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 0-470-84641-018The Natural History of Psychiatric Disorders:Early-onset Disease in Late Life andLate-onset IllnessJudith HaysDuke University Medical Center, Durham, NC, USAIs psychiatric pathology fundamentally different depending onwhen in the life course it emerges? Is the heterogeneity thatcharacterizes late life psychiatric disorders—their risk factors,presentation and course—partly resolved by distinguishingbetween ages of first onset? This chapter summarizes whystudying the onset of psychiatric illness is so difficult and, inspite of that difficulty, what distinguishes the epidemiology ofearly-onset disease in late life from late-onset illness.With respect to age of onset, the best-characterized DSM-IVdisorder (and our primary focus in this chapter) is majordepressive disorder (MDD). Some attention will also be directedto bipolar (BP) disorder and schizophrenia. Much less researchhas distinguished between early and late onset of dysthymia, ‘‘lateparaphrenia’’, or delusional disorder; we touch only briefly onthese subtypes. We do not discuss depressive and/or psychoticprodromes of dementia or psychiatric symptoms of other organicetiology, such as cancer or multiple sclerosis, with the exception ofdisorders related to cerebrovascular infarcts and depressionsecondary to cardiovascular disease.Studies of the prevalence and correlates of early-onset vs. lateonsetdisorders are treacherous for methodological reasons thatplague all psychiatric studies and all studies with retrospectivedesigns: determining who has what disorder and when it was firstdetected. Sometimes there is no consensus on the criteria for a‘‘case’’, because psychiatric disorders are based on clinical signsand symptoms and represent heterogeneous underlying pathophysiologicaland psychosocial causes. Subjects may be considereda case according to one set of criteria but not according to another.Elderly persons in particular report significant psychiatricsymptoms without meeting diagnostic criteria. Not infrequently,emergent symptoms may alter a diagnosis of long standing. Thus,clinical populations, from which many study samples are drawn,may be non-representative of all affected elders, due to varyingpatterns of help-seeking, clinical referral and symptom trajectories.All elderly populations in communities and institutions, are subjectto survival of the fittest, and early-onset subjects may besystematically absent due to death.Determining the precise age of onset is also problematical.Recall of specific dates may be compromised by memory lapse ortelescoping of events, cognitive impairment or a ‘‘reminder effect’’associated with multiple episodes. Classification of early-onset vs.late-onset depends on the cut-point chosen, which is oftenunspecified in diagnostic schema; across various studies, cutpointshave ranged between 20 and 60 years of age, although mostuse 45 or 50 years. For all of these reasons—diagnostic variability,selection bias, subject attrition and classification issues—estimatesof the prevalence and risk of early-onset and late-onset disordersvary dramatically, as described below. Nevertheless, this chapterdescribes the state of agreement regarding differences in early andlate affective and psychotic disorders.AFFECTIVE DISORDERSMajor Depressive DisorderThe prevalence of affective disorders (MDD/BP) is lower amongcommunity-dwelling elders than among younger populations 1,2 .Prevalence estimates of late-life MDD from large studies (n51000)range between 1% (USA) to 3.7% (Finland), and prevalence ofminor depression ranges from 8.3–23.2% 3–5 . In nursing homes,5.9–16.5% of patients demonstrate clinically significant depression6–7 . Among medical outpatients and inpatients, respectively,5–7% and 10–20% may meet criteria for MDD 8–10 . Of affectedelders in the community, van Ojen and colleagues 11 estimated that70% may have had a first onset after the age of 65, i.e. late-onsetdepression (LOD) (Amsterdam, Holland). In the ECA (USA)study, the mean age of onset of MDD for subjects older than 65years was 48.9 years, suggesting a large proportion of patientswith late-onset 1 .The most provocative etiological findings regarding age ofonset concern structural and functional brain abnormalitiesamong LOD patients. Depressed elderly patients tend to havemore abnormalities, particularly in the frontal regions, than docontrols, although not universally 12–14 . LOD patients tend topresent with more brain lesions than do patients with early onsetof depression (EOD) 12 , and subcortical and basal ganglia changeshave been associated with greater severity in LOD 15 . These resultsfrom MRI studies are suggestive when paired with results showingincreased vascular medical co-morbidity (e.g. hypertension, strokeand heart disease) among LOD patients 13,16 . Thus, risk of somesubtypes of LOD may be attributable to vascular impairment and,by implication, preventable, using heart-healthy strategies such asdiet, exercise and stress management. Where these results areheterogeneous, the inclusion or exclusion of subjects withcardiovascular histories may be a major factor 16,17 .At the other end of the modifiability spectrum, genotype mayaccount for differences in the causal webs of EOD and LOD.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