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 0-470-84641-091Aetiology, Genetics and Risk FactorsDavid J. Castle 1 and Robin M. Murray 21 Mental Health Research Institute and University of Melbourne, Melbourne, Australia and 2 Institute of Psychiatry, London, UKThere is considerable controversy about the classification of thelate-onset non-affective psychoses, and their relationship to‘‘typical’’ early-onset schizophrenia. Kraepelin delineated ‘‘paraphrenia’’,a late-onset delusional state with prominenthallucinations, as distinct from dementia praecox. Mayerperformed a follow-up study of a number of patients diagnosedby Kraepelin as having paraphrenia, and found that a highproportion had a longitudinal course of illness similar to that ofdementia praecox patients. This study challenged the distinctionbetween paraphrenia and dementia praecox and, once theBleulerian label ‘‘schizophrenia’’ had been widely adopted,‘‘paraphrenia’’ became a neglected term.The term was resurrected by Roth 1 as ‘‘late paraphrenia’’,although he used it to describe a rather different group of patients,namely those manifesting a paranoid delusional state withprominent hallucinations for the first time in very late life.Confusingly, ICD-9 retained Roth’s category, relabelled it‘‘paraphrenia’’, and subsumed it under ‘‘paranoid states’’; thishas been dropped altogether from ICD-10. Furthermore, definitionsof ‘‘late onset’’ range from over the age of 40 (after Feighneret al. 2 ) to over 60 (after Roth 1 ). The 3rd edition of the AmericanPsychiatric Association’s Diagnostic and Statistical Manual(DSM-III) set an age cut-off of 45 years for schizophrenia, sothat later-onset paranoid states were labelled ‘‘atypical psychosis’’or ‘‘paranoid (delusional) disorder’’. The revised editions of themanual (DSM-III-R and DSM-IV) removed this age stipulation,and it is now widely believed that schizophrenia can manifest forthe first time at any age.These changing conceptions make comparison across studiesdifficult. In this chapter, we refer to studies where a 40 year orlater cut-off is used. We employ the term ‘‘late paraphrenia’’ forthose patients with an illness akin to Roth’s description, with firstmanifestation usually after the age of 60. Delusional (paranoid)disorder is not specifically addressed here.GENETICSIt is generally accepted that schizophrenia tends to run in families.Gottesman and Shields 3 , pooling data from a number of familystudies, calculated the average morbid risk for schizophrenia(broadly defined) in first-degree relatives of schizophrenia probandsto be around 10%, compared with about 1% in the generalpopulation. Rates are generally lower when operational criteriasuch as those of DSM-III are applied, but the higher relative riskin first-degree relatives compared with the general populationremains. Twin studies consistently report higher concordancerates for schizophrenia in monozygotic (MZ) compared withdizygotic (DZ) twin pairs, suggesting that, in part at least, thisfamilial aggregation is due to genetic factors. This conclusion issupported by adoption studies, which show that biological risk forschizophrenia is carried with the proband, irrespective of familyenvironment (i.e. ‘‘adopted-away’’ offspring).Few studies have specifically assessed familial aggregation inlate-onset schizophrenia (see Table 91.1) and these all havemethodological shortcomings. Authors have often failed to give aclear definition of illness in either probands or relatives;standardized diagnostic instruments have not been employed;and assessments have not been blind to proband diagnosis.Furthermore, proband numbers are mostly small, and it is oftenunclear exactly how many family members were assessed, andwhether adjustments were made for those who were not. Also,because of the late onset of illness, many family members(siblings, parents) would have died and thus have been unavailablefor interview; it is also difficult to know whether relatives hadpassed through the period of risk for illness-onset. Controls haverarely been employed, reliance being placed on results fromindependent studies of earlier-onset patients, which have againused different methodologies and diagnostic criteria.Thus, the conclusions that can be drawn are limited. Overall,studies of ‘‘late paraphrenia’’ patients show rates of schizophreniain siblings that are intermediate between those for siblings ofearly-onset probands and the general population. The discrepancyin rates quoted for parents is probably due to problems inassessing the parental generation. Those studies with an earlierage cut-off report higher risks for schizophrenia in relativesapproaching those in the relatives of early-onset probands.However, these studies have used broad, non-specific definitionsof schizophrenia, and have thus probably overestimated rates.The very high rate in the study of Huber and colleagues (see Table91.1) is probably due to the misdiagnosis of patients with affectivedisorders, as they report no relatives with affective illness. Themore recent study of Howard et al. 4 , who employed a controlledfamily interview methodology, is more sound. These researchersassessed lifetime risk of schizophrenia and other psychiatricdisorders in 269 relatives of 47 late paraphrenia patients, andcompared the rates with those in 272 relatives of 42 elderly generalpopulation controls. The results, shown in Table 91.1, reveal nodifference in the risk between the two groups of relatives withrespect to schizophrenia, but do show the relatives of theschizophrenia probands to have a significantly elevated risk ofdepression (16.3% vs. 4.4% in controls).Kendler et al. 5 in a review of family and twin studies, found nostrong consistent relationship between age at onset of schizophreniaand risk for the illness in relatives. However, they did notspecifically investigate late-onset schizophrenia patients, and thePrinciples 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