Stanley Research Unit, St Davnet's Hospital, Monaghan, Ireland
School of Mathematics, Dublin Institute of Technology, Dublin, Ireland
Stanley Research Unit, Cluain Mhuire Family Centre, Blackrock, Co. Dublin, Ireland
Stanley Research Unit, St Davnet's Hospital, Monaghan, Ireland
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland
Correspondence: Professor John L. Waddington, Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland. Tel. +353 1 402 2245; fax: +353 1 402 2453; e-mail: jwadding{at}rcsi.ie
Declaration of interest Supported by the Stanley Medical Research Institute.
* Presented in part at the European First Episode Schizophrenia Network
Meeting, Whistler BC, Canada, 27 April 2001.
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ABSTRACT |
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Aims To conduct prolonged accrual of all cases of non-affective and affective psychotic illness on an epidemiologically complete basis.
Method Within the region covered by CavanMonaghan psychiatric service (population 102 810), all putative cases of first-episode psychosis were diagnosed using DSMIV.
Results From 1995 to 2000, 69 cases of psychosis were ascertained, the incidence being 2.3-fold lower in females than in males. On resolving the core diagnoses of schizophrenia and bipolar disorder, incidence of schizophrenia among women was 7.5-fold lower than among men whereas incidence of bipolar disorder among women was 6.6-fold lower than among men.
Conclusions This homogeneous population, which eliminates factors associated with urbanicity and minimises confounding factors such as socio-economic, ethnic and geographical diversity, shows a markedly reduced incidence among females both of schizophrenia and of bipolar disorder.
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INTRODUCTION |
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METHOD |
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Of the population of CavanMonaghan 92% were born in the Republic of Ireland (74% in their county of residence, 18% elsewhere in Ireland); 7% were born in the UK and 0.3% were born in the USA, the vast majority of whom had at least one Irish parent; 0.7% were born elsewhere; and 97% currently resided at the same location as 1 year previously. These counties are entirely rural, the largest town having a population of 5750, with a primarily agriculture-based economy; 81% of households are owner-occupied and 70% of private households have at least one car (Central Statistics Office, 1994). This attests to the ethnic and socio-economic homogeneity and the low social mobility of the study region.
Evolution of psychiatric care over the study
This study involves procedures for case identification and assessment in
close association with the Cavan-Monaghan psychiatric service, from which all
care derives. Therefore, it is necessary to outline its evolution over the
period of the study. At the start of this study in 1995, the
CavanMonaghan psychiatric service provided integrated, sector-based
care through clinical teams led by four consultants in general adult
psychiatry; two admission units were available, one at St Davnet's Hospital,
Monaghan, and the other at Cavan General Hospital. The service had pioneered
(in an Irish context) the development of rehabilitation psychiatry, leading to
the provision of substantial alternative residential supports in the
community. Specialist services for patients with enduring disabilities were
available on a sessional basis, and close links existed with primary care
services, bolstered by the provision of psychiatric general practitioner (GP)
liaison clinics for a period in most of these practices.
In 1998, the service was radically reorganised: a full-time specialist rehabilitation service was established; a new community mental health team was set up for Co Monaghan, with a central emphasis on the provision of home-based care for acute illness as an alternative to admission; a new community mental health team was set up for Co Cavan in 2000; and a specialist service in psychiatry for the elderly for CavanMonaghan was inaugurated in 2000, with acute beds in Cavan General Hospital and a day hospital in Monaghan. This model of care is community based with close links to primary care and geriatric services. In these specialist teams, domiciliary visiting and home-base working is emphasised. There is a high provision of psychiatric nurses in new specialist roles and there are multi-centre out-patient clinics together with day hospital and day centre services. Referrals to the service are predominantly from GPs, sometimes from Health Board agencies, and occasionally from the police; urgent referrals are seen immediately and all others are assessed within 3 weeks. Because of home-base working, admission rates have declined substantially since 1995, and in an Irish context are now very low (2.5/1000 in 2000); similarly, certification rates are very low (29/100 000 in 2000).
Accrual of cases
Under a protocol approved by the Ethics (Research) Committee of the North
Eastern Health Board, the Director of the CavanMonaghan psychiatric
service, each treating consultant and mental health teams, the fulcrum of case
identification is a clinical research fellow/registrar based at St Davnet's
Hospital, Monaghan. His/her appointment is structured with the North Eastern
Health Board to include two clinical sessions per week to this service, such
that the research fellow is also a registrar having an integral role therein;
thus, there is complementarity between the research and clinical roles of the
fellow/registrar, and between research and clinical assessments, to ensure
that the study is complementary to service provision.
The fellow/registrar remains in regular contact with all mental health teams who refer all putative cases of first-episode psychosis, of whatever provisional diagnosis, or none, and whether admitted to an acute unit or seen at an out-patient clinic or in their own home. It is standard practice for all GPs in the study region to refer new cases of psychosis to CavanMonaghan psychiatric service, and we are unaware of any precedent for this not occurring; on initiating the study, all GPs received a letter from the fellow/registrar emphasising the importance of case referral and accrual. Formal arrangements have been initiated to identify cases admitted to either of the two private psychiatric hospitals in Dublin. At St Patrick's Hospital, Dublin, its Ethics (Research) Committee has approved that the fellow/registrar be notified on periodic request of any occurrence of putative first-episode psychosis from Cavan or Monaghan; at St John of God Hospital, Co Dublin, our sister urban first-episode study operates in parallel with this rural study (Gervin et al, 1998; Browne et al 2000a,b), using a very similar protocol, under approval from its own Ethics (Research) Committee. The procedures are that on notification of any relevant case occurring, the fellow/registrar would write to the treating consultant in the private hospital asking for his/her consent to approach the patient or family, or for the consultant to ask the patient or family, as deemed appropriate.
Assessment of cases
There were no formal diagnostic criteria for entry into the study. The
primary inclusion criterion was clinical evidence for a first lifetime episode
of any psychotic illness; conversely, the primary exclusion criterion was any
previous presentation and/or treatment for psychotic illness, other than
initiation of treatment for the current episode at an earlier stage, for
example initiation of antipsychotics by a health professional before referral
to the CavanMonaghan psychiatric service, usually within the past
month. On notification of each case of putative first-episode psychosis, the
fellow/registrar sought to assess that individual as soon as practicable,
either on an acute admission ward, at a community clinic or in his/her own
home, as appropriate. Diagnosis was integral to, rather than any requirement
for, entry into the study and was in accordance with DSMIV criteria
(American Psychiatric Association,
1994). On obtaining informed consent, with parental participation
also for those aged 16-17 years (there were no cases aged <16 years),
patients were evaluated using the Structured Clinical Interview for
DSMIIIR (SCID; Spitzer
et al, 1987) and later DSMIV
(First et al, 1998),
to facilitate a DSMIV diagnosis; from inception to this analysis at
5-year follow-up, 9 of 69 first-episode cases (13%) have declined SCID
assessment and were diagnosed on the basis of all available clinical records,
particularly the extensive assessments made on admission by the relevant
mental health teams as described above. Additionally, psychopathological,
neuro-psychological, neurological, developmental and other assessments were
made, to be described in detail elsewhere.
Data analysis
Incidence was expressed as the annual number of cases per 100 000 of
population aged 15 years (73 638 (37 930 males, 35 708 females) of the
total population of 102 810) with, where appropriate, 95% confidence intervals
(CIs) for incidence rates and for incidence ratios and, particularly,
differences in incidence between the genders. These analyses were performed
using Stata Release 7 (Stata,
2001) in the Department of Epidemiology, Royal College of Surgeons
in Ireland. Other data are expressed as means (s.d.) and were analysed using
analysis of variance (ANOVA) followed by Student's t-test (2-tailed)
with pooled or separate variance estimates as appropriate.
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RESULTS |
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Incidence of psychosis by major diagnostic group
The number of cases and incidence of schizophrenia-spectrum
psychoses (schizophrenia, schizoaffective disorder or schizophreniform
disorder), affective psychoses (bipolar disorder or major
depressive disorder with psychotic features) and other psychoses
(four brief psychotic disorder, three delusional disorder, three psychosis due
to a general medical condition, three substance-induced psychosis, three
psychosis not otherwise specified), are given in
Table 1. For other
psychoses the incidence among women was 1.6-fold lower, for
affective psychoses 2.4-fold lower and for
schizophrenia-spectrum psychoses 2.7-fold lower (difference -8.7
(95% CI -14.9 to -2.5), P<0.05) than in men.
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Age at presentation (study entry) by major diagnostic group
Mean age at presentation (study entry)
(Table 2) was generally higher
in females than in males across diagnostic groups but in no instance was
statistical significance attained. This reflected the generally smaller number
but wider age range of cases among females; in particular, for
all psychotic diagnoses (P<0.01),
schizophrenia-spectrum psychoses (P<0.05),
schizoaffective disorder (P=0.08), schizophreniform disorder
(P<0.001), affective psychoses (P<0.01)
and major depressive disorder with psychotic features (P<0.01),
variance in age among females exceeded that among males, with ranges that
encompassed similar minima but extended to higher maxima in females.
Schizophrenia and bipolar disorder are considered specifically below, but no
such pattern was evident in relation to the group having other
psychoses.
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Incidence of psychosis and age at presentation (study entry) by
core diagnosis
The rank order of widening malefemale difference in incidence among
specific diagnostic groups was: major depressive disorder with psychotic
features < other psychoses < schizophreniform disorder
< schizoaffective disorder < bipolar disorder < schizophrenia
(Table 1). On resolving the
core diagnoses of schizophrenia and bipolar disorder, incidence
of schizophrenia among women (1.1/100 000/year) was 7.5-fold lower than in men
(8.4/100 000/year; difference -7.3 (95% CI -11.7 to -2.9),
P<0.05), whereas incidence of bipolar disorder among women
(0.6/100 000/year) was 6.6-fold lower than among men (3.7/100 000/year,
difference -3.1 (95% CI -6.1 to -0.1), P<0.05). For both of these
diagnostic groups the small number of female cases showed ages that were well
within the ranges, and similar to the means, encountered for their male
counterparts (Table 2).
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DISCUSSION |
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Methodologically, the structure adopted is one that utilises a clinical research fellow who also holds a registrar appointment and has clinical sessions within the relevant psychiatric service; thus, he/she functions, and is seen to function, as part of the team providing clinical care as well as fulfilling a research role. Together with the consensus agreement of the relevant ethics (research) committee, the clinical director of the psychiatric service, each treating consultant and mental health teams, this structure provides a firm and practical foundation on which to conduct such a study.
Incidence and age at presentation
Initial analysis of incidence over the first 5 years reveals, by design, a
heterogeneous population of psychoses that reflects the realities of
psychiatric practice in rural Ireland. Of particular note is a relatively low
incidence of substance-induced psychoses (0.8/100 000/year: 2 of
substance-induced schizophrenia-like psychosis, 1 of antidepressant-induced
mania); the present rate for substance-induced non-affective psychosis (2 of
69 cases (2.9%)) is lower than has been reported recently for urban
Nottingham, UK (8.4%; Cantwell et
al, 2000), but should be juxtaposed with a cultural
background of more widespread intake of alcohol, which experience suggests
might not be dissimilar to urban settings.
Patients presented over a wide age range, from cases in the teens through to psychotic disorders of late life. However, mean age at presentation, even for schizophrenia-spectrum psychoses, was around 30 years, this being slightly later for affective psychoses and for other psychoses. Given the enduring controversy as to how age at onset should be defined, both in concept and in practice, we adopt in the context of the present report the factual, unambiguous term age at presentation (study entry). In individual instances this may or may not be the same as age at onset, depending upon definition in terms of, among other things: first identifiable behavioural abnormality; first identifiable negative symptom; first identifiable positive symptom; maximum number of positive symptoms; or first contact with a psychiatric service (Jablensky, 1995; Hafner et al, 1998; McGorry & Jackson, 1999). There endures also the controversy over how long psychosis could have run unchecked after onset, however defined, before clinical presentation and treatment (duration of untreated psychosis; DUP), and the nature of its putative prognostic significance (McGlashan, 1999; Meagher et al, 2001; Norman & Malla, 2001). On this basis, age at onset+DUP=age at presentation (study entry). There is some weight of opinion (Jablensky, 1995) that age at first contact with a psychiatric service constitutes a practical, operational definition of age at onset, and for the present discussion this definition would be congruent with age at presentation (study entry) in a first-episode context.
From this, a mean age of about 30 years in the present study might seem at variance with the presumption in some quarters that at least schizophrenia-spectrum psychoses present typically in the late teens/early twenties. However, this presumption must be set against the following: the epidemiological completeness of the present study, without the usual imposition of some arbitrary upper age limit, results in it encompassing the totality of psychosis, without distillation through referral of instances of onset in old age to external psychogeriatric or other services for the elderly; many studies underpinning the presumption of typical onset in the late teens/early twenties derive from urban or mixed urbanrural populations, under the influence of factors which may differ in rural settings (Varma et al, 1997); although it might be argued that psychosis is more likely to be either managed or tolerated for longer domestically in rural settings because of greater social/family cohesion, there is little in the earlier histories of our patients to suggest that this is the case; although it is possible that access to psychiatric care is more restricted and hence delayed in rural settings, the reality is that the opposite is more likely to be the case (see Evolution of psychiatric care over the study). These latter arguments are in accordance with more general evidence that service utilisation does not appear to be reduced in rural as opposed to urban areas, either for schizophrenia (Thornicroft et al, 1993) or for affective psychosis (Parikh et al, 1996). Although these issues will be settled only by larger data-sets, mean age at presentation (study entry) reported here for incident schizophrenia is similar to age at onset reported previously: (a) for comparably ascertained, epidemiologically complete, prevalent populations in the CavanMonaghan region (Youssef et al, 1991, 1999); and (b) for other recent studies in urban (Balestrieri et al, 1997; Hafner et al, 1998) and in rural (Ran et al, 2001) settings.
In general, mean age at first presentation (study entry) was not significantly higher in females than in males. Although this might seem at variance with the presumption that at least for schizophrenia-spectrum psychoses age at onset is typically later in females than in males (Lewis, 1992; Jablensky, 1995), the present data indicate age at presentation (study entry) to have a wider range (similar minima but extending to higher maxima) in females, giving significantly greater variance rather than significantly greater means relative to males. This profile was evident for all diagnostic groups other than schizophrenia, bipolar disorder and other psychoses. Although these issues will also be settled only by larger data-sets, the lack of gender difference in mean age at presentation (study entry) in females reported here for incident schizophrenia is similar to the lack of gender difference in age at onset reported previously for comparably ascertained, epidemiologically complete, prevalent populations in the CavanMonaghan region (Youssef et al, 1991, 1999), where a prominent interaction between family history and gender was a considerably greater determinant thereof (Waddington & Youssef, 1996). Also, lack of gender difference in age at onset continues to be reported in several other systematic studies (Murthy et al, 1997; Suvisaari et al, 1998; Di Maggio et al, 2001).
Incidence in relation to gender: possible artefacts
A principal finding in the present study is an incidence of psychosis that
is substantially lower in females than in males. Although recent studies of
schizophrenia continue to indicate some male excess
(Iacono & Beiser, 1992;
Jablensky, 1995;
Di Maggio et al,
2001), this has rarely attained the present 2- to 3-fold overall
preponderance for psychosis, whereas the 7- to 8-fold preponderance for
schizophrenia recorded here concurs only with a recent report of 6-fold male
excess for schizophrenia in Micronesia
(Waldo, 1999). As the present
incidence value for schizophrenia in males (8.4/100 000/year) is similar to:
(a) previous incidence estimates across the genders (e.g. 8/100 000/year,
Der et al, 1990;
7/100 000/year, Drake et al,
2000; see also Jablensky,
1995); and (b) incidence estimates for narrowly
defined schizophrenia in the World Health Organisation 10-country
study, including Dublin City, Ireland (males 10/100 000/year, females 8/100
000/year; Jablensky et al,
1992), it must first be asked whether there is some methodological
basis for reduced case accrual among females.
As for many studies to date, it must be recognised that the modest number of cases accrued generates rather imprecise estimates of incidence rates. Subject to this concern, at least four potential sources of artefact suggest themselves in relation to psychosis in general, and to schizophrenia in particular. First, might female cases be more likely than male cases to remain managed or tolerated domestically, rather than to present clinically, because of greater social/family cohesion in rural settings? Any argument for greater domestic containment of psychosis among females would have as a corollary that any such containment should be more likely with decreasing severity of illness; however, in contradiction, the present data indicate the female deficit to be less apparent for schizoaffective disorder and depressive disorder with psychotic features, illnesses generally considered to be less severe than schizophrenia (Tsuang & Coryell, 1993).
Second, might female patients be more likely than males to present to private psychiatric hospitals in Dublin? Arrangements with the two Dublin hospitals that handle 98% of private psychiatric admissions in Ireland (Daly & Walsh, 2000; see Accrual of cases) have so far yielded three cases, all of whom were male.
Third, might females be more likely to enter the judicial rather than the medical system than males? Such an argument would be contradicted by a substantial body of evidence that any association between psychosis and violence to others, the primary reason for judicial involvement, is small, in particular synergism with substance misuse, and relates more to males than to females (Taylor & Buckley, 2000). More specifically, there is contemporary evidence (Mohan et al, 1997) that only 2% of females in Ireland's largest prison had a psychotic illness, and none were from CavanMonaghan.
Fourth, might those females in whom schizophrenia is destined to emerge be more likely to migrate prior to onset? Such a possibility would be at variance with evidence that the substantial majority of persons in CavanMonaghan were still resident not only at the same location as 1 year previously (97%) but also in the county of their birth (74%; see Study region) and that 75% of all people in Ireland born in CavanMonaghan still live there. Furthermore, such a possibility would be at variance also with the general observation that in emigrants there is usually an over-representation of those who are well, leaving behind relative enrichment of the unwell rather than the reverse.
Incidence in relation to gender: possible mechanisms
On this basis, the reduced incidence among females of psychosis in general,
and of schizophrenia in particular, appears to be a finding that requires
explanation in alternative terms. At least three factors may be relevant.
First, there is evidence that increasing stringency of operational diagnostic
criteria is associated with a particular reduction in the number of women who
receive a diagnosis of schizophrenia
(Jablensky et al,
1992; Castle et al,
1993); thus, as the present study utilised DSMIV criteria,
some relative diminution in incidence in females would be expected relative to
studies that have used less stringent criteria. Second, there endures a
controversy as to whether the incidence of schizophrenia has declined over
recent decades (Der et al,
1990). Among a diversity of both positive and negative studies,
those that have taken gender into account have noted in general a greater
decline in females than in males
(Jablensky, 1995;
Munk-Jorgensen, 1995;
Al Mousawi & Dunstan,
1998). Indeed, for a comparably ascertained, epidemiologically
complete, prevalent population of schizophrenia in the CavanMonaghan
region, we have reported a greater reduction in female cases than in males for
those born since 1940 (Waddington &
Youssef, 1994). On this basis, the declining
incidence controversy would predict some relative diminution in
incidence among females for the present study. Third, recent studies have
indicated an increased risk for schizophrenia in those having their
birth/early upbringing in urban as opposed to rural environments
(Lewis et al, 1992;
Mortensen et al,
1999), with a gradient that appears more pronounced for females
(Schelin et al,
2000). This would predict for the present study some preferential
diminution in incidence among females.
Notably, all of the above factors, each of which alone could result in some reduction in incidence among females, apply to the present study. This confluence of effects might synergise to prominently deflate incidence among females relative to males. Yet such putative synergism, deriving primarily from studies on schizophrenia, remains circumstantial and fails to resolve the specific nature of the underlying causal factor(s).
Incidence in relation to diagnosis
However, some clues may derive from the most prominent reduction in
incidence among females being found not only for schizophrenia but also for
bipolar disorder. The relationship between schizophrenia and bipolar disorder
has engendered one of the longest controversies within the discipline of
psychiatry; specifically, do these diagnoses constitute distinct entities, or
represent positions along a continuum of psychosis defined by the interplay of
overlapping aetiological factors and pathophysiological processes, such that
we are dealing with a human condition which can vary along several dimensions
and the parcellation of which into discrete disorders is a nosological
artefact of history (Jablensky,
1999; Torrey & Knable,
1999; Waddington,
2002)? That schizophrenia and bipolar disorder evidence here such
congruence of incidence profiles in relation to gender indicates the operation
of some factor(s) that exert a comparable effect across psychotic diagnoses in
general and across these core diagnoses in particular.
In this report we outline the opportunities and challenges in conducting a prospective first-episode study within a rural region of ethnic, socio-economic and geographical homogeneity, on an epidemiologically complete basis. Continuing accrual of cases will maximise the opportunity for systematic epidemiological, clinical and biological comparisons between homogeneous populations of the psychoses, so as to realise the full potential of this approach.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) DSMIV). Washington, DC: APA.
Balestrieri, M., Rucci, P. & Nicolaou, S. (1997) Gender-specific decline and seasonality of births in operationally defined schizophrenics in Italy. Schizophrenia Research, 27, 73-81.[CrossRef][Medline]
Bromet, E. J. & Fennig, S. (1999) Epidemiology and natural history of schizophrenia. Biological Psychiatry, 46, 871-881.[CrossRef][Medline]
Browne, S., Clarke, M., Gervin, G., et al
(2000a) Determinants of quality of life at first
presentation with schizophrenia. British Journal of
Psychiatry, 176,
173-176.
Browne, S., Clarke, M., Gervin, G., et al (2000b) Determinants of neurological dysfunction in first episode schizophrenia. Psychological Medicine, 30, 1433-1441.[CrossRef][Medline]
Cantwell, R., Brewin, J., Glazebrook, C., et al (2000) Prevalence of substance misuse in first-episode psychosis. British Journal of Psychiatry, 174, 150-153.[Abstract]
Castle, D. J., Wessely, S. & Murray, R. M. (1993) Sex and schizophrenia: effects of diagnostic stringency, and associations with premorbid variables. British Journal of Psychiatry, 162, 658-664.[Abstract]
Central Statistics Office (1993a) County Cavan. Local Population Report 28. Dublin: Government Stationery Office.
Central Statistics Office (1993b) County Monaghan. Local Population Report 29. Dublin: Government Stationery Office.
Central Statistics Office (1994) Counties of Cavan, Louth and Monaghan. Local Population Report 4. Dublin: Government Stationery Office.
Chatterjee, A. & Lieberman, J. A. (1999) Studies of biological variables in first-episode schizophrenia: a comprehensive review. In The Recognition and Management of Early Psychosis (eds P.D. McGorry & H.J. Jackson), pp. 115-152. Cambridge: Cambridge University Press.
Daly, A. & Walsh, D. (2000) Irish Psychiatric Services: Activities 1999. Dublin: Health Research Board.
Der, G., Gupta, S. & Murray, R. M. (1990) Is schizophrenia disappearing? Lancet, 335, 513-516.[Medline]
Di Maggio, C., Martinez, M., Menard, J.-F., et al
(2001) Evidence of a cohort effect for age at onset of
schizophrenia. American Journal of Psychiatry,
158,
489-492.
Drake, R. J., Haley, C. J., Akhtar, S., et al
(2000) Causes and consequences of duration of untreated
psychosis in schizophrenia. British Journal of
Psychiatry, 177,
511-515.
First, M. B., Spitzer, R. L., Gibbon, M., et al (1998) Structured Clinical Interview for DSMIV Axis I Disorder Patient Edition (SCID-I/P). New York: New York State Psychiatric Institute.
Gervin, M., Browne, S., Lane, A., et al
(1998) Spontaneous abnormal involuntary movements in
first-episode schizophrenia and schizophreniform disorder: baseline rate in a
group of patients from an Irish catchment area. American Journal of
Psychiatry, 155,
1202-1206.
Hafner, H., an der Heiden, W., Behrens, S., et al (1998) Causes and consequences of the gender difference in age at onset of schizophrenia. Schizophrenia Bulletin, 24, 99-113.[Medline]
Iacono, W. & Beiser, M. (1992) Where are the women in first-episode studies of schizophrenia? Schizophrenia Bulletin, 18, 471-480.[Medline]
Jablensky, A. (1995) Schizophrenia: the epidemiological horizon. In Schizophrenia (eds S. R. Hirsch & D. R. Weinberger), pp. 206-252. Oxford: Blackwell.
Jablensky, A. (1999) The conflict of the nosologists: views on schizophrenia and manicdepressive illness in the early part of the 20th century. Schizophrenia Research, 39, 95-100.[CrossRef][Medline]
Jablensky, A. Sartorius, N., Ernberg, G., et al (1992) Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study. Psychological Medicine. Monograph Supplement, 20, 1-97.[Medline]
Kirch, D. G., Keith, S. J. & Matthews, S. M. (1992) Research on first-episode psychosis: report on a National Institute of Mental Health Workshop. Schizophrenia Bulletin, 18, 179-182.[CrossRef][Medline]
Lewis, S. W. (1992) Sex and schizophrenia: vive la difference. British Journal of Psychiatry, 161, 445-450.[Medline]
Lewis, G., David, A., Andreassen, S., et al (1992) Schizophrenia and city life. Lancet, 340, 137-140.[Medline]
McGlashan, T. H. (1999) Duration of untreated psychosis in first-episode schizophrenia: marker or determinant of course. Biological Psychiatry, 46, 899-907.[CrossRef][Medline]
McGorry, P. D. & Jackson, H. J. (1999) The Recognition and Management of Early Psychosis. Cambridge: Cambridge University Press.
Meagher, D. J., Quinn, J. F., Murphy, P., et al (2001) Relationship of the factor structure of psychopathology in schizophrenia to the timing of initial intervention with antipsychotics. Schizophrenia Research, 50, 95-103.[CrossRef][Medline]
Mohan, D., Scully, P., Collins, C., et al (1997) Psychiatric disorder in an Irish female prison. Criminal Behaviour and Mental Health, 7, 229-235.
Mortensen, P. B., Pedersen, C. B., Westergaard, T., et
al (1999) Effects of family history and place and season
of birth on the risk of schizophrenia. New England Journal of
Medicine, 340,
603-608.
Munk-Jorgensen, P. (1995) Decreasing rates of incident schizophrenia cases in psychiatric service: a review of the literature. European Psychiatry, 10, 129-141.[CrossRef]
Murthy, G. V., Janakiramaiah, N., Gangadhar, B. N., et al (1997) Sex differences in age at onset of schizophrenia: discrepant findings in India. Acta Psychiatrica Scandinavica, 97, 321-325.
Norman, R. M. G. & Malla, A. K. (2001) Duration of untreated psychosis: a critical examination of the concept and its importance. Psychological Medicine, 31, 381-400.[Medline]
Parikh, S. V., Wasylenki, D., Goering, P., et al (1996) Mood disorders: rural/urban differences in prevalence, health care utilization, and disability in Ontario. Journal of Affective Disorders, 26, 57-65.[CrossRef]
Ran, M., Xiang, M., Huang, M., et al
(2001) Natural course of schizophrenia: 2-year follow-up
study in a rural Chinese community. British Journal of
Psychiatry, 178,
154-158.
Schelin, E. M., Munk-Jorgensen, P., Olesen, A. V., et al (2000) Regional differences in schizophrenia incidence in Denmark. Acta Psychiatrica Scandinavica, 101, 293-299.[CrossRef][Medline]
Spitzer, R. L., Williams, J. B. & Gibbon, J. (1987) Structured Clinical Interview for DSMIIIRPatient Version (SCIDP). New York: New York State Psychiatric Institute.
Stata (2001) Stata Release 7. College Station, TX: Stata Corporation.
Suvisaari, J. M., Haukka, J., Tanskanen, A., et al (1998) Age at onset and outcome in schizophrenia are related to the degree of familial loading. British Journal of Psychiatry, 173, 494-500.[Abstract]
Taylor, P. & Buckley, P. (2000) Treating violence in the context of schizophrenia. In Schizophrenia and Mood Disorders: the New Drug Therapies in Clinical Practice (eds P. F. Buckley & J. L. Waddington), pp. 297-316. Oxford: Butterworth-Heinemann.
Thornicroft, G., Bisoffi, G., De Salvia D, et al (1993) Urbanrural differences in the associations between social deprivation and psychiatric service utilization in schizophrenia and all diagnoses: a case-register study in Northern Italy. Psychological Medicine, 23, 487-496.[Medline]
Torrey, E. F. & Knable, M. B. (1999) Are schizophrenia and bipolar disorder one disease or two? Schizophrenia Research, 39, 93-163.[CrossRef]
Tsuang, D. & Coryell, W. (1993) An 8-year follow-up of patients with DSMIIIR psychotic depression, schizoaffective disorder, and schizophrenia. American Journal of Psychiatry, 150, 1182-1188.[Abstract]
Varma, V. K., Wig, N. N., Phookun, H. R., et al (1997) First-onset schizophrenia in the community: relationship of urbanisation with onset, early manifestations and typology. Acta Psychiatrica Scandinavica, 96, 431-438.[Medline]
Waddington, J. L. (2002) Schizophrenia and bipolar disorder as putative dopamine-linked illness: neurodevelopmental origins and lifetime trajectory. In Dopamine Receptors and Transporters (eds A. Sidhu, M. Laruelle & P. Vernier). New York: Marcel Dekker (in press).
Waddington, J. L. & Youssef, H. A. (1994) Evidence for a gender-specific decline in the rate of schizophrenia in rural Ireland over a 50-year period. British Journal of Psychiatry, 164, 171-176.[Abstract]
Waddington, J. L. & Youssef, H. A. (1996) Familial-genetic and reproductive epidemiology of schizophrenia in rural Ireland: age at onset, familial morbid risk and parental fertility. Acta Psychiatrica Scandinavica, 93, 62-68.[Medline]
Waldo, M. C. (1999) Schizophrenia in Kosrae, Micronesia: prevalence, gender ratios, and clinical symptomatology. Schizophrenia Research, 35, 175-181.[CrossRef][Medline]
Youssef, H. A., Kinsella, A. & Waddington, J. L. (1991) Evidence for geographical variations in the prevalence of schizophrenia in rural Ireland. Archives of General Psychiatry, 48, 254-258.[Abstract]
Youssef, H. A., Scully, P. J., Kinsella, A., et al (1999) Geographical variation in rate of schizophrenia in rural Ireland by place at birth vs place at onset of psychosis. Schizophrenia Research, 37, 233-243.[CrossRef][Medline]