Schizophrenia Research Forum - A Catalyst for Creative Thinking

Live Discussion: The New Epidemiology of Schizophrenia


John McGrath

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Epidemiologists have offered no shortage of leads to the etiology of schizophrenia, but it is no easy task to turn these findings into practical use—either for prevention or treatment. On 11 April, John McGrath of the University of Queensland, Australia, led us in a discussion of the challenges of turning epidemiologic data into new ideas for prevention and treatment. As we await the transcript posting, we invite you to read two of his recent editorials, from Schizophrenia Bulletin and the Archives of General Psychiatry. Please also read and respond to the comments left below.

Our special thanks to the Archives of General Psychiatry for granting open access to this editorial:

McGrath JJ. The surprisingly rich contours of schizophrenia epidemiology. Arch Gen Psychiatry. 2007 Jan;64(1):14-6. View article

John J McGrath. Variations in the Incidence of Schizophrenia: Data Versus Dogma. Schizophr Bull, January 2006; 32: 195-197. View article

View Transcript of Live Discussion — Posted 24 May 2007

View Comments By:
Jim van Os — Posted 4 April 2007
James Kirkbride — Posted 5 April 2007
Jean-Paul Selten — Posted 5 April 2007
Craig Morgan — Posted 9 April 2007
Jonathan Burns — Posted 9 April 2007
Brian Chiko — Posted 10 April 2007
Fuller Torrey — Posted 10 April 2007
Assen Jablensky — Posted 10 April 2007
Jean-Paul Selten — Posted 10 April 2007
Paul Fearon — Posted 10 April 2007
Dana March — Posted 10 April 2007
— Posted 10 April 2007
Sukanta Saha, Saha Sukanta — Posted 11 April 2007
Joy Welham — Posted 11 April 2007
Vera A. Morgan — Posted 11 April 2007
Robert Yolken — Posted 11 April 2007
Preben Bo Mortensen — Posted 11 April 2007
Paul Patterson — Posted 11 April 2007
Patricia Estani — Posted 18 April 2007
Jan van Dijk — Posted 30 April 2007
David Yates — Posted 23 May 2007
Petar Marinov — Posted 29 May 2007
Huda Shalhoub — Posted 13 March 2009


Background Text
By John McGrath

If forgetting that schizophrenia was a brain disease was one of the great aberrations of twentieth-century medicine, ignoring variations in the incidence of schizophrenia must rank as one of the great aberrations of modern epidemiology. However, research has recently provided us with data that cannot be ignored. The incidence of schizophrenia varies widely among sites, and varies according to a range of demographic variables including sex, urbanicity of place of birth/residence, paternal age, season of birth, and migrant status. High-quality prospective cohort studies have also strengthened the case that cannabis is a risk-modifying factor for schizophrenia.

The target articles outline some of the major features of the “new epidemiology” of schizophrenia. The commentary in the Archives of General Psychiatry canvasses various options about how to get the best “bang for our buck” from future epidemiological studies. It is argued that the clues being generated by schizophrenia epidemiology are too important to ignore.

The discussion will be broad-ranging, and we encourage the readers of Schizophrenia Research Forum to contribute topics for discussion and debate prior to the Live Discussion. For example:

1. What type of epidemiological research needs to be done now?

2. How can we avoid “circular epidemiology” where research perseverates at the ecological level, and fails to move to more refined analytic methods or experimental studies?

3. How can we engage neuroscience in helping to unravel the clues emerging from epidemiology?


Transcript

Attendees/Participants
Simge Aykan, Dokuz Eylul University, Turkey
Elizabeth Cantor-Graae, Lund University, Division of Social Medicine and Global Health
Michelle Chandley, Department of Psychiatry Quillen College of Medicine, East Tennessee State University
Brian Chiko, Schizophrenia.com
Alex Cohen, Harvard Medical School
Gillian Doody, University of Nottingham, UK
Claudia Harrington, Johnson & Johnson
Keith Jarvie, Clera Inc.
Dana March, Department of Epidemiology, Columbia University
Eileen McGinn, Hunter-Brookdale New York, New York
Vera Morgan, UWA School of Psychiatry & Clinical Neurosciences, Perth WA Australia
Preben Bo Mortensen, NCRR, Aarhus University, Denmark
Huan Ngo, Yale Medical School, Section of Infectious Diseases
Greg Price, CCRN Perth
Eugenia Radulescu, CBDB/NIMH
Sukanta Saha, Queensland Centre for Mental Health Research
James Scott, Royal Children's Hospital and University of Queensland
Jean-Paul Selten, Department of Psychiatry, Utrecht University, Netherlands
Ezra Susser, Columbia University, New York
Jaana Suvisaari, National Public Health Institute, Helsinki, Finland
Hao Tan, NIMH
Joy Welham, Queensland Center for Mental Health Research
Dieter Wildenauer, Center for Clinical Research in Neuropsychiatry, University of Western Australia
Name withheld, Layperson
Robert Yolken, Johns Hopkins School of Medicine

Note: The transcript has been edited for clarity and accuracy.


Hakon Heimer
Let's start off by having everybody already in the "room" introduce themselves: I'm Hakon Heimer, editor of the Schizophrenia Research Forum.

John McGrath
John McGrath University of Queensland and Queensland Centre for Mental Health Research.

Dana March
Dana March, Department of Epidemiology, Columbia University; glad to be here!

Alex Cohen
Alex Cohen, Dept of Social Medicine, Harvard Medical School.

Jean-Paul Selten
Jean-Paul Selten, psychiatrist and epidemiologist at Utrecht University, the Netherlands.

Claudia Harrington
Claudia Harrington, Manager-Program Coordination, Johnson & Johnson Pharmaceutical Research & Development.

Michelle Chandley
Michelle Chandley, Department of Psychiatry, Quillen College of Medicine, Johnson City Tennessee.

Hakon Heimer
If you haven't chatted before, you'll see that many things can happen at once in the chat room. So, while the rest of you introduce yourselves, I would like to introduce and thank our chat leader, John McGrath.

Huan Ngo
Huan Ngo, Yale Infectious Diseases Section. Hello.

Keith Jarvie
Keith Jarvie, Dir. Drug Discovery, Clera Inc.; Board Chair, Ontario Mental Health Foundation, Toronto, Canada.

Hakon Heimer
In the informal spirit of this event, and because I think most people here are at least acquaintances, I won't go into any length about his biography and work, except to say that John is Director, Queensland Centre for Mental Health Research, in the Land Down Under. He has varied interests in research, but especially a record of work and recent provocative reviews in epidemiology. I'll now turn the floor over to John.

John McGrath
Hi, everyone. Thanks for joining the discussion and many thanks to the folks who have already contributed comments. We have lots of different topics that we can focus on.

Ezra Susser
Ezra Susser, Columbia University; glad to be here.

Vera Morgan
Vera Morgan, Neuropsychiatric Epidemiology Research Unit, University of Western Australia. Hi.

Greg Price
Greg Price, Centre for Clinical Research in Neuropsychiatry, UWA, Perth, WA. Good evening.

John McGrath
Lots of old friends here—should be fun!

Eileen McGinn
Eileen McGinn, student, Hunter-Brookdale.

Name withheld
I am a parent who has a daughter with schizophrenia. Thank you all who are working on solutions in mental health.

Hakon Heimer
Welcome. We're glad to have someone from the "community" sitting in. (Standard disclaimer—we can't discuss individual cases.)

Joy Welham
Joy Welham, QCMHR, Queensland.

John McGrath
Firstly, I am feeling a bit guilty that, as a “true believer” in epidemiology, I might have pushed the need to link epidemiology with neuroscience too strongly in the Archives commentary. Many of the commentators (James Kirkbride, Jean-Paul Selten, Paul Fearon, Dana March, Craig Morgan, etc.), have reminded us of the need for more precise social psychiatry—concepts like the buffering capacity of social capital, the role of social defeat in minority groups, etc. However, I still worry that left to our own resources, epidemiology will get stuck in the “circular epidemiology” phase of ongoing replication studies, with little added value. So, my friends, to start the discussion, will the new clues from social psychiatry be wasted and turned into a modern “season of birth” effect = endless, mindless (= dumb) replication, less work on specific candidate risk factors, etc.… Your thoughts?

Dana March
John, it seems as though we need to pay particular attention to levels of organization in our studies; research at one level of organization can lead to research on other levels of organization. Paternal age is a fine example—we can move down to the biological level from the social level, or vice versa. But, conceiving pathways and mechanisms is key.

John McGrath
Thanks, Dana—pathways are the key, but can social psychiatry provide us with a royal road to pathways.... Is it the best category of observation? Convince me!

Dana March
Moving across levels can be done, of course; observation can be coupled with experimentation—the latter is most easily done at micro levels. So, while social psychiatry may not constitute the Royal Road per se, it provides a much needed compass.

Jean-Paul Selten
I agree with John and the need to link epidemiology with neuroscience. We will have to explain how the environment impacts upon brain functioning or structure.

John McGrath
Jean-Paul and Liza, do you need any more studies showing that migrant status is a risk factor? Can more refined epidemiology studies provide extra clues on mechanism of action?

Elizabeth Cantor-Graae
We know that migrant status per se is a risk factor; we still don't know why.

Jean-Paul Selten
I do not think we need any more. More refined studies are needed indeed, for example, to test the social defeat hypothesis. We need to know whether the subjects from ethnic minority groups who develop psychosis have indeed experienced social defeat (disprove the ecological fallacy).

Dana March
Migrant status may only be important when considering minority status; we do need studies in Western Europe and in other contexts to refine our understanding of mechanisms. What is it about being a migrant or a minority? Is it discrimination by the majority, breaking social ties, material deprivation, etc.? We need competing hypotheses to move forward.

John McGrath
Thanks, Jean-Paul and Liza and Dana. Okay, so we can refine the category of observation to specific categories, but I wonder if it will all boil down to stress = bad for the brain? What is so special about migrant stress?

Jean-Paul Selten
Liza and I believe it is humiliation. We specified the nature of the stressor.

Ezra Susser
My view is that we need better measures of both social/societal and brain/biological factors, and should not focus on one to the exclusion of the other. In terms of social/societal, we find strong effects of being a migrant or minority, but we don't find strong effects of family SES on schizophrenia, which suggests that it doesn't simply boil down to stress. We need to conceptualize and measure the relevant social variable.

Dana March
Not so convinced about stress, but that remains to be seen. Seems like living in a context that is potentially discriminatory or excluding is key. Could be a stress effect on the individual case; could be epigenetic when a mom moves, encounters discrimination, etc. Our power of resolution is limited in some senses, so we have to form theories and hypotheses about these effects. And, of course, measuring social context is key to that.

Jean-Paul Selten
I agree with Ezra. If the stress of poverty were important, we would find millions of patients in the Third World.

Elizabeth Cantor-Graae
Thanks, Jean-Paul. I would like to add that social defeat may be especially important as a stressor, because the brain is formed through contact with other persons. Man is a social being; thus, the social context may be vital for certain processes in the brain.

Eileen McGinn
Yes, I work with immigrants in New York City. Some already speak English, some are asylees with no family here, some are professionals who can reasonably find a decent job, some have found good networks. Their culture of origin also counts.

John McGrath
So the challenge for our field is to refine stress into more types (a taxonomy of stress), and then measure carefully.

Jean-Paul Selten
Yes!

Huan Ngo
If stress and humiliation, then what are the underlying genetics that predispose specific immigrants to develop schizophrenia.

Dana March
John, Jean-Paul, I am wary of pursuing stress exclusively. You don't necessarily see elevated rates of other mental disorders in minorities. We need to think about social exposures that may be particularly psychotogenic—is that necessarily solely stress related?

Vera Morgan
A general comment. The third-generation epidemiological studies are facing the problems of the older first-generation "social psychiatry" studies in which researchers are confronted with the very fuzzy boundaries of the social constructs they are working with. We need better ways of operationalizing these.

Robert Yolken
I would like to suggest that we also consider infectious disease explanations for increased incidence of schizophrenia in immigrants to Europe. While we think that Europe has fewer infections than Africa or Asia, that is not actually always the case. For example, there are a number of viruses which require the high density of European cities or large expanses of agriculture that are not common in most rural areas of Africa or Asia.

John McGrath
Hi, Bob. Okay, lets broaden the discussion to include other factors like infection. I personally feel that it is not politically correct to suggest that biological factors may be the main factors driving schizophrenia in migrants, rather than sociopolitically mediated factors. For example, some groups, when sorted by ancient geographical origin (no need to use confusing term race/ethnicity), have different prevalence of risk haplotypes. This is ignored. Dark-skinned people are more likely to have low vitamin D, and perhaps other biological factors related to nutrition and propensity to infection. Some of these may be downstream from social factors, but some of us are not so comfortable talking about this topic because we risk being labeled “biological reductionists” and can be cast as uncaring, etc.

Jean-Paul Selten
It is good to consider all possible explanations, including biological ones. It seems to me, however, that biological explanations do not fit the data.

Dana March
John, I think about biological mechanisms for social exposures; the evidence points to that—I agree with Jean-Paul.

Elizabeth Cantor-Graae
I think the latest batch of studies on victimization during childhood as a risk factor for schizophrenia is nicely in line with these more "social" theories, although the influence of "biology" can never be entirely excluded. Does it have to be either/or?

John McGrath
Bob, infection will not go away, but I feel we are reliant on banked collections to get traction on these, and they are a limited resource. The PKU/filter paper samples will be a help, as you recently used for T. gondii with Preben Mortensen and colleagues (Mortensen et al., 2007).

Robert Yolken
As far as I know, there has not been a comprehensive study of infectious or nutritional exposures in immigrants, so there are not any data to fit. I think that this is a good area to study. It might also explain differences between what is seen in immigration to different areas—such as to the U.S. as compared to Europe.

Dana March
The associations with infections or nutritional factors are not nearly as strong as associations we see in migrants. We know famine is a risk factor, but it's unclear what nutritional deficiency is at work with that.

Robert Yolken
Also, as stress is a well-known factor which affects the immune system—along with nutrition—these types of approaches are not at all mutually exclusive.

Ezra Susser
Bob, I agree that we should keep our mind open about infections, and other factors, too. Nonetheless, it’s hard to explain some of the current findings, such as findings on ethnic density, except with social explanations.

John McGrath
I can't resist infectious agents as candidates because they are so potentially powerful from a public health perspective. I am not so sure we can eliminate social defeat or childhood trauma, etc. Should we keep looking for candidates that we can do something about, like the drunk looking for his keys under the lamp post?

Claudia Harrington
John, is it not the biological/neurological response from the social trauma that we need to focus on, and is that not the manner to do something about the social aspects?

John McGrath
Yes, Claudia, we have to keep the focus on the neurobiological reactions to social trauma. This can be modeled in healthy controls and patients to a certain extent. But, as we all know, we have a long way to go to understand the role of stress in brain function—a lot of the neuropsychobiology literature has a 1960s feel to it (e.g., cortisol levels, HPA axis etc.). Sorry if this offends anyone!

Claudia Harrington
John, I agree. I think that the psychosomatic aspect of any mental illness is also well ignored and a better understanding of the relationship between the social and the biological is necessary!

Ezra Susser
John, I wonder if you could say something about how the vitamin D story might fit with the current data on immigrants?

John McGrath
Ezra, the vitamin D hypothesis is now strong for rats and mice, but we are still working on human data. The assay needed to measure vitamin D in neonatal dried blood spots is still under development. Also, the vitamin D hypothesis is pitched at prenatal exposures (= second-generation migrants) and I am not convinced about first-generation (= adult exposures).

James Scott
John and Jean-Paul, perhaps the problem is that as schizophrenia is such a heterogenic disorder, there may be so many etiological factors that are involved. Is the problem that the broad psychosis phenotype is encapsulating many different disorders?

Jean-Paul Selten
Sorry, I must leave. Thank you!

Hakon Heimer
Thanks for coming, Jean-Paul.

Vera Morgan
The discussion raises a number of putative risk factors including nutrition, stress, infection. The problem is that many of these are not specific to schizophrenia. How do we, as epidemiologists, deal with this?

Ezra Susser
Vera, I am not sure that we require specificity of effect to find causes. In any case, though, the effect of early prenatal famine is rather specific to schizophrenia, though not entirely specific (e.g., also neural tube defects).

Dana March
John, because we can't eliminate social defeat doesn't mean it and other social hypotheses are unworthy of rigorous investigation. A psychotogenic set of social practices provides a good rationale for intervention! Are we just uncomfortable with social interventions as epidemiologists used to being more proximal to the individual, more biological?

Claudia Harrington
Dana, I agree with you completely. However, there cannot be a separation between the social and the biological aspects of schizophrenia; they are completely interrelated.

Dana March
Claudia, we can tease them apart in studies—focusing on social in one and biological in the other; I don't think we need all-encompassing studies necessarily to answer everything. I think we just need to work closely together, with strong hypotheses, and rigorous methods.

Claudia Harrington
Dana, agreed around the strength of the data, but I think after looking at the individual aspects, the correlation perspective needs to be researched as well. We know that schizophrenia cannot be treated with psychotherapy alone and therefore, the biological aspects of the disease need to be focused on relative to their treatment success!

Dana March
Claudia, the treatment (e.g., antipsychotics) acts at the biological level. At the social level, what we are trying to tease apart is the causes of variation in incidence, a group-level phenomenon. Etiology, at this stage, is distinct from treatment. The point of considering broad pathways is that social environmental factors winnow their way through many levels into the body and act at a biological level. That's where treatment enters the picture.

John McGrath
My friends, I am looking at the clock. Liza reminded us about childhood victimization and trauma. Anyone like to comment on where this slightly controversial field needs to go next? James, do you want to comment?

Huan Ngo
With the complexity of biological and social factors, do we need a mathematical perspective to consolidate all factors into a comprehensive assessment of interconnection and weight of each variable? Otherwise, individual perspectives can be debated for several decades, whereas Wanda is wondering how her daughter is going to get better.

Name withheld
Huan, thank you and all for your empathy to finding the cure. I hope that my daughter can contribute to that end through her participation in research.

Sukanta Saha
Huan, what type of mathematical model are you proposing? Is there anything worked out?

John McGrath
Huan, mathematical models will be essential to understand systems biology, but our understanding is too imperfect at this stage.

Claudia Harrington
Huan and John, I think that trying to use mathematical models will cause too much generalization at this point. There are too many individual factors to lump everything together as one.

Eileen McGinn
Nutrition is important prenatally (famine) and there is emerging and converging evidence about EPA and DHA (omega 3, fish oil) for many symptoms in cognitive, mood, and behavioral disorders.

Elizabeth Cantor-Graae
Can nutritional factors explain the broad range of ethnic minority groups that have been implicated in migrant studies? We have everything from Moroccans to Greenlanders!

Ezra Susser
I tend to believe that prenatal nutrition acts at one point in the life cycle, and the unknown causes of the increased risk in migrants at a later point.

Dana March
Ezra, you raise a great point about timing of exposures and potential pathways.

Elizabeth Cantor-Graae
I agree with Dana (and Ezra).

John McGrath
Everyone, we agree that broad biosocial, etc., perspectives are needed. In his role as devil's advocate, Assen suggests that we have a moratorium on observational epidemiology (incidence, prevalence, course, etc.) (see comment by Assen Jablensky). Will we learn anything new? Anyone like to bite on this hook?

Dana March
John, I'll bite. How can we refine our understanding of timing and type of exposures without the assistance of observational epidemiology? Ethical issues, of course, prohibit us experimenting in the way that we might like to isolate causes and get at etiologic processes. You convince me now.

John McGrath
Dana, we do need to refine exposures. No one has mentioned cannabis yet, but I see this as a reasonable example of epidemiology providing good enough evidence that it is a risk modifying factor...so we need to plan major epidemiology studies that capture this exposure in a more precise way.

Dana March
John, I agree. And, of course, we would need to plan them in the Netherlands....

John McGrath
Dana, the site of future studies—good point. Will we learn much more by looking at the same sites? We have very good population-based data from places like Denmark and Finland, but I crave more studies from India and Ethiopia!

Dana March
John, strikes me that we would need to have a better idea about what it is about cannabis in order to do that. Cannabis is not the same everywhere, and lots of folks smoke cannabis laced with other chemicals (e.g., formaldehyde). How do we work to narrow that down?

John McGrath
Dana, cannabis is a mystery to me, but I am sure it has potential. I was titillated by the potential for COMT and cannabis to show a gene by environment interaction, but I am not sure if this is still holding up.

Dana March
John, not sure either, but glad you raised the issue.

Elizabeth Cantor-Graae
We need more epidemiological input from low-income countries. After all, they have a greater concentration of these putative stressors than we in Europe (and the U.S.) have.

Huan Ngo
John, Elizabeth, low-income countries have more stressors, but they are dying much younger from malaria and tropical diseases and skew the incidence of early adulthood onset of psychosis.

John McGrath
My friends, we only have a limited time left. Does anyone have a burning topic to raise?

Eileen McGinn
Burning topic: multiple comorbidities of medical and psychiatric illnesses, with drug-naive and drug-exposed patients.

Dana March
Eileen, do you mean physical illnesses resulting from treatment of schizophrenia? Diabetes, for instance?

John McGrath
Eileen, physical comorbidity is a topic that is attractive to governments to fund, it has more proximal outcomes, and it may contribute to ultimate causes (perhaps).

Eileen McGinn
Data seem to indicate that there may be biological factors like insulin resistance and inflammation already in place in some people with psychological diagnoses. Of course, treatment-emergent drug adverse effects may make this worse in some people.

Preben Bo Mortensen
Just one oblique comment: My main concern is not whether all these epidemiological signals we are discussing are there, or if they are worthwhile producing. My concern is, how do we move to the level of causality rather than association? I simply think we need to put in more effort on measurement. For example, we need to ask specifically, can the distribution of exposure to a given infection explain the distribution of schizophrenia? Across immigrant groups and back this with data, the same goes for risk genes, etc. It will be a long and difficult process, but without it we will be stuck with speculation.

Dana March
Preben, I agree with you. Problem is the distribution of social factors, for instance, is difficult to get at; we need to refine our conceptualization and measurement of social factors. We need sociologists on board! Cross-disciplinary research is key.

John McGrath
Thanks Preben...moving to the level of causality is central, but epidemiology is hopeless at this level. I worry that unless we build strong links to neuroscience in order to examine specific, fine-grain mechanisms of action, then we will be cursed with ecological studies for decades. Maybe I am too optimistic about the powers of neuroscience...but the more I work with neuroscientists, the more I think they need us to point them in the right direction.

Dana March
John, same for the geneticists.

Preben Bo Mortensen
Thanks, John, but I'm more optimistic. I think we can move to that level; it all depends on the data and samples we can get at and our level of success in bringing epidemiology thinking into more biological fields of schizophrenia research.

John McGrath
Preben, I am energized by your optimism! Your contribution to epidemiology is an inspiration...and your PKU samples may hold the key to many mysteries of schizophrenia.

Preben Bo Mortensen
Sorry, guys, have to go again; thank you very much John, for setting this up.

Dana March
Bye, Preben!

John McGrath
Dana. Yes we need links to geneticists, but I sometimes think that they are as lost as we are...but maybe I have a bad dose of gene envy. There was a commentary in the BMJ several years ago about a “flat earth approach” to looking for genes. The instructions for development are distributed across many domains, only some of which are in the base pair sequence. I think those of us who have been raised on the neurodevelopmental hypothesis have a healthy balance of genes and environment.

Dana March
John, I agree—it's just a challenge, perhaps one attributable to the sociology of science.

Hakon Heimer
All, are there any ways to get this (dynamic) group to join together in efforts that will create traction? Or are any such efforts ongoing that should particularly be encouraged?

Ezra Susser
John, I like Hakon's idea. This has been thoroughly enjoyable, and I'd love to continue to exchange ideas with this group.

Dana March
Ezra, Hakon, agreed.

Ezra Susser
Hakon, John, others, how about another epidemiology discussion, but we could have a specific focus?

Sukanta Saha
I agree with Ezra, specific ideas!

Hakon Heimer
Certainly, regular SRF discussions on epidemiology can be on the menu. Volunteers to lead future chats are encouraged to apply. I read an interview with an inventor who said that his modus operandi was to look for things that "sucked" (yes, he's American) and figure out how to get around that. Is there a value to a future SRF discussion that focuses on institutional or systemic roadblocks (everyone could nominate a favorite) and then trying to find ways to solve one or two? In the gene hunter world, I see, there are always discussions about how to get people to combine their cohorts. Parallels in epidemiology?

Ezra Susser
Yes, there are definitely parallels, Hakon, and this could be useful as well as interesting.

Dana March
Hakon, combining cohorts, bringing together folks from different studies is key to moving forward. Ezra heads a center at Columbia (IMPRINTS) that does just that. Would be nice to have SRF as a forum for those types of ideas.

John McGrath
Hakon and Ezra, can epidemiology get its act together? In his commentary, Paul Fearon reminds us of the crop of first episodes currently being examined for follow-up; closer collaboration between these groups worldwide would not only be informative but also, dare one say it?, relatively cost-effective.

Ezra Susser
Hakon, perhaps you should take ideas for future topics and volunteers for leading them. There might be someone with a great topic and eager to lead a discussion. Otherwise, though, I'd be willing to co-lead one with Dana.

Dana March
John, thank you so much for leading a stimulating discussion. Hakon, will be in touch.

Name withheld
As a layperson, it's awesome to eavesdrop on candid brainstorming. Thanks very much.

Sukanta Saha
Thanks, John and everybody for this warm discussion. It would be nice to attend future forum discussions.

Hakon Heimer
Ezra, as soon as you asked for volunteers, people started leaving the room. ;-) Thanks to all! And especially to John for leading this and preparing the background text. Anyone interested in leading a future discussion on a specific topic, please e-mail me.

Brian Chiko
Hi everyone, this is Brian Chiko from Schizophrenia.com here. I just wanted to offer our assistance to any group doing nonprofit research who needs help recruiting subjects for their studies—we're happy to help. We get over 450,000 visitors each month—many of whom have family members who have schizophrenia.

John McGrath
Brian, thanks for this and great to have your famous Web page crosslinking to SRF.

Ezra Susser
Have to go now. Thanks, John, Hakon, and everyone else—a great and lively discussion.

Huan Ngo
Thanks, John, Hakon.

John McGrath
Hakon. Time to wind up? We Australians are now past midnight!?

Hakon Heimer
Absolutely. Off to bed/breakfast/dinner for everyone!

Joy Welham
Thanks John, Hakon, and other participants for a very instructive (and enjoyable) chat.

John McGrath
Thanks, everyone, and goodnight from Brisbane. Feel free to send more comments or afterthoughts to SRF.

Comments on Online Discussion
Comment by:  Jim van Os
Submitted 4 April 2007
Posted 4 April 2007

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 OsComment by:  James Kirkbride
Submitted 5 April 2007
Posted 5 April 2007

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

View all comments by James KirkbrideComment by:  Jean-Paul Selten
Submitted 5 April 2007
Posted 5 April 2007

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!

View all comments by Jean-Paul SeltenComment by:  Craig Morgan
Submitted 9 April 2007
Posted 9 April 2007

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.

View all comments by Craig MorganComment by:  Jonathan Burns
Submitted 5 April 2007
Posted 9 April 2007

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.

View all comments by Jonathan BurnsComment by:  Brian Chiko
Submitted 10 April 2007
Posted 10 April 2007

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 ChikoComment by:  Fuller Torrey
Submitted 10 April 2007
Posted 10 April 2007

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 TorreyComment by:  Assen Jablensky
Submitted 10 April 2007
Posted 10 April 2007

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?

View all comments by Assen JablenskyComment by:  Jean-Paul Selten
Submitted 10 April 2007
Posted 10 April 2007

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 SeltenComment by:  Paul Fearon
Submitted 10 April 2007
Posted 10 April 2007

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 FearonComment by:  Dana March
Submitted 10 April 2007
Posted 10 April 2007

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.

View all comments by Dana MarchComment by:  Sukanta SahaSaha Sukanta
Submitted 11 April 2007
Posted 11 April 2007

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?

View all comments by Sukanta Saha
View all comments by Saha SukantaComment by:  Joy Welham
Submitted 11 April 2007
Posted 11 April 2007

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?

View all comments by Joy WelhamComment by:  Vera A. Morgan
Submitted 11 April 2007
Posted 11 April 2007

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. MorganComment by:  Robert Yolken
Submitted 11 April 2007
Posted 11 April 2007

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 YolkenComment by:  Preben Bo Mortensen
Submitted 11 April 2007
Posted 11 April 2007

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.

View all comments by Preben Bo MortensenComment by:  Paul Patterson
Submitted 11 April 2007
Posted 11 April 2007

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

View all comments by Paul PattersonComment by:  Patricia Estani
Submitted 12 April 2007
Posted 18 April 2007

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 EstaniComment by:  Jan van Dijk
Submitted 27 April 2007
Posted 30 April 2007

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 DijkComment by:  David Yates
Submitted 23 May 2007
Posted 23 May 2007

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.

View all comments by David YatesComment by:  Petar Marinov
Submitted 27 May 2007
Posted 29 May 2007

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 MarinovComment by:  Huda Shalhoub
Submitted 4 March 2009
Posted 13 March 2009

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

View all comments by Huda Shalhoub