Major depressive disorder is associated with high mortality, much of which is accounted for by suicide; however, it is not the only cause. For example, depressed individuals ad- mitted to nursing homes have a markedly increased likelihood of death in the first year. In- dividuals frequently present with tearfulness, irritability, brooding, obsessive rumination, anxiety, phobias, excessive worry over physical health, and complaints of pain (e.g., head- aches; joint, abdominal, or other pains). In children, separation anxiety may occur.
Although an extensive literature exists describing neuroanatomical, neuroendocrino- logical, and neurophysiological correlates of major depressive disorder, no laboratory test has yielded results of sufficient sensitivity and specificity to be used as a diagnostic tool for this disorder. Until recently, hypothalamic-pituitary-adrenal axis hyperactivity had been the most extensively investigated abnormality associated with major depressive episodes, and it appears to be associated with melancholia, 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. Additionally, functional cific neural systems supporting emotion processing, reward seeking, and emotion regula- tion in adults with major depression.
Twelve—month prevalence of major depressive disorder in the United States is approximately 7%, with marked differences by age group such that 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 than males beginning in early adolescence.
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 205; however, first onset in late life is not uncommon.
The course of major depressive disorder is quite variable, such that some individuals rarely, if ever, experience remission (a period of 2 or more months with no symptoms, or only one or two symptoms to no more than a mild degree), while others experience many years with few or no symptoms between discrete episodes. It is important to distinguish individuals who present for treatment during an exacerbation of a chronic depressive ill- ness from those whose symptoms developed recently. Chronicity of depressive symptoms substantially increases the likelihood of underlying personality, anxiety, and substance use disorders and decreases the likelihood that treatment will be followed by full symp- tom resolution. It is therefore useful to ask individuals presenting with depressive symp- toms to identify the last period of at least 2 months during which they were entirely free of depressive symptoms.
Recovery typically begins within 3 months of onset for two in five individuals with ma- jor depression and within 1 year for four in five individuals. Recency of onset is a strong determinant of the likelihood of near-term recovery, and many individuals who have been depressed only for several months can be expected to recover spontaneously. Features as- sociated with lower recovery rates, other than current episode duration, include psychotic features, prominent anxiety, personality disorders, and symptom severity.
The risk of recurrence becomes progessively lower over time as the duration of re- mission increases. The risk is higher in individuals whose preceding episode was severe, in younger individuals, and in individuals who have already experienced multiple epi- sodes. The persistence of even mild depressive symptoms during remission is a powerful predictor of recurrence.