In our cohort of 2.27 million people, 34 494 (1.5%) had a history of epilepsy, with a median age of 14.7 at the first admission. During follow-up, 276 (0.8%) of them were later admitted to hospital for schizophrenia and 519 (1.5%) for schizophrenia-like psychosis. The median duration between the first admission for epilepsy and the first admission of schizophrenia or of schizophrenia-like psychosis was 8.2 years or 8.0 years, respectively. displays the distribution of cases and person years at risk in our cohort.
Distribution of cases with schizophrenia and schizophrenia-like psychosis and person years at risk in the study cohort of 2.27 million people
Main effect of epilepsy
A history of epilepsy was associated with an increased risk of schizophrenia or schizophrenia-like psychosis; and the effect remained virtually unchanged when we controlled for various potential confounders (). People with epilepsy had 2.48 times the risk of schizophrenia (95% confidence interval 2.20 to 2.80) and 2.93 times the risk of schizophrenia-like psychosis (2.69 to 3.20) compared with the general population.
Relative risk (95% confidence interval) of schizophrenia and schizophrenia-like psychosis associated with epilepsy and family history of psychosis and epilepsy
The impact of epilepsy on the risk of schizophrenia or schizophrenia-like psychosis was not statistically different by sex (test of sex interaction: P = 0.31 for schizophrenia, P = 0.51 for schizophrenia-like psychosis) but differed significantly by age (P < 0.01 for schizophrenia, P = 0.04 for schizophrenia-like psychosis). Stratified analyses by age showed that the relative risk of schizophrenia was 2.03 (1.67 to 2.47), 2.28 (1.88 to 2.78), and 4.00 (3.14 to 5.09) for people aged 15-24, 25-34, and ≥35, respectively. The corresponding relative risks for schizophrenia-like psychosis were 2.38 (2.07 to 2.74), 3.13 (2.73 to 3.58), and 3.77 (3.08 to 4.61).
These results were virtually unchanged when we excluded people who were registered with epilepsy for the first time between 1977 and 1982, although some of these people could be prevalent cases with onset of epilepsy before January 1977 (data not shown).
Family history of psychosis and epilepsy
A family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis after we adjusted for personal history of epilepsy (). A family history of schizophrenia increased the risk of schizophrenia by a factor of 7.57 (6.98 to 8.20) and the risk of schizophrenia-like psychosis by a factor of 6.24 (5.83 to 6.69), while the figures for family history of epilepsy were 1.11 (1.01 to 1.22) for schizophrenia and 1.20 (1.11 to 1.29) for schizophrenia-like psychosis.
Moreover, our data indicate that the effect of both personal and familial history of epilepsy interacted with the effect of a family history of psychosis (test of interaction: P = 0.0081 and P = 0.0732, respectively, for schizophrenia-like psychosis). shows that a personal history of epilepsy had a stronger effect on the risk for schizophrenia or schizophrenia-like psychosis in people without a family history of psychosis than for people with it. At the same time, a family history of epilepsy significantly increased the risk only for people with no family history of psychosis.
Adjusted relative risks* (95% confidence intervals) associated with epilepsy in cases and family relatives, stratified analysis according to family history of psychosis†
Type of epilepsy, age at admission, and number of admissions
All types of epilepsy significantly increased the risk of developing schizophrenia or schizophrenia-like psychosis (). The relative risk associated with complex partial epilepsy was slightly higher than the others, but the differences were not significant.
Relative risks* for schizophrenia and like psychosis according to type of epilepsy
The effect of epilepsy differed significantly according to age at first admission for epilepsy and number of admissions. The relative risk increased consistently with increasing age at onset (). For every five year increase in age at diagnosis the increase was linear, resulting in an analogous relative risk of 1.20 (1.12 to 1.28, P < 0.0001) for schizophrenia of 1.20 (1.14 to 1.26, P < 0.0001) for schizophrenia-like psychosis. This effect was also evident when we stratified analyses by age. The relative risk for schizophrenia or schizophrenia-like psychosis also tended to be higher for people with multiple admissions for epilepsy.
Relative risks (95% confidence intervals) of schizophrenia or schizophrenia-like psychosis in relation to age at first admission and total number of admissions for epilepsy