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These disorders are ubiquitous in all societies and cause considerable suffering. These disorders, while manifesting themselves as changes in mental life, are nevertheless clearly mediated by brain function. They assume importance for psychiatrists and neurologists but are embedded in the practices of virtually all branches of medicine.


Depression is perhaps the cause of more grief and misery than any other single disease to which humankind is subject. This view, expressed by Kline more than 50 years ago, is still shared by almost everyone in the field of mental health and the several forms of depression taken together are the most frequent of all psychiatric illnesses. The term “depression” denotes both a state of being and a more formally defined psychiatric disorder. The Global Burden of Disease Study 2019 affirms this view and estimates that depression is the fourth leading serious illness cause of disability in adolescents and young adults and a major contributor to self-harm and suicide deaths (GBD 2019). In a general hospital, as indicated in the previous chapter, depression accounted for an estimated 50 percent of psychiatric consultations and 12 percent of all admissions.

Although depression has been known to physicians for more than 2,000 years (melancholia is described in the writings of Hippocrates), it has been difficult to separate the medical aspects (Kraepelinian concept) from the psychologic reaction (Meyerian concept). In other words, is it basically a biologic derangement or a response to psychosocial stress? A balanced position is that both are correct—that is, there are two basic substrates for depression: exogenous (an apparent cause) and endogenous (with no overt external cause), and that there is an interplay between them and biologic susceptibility to either one. The boundaries between a biological disease and the medicalization of everyday life are therefore blurred. However, clinical and physiological states of depression that do not accord with external circumstances, when prolonged or severe, constitute an illness and recurrent bouts can probably be said to constitute a disease.

In respect to endogenous depression and the related condition of bipolar disease, genetic and neurochemical data cited further support the Kraepelinian view of a disease state. Nevertheless, a lay concept persists, perpetuated by process-oriented psychiatrists, that events in one’s life, either distant or current, underlie all types of depressive illnesses. A potential consequence of this view is the assumption that an inability to deal with these stresses represents a personal failure of sorts, and this, in turn, may inhibit the acceptance of psychiatric help. It is in this subject of depression that the interplay between our ongoing internal conversation and brain states meets. As noted further on, the difficulties of daily life can entrain the circuits that correspond to depressive feeling and affect. Seeking causality in either direction is complicated and self-referential; for example, functional imaging that purports to show patterns of depression may be the brain representation of that ...

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