Vol 4 n° 1 - Pathophysiology of Depression
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Major depression is a serious disorder of enormous soci- ological and clinical relevance. The discovery of antide- pressant drugs in the 1950s led to the first biochemical hypothesis  of  depression,  which  suggested  that  an impairment in central monoaminergic function was the major lesion underlying the disorder. Basic research in all fields of neuroscience (including genetics) and the discovery of new antidepressant drugs have revolution- ized our understanding of the mechanisms underlying depression and drug action. There is no doubt that the monoaminergic system is one of the cornerstones of these mechanisms, but multiple interactions with other brain systems and the regulation of central nervous sys- tem function must also be taken into account. In spite of all the progress achieved so far, we must be aware that many open questions remain to be resolved in the future. epression is a potentially life-threatening dis- order that affects hundreds of millions of people all over the world. It can occur at any age from childhood to late life and is a tremendous cost to society as this disorder causes severe distress and disruption of life and, if left untreated, can be fatal. The psychopatho- logical state involves a triad of symptoms with low or depressed mood, anhedonia, and low energy or fatigue. Other symptoms, such as sleep and psychomotor dis- turbances, feelings of guilt, low self-esteem, suicidal tendencies, as well as autonomic and gastrointestinal disturbances, are also often present. Depression is not a homogeneous disorder, but a complex phenomenon, which has many subtypes and probably more than one etiology. It includes a predisposition to episodic and often progressive mood disturbances, differences in symptomatology ranging from mild to severe symp- toms with or without psychotic features, and interac- tions with other psychiatric and somatic disorders. Classification, prevalence, and course of depression At present, the essence of major depressive disorder is a clinical  course  that  is  characterized  by  one  or  more major depressive episodes without a history of manic, mixed, or hypomanic episodes, according to the criteria of the Diagnostic and Statistical Manual of Mental Health, Fourth Edition (DSM-IV).1 For an appropriate diagnosis, five of the following nine DSM-IV symptoms must be present continuously for a minimum 2-week period: (i) depressed mood; (ii) loss of interest or pleasure; (iii) sig- nificant weight or appetite alteration; (iv) insomnia or hyposomnia; (v) psychomotor agitation or retardation; (vi) fatigue or loss of energy; (vii) feelings of worthless- ness; (viii) diminished ability to think or concentrate or indecisiveness; and (ix) suicidal ideation. Historically, there has been lengthy discussion on the basis and classification of depression.Two different con- cepts, Emil Kraepelin’s formulation of depression as a disease and Sigmund Freud’s view of depression as a Pathophysiology of depression and mechanisms of treatment Brigitta Bondy, MD Keywords: depression; monoamine; serotonin; norepinephrine; treatment; genetics; neurobiology Author  affiliations:  Psychiatric  Clinic  of  University  Munich, Department  of Neurochemistry, Munich, Germany Address for correspondence: Psychiatric Clinic of University Munich, Department of Neurochemistry, Nußbaumstraße 7, D-80336 Munich, Germany
(e-mail: bb@psy.med.uni-muenchen.de) D 7 S t a t e   o f   t h e   a r t Dialogues Clin Neurosci.  2002;4:7-20.