Major Depressive Disorder may begin at any age, with an average age at onset in the mid-20s. Epidemiological data suggest that the age at onset is decreasing for those born more recently. The course of Major Depressive Disorder, Recurrent, is variable. Some people have isolated episodes that are separated by many years without any depressive symptoms, whereas others have clusters of episodes, and still others have increasingly frequent episodes as they grow older. Some evidence suggests that the periods of remission generally last longer early in the course of the disorder. The number of prior episodes predicts the likelihood of developing a subsequent Major Depressive Episode. At least 60% of individuals with Major Depressive Disorder, Single Episode, can be expected to have a second episode. Individuals who have had two episodes have a 70% chance of having a third, and individuals who have had three episodes have a 90% chance of having a fourth. About 5%-10% of individuals with Major Depressive Disorder, Single Episode, subsequently develop a Manic Episode (i.e., develop Bipolar I Disorder).
Major Depressive Episodes may end completely (in about two-thirds of cases), or only partially or not at all (in about one-third of cases). For individuals who have only partial remission, there is a greater likelihood of developing additional episodes and of continuing the pattern of partial interepisode recovery. The longitudinal course specifiers With Full Interepisode Recovery and Without Full Interepisode Recovery may therefore have prognostic value. A number of individuals have preexisting Dysthymic Disorder prior to the onset of Major Depressive Disorder, Single Episode. Some evidence suggests that these individuals are more likely to have additional Major Depressive Episodes, have poorer interepisode recovery, and may require additional acute-phase treatment and a longer period of continuing treatment to attain and maintain a more thorough and longer-lasting euthymic state.
Follow-up naturalistic studies suggested that 1 year after the diagnosis of a Major Depressive Episode, 40% of individuals still have symptoms that are sufficiently severe to meet criteria for a full Major Depressive Episode, roughly 20% continue to have some symptoms that no longer meet full criteria for a Major Depressive Episode (i.e., Major Depressive Disorder, In Partial Remission), and 40% have no Mood Disorder. The severity of the initial Major Depressive Episode appears to predict persistence. Chronic general medical conditions are also a risk factor for more persistent episodes.
Episodes of Major Depressive Disorder often follow a severe psychosocial stressor, such as the death of a loved one or divorce. Studies suggest that psychosocial events (stressors) may play a more significant role in the precipitation of the first or second episodes of Major Depressive Disorder and may play less of a role in the onset of subsequent episodes. Chronic general medical conditions and Substance Dependence (particularly Alcohol or Cocaine Dependence) may contribute to the onset or exacerbation of Major Depressive Disorder.
It is difficult to predict whether the first episode of a Major Depressive Disorder in a young person will ultimately evolve into a Bipolar Disorder. Some data suggest that the acute onset of severe depression, especially with psychotic features and psychomotor retardation, in a young person without prepubertal psychopathology is more likely to predict a bipolar course. A family history of Bipolar Disorder may also be suggestive of subsequent development of Bipolar Disorder.
Major Depressive Disorder is 1.5-3 times more common among first-degree biological relatives of persons with this disorder than among the general population. There is evidence for an increased risk of Alcohol Dependence in adult first-degree biological relatives, and there may be an increased incidence of an Anxiety Disorder (e.g., Panic Disorder, Social Phobia) or Attention-Deficit/Hyperactivity Disorder in the children of adults with Major Depressive Disorder.