The dopamine hypothesis of schizophrenia and the emphasis on other neurotransmitters, most notably norepinephrine, serotonin, and acetylcholine, in the pathogenesis of depression, have focused attention away from substantial evidence implicating dopamine in affective disorders. The clinical evidence includes alterations in depressive symptoms with aging (concomitant with possible changes in dopamine metabolism), potential dopaminergic involvement in several subtypes of depression, similarities between some of the symptoms of Parkinson's disease and those of depression (including psychomotor retardation and diminished motivation), and potential dopaminergic abnormalities in seasonal mood disorder. The biochemical evidence in patients with depression derives from studies of homovanillic acid, a dopamine metabolite, indicating diminished dopamine turnover. In addition, there is a considerable amount of pharmacologic evidence regarding the efficacy of antidepressants with dopaminergic effects in the treatment of depression. We conclude that dopamine likely contributes significantly to the pathophysiology of depression. However, the role of dopamine in this syndrome must be understood in the context of existing theories involving other neurotransmitters which may act independently, and interact with dopamine and other neurochemicals, to contribute to depression.

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Altered platelet morphology and function have been reported in patients with diabetes. They are likely to be associated with the pathological processes and increased risk of vascular disease seen in these patients. Mean platelet volume (MPV), platelet count, and megakaryocyte (MK) ploidy (DNA content) were measured in (1) nondiabetics with normal coronary arteries, (2) nondiabetics with coronary artery atherosclerosis, (3) diabetics without evidence of vascular complications, and (4) diabetics with vascular disease. The platelet count (+/- SD) was increased in all groups but only significantly in the diabetics with vascular disease (236 +/- 65 versus 250 +/- 54 versus 257 +/- 64 versus 295 +/- 90 [P < or = .05] x 10(9)/L, for groups, I, II, II, and IV, respectively). The MPV was significantly increased in patients with atherosclerosis (7.0 +/- 0.4 versus 8.0 +/- 1.2 [P < or = .05] versus 7.2 +/- 0.9 versus 8.1 +/- 0.9 [P < or = .05] IL). Geometric mean MK ploidy was significantly increased in all groups compared with controls (16 +/- 1.5 versus 18.7 +/- 1.8 [P < or = .05] versus 19.8 +/- 1.6 [P < or = .05] versus 20.1 +/- 2.7 [P < or = .05]). Furthermore, some patients with vascular disease and/or diabetes had a modal ploidy shift from 16 (the normal mammalian modal ploidy) to 32, with a concomitant reduction of MKs in the 8 and 16 ploidy classes. This shift was seen particularly in the diabetics with vascular disease (P = .007). Interleukin-6 (IL-6) levels were measured and were elevated in patients with atherosclerosis; the highest levels were found in the diabetic patients (0.7 +/- 0.9 versus 5.3 +/- 5.5 [P < or = .05] versus 2.5 +/- 2.8 versus 6.7 +/- 5.5 [P < or = .05] ng/L). In the diabetic patients with atherosclerosis, fibrinogen levels were also increased (2.85 +/- 0.76 versus 3.34 +/- 1.32 versus 2.43 +/- 1.50 versus 5.59 +/- 1.72 [P< or = .05] g/L). Furthermore, IL-6 levels correlated with MK ploidy (r = .45, P = .009) and fibrinogen levels (r = .5, P = .0001). This study demonstrates that patients with vascular disease, particularly diabetics, have an altered MK ploidy distribution, showing a shift toward higher ploidy in association with an increased platelet mass (count x volume). Changes in platelets in diabetes probably reflect MK changes, which themselves are a response to systemic change.

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