or systematic genome-wide association studies. The latter have not yet been attempted for depression, but several linkage studies have been or will soon be reported for MDD and related
Future Directions
Depression is a complex and multifactorial trait with important genetic and nongenetic contributory factors. Many methods and strategies will be applied, some of them not yet feasible or even imagined. However, a number of directions can be anticipated which are likely to be fruitful, including (at least) the following.
The positional cloning strategy will certainly be pursued using increasingly powerful methods to scan the genome for regions likely to contain relevant genes and then to search
References (130)
- et al.
Predisposition locus for major depression at chromosome 12q22–12q23.2
Am J Hum Genet
(2003) - et al.
Volumetric reduction in left subgenual prefrontal cortex in early onset depression
Biol Psychiatry
(2002) - et al.
Electroencephalographic measures of regional hemispheric activity in offspring at risk for depressive disorders
Biol Psychiatry
(2005) - et al.
The relationship of age of onset in unipolar affective illness to risk of alcoholism and depression in parents
J Psychiatr Res
(1977) - et al.
Using haplotype blocks to map human complex trait loci
Trends Genet
(2003) Neuroimaging and neuropathological studies of depressionImplications for the cognitive-emotional features of mood disorders
Curr Opin Neurobiol
(2001)- et al.
Mass-spectrometry DNA sequencing
Mutat Res
(2005) - et al.
Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disordersThe role of the hypothalamus-pituitary-adrenal axis
Biol Psychology
(2001) - et al.
Bipolar IICombine or keep separate
J Affect Disord
(1985) - et al.
Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families
Am J Hum Genet
(2004)