There seems to be a series of conceptual problems regarding depressive illness and its classification. First, there is the problem of whether these illnesses have some biological function, whether they represent attempts on the part of human organisms to deal with or escape from situations of stress, or whether they should be thought of simply as psychologically meaningless events. Eysenck (1960) and Wolpe (1958) make it clear that they regard neurotic symptoms as meaningless, maladaptive patterns which can and should be removed by suggestion, deconditioning and behaviour therapy. Similarly, Mayer-Gross, Slater and Roth (1955) reject the suggestion that depressive illness may have an adaptive function. By contrast, clinical medicine, though resting heavily on the mechanistic causality models of physics and chemistry, does give some implicit recognition of biological purpose in physical illness. Thus, pneumonia represents not only the phenomenon of invasion of pulmonary tissue by infective agents, but also the phenomenon of bodily defence against such invasion. When such defence does not exist, the patient seldom gets to the physician in time to be diagnosed. That depressive illness might have an analogous biological function was suggested by Freud (1917) and elaborated in impressive detail by Lewis (1934). The converse view that depressive illness represents a breakdown in adaptive function is based on the views of Kraepelin (1913) who attributed the dominant place in the depressive group of illnesses to manic-depressive psychosis with its known hereditary basis. That hereditary factors do operate in the manic-depressive group proper seems to have been demonstrated more than adequately by Slater (1938) and Kallmann (1950). The evidence regarding other depressive reactions, whether recurrent or involutional, seems far from impressive. Nevertheless, Mayer-Gross et al. take the view that affective illness is primarily a question of constitution, that the content of the depression may be understandable in terms of the patient's life situation, but that the causes of breakdown given by relatives of patients are really symptoms of the oncoming illness. Interestingly enough, Henderson and Gillespie (1956) classify affective illness into manic-depressive and involutional depression, and note the importance of social factors (p. 276).

Depression is a major health problem where most patients are not effectively treated. This problem is compounded in children where only two antidepressants are clinically approved. Both are selective serotonin (5‐HT) reuptake inhibitors (SSRIs), which are often less efficacious in young populations compared to adults. We found the antidepressant‐like effects of SSRIs in juvenile mice (21 days post‐partum) was reduced relative to adult mice; however, there was no difference in expression of hippocampal 5‐HT transporter (SERT), the target protein of SSRIs, to account for the reduced SSRI efficacy. Increased extracellular 5‐HT after SSRI treatment is thought to trigger downstream events for therapeutic response. Our data suggests transporters capable of 5‐HT uptake other than SERT, such as organic cation transporters (OCTs) and the plasma membrane monoamine transporter (PMAT), may be preventing extracellular 5‐HT from climbing to therapeutically relevant levels after SSRI treatment. The binding site density of [3H]decynium‐22 (D22), an OCTs/PMAT blocker, was greater in juvenile mice than adults. Western blots revealed the greater [3H]D22 binding was likely driven by greater PMAT protein expression in juvenile mice. In our preliminary studies, D22 (0.01mg/kg) produced antidepressant‐like effects in juvenile but not adult mice. Using in vivo chronoamperometry, a technique which measures region specific 5‐HT clearance in brain, studies are underway to determine whether the antidepressant‐like effects of D22 in juvenile and adolescent mice are related to its ability to inhibit 5‐HT clearance.Support: NIH MH093320 / MH064489