Table 2 Risk increasing effect of the risk factors life-time depression and high neuroticism on the broad psychosis outcome for those with onset of first psychotic symptoms in young age (18–34 years), middle age (35–49 years) and old age (50– 64 years) Depression Neuroticism Age at onset Young Middle Old Young Middle Old Risk factor Yes 8.8% 5.1% 3.7% 7.4% 5.2% 3.8% No 2.3% 2.5% 2.0% 2.1% 2.4% 1.5% Risk differences 6.5% 2.5% 1.7% 5.3% 2.8% 2.2% 291 95% CI 3.3%, 9.7% 0.4%, 4.7% )0.7%, 4.1% 2.9%, 10% 0.8%, 5% 0.2%, 4.2% Effect sizes are expressed as risk differences between those who had the risk factor and later on developed the psychosis outcome (yes) and those who did not have the risk factor but still developed the psychosis outcome (no). j Risk factors Age effect modification Main effects of risk factors on the broad psychosis outcome in NEMESIS have been described in other reports [4, 21, 30, 34, 35, 62, 66]. Signiﬁcant interac- tions with age at onset were found for depression (Risk difference = )2.2%, 95% CI = )4.1%, )0.3%) and family history (FH) of treated delusions/halluci- nations (RD = 3.3%, 95% CI = 0.3%, 6.2%), suggest- ing that the effects of both varied across age groups. The negligible prevalence, however, of FH treated delusions/ hallucinations in those having the broad psychosis outcome made further analysis impracti- cable (n = 3, all in the middle group). Statistical trends for interaction were observed for sex (RD = )1.3%, 95% CI = )0.8%, 2.7%), neuroticism (RD = )1.5%, 95% CI = )3.1%, 0.1%) and hearing impairment (RD = )5.9%, 95% CI = )12.1%, 0.2%). For the latter, the prevalence was too small to carry out stratiﬁed analyses, leaving depression, neuroti- cism and sex as targets for further analyses. Age at onset and depression Stratiﬁed comparisons (Table 2) demonstrated that baseline depressive symptoms signiﬁcantly increased the risk for developing the broad psychosis outcome within a three-year interval in the young (RD = 6.5%, 95% CI = 3.3%, 9.7%) and middle group (RD = 2.5%, 95% CI = 0.4%, 4.7%), but not in the old group (RD = 1.7%, 95% CI = )0.7%, 4.1%) (Table 2). In the youngest group, 8.8% of those reporting life-time depressive symptoms at baseline had the broad psy- chosis outcome 3 years later as opposed to 2.3% of those reporting no depressive symptoms. In the old group, 3.7% of those reporting life-time depressive symptoms developed the broad psychosis outcome as opposed to 2.0% of those reporting no depressive symptoms. The absolute RD between the young and the old group was signiﬁcant (RD = 4.8%, 95% CI = 0.8%, 8.8%). Thus, the risk-increasing effect of depression declined by a factor of 3.8 (6.5% / 1.7%) with age at onset. Age at onset and neuroticism A signiﬁcant risk-increasing effect of neuroticism was observed for the young (RD = 5.3%, 95% CI = 2.7%, 7.9%), middle (RD = 2.8%, 95% CI = 0.8%, 4.9%) and old group (RD = 2.2%, 95% CI = 0.2%, 4.2%). In the young group, 7.4% of those with high neuroticism scores at baseline developed the broad psychosis outcome, versus 2.1% of those with low neuroticism scores. These ﬁgures dropped to 5.2 % vs. 2.4% in middle age with further pro- gression to 3.8% vs. 1.5% in old age. The absolute RD between the young and the old group, however, did not reach signiﬁcance (RD = 3.1%, 95% CI = )0.2%, 6.4%). Thus, the risk increasing effect of neuroticism declined by a factor of 2.4 (5.3%/ 2.2%) with age at onset. Age at onset and sex The overall interaction between sex and age showed a trend towards signiﬁcance, but no clear effect was apparent after stratiﬁcation for age at onset. No greater risk for female sex was found in the young (RD = 1.7%, 95% CI = )0.4%, 3.7%), the middle (RD = 0.4%, 95% CI = )1.4%, 2.1%) or the old group (RD = )0.9%, 95% CI = )2.7%, 0.9%). Discussion j Incidence With an annual incidence of 0.3%, the community rate for (clinically relevant, but mostly untreated) non-affective, non-organic psychotic symptoms with late-onset was twenty times higher than the rate of treated clinical disorders reported previously [9, 11, 18, 32, 64]. Of all new ‘‘cases’’, 21% were over 50 years of age at illness onset, which is in line with previous ﬁndings [27, 31]. Similar disparities between clinical and community levels have been published with re- gard to prevalence rates of psychotic symptoms among the cognitively intact old [10, 24] and very old [43]. Psychosis in old age seems much more common