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Depression through the ages
Neurobiology of Aging, Vol. 9, p. 125. Pergamon Journals Ltd., 1988. Printed in the U.S.A.
0197-4580/88 $3.00 + .00
Depression Through the Ages TREY SUNDERLAND
National Institute of Mental Health, Bethesda, MD 20892
This commentary praises the authors' substantial achievement in their review of the controversial area of biological modeling in depression. While definitive conclusions are as of yet impractical, particularly in reference to the multifaceted but largely uncharted relationship between aging and depression, students of the field will be well served to have this reveiw as one of their starting points.
VEITH and Raskind have presented a thorough and interesting review of the biological theories of depression which have been proposed and investigated over the last twenty years. This scholarly paper presents a detailed and wellreferenced characterization of major biochemical findings from the original reserpine depletion model through the most up-to-date information concerning alpha-2 adrenergic function. The evidence for certain biological differences between depressed patients and normal controls is indeed compelling, but the identification of a unifying central nervous system (CNS) hypothesis or specific CNS abnormality in depression has been elusive, despite the repeated attempts of numerous investigators. The authors have added another variable to the already complicated equation surrounding depression research, that of aging. As they point out, the reasons for investigating the influence of aging on depression include the widely held assumption that the incidence of depression goes up with age. In addition, several of the well-known concomitants of depression (i.e., sleep disturbances, autonomic system dysfunction, and disturbed hypothalamic-pituitary-adrenal (HPA) axis function) are commonly associated with aging. Despite the current uncertainty as to the true epidemiology of depression in the aged population, the association between age and depression is fertile research territory. If there is indeed some biochemical change with aging that "predisposes" older individuals for depression, then there may also emerge possible preventive or therapeutic strategies applicable to young and old patients alike. Unfortunately, biological research with the elderly is still in its infancy. As acknowledged by the authors, precious little is known about the workings of the major neurotransmitter systems with age. While more information is available concerning the effects of age on the HPA axis, the ultimate regulation of that system is unclear for all age groups. Perhaps the best studied areas regarding depression and the aging process are those of the sympathetic nervous system and sleep physiology. These two models are expertly reviewed by the authors who provide state of the art information, in large part from their own laboratories and those of colleagues. It is at this point that our understanding of the process of aging and models of depression are closest, yet
still the biologic markers, while "intriguing," are inconclusive and require "further explanation." Veith and Raskind do not overstate our current knowledge; indeed, they chronicle the previous findings in an orderly fashion and frequently point out the weaknesses in our models. One of the confounding variables of any research with depression and the elderly is the diagnostic nomenclature. It is generally known to geriatricians that clinical presentations with the classic neurovegetative symptoms of depression are rare in older patients. Typically, they present with apathy, dysphoria, somatic complaints, and sleep disturbances. As a result, some symptoms of so-called "normal aging" may well be evidence of a partial or atypical depression in the older patient, thus clouding the diagnostic distinctions in previous studies. In addition, there is little psychopharmacologic research regarding differential responsiveness amongst the various antidepressant drugs across age groups. Rather, most psycho-pharmacologic studies in the elderly have concentrated on straightforward issues of therapeutic efficacy and clinical side effect profiles. The possibility of biochemical differentiation between elderly and young depressives have not been definitively addressed. As with many broad reviews, Veith and Raskind's title: "Aging and the Neurobiology of Depression" invites the reader to contemplate a vast amount of information in the hopes of achieving a new synthesis and reaching novel conclusions. Perhaps by design of the authors, one is instead left with the haunting question " W h y is more not known after all these years?" Rather than answering all our questions about depression research, Veith and Raskind have skillfully presented the current models as they are and made numerous suggestions about future studies, particularly as related to the effects of aging. While aging itself is not represented strictly as another model of depression, per se, it does allow for the study of certain symptoms, especially those associated with atypical depression, and invites comparisons with studies of depression in young adults. Thus, by thoughtfully reviewing our current neurochemical knowledge base regarding depression and aging, Veith and Raskind have cautiously retained us of the limitations of mononeurotransmitter models to explain complex biologic f'mdings and suggested future directions to pursue.
125
0197-4580/88 $3.00 + .00
Depression Through the Ages TREY SUNDERLAND
National Institute of Mental Health, Bethesda, MD 20892
This commentary praises the authors' substantial achievement in their review of the controversial area of biological modeling in depression. While definitive conclusions are as of yet impractical, particularly in reference to the multifaceted but largely uncharted relationship between aging and depression, students of the field will be well served to have this reveiw as one of their starting points.
VEITH and Raskind have presented a thorough and interesting review of the biological theories of depression which have been proposed and investigated over the last twenty years. This scholarly paper presents a detailed and wellreferenced characterization of major biochemical findings from the original reserpine depletion model through the most up-to-date information concerning alpha-2 adrenergic function. The evidence for certain biological differences between depressed patients and normal controls is indeed compelling, but the identification of a unifying central nervous system (CNS) hypothesis or specific CNS abnormality in depression has been elusive, despite the repeated attempts of numerous investigators. The authors have added another variable to the already complicated equation surrounding depression research, that of aging. As they point out, the reasons for investigating the influence of aging on depression include the widely held assumption that the incidence of depression goes up with age. In addition, several of the well-known concomitants of depression (i.e., sleep disturbances, autonomic system dysfunction, and disturbed hypothalamic-pituitary-adrenal (HPA) axis function) are commonly associated with aging. Despite the current uncertainty as to the true epidemiology of depression in the aged population, the association between age and depression is fertile research territory. If there is indeed some biochemical change with aging that "predisposes" older individuals for depression, then there may also emerge possible preventive or therapeutic strategies applicable to young and old patients alike. Unfortunately, biological research with the elderly is still in its infancy. As acknowledged by the authors, precious little is known about the workings of the major neurotransmitter systems with age. While more information is available concerning the effects of age on the HPA axis, the ultimate regulation of that system is unclear for all age groups. Perhaps the best studied areas regarding depression and the aging process are those of the sympathetic nervous system and sleep physiology. These two models are expertly reviewed by the authors who provide state of the art information, in large part from their own laboratories and those of colleagues. It is at this point that our understanding of the process of aging and models of depression are closest, yet
still the biologic markers, while "intriguing," are inconclusive and require "further explanation." Veith and Raskind do not overstate our current knowledge; indeed, they chronicle the previous findings in an orderly fashion and frequently point out the weaknesses in our models. One of the confounding variables of any research with depression and the elderly is the diagnostic nomenclature. It is generally known to geriatricians that clinical presentations with the classic neurovegetative symptoms of depression are rare in older patients. Typically, they present with apathy, dysphoria, somatic complaints, and sleep disturbances. As a result, some symptoms of so-called "normal aging" may well be evidence of a partial or atypical depression in the older patient, thus clouding the diagnostic distinctions in previous studies. In addition, there is little psychopharmacologic research regarding differential responsiveness amongst the various antidepressant drugs across age groups. Rather, most psycho-pharmacologic studies in the elderly have concentrated on straightforward issues of therapeutic efficacy and clinical side effect profiles. The possibility of biochemical differentiation between elderly and young depressives have not been definitively addressed. As with many broad reviews, Veith and Raskind's title: "Aging and the Neurobiology of Depression" invites the reader to contemplate a vast amount of information in the hopes of achieving a new synthesis and reaching novel conclusions. Perhaps by design of the authors, one is instead left with the haunting question " W h y is more not known after all these years?" Rather than answering all our questions about depression research, Veith and Raskind have skillfully presented the current models as they are and made numerous suggestions about future studies, particularly as related to the effects of aging. While aging itself is not represented strictly as another model of depression, per se, it does allow for the study of certain symptoms, especially those associated with atypical depression, and invites comparisons with studies of depression in young adults. Thus, by thoughtfully reviewing our current neurochemical knowledge base regarding depression and aging, Veith and Raskind have cautiously retained us of the limitations of mononeurotransmitter models to explain complex biologic f'mdings and suggested future directions to pursue.
125