No significant association between prenatal exposure to poliovirus epidemics and psychosis

Matthew Cahill, David Chant, Joy Welham, John McGrath

Objective:

To examine the association between prenatal exposure to poliovirus infectionand later development of schizophrenia or affective psychosis in a Southern Hemispherepsychiatric register.

Methods:

We calculated rates of poliomyelitis cases per 10 000 background population andrates for schizophrenia (n = 6078) and affective psychosis (n = 3707) per 10 000 births for theperiod 1930–1964. Empirically weighted regression was used to measure the associationbetween a given psychosis birth-rate and a poliomyelitis epidemic during gestation.

Results:

There was no statistically significant association between exposure to a poliomy-elitis epidemic during gestation and subsequent development of schizophrenia or affectivepsychosis.

Conclusions:

The lack of a consistent statistically significant association between poliovirusepidemics and schizophrenia suggests that either poliovirus may have a small effect which isonly detectable with large data-sets and/or the effect may be modified by location. Furtherinvestigation of such inconsistencies may help elucidate candidate risk-modifying factors forschizophrenia.

Key words:

Australian and New Zealand Journal of Psychiatry 2002; 36:373–375

aetiology, affective psychosis, poliovirus, prenatal exposure, schizophrenia.

The hypothesis that viruses or other infectious agentsmay cause schizophrenia or other serious psychiatricdisorders dates back to the 19th century. Over recentdecades, many studies have examined the putative roleof prenatal viral infection as a risk factor for schizo-phrenia [1]. A number of authors have suggested thatprenatal infection with polioviruses could contribute tothe development of schizophrenia [2]. However, pre-vious studies comparing the incidence of poliomyelitisand the number of births of individuals who developschizophrenia have yielded mixed results. In the UnitedStates, neither Watson and colleagues [3] nor Torrey and

colleagues [4] found an association in Minnesota, whereasthe latter study found a significant correlation in Con-necticut, where poliomyelitis preceded the schizophreniabirths by 18 months. A study in England and Wales [5]found no relationship between the number of deathsfrom poliovirus and schizophrenia; however, death is arare outcome of poliovirus infection and may not be anaccurate index of the onset or ending of an epidemic.The most recent study [6], using a large Finnish samplewith accurate psychiatric and poliomyelitis incidencedata, found a weak but significant association betweenpoliomyelitis and births five months later of individualswho developed schizophrenia later in life.

To date, however, no study has examined linksbetween poliomyelitis epidemics and schizophrenia birthrates in the Southern Hemisphere. Given that the epi-demiological profile of schizophrenia may be differentin the Southern Hemisphere, for instance in seasonalityof birth [7], and season of first admission [8], such a

Matthew Cahill, Research Associate; David Chant, Principal ResearchFellow; Joy Welham, Senior Scientist (Epidemiology) (Correspondence);John McGrath, Director

Queensland Centre for Schizophrenia Research, Wolston Park Hos-pital, Wacol, Queensland 4076, Australia Email: joy@wph.uq.edu.au

Received 7 June 2001; revised 9 October 2001; accepted 26 November2001.

374 PRENATAL POLIOVIRUS AND PSYCHOSIS

study is relevant. The specificity of the associationbetween poliomyelitis epidemics and schizophrenia versusaffective psychosis also warrants examination. Using alarge dataset from Queensland, Australia, the aim of thisstudy was to test whether there was any associationbetween prenatal exposure to poliovirus epidemics andthe later development of either schizophrenia or affec-tive psychosis.

Method

All Australian cases born between January 1930 and December1964 and first registered between 1972 and 1991 with an ICD8 or 9diagnosis of schizophrenia (ICD295.

x

;

n

= 6078) or affective psycho-sis (ICD296.

x

;

n

= 3707), were extracted from the Queensland MentalHealth Statistics System, a state-wide public psychiatric register.

For the same period, monthly counts of cases of poliomyelitis wereobtained from the Annual Reports of Queensland Health Department.Similarly information on background population numbers and monthlytotals of general population births for Queensland were obtained fromthe Australian Bureau of Statistics. Using these data, we calculatedrates per 10 000 background population for poliomyelitis and rates per10 000 general population births for the psychoses.

The eight identified poliomyelitis epidemics peaked in eithersummer or early autumn: February 1932, March 1938, January 1941,December 1945, April 1951, March 1953, March 1955 and January 1962.During these eight epidemics, the mean poliomyelitis cases per monthwas 36.15 (SD = 36.99), compared with 2.32 (SD = 5.21) in non-epidemic months.

A ‘poliomyelitis window’ was constructed for the months surround-ing the eight peak poliomyelitis rates. To supply a simple model for theextent of the epidemic, poliomyelitis was deemed to be active withinthis window. Thus, based on 24 months surrounding each of theepidemic peaks, the ratio of the psychosis birth rates within the polioepidemic window and the birth rates in remaining nonepidemic monthsprovides an estimate of the relative risk of psychosis attributable to thepoliomyelitis epidemic.

We examined three windows of different lengths – namely 6, 8 and10 months. The latter covers possible prenatal exposures from con-ception to 10 months postnatal and compares epidemic months with acombination of the 7 months preceding and 7 months following theepidemic window, thus controlling for seasonality. It also includes thefifth month following the epidemic, which was found to be associatedwith polio in the Finnish study.

An empirically weighted regression was used, in which the pooledpsychosis birth rates

R

h

are regressed on

X

h

,

h

= – 12, . . . , 12, where

R

h

is the mean of eight corresponding rates over the period 1930–1964.The reciprocal of the sample variance of

R

h

provides the weights, and

X

h

is an indicator variable, equal to unity within a poliomyelitiswindow, and zero elsewhere. These analyses were performed on allsubjects, and repeated for males and females separately, using PROCIML in SAS version 7 [9].

Power analysis suggested that the number of patients with schizo-phrenia in this sample would have sufficient power (82%) to detect (atp < 0.05) a relative risk as low as 1.175. For affective psychosis, thestudy had sufficient power (95%) to detect (at p < 0.05) a relative riskas low as 1.30.

Results

Taken over the period of the window, there were no statisticallysignificant associations between psychosis rates and poliomyelitis epi-demics.

Figure 1 displays the pooled rates of schizophrenia and affectivepsychosis surrounding the poliomyelitis peaks for the 8-month window– which showed the largest relative risk. Here the risk for schizo-phrenia was estimated to be 1.04 (95% CI 0.93, 1.16) while foraffective psychosis it was 0.99 (95% CI 0.85, 1.15).

No significant associations were found when the poliomyelitiswindow was adjusted to 6 or 10 months, nor when any of the analyseswere conducted for males and females separately (data not shown).

Discussion

Our study found no significant association betweenprenatal exposure to poliomyelitis epidemics and increasedrates of schizophrenia and affective psychosis. When thesame analysis was conducted on males and femalesseparately, the results did not change.

One strength of the study was that we included state-wide data, which allowed us to calculate rates for boththe psychiatric disorders and poliomyelitis. During thestudy period, Queensland experienced eight clearly demar-cated poliomyelitis epidemics; however, given this wasan ecological analysis, we could not determine the expo-sure status of mothers of those who developed a psycho-sis. The register was designed primarily for administrativepurposes and thus the reliability of diagnoses may besuboptimal, and may overestimate case birth rates (becausethe numerator includes cases born in other Australianstates, whereas the denominator covers only Queenslandbirths and between-state migration is unlikely to besystematically linked to poliomyelitis epidemics). Never-theless, any true association between poliomyelitis epi-demics and psychosis birth rates would be more difficultto detect. In addition, our study did not have sufficientpower to detect the small effect size found for schizo-phrenia in the Finnish study (i.e. a relative risk of 1.05,95% CI 1.00–1.11). To exclude a true but weak effect ofpolio, larger sample sizes and/or meta-analysis would berequired. This may be important given that exposuresassociated with small effect sizes, if prevalent, mayaccount for sizeable population attributable risks.

While we found no association between prenatal expo-sure to poliomyelitis epidemics and increased risk ofschizophrenia, an association has been found in someother sites. It is possible that poliovirus epidemics mayact as proxy markers of other risk-modifying factors (forexample, staying indoors may result in hypovitaminosis D[10], or transmission of viruses may differ in warm versuscold climates). These other risk factors associated withpoliomyelitis epidemics may not be uniformly distributed

M. CAHILL, D. CHANT, J. WELHAM, J. M

C

GRATH 375

(in timing, place and/or strength). There has been arelative poverty of novel non-genetic risk factors forpsychoses. We believe that poliovirus warrants furtherstudy, and that inconsistencies between sites may pro-vide fertile ground for the refinement of candidate risk-modifying factors of schizophrenia.

Acknowledgement

The Stanley Foundation supported this project.

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Figure 1. Using an 8-month window, pooled rates for schizophrenia births and affective psychosis births (per 10 000 births), and poliomyelitis rate (per 10 000 population) around the peaks of eight polio epidemics (1930–1964).