Mood disorders can be roughly sub-classified into unipolar mania, bipolar disorder, and unipolar depression.⁽²⁾ The three groups differ significantly as regards family history, personality, course and outcome, including mortality. Unipolar mania has not yet been studied extensively, and for this reason will not be dealt with here.

Distinguishing between bipolar disorder and unipolar depressive disorder is hampered by the fact that the diagnosis of unipolar depression is always uncertain. Many depressives are hidden bipolar patients: a long-term follow-up study over 27 years showed a constant rate of diagnostic change from depression to hypomania of 1.25 per cent per year of follow-up. As a consequence of this diagnostic instability, the exact ratio of bipolar to unipolar depressive subjects in the population is unknown; modern estimates range from 1:5 to 1:1. The discussion of bipolar disorder has therefore to take account of its unipolar counterpart.

In patients admitted to hospital between 1913 and 1940 and not treated by electroconvulsive therapy or modern psychotropic drugs, bipolar disorder clearly manifested earlier than unipolar depression; this finding is confirmed by modern community studies. In most patients bipolar disorder begins during adolescence but in some cases may already manifest in childhood. Unfortunately pediatric psychiatry cannot yet provide prospective data from large representative community studies on the onset and course of bipolar disorder starting in childhood or adolescence.

In the offspring of bipolar parents social functioning up to the age of 18 develops normally before the onset of their illness.

Bipolar disorders usually begin as depression, and it takes a further 5 years on average until the first manic syndrome manifests.⁽³⁾ There may be unspecific prodromal symptoms in the form of mood lability, vegetative lability, somatization, or being hyper-alert or easily excited; there may also be discrete cognitive impairment present before the onset of the affective disorder.⁽⁴⁾ After the onset of the disorder social functioning often begins to be impaired.

The first depressive and manic manifestations are commonly mild, brief, or uncharacteristic, and are often only diagnosed in retrospect after years.

Prospective epidemiological studies in adolescents and young adults found the onset of bipolar disorder to occur in the teens (with means and medians around 15 years or later), whereas studies of hospitalized patients date its onset in retrospect in the early 20s or in the 30s.

Bipolar-I illness manifests earlier than bipolar-II and psychotic bipolar disorder. Late-onset bipolar disorder is extremely rare but does occur and may be associated with specific neuropathology. An early age of onset of the disorder, usually manifesting as depression, is correlated with suicidality, comorbid substance-use disorder and a rapid cycling course.

A two-peak distribution of the age of onset has sometimes been described for both bipolar disorder and depression in men and women, with no specific association in women between the second peak and the menopause.

Most episodes are short, but 10 to 20 per cent become chronic (lasting more than 2 years); the distribution of episode length is log normal, and therefore percentiles and not averages should be used as parameters. Using data collected a century ago on the natural length of episodes of mania and bipolar disorder, mainly among hospitalized patients, it is possible to compute a median length of 4 to 6 months for mania and 5 to 6 months for bipolar disorder. These figures do not differ from those obtained today despite a wide range of antimanic and antidepressant treatments. Among hospitalized bipolar patients episode length (median) was 4.2 months; 25 per cent of bipolar episodes lasted more than 7.3 months.

About 20 to 30 per cent of episodes are biphasic (mania with subsequent switch into depression, or depression with subsequent, switch into hypomania/mania); such high switch rates were already observed before the introduction of electroconvulsive therapy and antidepressants. An effective treatment does not induce a switch but increases (compared to placebos) the rates of responders; and the response is a precondition for the natural switch.

Recurrence is typical of mood disorders. It can be described by the number of episodes, the length of intervals (measured from remission to the onset of a new episode), and the length of cycles
(measured from the beginning of one episode to the beginning of the next). In prospective studies, time to the onset of a new episode is frequently used as a parameter for survival analyses and frailty analyses of recurrence.

In both bipolar disorder and unipolar depression the time from the first to the second episode is on average much longer than from the second to the third episode and so on. This progressive shortening of cycles and free intervals then levels off and fluctuates around a certain (but still variable) individual limit. Most published data on interval length or cycle length are methodologically flawed because they have not been corrected for the number of episodes/cycles observed. Nonetheless, multiple episodes obviously follow each other in more rapid succession than a few episodes distributed over a lifetime. Statistically, a normal distribution of cycle length can be obtained by log n transformation. Even after taking episode numbers into account, there is a clear intraindividual trend to a progressive shortening of cycle length, as demonstrated by frailty analyses⁽⁵⁾ dimming the prognosis for both bipolar disorder and unipolar depression. Initial cycle length tends to be shorter in late-onset than in early-onset mood disorders, increasing the risk of recurrence in the elderly.

Precipitating events play an important role in the onset of the first few affective episodes; thereafter recurrence seems to become gradually autonomous with stressful events contributing little or nothing to the process. Stressors may not only precipitate episodes but also increase a pre-existent vulnerability, sensitizing the individual and thereby making him or her more vulnerable to further episodes (kindling effect). In bipolar illness there is no difference in the quality or quantity of stressors precipitating depressive and manic episodes; a legacy or the loss of a relative can induce depression or mania. The sensitivity to stressors has also a genetic component.

Over a patient’s lifetime his condition continuously fluctuates on a dimension of severity, which ranges from psychotic, via major and minor syndromes (cyclothymic and minor bipolar disorders), cyclothymic temperament within the norm, symptomatic to symptom-free.

The NIMH Collaborative Depression Study with annual assessments of outpatients over an average of 13 years, demonstrated that bipolar-II patients spent slightly more time with symptoms/ syndromes (33 per cent) than bipolar-I patients (27 per cent). In both subtypes of bipolar disorders depressive periods were three times more common than manic periods⁽⁶⁾ but bipolar-I patients suffered more from psychotic features. In a 25-year follow-up study of hospitalized mood disorder patients, manic and depressive episodes were about equally present in bipolar-I patients, whereas in bipolar-II patients the course was dominated by depression.

Daily assessments of the course by the life-chart methodology over more than 3 years confirmed that bipolar outpatients spent a three-fold greater amount of time in depression than hypomania. But it was also shown that bipolar-I patients spent significantly more time in hypomania than their bipolar-II counterparts but an equal time in depression; in more than half the time the patients were euthymic.

Over lifetime bipolar patients experience twice as many episodes as unipolar depressives, a difference which is not explained by the manifestation of manic episodes in addition to depression. The total number of episodes observed depends on the length of observation. In a 22- to 26-year follow-up study, bipolar patients experienced a median of 10 episodes, but depressive patients only four. A family history of mood disorders increases recurrence. The proportion of mania to depression remains fairly stable across multiple episodes, but over their lifetime patients spend more time in depression than in mania.