Major Depressive Disorder 165
Although an extensive literature exists de scribing neuroanatomi cal, neuroendocrino-
logical, and neurophysiological correlates of major depressive disord er, no laboratory test
has yielded results of sufficient sensitivity and specificity to be used as a diagnostic tool for
this disorder. Until recently, hypothalamic-pit uitary-adrenal axis hyperactivity had been
the most extensively investigated abnormalit y associated with major depressive episodes,
and it appears to be associated with melancho lia, psychotic features, and risks for eventual
suicide. Molecular studies have also implicated peripheral factors, including genetic vari-
ants in neurotrophic factors and pro-inflammatory cytokines. A dditionally, functional
magnetic resonance imaging stud ies provide evidence  for functional ab normalities in spe-
cific neural systems supporting emotion processing, reward seeking, and emotion regula-
tion in adults with major depression. 
Prevalence
Twelve-month prevalence of major depressive disorder in the United States is approximately
7%, with marked differences by age group such th at the prevalence in 18- to 29-year-old indi-
viduals is threefold higher than the prevalence in individuals age 60 years or older. Females ex-
perience 1.5- to 3-fold higher rates th an males beginning in early adolescence.
Development and Course
Major depressive disorder may first appear at any age, but the likelihood of onset in-
creases markedly with puberty. In the United States, incidence appears to peak in the 20s;
however, first onset in la te life is not uncommon. 
The course of major depressive  disorder is quite variable, such that some individuals
rarely, if ever, experience re mission (a period of 2 or more  months with no symptoms, or