Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-072NeurochemistryL. S. Schneider, updated by M. T. Abou-Saleh 1St George’s Hospital Medical School, London, UKAs a preface to this chapter, it is important to consider that majordepression is characterized and defined by descriptive, notbiological, criteria, making it unlikely that a neurochemicalfinding could adequately characterize the disorder. The underlyingvalidity of the diagnosis is assessed against other descriptivefeatures of the illness such as symptoms, course, treatmentoutcome and biological changes. Yet people who manifest similarclinical phenomenology may not necessarily share similarpathophysiology. Major depression is heterogeneous in itsexpression, possessing various phenomenology, family historyand course. Therefore, the underlying biology of each subtypewould be expected to be distinct from others. This, however, isoften not the case.In the elderly, a neurochemical characteristic of depressionwould have to be sufficiently specific to distinguish depressionfrom dementia or from secondary depression. In addition,neurochemical differences would be expected between late-onsetand early-onset depression, or delusional and non-delusionaldepression, thus helping to validate these putative subtypes.elderly, such as the dexamethasone suppression test (DST),thyroid releasing hormone (TRH) test and platelet monoamineoxidase (MAO) activity, as discussed below, may change inphysical disease as well as in depression, so that their adequateevaluation requires consideration of the effects of medical illness6–8 .LATE-ONSET VS. EARLY-ONSET DEPRESSIONEarly-onset depressives, i.e. patients with depression first occurringearlier in life, may be biologically distinguished fromsimilarly-aged patients with late-onset depression. For example,late-onset elderly patients have a lower sedation threshold toamobarbital (both before and after treatment) than early-onsetdepressives 9 ; they may have greater corticol atrophy andventricular enlargement; and they may have relatively increasedplatelet MAO activity (see below).PRIMARY DEMENTIA VS. PRIMARY DEPRESSIONIN THE ELDERLYBoth of these disorders share certain neurochemical characteristicsand behavioural symptoms. For example, noradrenergicdeficits are common to both disorders. Interestingly, greaterneuronal loss in the nucleus locus coeruleus, the main noradrenergicoutflow to the cortex, occurred in Alzheimer’s disease (AD)patients who showed clinical manifestations of depression beforedeath than in those who did not 1,2 . Similarly, primary dementiapatients with major depression had over a 10-fold greaterreduction in norepinephrine (noradrenaline) than non-depresseddementia patients 3 , suggesting that, at least among elderlypatients, noradrenergic functions may play a role in secondarydepression.Cerebrospinal fluid (CSF) studies demonstrate decreasedconcentrations of somatostatin in both major depression andAD patients, often with no differences in monoamine metabolites4 .SECONDARY VS. PRIMARY DEPRESSIONSignificant depressive symptomatology is common in oldergroups, who are more likely to be medically ill, and depressivesymptoms in medically ill patients range from 10% to 50% 5 .However, the neurochemistry associated with depression in theDELUSIONAL VS. NON-DELUSIONAL DEPRESSIONDelusional depression may represent a distinct clinical subgroupand be more common among patients with late-onset depression10 . Yet there is little evidence for biological differencesbetween groups of depressed patients with and without delusions.For example, urinary MGPG (3-methoxy-4-hydroxy-phenylglycol),a metabolite of norepinephrine, has been reported to bereduced 11 , increased 12 and not different 13 in delusionally depressedpatients. Similarly, serum levels of dopamine-b-hydro-oxylasehave been reported to be both lower 14 and not different 15 indelusional depression.BIOLOGICAL CHANGES IN AGING ANDDEPRESSIONMany of the neurobiological changes associated with aging aresimilar to those that occur with depression. For example, normalaging and depression are both associated with decreased brainconcentrations of serotonin, dopamine, norepinephrine, theirmetabolites, increased brain MAO-B activity, increasedhypothalamic–pituitary–adrenal (HPA) activity and increasedsympathetic nervous system activity 16 .Principles and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd