John makes some excellent points, and his papers help us understand the epidemiology of schizophrenia. I have two points.

1. I was fascinated by the Finnish study published in the Archives of General Psychiatry (Perala et al., 2007); this paper showed the incidence of psychotic disorders was 3.5 percent, of which the diagnosis "schizophrenia" only represented 25 percent! I think we may be missing the point by focusing on a diagnostic category (the criteria of which constantly change) that only represents a minor fraction of the total psychosis morbidity force.

2. The second issue is that not all expression of the psychosis phenotype may be pathological, and that much can be learned by focusing on its subclinical expression.

View all comments by Jim van Os

The variation in incidence rates from epidemiological studies is now clear to see, not least in terms of ethnicity and urbanicity. I think that we now need to move beyond studies which show such variation to developing models which attempt to elicit the specific environmental "risk factors" which presumably underpin these effects; most likely operating with gene-environment and other interactions.

Future epidemiological studies will need to be more sensitive to the environment and person-environment (cross-level) interactions. It is likely that different environmental exposures have differing "doses" depending on individual susceptibility, particularly given exposure to the ubiquitous risk factors of ethnicity and urbanicity.

Furthermore, I think it will be crucial to elucidate the critical timing of exposure to (socio)environmental factors, be these close to birth, during childhood or adolescence, or close to onset of disorder. I believe all three time points will have a role to play. Clearly, longitudinal multilevel studies will represent the gold standard of...  Read more

The variation in incidence rates from epidemiological studies is now clear to see, not least in terms of ethnicity and urbanicity. I think that we now need to move beyond studies which show such variation to developing models which attempt to elicit the specific environmental "risk factors" which presumably underpin these effects; most likely operating with gene-environment and other interactions.

Future epidemiological studies will need to be more sensitive to the environment and person-environment (cross-level) interactions. It is likely that different environmental exposures have differing "doses" depending on individual susceptibility, particularly given exposure to the ubiquitous risk factors of ethnicity and urbanicity.

Furthermore, I think it will be crucial to elucidate the critical timing of exposure to (socio)environmental factors, be these close to birth, during childhood or adolescence, or close to onset of disorder. I believe all three time points will have a role to play. Clearly, longitudinal multilevel studies will represent the gold standard of observational studies in this respect.

There is a need to get beyond purely epidemiological research and develop ties and collaborations with neuroscientists. I am interested in testing hypotheses around how social capital at the neighborhood level may be relevant to the etiology of schizophrenia, a topic which may initially appear a long way from neuroscience. But Jean-Paul Selten (2005) and colleagues have proposed some interesting models as to how social defeat may be relevant to psychosis, and I think we need to develop and extend our theories of such models to bridge the gap between neuroscience and epidemiology.

I look forward to participating in the live discussion next week.

References:

Selten JP, Cantor-Graae E. Social defeat: risk factor for schizophrenia? Br J Psychiatry. 2005 Aug 1;187():101-2. Abstract

The points made by John are timely and excellent indeed. I take the opportunity to place some remarks upon the silent epidemic of psychotic disorders among immigrants from non-western countries in Western Europe and about the sociology of science. There are at least three reasons for the concealment of this epidemic:

1. The immigrants are ashamed and ignore it. They threaten psychiatrists and journal editors with accusations of racism.

2. The politicians do not feel confident about psychiatric diagnosis or psychiatric epidemiology and are afraid of being accused of "racism."

3. Many psychiatrists are hopelessly in love with DNA and MRI, cannot change their fixed ideas about equal incidence rates across place and time, or lack the courage to shift their research focus.

The first step forward is to bring this epidemic and the dangers of illicit drug abuse to the attention of the media. Things become "true" when they are on television! We can hope that policy makers at Medical Research Councils, who divide the money, will then encourage researchers to spend their...  Read more

The points made by John are timely and excellent indeed. I take the opportunity to place some remarks upon the silent epidemic of psychotic disorders among immigrants from non-western countries in Western Europe and about the sociology of science. There are at least three reasons for the concealment of this epidemic:

1. The immigrants are ashamed and ignore it. They threaten psychiatrists and journal editors with accusations of racism.

2. The politicians do not feel confident about psychiatric diagnosis or psychiatric epidemiology and are afraid of being accused of "racism."

3. Many psychiatrists are hopelessly in love with DNA and MRI, cannot change their fixed ideas about equal incidence rates across place and time, or lack the courage to shift their research focus.

The first step forward is to bring this epidemic and the dangers of illicit drug abuse to the attention of the media. Things become "true" when they are on television! We can hope that policy makers at Medical Research Councils, who divide the money, will then encourage researchers to spend their time in a more intelligent way. And we will see a renaissance of psychiatric epidemiology!

The variations in the incidence and prevalence of psychosis point strongly towards the social environment, broadly construed, as being important in etiology.

However, as John McGrath notes, the data offer “clues” only. In the epidemiological research to date, the variables used to represent social environments and experience are usually crude dichotomies—urban vs. rural, migrant vs. non-migrant, abused vs. non-abused. With regard to urbanicity and migration, one consequence is that the precise meaning of observed associations is unclear, and the relevant social conditions or experiences that these variables may index remain unknown.

This suggests a need to engage the social (as well as neuro) sciences in helping unravel these new epidemiological "clues." We need to develop appropriate conceptual maps and measurement tools that allow us to study complex social processes, and the contexts in which they occur, if we are to fully understand the nature of the associations between, say, migration and psychosis. These are the very issues that social scientists have...  Read more

The variations in the incidence and prevalence of psychosis point strongly towards the social environment, broadly construed, as being important in etiology.

However, as John McGrath notes, the data offer “clues” only. In the epidemiological research to date, the variables used to represent social environments and experience are usually crude dichotomies—urban vs. rural, migrant vs. non-migrant, abused vs. non-abused. With regard to urbanicity and migration, one consequence is that the precise meaning of observed associations is unclear, and the relevant social conditions or experiences that these variables may index remain unknown.

This suggests a need to engage the social (as well as neuro) sciences in helping unravel these new epidemiological "clues." We need to develop appropriate conceptual maps and measurement tools that allow us to study complex social processes, and the contexts in which they occur, if we are to fully understand the nature of the associations between, say, migration and psychosis. These are the very issues that social scientists have been grappling with for at least the past century. There are already available a range of well-developed theoretical frameworks and methodological tools for investigating a wide variety of social contexts and experiences, including social fragmentation, social capital, social networks, discrimination, childhood trauma and abuse, and life events.

Of course, the resources, number of subjects, and complexity of analyses required to conduct such research are considerable, particularly given the added need to include data that cut across different levels of analysis (e.g., individual and neighborhood) or domains (e.g., social, genetic, biochemical). Clearly, no single study will be able to achieve this, and this suggests the need for programs of research in which efforts to measure social exposures match the sophistication of those used to investigate genes and biochemistry.

Exposing the myth of constant prevalence and incidence rates of schizophrenia is a welcome development for those of us who don't buy into the reductionist gene-centric view of psychiatric disorders. While genetic vulnerability is indisputable, it is ostrich-like behavior to ignore (or pay lip-service) to environmental factors that mediate expression of psychosis in vulnerable individuals.

Jim's point above regarding our diagnostic focus on schizophrenia rather than on psychosis is very important. Studies of first-episode psychosis (FEP) are essential if one is looking at the social environment and its impact on incidence, because one assumes that the likelihood of "social drift" (as an explanation) can be diminished if one is investigating the illness at its onset. In other words, it is easier to argue for an etiological role for environmental factors, if one is looking at FEP.

Despite John's frustration with ecological methodologies, I have just calculated a retrospective treated incidence for FEP for each of seven municipalities here in Durban, South Africa. I...  Read more

Exposing the myth of constant prevalence and incidence rates of schizophrenia is a welcome development for those of us who don't buy into the reductionist gene-centric view of psychiatric disorders. While genetic vulnerability is indisputable, it is ostrich-like behavior to ignore (or pay lip-service) to environmental factors that mediate expression of psychosis in vulnerable individuals.

Jim's point above regarding our diagnostic focus on schizophrenia rather than on psychosis is very important. Studies of first-episode psychosis (FEP) are essential if one is looking at the social environment and its impact on incidence, because one assumes that the likelihood of "social drift" (as an explanation) can be diminished if one is investigating the illness at its onset. In other words, it is easier to argue for an etiological role for environmental factors, if one is looking at FEP.

Despite John's frustration with ecological methodologies, I have just calculated a retrospective treated incidence for FEP for each of seven municipalities here in Durban, South Africa. I correlated treated incidence with a measure of income inequality for each of the municipalities and found a strongly significant relationship (unpublished). The greater the rich-poor gap, the greater the treated incidence (NB controlled for urbanicity). To me this makes sense, in the light of the work of Richard Wilkinson in the 1990s, showing that increasing income inequality reduces life expectancy, increases cardiovascular risk, and is generally bad for your health (1996).

How can anyone continue to deny a role for psychosocial and environmental factors in converting genetic vulnerability to psychotic disorder?

References:
Wilkinson RG (1996) Unhealthy Societies: The Afflictions of Inequality. Routledge, London.

At Schizophrenia.com (a non-profit, family oriented schizophrenia education site) we feel that research into schizophrenia epidemiology is vitally important, yet seriously underfunded. We applaud the increased efforts in this important field.

We are also, however, making efforts to educate the public about what recent research is suggesting, and identifying actions that families with a history of schizophrenia may want to consider to lower their risks. As part of this effort we've created a Preventing Schizophrenia section of the web site, which attempts to summarize the state of the research in areas where it can help drive individual and family actions that seem likely to lower risk for future generations. We welcome your comments on this section.

View all comments by Brian Chiko

John McGrath has made a major contribution to the epidemiology of schizophrenia, probably the most important contribution since the work of Dr. Edward Hare. By questioning the received wisdom of the textbooks and showing that the incidence of schizopohrneia varies widely, he has opened up new avenues for research. Most such research will have to be done in Europe, especially in Scandanavia, where appropriate databases exist. In the United States, few resources are available that can be used for epidemiological studies, and consequently American interest in such studies is minimal.

In terms of future directions, it would be interesting to link some of the prevalence data to the birth seasonality data, e.g., is the seasonal birth excess greater in those areas where the incidence is higher?

View all comments by Fuller Torrey

I have decided to play the role of advocatus diaboli and pose three critical questions which I think are fundamental to defining the role of epidemiology in the present state of schizophrenia research. I'll be greatly interested in the proceedings.

1. What should be the role of epidemiology in the rapidly changing field of research into the etiology and pathogenesis of schizophrenia? Much of what is now driving schizophrenia research and is potentially promising, happens to be within the domains of neuroscience and genetics. Considering that (in contrast to diseases such as cancer) we are at least a decade away from examining population distributions of proven genetic risk polymorphisms for the disorder, can epidemiology at present offer a meaningful complementary approach and disciplinary partnership to neuroscience and genetics?

2. A good deal of the science of epidemiology is about the effects of environmental risk exposures and their interactions with intrinsic genetic vulnerabilities. So far, no single environmental exposure has been definitively...  Read more

I have decided to play the role of advocatus diaboli and pose three critical questions which I think are fundamental to defining the role of epidemiology in the present state of schizophrenia research. I'll be greatly interested in the proceedings.

1. What should be the role of epidemiology in the rapidly changing field of research into the etiology and pathogenesis of schizophrenia? Much of what is now driving schizophrenia research and is potentially promising, happens to be within the domains of neuroscience and genetics. Considering that (in contrast to diseases such as cancer) we are at least a decade away from examining population distributions of proven genetic risk polymorphisms for the disorder, can epidemiology at present offer a meaningful complementary approach and disciplinary partnership to neuroscience and genetics?

2. A good deal of the science of epidemiology is about the effects of environmental risk exposures and their interactions with intrinsic genetic vulnerabilities. So far, no single environmental exposure has been definitively demonstrated to be either necessary or sufficient to explain the variance in the incidence/prevalence, or the clinical manifestations and course of schizophrenia. Genetic studies, mainly based on twin data and using variance component analysis methodology, point to unspecified, non-shared environmental influences that appear to be individually idiosyncratic and non-generalizable. This appears to be in contrast with well replicated findings of the "classical" epidemiology of schizophrenia, which reported high odds ratios for ecological risk factors, such as low socioeconomic status, season of birth, or similar exposures. How can these two strands of research be reconciled?

3. Is there any point in the near future for further studies into the descriptive epidemiology of schizophrenia, i.e. incidence and prevalence, or course and outcome? What new knowledge is there to be gained? The relevance of this question is underscored by the increasing realization (anticipated by Bleuler) that schizophrenia is not a monolithic disease but a syndrome that may be the "final common pathway" for a variety of underlying causes and processes. Our present diagnostic tools may be too crude to enable reasonable discernment, and the "endophenotype" approach is not yet quite there to rescue the effort. Shall we declare, for a while, a voluntary moratorium on any ambitions for etiological research and limit ourselves to useful practical studies on service utilization, socioeconomic gradients, disability, effects of treatments, and the like?

We complain that fixed ideas about the epidemiology of psychosis do not disappear from textbooks. I propose that we write to the editors of the 5 or 10 most important textbooks to make this point.

View all comments by Jean-Paul Selten

I agree with many of the comments already made.

I do however respectfully question Prof. Jablensky's third 'Devil's Advocate' point regarding outcome studies. At a time when the oft quoted finding from the WHO studies regarding the supposed better outcome in developing countries is increasingly being questioned (often by the original investigators themselves), surely there is a need for more studies with rigorous follow up. Not only may they provide us with information that may inform aetiology, but they might just allow us to start to answer that most basic of questions (which we still cannot answer!): 'Will my son/daughter get better or remain as they are?'

There does seem to be a window of opportunity at the moment. There have been several first onset studies over the last decade, most of which have been epidemiologically based. Many of these are engaging in follow-ups (of admittedly different time intervals etc). Surely a closer collaboration between these groups worldwide would not only be informative but also, dare one say it, relatively cost-effective??

View all comments by Paul Fearon

John McGrath asserts that we must be "slaves to the data" in his Schizophrenia Bulletin commentary. Our data doesn’t just drive us, however. Data generated depend on the questions we ask, and the questions we ask shape our approaches and the data we collect, or employ.

In the kernels for our live discussion, there is an emphasis on future studies of schizophrenia, in which we can tailor our search for environmental risk factors. Let us not forget, however, the trove of available longitudinal data, which with careful consideration and creativity, can be plumbed for clues to etiology, particularly the timing of relevant exposures. Travel across the epidemiologic landscape is far from complete, and our studies, especially those begun many decades ago, are far from exhausted.

Like extant epidemiologic data, information from specialized studies conducted within the bounds of other disciplines has not been completely mined. To understand the full range and sequence of causes of schizophrenia, research from genetics, neuroscience, psychology, sociology, and even history,...  Read more

John McGrath asserts that we must be "slaves to the data" in his Schizophrenia Bulletin commentary. Our data doesn’t just drive us, however. Data generated depend on the questions we ask, and the questions we ask shape our approaches and the data we collect, or employ.

In the kernels for our live discussion, there is an emphasis on future studies of schizophrenia, in which we can tailor our search for environmental risk factors. Let us not forget, however, the trove of available longitudinal data, which with careful consideration and creativity, can be plumbed for clues to etiology, particularly the timing of relevant exposures. Travel across the epidemiologic landscape is far from complete, and our studies, especially those begun many decades ago, are far from exhausted.

Like extant epidemiologic data, information from specialized studies conducted within the bounds of other disciplines has not been completely mined. To understand the full range and sequence of causes of schizophrenia, research from genetics, neuroscience, psychology, sociology, and even history, should be integrated. In so doing, our efforts can take into account evidence at various levels of organization (e.g., the individual, family, neighborhood, and nation) and across time (e.g., the individual life course and historical time). Epidemiology is well positioned to unify specialized knowledge from each of these areas. We should take that coordinating role seriously.

Sharpening our understanding of the causes of schizophrenia is our charge. With an integrative and collaborative approach harnessing the knowledge gained from extant and future epidemiologic studies, as well as from other disciplines—ranging from sociology to genetics—epidemiology can shift its role from a blunt tool to a cutting edge. It is up to the new generation of researchers to move forward both incisively and accordingly.

The variation in the incidence of schizophrenia is now firmly established. There is also large body of evidence to suggest that prevalence, and mortality (Arch Gen Psychiatry 2007 in press) in schizophrenia varies widely among sites. I agree with Jean-Paul Selten that it is timely to write to the editors of the important text books to correct it. The ‘silent epidemic’ of psychotic disorders among immigrants in many parts of the world also needs to be documented. As an immigrant I can see the problem of psychotic illness among various groups.

I am an advocate of more epidemiological studies from different populations to answer what’s and why’s? Firstly, as Craig Morgan wrote, the precise meaning of associations between observed dichotomised variations (male/female, urban/rural, and migrant/non-migrants) is not clear. Secondly, in our systematic reviews of incidence, prevalence, and mortality, we found very few studies from developing countries. We do not know whether these dichotomised variations are the same across populations. For example, an influential study from...  Read more

The variation in the incidence of schizophrenia is now firmly established. There is also large body of evidence to suggest that prevalence, and mortality (Arch Gen Psychiatry 2007 in press) in schizophrenia varies widely among sites. I agree with Jean-Paul Selten that it is timely to write to the editors of the important text books to correct it. The ‘silent epidemic’ of psychotic disorders among immigrants in many parts of the world also needs to be documented. As an immigrant I can see the problem of psychotic illness among various groups.

I am an advocate of more epidemiological studies from different populations to answer what’s and why’s? Firstly, as Craig Morgan wrote, the precise meaning of associations between observed dichotomised variations (male/female, urban/rural, and migrant/non-migrants) is not clear. Secondly, in our systematic reviews of incidence, prevalence, and mortality, we found very few studies from developing countries. We do not know whether these dichotomised variations are the same across populations. For example, an influential study from China (Phillips et al., 2004) showed that unlike many countries, prevalence of both schizophrenia and suicide in females are higher compared to males. In contrast, a very high male:female ratio (5:1) of lifetime prevalence of schizophrenia has been reported from an Ethiopian study (Kebede et al., 2003). Don’t we need closer scrutiny of these variations across populations, sexes, and groups?

There have been some varied and interesting comments about the “New Epidemiology of Schizophrenia”

Similar debates about the future of epidemiology have taken place in other areas, but this seems to be resolving into a healthy mix of studies. A personal brief survey of topics covered in contemporary general epidemiological journals, such as the current edition of the International Journal of Epidemiology, shows a range of studies conducted at multiple levels—from the social and geographical, through to the genetic, with some studies modelling genetic and environmental interactions. Can this be the future of the epidemiology of schizophrenia, at least the foreseeable future?

I’d like to add a comment and a question. The comment is: Although socio-demographic factors may be associated with variation in incidence/prevalence over time and place, other factors may also be operating: infectious agents and climate come to mind. There may well be an interaction between these and the genetic and socio-demographic factors already discussed.

The question is: There is...  Read more

There have been some varied and interesting comments about the “New Epidemiology of Schizophrenia”

Similar debates about the future of epidemiology have taken place in other areas, but this seems to be resolving into a healthy mix of studies. A personal brief survey of topics covered in contemporary general epidemiological journals, such as the current edition of the International Journal of Epidemiology, shows a range of studies conducted at multiple levels—from the social and geographical, through to the genetic, with some studies modelling genetic and environmental interactions. Can this be the future of the epidemiology of schizophrenia, at least the foreseeable future?

I’d like to add a comment and a question. The comment is: Although socio-demographic factors may be associated with variation in incidence/prevalence over time and place, other factors may also be operating: infectious agents and climate come to mind. There may well be an interaction between these and the genetic and socio-demographic factors already discussed.

The question is: There is growing interest in animal models of schizophrenia. However, to what extent can various environmental risk factors for schizophrenia be modelled in animals? Certain hypotheses which have their origins in epidemiology are currently being tested via animal models. (For examples see recent papers by Professor McGrath and also Robertson et al., 2006). Are there limits to this approach?

An issue of critical importance, and relevant to comments raised by Assen Jablensky and Paul Fearon, is the funding of longitudinal incidence studies. While grant funding bodies steer away from these, most governments are reticent to put money into studies that are so costly and time-consuming. The government timeline for funding is, more often than not, related to that government's cycle in office: they want results that they can use with political expedience. How do schizophrenia researchers persuade governments to fund long-term research programs that will help build up the bank of epidemiological evidence?

View all comments by Vera A. Morgan

The question of whether one can develop animal models for environmental exposures is an interesting one. Models can be developed for relatively high risk exposures, such as smoking and lung cancer. However, they are more difficult to develop for more subtle exposures where only some of the exposed animals will develop the consequences of the exposures and where some of the risk may be genetically determined. The development of relevant animal models for these types of exposures remains an important goal for research into complex disorders.

View all comments by Robert Yolken

I think Assen Jablensky's concerns regarding the potential for epidemiology to contribute to the identification of causes are very relevant. However, I do not agree that "we are at least a decade away from examining population distributions of proven genetic risk polymorphisms for the disorder," and I think that this is certainly a necessary next step of the highest priority. From an epidemiological point of view it is of course the most important set of confounders and/or interacting agents for any environmental factor we could suspect. However I think it is less well realized at present that this is equally important for the progress of genetic studies. I think one of the real benefits epidemiology can bring to the field is a more rigorous description and handling of biases and confounders that are mostly ignored in genetic studies (let alone neuroimaging), and bringing this perspective into the field will be necessary. So, rigorous design with a strong sense of the population base of the study, and more exact measurement of the exposures/confounders in question seem to me...  Read more

I think Assen Jablensky's concerns regarding the potential for epidemiology to contribute to the identification of causes are very relevant. However, I do not agree that "we are at least a decade away from examining population distributions of proven genetic risk polymorphisms for the disorder," and I think that this is certainly a necessary next step of the highest priority. From an epidemiological point of view it is of course the most important set of confounders and/or interacting agents for any environmental factor we could suspect. However I think it is less well realized at present that this is equally important for the progress of genetic studies. I think one of the real benefits epidemiology can bring to the field is a more rigorous description and handling of biases and confounders that are mostly ignored in genetic studies (let alone neuroimaging), and bringing this perspective into the field will be necessary. So, rigorous design with a strong sense of the population base of the study, and more exact measurement of the exposures/confounders in question seem to me to be the key thing, and I think, as I said, it is not far away, here and elsewhere.

Regarding the question of whether there are useful animal models based on epidemiological findings, the answer is certainly yes.

For schizophrenia, there are now quite a few papers based on the findings (most definitively from Allan Brown and colleagues) that maternal respiratory infection increases the risk in the offspring. They calculate that this risk factor can account for 14-21 percent of schizophrenia cases. Mice given a respiratory infection at mid-gestation yield offspring with striking abnormalities in behaviors related to schizophrenia (anxiety, social interaction, latent inhibition, prepulse inhibition), some of which can be corrected by antipsychotic drugs. The effect of maternal infection on fetal brain development can be mimicked by activating the maternal immune response by injection of dsRNA. Thus, the virus is not required, and other mechanisms of activating the maternal immune response can presumably cause similar changes in the offspring. We have recently found that the cytokine IL-6 mediates the effects of maternal immune activation on the...  Read more

Regarding the question of whether there are useful animal models based on epidemiological findings, the answer is certainly yes.

For schizophrenia, there are now quite a few papers based on the findings (most definitively from Allan Brown and colleagues) that maternal respiratory infection increases the risk in the offspring. They calculate that this risk factor can account for 14-21 percent of schizophrenia cases. Mice given a respiratory infection at mid-gestation yield offspring with striking abnormalities in behaviors related to schizophrenia (anxiety, social interaction, latent inhibition, prepulse inhibition), some of which can be corrected by antipsychotic drugs. The effect of maternal infection on fetal brain development can be mimicked by activating the maternal immune response by injection of dsRNA. Thus, the virus is not required, and other mechanisms of activating the maternal immune response can presumably cause similar changes in the offspring. We have recently found that the cytokine IL-6 mediates the effects of maternal immune activation on the fetus.

It is also of interest that Brown et al. have recently found that there are structural differences between the brains of schizophrenic subjects whose mothers did or did not experience viral infection during pregnancy. Thus, it will be worthwhile to search for such changes in the mouse model. It is also important to use this model to test for interactions between the maternal infection risk factor and the strongest candidate genes now identified.

Early epidemiological studies also showed that maternal rubella infection strongly increases the risk for autism in the offspring. Other investigators have shown that maternal exposure to valproate or thalidomide increased the risk for autism as well. There are very interesting mouse models based on these last two risk factors.

It is also important to point out that David Barker's theory of "fetal origins of adult disease" is a broader context for these epidemiological findings on mental illness; that is, a variety of insults during gestation can lead to increased risk for many chronic illnesses. This was recently highlighted in a fascinating paper entitled, "Is the 1918 influenza pandemic over?" by Almond.

References:

Almond D. J Political Economy. 2006;114:672-712.

Brown AS. Prenatal infection as a risk factor for schizophrenia. Schizophr Bull. 2006 Apr 1;32(2):200-2. Abstract

Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J. The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci. 2006 May 3;26(18):4752-62. Abstract

Patterson PH. (2006) In Understanding Autism, Eds. Moldin and Rubenstein, Taylor and Francis, pp. 277-302.

Shi L, Fatemi SH, Sidwell RW, Patterson PH. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci. 2003 Jan 1;23(1):297-302. Abstract

I would like to agree with two points from Dr. Jablensy's excellent commentary.

In the field of the new epidemidemiology of schizophrenia, I think that the temporal projection of the sistematic gradients of several variables, such as the variables of urbanicity and sex, for example, could help researchers to design some strategies of prevention with the collaboration of other professionals of the medical services.

In this sense, research on the risk factors could make the field of epidemiology a more dynamic and a more contributive field in relation to the pathogenesis and the causes of the disease. Thus, the epidemiology could tell us substantial information about the relationships between genetic polymorphisms and the environmment.

View all comments by Patricia Estani

The papers of McGrath reminded us that the incidence of schizophrenia is significantly higher in males than in females with a male:female risk ratio of 1.4:1. Interestingly the first whole-genome association study of Todd Lencz et al. (Lencz et al., 2007) revealed a novel schizophrenia locus that is present on both chromosomes X and Y. Since there is only a clear difference in the two sex chromosomes, I wonder if this schizophrenia locus can explain this variation in incidence by sex?

References:

Lencz T, Morgan TV, Athanasiou M, Dain B, Reed CR, Kane JM, Kucherlapati R, Malhotra AK. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol Psych. 2007, March 20. Advanced online publication.

View all comments by Jan van Dijk

A few comments from a clinician and a carer.

Is their some merit in dividing schizophrenia outcome into silent and florid? The condition fluctuates. Sometimes there is not enough visible behavior to make for a diagnosis. The DSM, which lists delusional illness, schizoaffective disorder, schizophreniform disorder, even psychosis accompanying physical illness, allows for sharpness of definition, appreciation, and overlapping such as to negate comparability between populations. Yet the condition can be there in the very restricted and limited lifestyle.

The illness expression, and therefore the diagnostic listing, will anyhow vary as the proportion of people in any population divide into different personality types: the introvert, anancastic, obsessional people may develop negative schizophrenia; the extrovert, sociable, novelty-seeking people, more florid—‘positive'— illness.

The social and domestic life of women in growing up, and in the balance of relationships is different from that of men. The age at which schizophrenia arrives—after or...  Read more

A few comments from a clinician and a carer.

Is their some merit in dividing schizophrenia outcome into silent and florid? The condition fluctuates. Sometimes there is not enough visible behavior to make for a diagnosis. The DSM, which lists delusional illness, schizoaffective disorder, schizophreniform disorder, even psychosis accompanying physical illness, allows for sharpness of definition, appreciation, and overlapping such as to negate comparability between populations. Yet the condition can be there in the very restricted and limited lifestyle.

The illness expression, and therefore the diagnostic listing, will anyhow vary as the proportion of people in any population divide into different personality types: the introvert, anancastic, obsessional people may develop negative schizophrenia; the extrovert, sociable, novelty-seeking people, more florid—‘positive'— illness.

The social and domestic life of women in growing up, and in the balance of relationships is different from that of men. The age at which schizophrenia arrives—after or before the accumulation of living skill—makes the expression and outcome likely to be different later on.

Thus, is there one schizophrenia, but its degree of expression and degree of exhibition, and therefore its capture, will vary with the personality and the degree of ‘stress’? Is it better to stick to the 'core' population for epidemiology?

Some further questions/comments:

Is their some merit in holding this in mind? There is a proportion of people {S+} who are genetically born to be liable to schizophrenia (added to by the sperm of old fathers); the other proportion is not going to get it.

When and how the illness declares itself, to be recognized, will depend on the degree of difficulty S+ people come across in their lives, or impose on themselves, and the level and durability of supportive companionship. Losing the backing of family certainties during adolescence is one such time of social, biological and relationship turmoil and uncertainty. Smoking cannabis is another. In general, the illness fault— the inability to hold on to relevant material and then to draw draw upon it to deal with outside stress— is another. Lack of steady companionship support in anxious situations is another. Lacking the ability to ‘distance’ is another? Third world villages may allow more space and a simpler living structure. Not having found an external framework to provide a living schedule of engagement leaves the potentially ill vulnerable.

Is there some merit in taking out of this a general theme? Whether the illness shows itself in S+ depends upon the life challenges. Cannabis or khat or amphetamine will bring forward an earlier and more florid expression of the illness in populations that allow for their cultural acceptance. Street drug usage, brought in by parents of immigrants maintains its cultural usage against the host mores. The drug use will bring forward an illness and it will be more florid and be recognizable more easily. Migration lands people within their own ghetto culture. The challenge of integrating together with growing up and emancipating is stressful and will bring out recognizable schizophrenia that in other conditions would be silent and tolerated.

The expression of schizophrenia will depend on somebody actually looking out for it recognizing it and listing it. The visibility of it will vary depending on the snapshot or the duration of the time of observation. But the overall population that started out with the liability would be a constant, in all populations.

The discussion is very interesting. From a forensic point of view we found 8.3/1 male/female ratio in Bulgaria with respect to homicidal schizophrenic offenders (Marinov, 2006). I wonder if this huge difference in aggressivity is related to the gender distribution or whether it can be explained mainly by hormonal differences.

References:
Marinov, P. (2006). Proximity of the victim to the perpetrator of schizophrenic and nonschizophrenic homicides ­ an attempt for comparative analysis. Receptor. 3, 49-53.

View all comments by Petar Marinov

The discussions set forth have been well expressed in terms of their explanations that the incidence and prevalence of schizophrenia are not uniform across different variables (migrants vs. non-migrants, males/females, and urban/rural) and that we need to do something about disseminating such knowledge. In terms of exploring the current situation, I would say that for those who are willing to dig deeper into the breadth of research on the topic, they will not be able to miss this fact as there have been well-established meta-analyses and well-grounded research findings up to this date that unambiguously share that knowledge (such as Cantor-Graae and Selten, 2005).

The question to ask at this point in time in terms of advancing our repertoires to improve treatment and the etiological factors behind schizophrenia's variations would be to start using a microscopic view, in contrast to large-scale studies (i.e., epidemiological and longitudinal) that now are only statistically quantifying what we already know.

One way of...  Read more

The discussions set forth have been well expressed in terms of their explanations that the incidence and prevalence of schizophrenia are not uniform across different variables (migrants vs. non-migrants, males/females, and urban/rural) and that we need to do something about disseminating such knowledge. In terms of exploring the current situation, I would say that for those who are willing to dig deeper into the breadth of research on the topic, they will not be able to miss this fact as there have been well-established meta-analyses and well-grounded research findings up to this date that unambiguously share that knowledge (such as Cantor-Graae and Selten, 2005).

The question to ask at this point in time in terms of advancing our repertoires to improve treatment and the etiological factors behind schizophrenia's variations would be to start using a microscopic view, in contrast to large-scale studies (i.e., epidemiological and longitudinal) that now are only statistically quantifying what we already know.

One way of performing research on the topic would be to use other disciplines such as medical anthropology to qualitatively explore the different dyadic relationships between migrant versus non-migrant patients suffering from schizophrenia, their symptoms, and the interpretations of their differences. As such, one can then be able to unlock the key factors that not only tell us the differences but might also shed light on ways to engage systems into knowing how to treat and prevent schizophrenia from being selective in the future.

References:

Cantor-Graae E, Selten JP. Schizophrenia and migration: a meta-analysis and review. Am J Psychiatry. 2005 Jan 1;162(1):12-24. Abstract