Mohammed T. Abou-Saleh

504 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYTable 91.1Family studies in late-onset schizophreniaReference No. No. Age Definition of illness Risk of schizophrenia Risk of affective disorder53 a 65 440 Schneiderian first rank Siblings: 9.8% Not statedParents: 4.4% (9 of 24late-onset)25 57 460 ‘‘Late paraphrenia’’ Siblings: 2.5% Not statedParents: 0Children: 7.3%Nephews/nieces: 3.1%14 93 460 ‘‘Late paraphrenia’’ 5 relatives (2 late-onset) 16 relatives43 45 465 Systematized delusions with or Siblings: 2.3%Not statedwithout hallucinations Fathers: 2.2%Mothers: 4.4%44 a 110 440 Schneiderian first rank 19.4% 0%54 a 62 cases: 58 early-onset controls 450 Late- vs. early-onset schizophrenia(definition of illness not stated)10.8% vs. 17.7% in earlyonsetpatients2.0% vs. 6.6% in earlyonsetpatients48 35 cases; 35 affective disorder 444 ‘‘Persistent delusions’’ with no 5 relatives vs. 3 relatives of 0 relatives vs. 12 relatives ofcontrolsaffective features4 47 cases; 42 controls 460 ‘‘Late paraphrenia’’ (cases) vs.non-psychiatric controlsa Quoted by Volavka 55 (1985).From ref. 56, with permission.controlsNarrow age range (15–50years): 1.3% in cases andcontrols; wide age range(15–90 years): 2.3%cases, 2.2% controlscontrols21 relatives of cases vs. 6relatives of controls(p=0.003)afforded an opportunity to do this. The sample consisted of 91%data reviewed here suggest that there may indeed be a gradient ofall ages at onset. The Camberwell Register First Episode Study 9 medication in late life.familial risk, dependent upon age of onset of the proband. Such anotion is compatible with the idea that late-onset patients have asmaller genetic loading than those with early onset and thusrequire more ‘‘environmental events’’ to manifest the illness. Thisconception presumes a multifactorial ‘‘vulnerability/stress’’ or‘‘continuum of liability’’ model of schizophrenia that is useful inas far as it produces testable hypotheses. For example, Holden 6 ,ina study of 47 cases of paranoid psychosis with onset after the ageof 60, found that deafness, which is considered a risk factor forlate-onset schizophrenia (see below), was inversely related tofamily history of psychiatric illness.An equally parsimonious explanation for the intermediatefamily risk in late-onset probands is that it is due to the greaterproportion of such patients who have a less genetic subtype ofillness. For example, paranoid ideation is common in late-onsetschizophrenia patients, and Tsuang and Winokur 7 and Tsuang etof all patients (n=477) with a non-affective psychotic disorder,from a defined catchment area, who made their first contact withthe psychiatric services over the period 1965–1984. Patients wererediagnosed according to a range of operational definitions forpsychotic disorders, using the OPCRIT diagnostic system. Age-atonsetincidence curves were established for both sexes, using thebase population figures as the denominator. Not only was themean age at onset later for females, but the distributions of onsetage for the two sexes were not isomorphic; males showed adramatic early peak and a lesser mid-life peak, whilst femalesshowed three peaks of onset, one in very late life. When subjectedto an admixture analysis, the distributions for males showed twoage distributions, with modal ages at onset of 21 and 39 years,whilst for females there were three distributions, with modalonsets at 22, 37 and 62 years 10 .A possible explanation for the female excess in late-onsetal. 8 have reported that patients with the paranoid subtype of schizophrenia is that female schizophrenia patients are somehowschizophrenia have later onset and fewer affected relatives than dothe more disorganized ‘‘hebephrenia’’ patients. Furthermore, atleast some patients labelled ‘‘late-onset schizophrenics’’ have anorganic illness (see below), and such patients would be expected tohave a low family risk for schizophrenia. Also, the family loadingfor affective disorder found in some studies (see above) suggeststhat at least some patients with late-onset schizophrenia haveaetiological links with affective disorder.‘‘protected’’ from the manifestations of disease at earlier ages.For example, Seeman 11 has suggested that the antidopaminergicaction of oestrogen has such a protective function, with theillness manifesting perimenopausally when oestrogen levels fall.This theory gains support from animal and clinical studies thatshow that oestrogen has antidopaminergic properties. However,as described above, the incidence curves for schizophrenia inwomen do not mirror the menopausal fall in oestrogen levels,and the disease can manifest for the first time at very advancedages.FEMALE GENDERA further consideration in attempting to explain the femaleexcess amongst late-onset schizophrenia patients is the fact thatAll studies of late-onset schizophrenia that have included bothsexes have attested to an excess of women. Table 91.2 shows datafrom a representative sample of such studies, which confirm thatthis female excess is robust to more- or less-restrictive definitionsof illness. This excess cannot be explained on the basis of therelative longevity of women.What is also evident from the data in Table 91.2, is that theolder the sample, the greater the female excess. Few studies haveassessed gender differences in non-affective psychoses in anepidemiologically-based sample of patients, ascertained acrossthe brains of males and females age differently. Of particularinterest is the differential rate of loss of dopamine D2 receptors,with loss being more precipitous in men than in women. Thus,young males have a relative excess of D2 receptors compared withfemales, but in older females this gender difference is reversed 12 .This differential loss of D2 receptors between the sexes couldconceivably play a part in the vulnerability of females to themanifestation of schizophrenia in late life and might also account,in part at least, for the particular female vulnerability to thedevelopment of tardive dyskinesia on exposure to neuroleptic