Major Depressive Disorder

In medicine, depression is a highly significant condition that manifests through various nosological entities, the most common of which is major depressive disorder.

The essential feature of this disorder is a clinical course marked by one or more major depressive episodes, in the absence of any previous history of manic, mixed, or hypomanic episodes.

Additionally, for an episode to qualify for diagnosis, the following conditions must also be met:

• The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
• The symptoms are not attributable to the direct physiological effects of a substance (e.g., medications, drugs) or a general medical condition (e.g., hypothyroidism)
• The criteria for a mixed episode (i.e., simultaneous presence of depressive and manic symptoms) must not be met

Note: In children and adolescents, irritable mood may be present instead of depressed mood.

The most severe consequence of this condition is death by suicide, which occurs in approximately 15% of patients. A certain familial predisposition has also been observed, with the disorder being 1.5 to 3 times more common among first-degree relatives of affected individuals than in the general population.

When only one major depressive episode occurs, the diagnosis is major depressive disorder, single episode; if two or more distinct episodes are present, it is termed major depressive disorder, recurrent. In some cases, this distinction can be challenging—especially when a single episode features fluctuations in symptom intensity that may mimic a relapse. To consider an episode concluded, the diagnostic criteria must no longer be met for at least two months.

The disorder can begin at any age, with an average age of onset around 25 years. In recurrent cases, the course is highly variable: some patients experience isolated episodes followed by long periods of wellness, others have clusters of closely spaced episodes, while still others show increasingly frequent episodes with advancing age.

Major depressive disorders are classified based on the characteristics of the most recent (or only) major depressive episode. Recurrent cases can be further differentiated based on the pattern of inter-episode recovery:

• With full inter-episode recovery: when a complete remission occurred between the two most recent episodes.
• Without full inter-episode recovery: when complete symptomatic remission did not occur between the two most recent episodes.

The term major depressive disorder with seasonal pattern is used when a recurring temporal relationship exists between episode onset and a particular season of the year. Most commonly, episodes begin in autumn or winter and remit in spring; summer recurrences are less common.

To establish this diagnosis, the seasonal pattern of onset and remission must have been present for the past two years, without any non-seasonal episodes during that period, and the seasonal episodes must outnumber non-seasonal ones over the patient’s lifetime. Moreover, the pattern must not be attributable to seasonal psychosocial stressors (e.g., school or work schedules). Winter seasonality is more frequent at higher latitudes, among younger individuals, and in women.

Finally, it is important to remember that if manic, mixed, or hypomanic symptoms emerge during the course of a major depressive episode, the diagnosis must be revised to bipolar disorder.

References
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). American Psychiatric Publishing. 2013.
2. Rush AJ et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917.
3. Belmaker RH et al. Major depressive disorder. N Engl J Med. 2008;358(1):55-68.
4. Kendler KS et al. The genetic epidemiology of major depression: implications for classification. Dialogues Clin Neurosci. 2001;3(1):7-20.
5. Kessler RC et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289(23):3095-3105.
6. Fava M et al. Residual symptoms in major depression: what do they mean? J Clin Psychiatry. 2006;67(8):1041-1050.
7. Drevets WC et al. Functional anatomical correlates of psychomotor retardation in depression. J Affect Disord. 2008;108(1-2):29-36.
8. Nemeroff CB. The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull. 2003;37(4):133-146.
9. Sheline YI et al. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001;50(9):651-658.
10. Hirschfeld RM. Long-term side effects of antidepressants. J Clin Psychiatry. 2003;64 Suppl 18:20-24.