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Updated 5 March 2009 E-mail discussion
Printable version

Live Discussion: The Role of the Social Environment in Psychiatric Research: Outstanding Challenges and Future Directions

Dana March

James Kirkbride

Wim Veling

On 17 March 2009, we hosted a live discussion of fresh new ideas in the epidemiology of schizophrenia. Discussion leaders Dana March of Columbia University, James Kirkbride of the University of Cambridge, and Wim Veling of Parnassia Psychiatric Institute delivered a wide-ranging discussion of social factors such as migration, ethnicity, and urbanicity, but also asked how this research could benefit from genetic insights. Finally, they discussed possible biological mechanisms that might transduce social factors into psychosis.

View Transcript of Live Discussion — Posted 8 July 2009

View Comments By:
John McGrath — Posted 6 March 2009
Kathryn Abel — Posted 6 March 2009
Paul Fearon — Posted 9 March 2009
Erika Cilengir — Posted 13 March 2009
Jan Golembiewski — Posted 13 March 2009
David Yates — Posted 13 March 2009
Jan Golembiewski — Posted 16 March 2009
Amresh Shrivastava — Posted 16 March 2009
Jean-Paul Selten — Posted 16 March 2009
Alberto Arregui — Posted 16 March 2009
Brian Chiko — Posted 17 March 2009
German Torres, Diana Ayubcha, Sherry M. Zakhary — Posted 17 March 2009
Vera A. Morgan — Posted 17 March 2009
Kiumars Lalezarzadeh — Posted 17 March 2009
Karl-Ludvig Reichelt — Posted 17 March 2009
Peter Jones — Posted 19 March 2009

I. Background

1. Elucidation of several factors well established: migration, ethnicity, urbanicity
The study of social causes of schizophrenia, once a dominant focus of attention, has been reinvigorated in the current era. This growing area of study draws on evidence from analyses of migration, ethnicity, and urbanicity. Recent and ongoing work grows out of interest in work linking migration and schizophrenia. Evidence indicates that migration itself is not the important exposure, since second-generation migrants appear more at risk (Cantor-Graae and Selten, 2005).

Studies of ethnicity and race, stimulated by the migration work, show that racial and ethnic minorities are at markedly increased risk of schizophrenia, compared to their majority native-born counterparts (Fearon et al., 2006; Veling et al., 2006; Bresnahan et al., 2007). Interestingly, ethnic minorities who live in areas with greater concentrations of other ethnic minorities are less at risk than ethnic minorities who live in areas with few ethnic minorities (Boydell et al., 2001; Veling et al., 2007). One possible explanation is the lack of discrimination, which has been associated with increased risk (Veling et al., 2007). Still, these findings leave many questions unanswered, and evidence is lacking across settings.

Finally, studies of urbanicity indicate that people born in urban areas are about two times more likely to develop schizophrenia than those born in less densely populated areas (e.g., Mortensen and Pedersen, 1999). However, what it is about being born in an urban area remains elusive—the relevant exposures may be physical (e.g., infection, toxins, nutrition) or social (e.g., crowding, adversity) in nature. Moreover, it is unclear whether this finding holds across a range of settings, since the bulk of evidence comes from Western Europe (March et al., 2008).

Together, studies of migration, ethnicity, and urbanicity frame a set of compelling questions that are being taken up by a new wave of research. Here we address the conceptual and methodological aspects of this work that currently make it one of the most interesting frontiers of schizophrenia research.

2. From risk indicators to causes
One of the central paradoxes in the social epidemiology of schizophrenia and other psychoses is that while urbanicity and black and minority ethnic status are associated with increased rates of disorder, they are ubiquitous “exposures” with little specificity. Many millions of people are exposed to these factors, but roughly only 50 per 100,000 people per year will go on to develop the disorder (Kirkbride et al., 2006). These factors may be better described as risk indicators—associated with an increased risk of psychoses, but not of themselves etiologically relevant. Rather, they lie on the causal pathway and present markers of risk for factors which lie closer to the causal genetic, individual, and environmental effects we will need to elicit before it will be possible to think about identifying environmental factors which offer potentially tangible public health prevention targets. Current research should focus on identifying risk factors for psychoses with greater specificity to allow us to resolve this paradox. So far, there have been important contributions from two streams of research, elucidating distinct genetic and environmental risks for psychotic disorders (McGrath et al., 2004; International Scizophrenia Consortium, 2008). To understand the likely complexity in the etiology of psychosis, we now need to move toward investigating how social factors interact with underlying genetic vulnerability to increase the risk of psychosis for some, but not all, individuals. Important contributions in this regard are beginning to emerge (Caspi et al., 2005), but we will need to develop a better understanding of the likely multifactorial, multilevel structure of exposures which increase and protect against the onset of psychosis across the life course, elucidating the critical time periods where these factors have the greatest effect (March and Susser, 2006).

3. Possible biological mechanisms
There is general consensus that heightened dopaminergic transmission plays a central role in schizophrenia. Several studies demonstrated that (untreated) schizophrenia patients have an increased mesolimbic dopamine release after acute amphetamine challenge (Laruelle et al., 1996; Abi-Dargham et al., 1998), suggesting an abnormal responsiveness of dopaminergic neurons. The question remains as to what causes this hypersensitivity to dopamine. It has been speculated that dopamine dysregulation arises from genetic factors, such as the valine-to-methionine (Val/Met) polymorphism in the catechol-O-methyl transferase (COMT) gene, which is involved in dopamine metabolism (Williams et al., 2007). Dopamine dysregulation might also be caused by early environmental insults such as prenatal infections, malnutrition, or obstetric complications, and by social stress in adolescence or early adult life (Howes et al., 2004). Several neurobiological models suggest links among stress, the hypothalamic-pituitary-adrenal (HPA) axis, and dopamine activity (Corcoran et al., 2003). Animal experiments have shown that exposure to stress as well as the biological induction of HPA activation enhance the behavioral response of rats to dopamine agonists (Covington and Miczek, 2001), and lead to mesolimbic dopaminergic hyperactivity (Tidey and Miczek, 1996). Thus, social stress may lead to (further) dysregulation of the dopamine system through an augmenting effect of the HPA axis on dopamine synthesis and release (Walker and Diforio, 1997). At the same time, it is likely that there is a reciprocal effect such that heightened sensitivity to dopamine influences HPA activation and thus renders the individual hyper-responsive to stress, consistent with recent human studies that found that individuals who are genetically vulnerable to psychosis are more emotionally and behaviorally sensitive to daily life stress than are healthy controls (Myin-Germeys et al., 2001). Consequently, if the results of the animal experiments can be extended to humans, it is possible that chronic exposure to social stress leads to disturbances in dopamine function and further to the development of psychosis.

But several challenges remain

1. Understanding the broader social processes which underpin social epidemiology.
2. Understanding historical timing of social events and historical changes in social factors.
3. Understanding critical timing of exposures across the life course.
4. Understanding interactions (interplay) between genes and environment to increased risk of schizophrenia.
5. Elucidating biological processes which link social factors to onset of schizophrenia—dopamine pathways, hippocampus changes, epigenetics, etc.
6. Understanding the contextual nature of risk factors—different factors in different populations (both genetic and environmental variation).
7. Construct refinement in gXe interactions—types of interactions.

II. Questions for Discussion

We need a better understanding of the phenotype, genotype, and envirome (greater specificity). What to target first? Candidate genes? What putative mechanisms are worth pursuing?

How do we design studies to deal with the complexities in etiology, and the particular complexities in social etiology?

How do we integrate systematically the individual life course?

How do we reconcile different contextual mechanisms in different settings to have meaningful public health implications?

1. Construct refinement/meaning
What are we actually capturing when we measure urbanicity or ethnic density? Examining critically the constructs of interest is a key step in understanding mechanisms. Part of this is trying to understand the broader social processes that create the conditions we ultimately measure as exposures of interest (e.g., population density, percent minority composition). With urbanicity, for instance, how do areas become densely populated? What are the patterns of urbanization and suburbanization in a given geographic location?

2. Study designs
We propose that it is necessary to design studies that investigate multiple levels of causation, because the complex etiology of schizophrenia involves factors acting at the level of genes, individuals, ethnic/racial groups, and neighborhoods. It is likely that higher-order interactions between genes and environment, and/or genes and genes, and/or environment and environment, determine the development of schizophrenia. Many different pathways are conceivable. This complexity requires research with carefully specified hypotheses and large samples in varying social contexts. But how can we accomplish that?

3. Time
Both historical time and timing of exposure during the life course are critical to understanding contextual effects. Indeed, period and cohort effects may exist with contextual exposures; beyond that, to understand better broader social processes, a historical view is beneficial. For example, in the work being conducted in Oakland, urbanization and suburbanization during the 1940s and 1950s created particular and identifiable patterns of urbanicity by race (hence “ethnic” density) and SES. Different patterns may be observed in other locations at other times. Understanding particulars may just help us wrap our minds around the generalizable; they are not mutually exclusive.

With respect to timing of exposure, we know population density has the greatest effect at birth. Ethnic density seems to operate around the time of illness onset—or does it? We need to examine these contextual exposures systematically across the life course in order to understand potential mechanisms.

Construct refinement by understanding broader social processes with a historical perspective and consideration of the individual life course will also inform the potential confounds we measure and include in our models.

If further studies would find more (specific) evidence for a social etiology of schizophrenia, public health interventions might be developed to prevent psychosis. These interventions may include strategies to diminish social isolation, increase social capital, and facilitate access to this capital. It may be feasible to strengthen social structures within social groups and within neighborhoods.

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

Kirkbride JB, Fearon P, Morgan C, Dazzan P, Morgan K, Tarrant J, Lloyd T, Holloway J, Hutchinson G, Leff JP, Mallett RM, Harrison GL, Murray RM, Jones PB. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Arch Gen Psychiatry. 2006 Mar 1;63(3):250-8. Abstract

Veling W, Selten JP, Veen N, Laan W, Blom JD, Hoek HW. Incidence of schizophrenia among ethnic minorities in the Netherlands: a four-year first-contact study. Schizophr Res. 2006 Sep 1;86(1-3):189-93. Abstract

Bresnahan M, Begg MD, Brown A, Schaefer C, Sohler N, Insel B, Vella L, Susser E. Race and risk of schizophrenia in a US birth cohort: another example of health disparity? Int J Epidemiol. 2007 Aug 1;36(4):751-8. Abstract

Boydell J, van Os J, McKenzie K, Allardyce J, Goel R, McCreadie RG, Murray RM. Incidence of schizophrenia in ethnic minorities in London: ecological study into interactions with environment. BMJ. 2001 Dec 8;323(7325):1336-8. Abstract

Veling W, Susser E, van Os J, Mackenbach JP, Selten JP, Hoek HW. Ethnic density of neighborhoods and incidence of psychotic disorders among immigrants. Am J Psychiatry. 2008 Jan 1;165(1):66-73. Abstract

Veling W, Selten JP, Susser E, Laan W, Mackenbach JP, Hoek HW. Discrimination and the incidence of psychotic disorders among ethnic minorities in The Netherlands. Int J Epidemiol. 2007 Aug 1;36(4):761-8. Abstract

Mortensen PB, Pedersen CB, Westergaard T, Wohlfahrt J, Ewald H, Mors O, Andersen PK, Melbye M. Effects of family history and place and season of birth on the risk of schizophrenia. N Engl J Med. 1999 Feb 25;340(8):603-8. Abstract

March D, Hatch SL, Morgan C, Kirkbride JB, Bresnahan M, Fearon P, Susser E. Psychosis and place. Epidemiol Rev. 2008 Jan 1;30():84-100. Abstract

Kirkbride JB, Fearon P, Morgan C, Dazzan P, Morgan K, Tarrant J, Lloyd T, Holloway J, Hutchinson G, Leff JP, Mallett RM, Harrison GL, Murray RM, Jones PB. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Arch Gen Psychiatry. 2006 Mar 1;63(3):250-8. Abstract

McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med. 2004 Apr 28;2():13. Abstract

[No authors listed]. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. 2008 Sep 11;455(7210):237-41. Abstract

Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005 May 15;57(10):1117-27. Abstract

March D, Susser E. The eco- in eco-epidemiology. Int J Epidemiol. 2006 Dec 1;35(6):1379-83. Abstract

Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9235-40. Abstract

Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry. 1998 Jun 1;155(6):761-7. Abstract

Williams HJ, Owen MJ, O'Donovan MC. Is COMT a susceptibility gene for schizophrenia? Schizophr Bull. 2007 May 1;33(3):635-41. Abstract

Howes OD, McDonald C, Cannon M, Arseneault L, Boydell J, Murray RM. Pathways to schizophrenia: the impact of environmental factors. Int J Neuropsychopharmacol. 2004 Mar 1;7 Suppl 1():S7-S13. Abstract

Corcoran C, Walker E, Huot R, Mittal V, Tessner K, Kestler L, Malaspina D. The stress cascade and schizophrenia: etiology and onset. Schizophr Bull. 2003 Jan 1;29(4):671-92. Abstract

Covington HE, Miczek KA. Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration "binges". Psychopharmacology (Berl). 2001 Dec 1;158(4):388-98. Abstract

Tidey JW, Miczek KA. Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study. Brain Res. 1996 May 20;721(1-2):140-9. Abstract

Walker EF, Diforio D. Schizophrenia: a neural diathesis-stress model. Psychol Rev. 1997 Oct 1;104(4):667-85. Abstract

Myin-Germeys I, van Os J, Schwartz JE, Stone AA, Delespaul PA. Emotional reactivity to daily life stress in psychosis. Arch Gen Psychiatry. 2001 Dec 1;58(12):1137-44. Abstract

Comments on Online Discussion
Comment by:  John McGrath, SRF Advisor
Submitted 4 March 2009 Posted 6 March 2009

Excellent background document—thanks!

I have a couple of quick comments which are really “free associations” based on the target document.

1. We need to think about specificity of outcome, as well as specificity of exposure. With respect to urbanicity, this seems to link to schizophrenia but not bipolar. Why is it so?

2. When it comes to looking at GxE interactions, I keep thinking about the wonderful paper from Irv Gottesman’s group (Turkheimer et al., 2003) about the interaction between socioeconomic status and the heritability of IQ in young children (a nested twin study in a large U.S. birth cohort). Mindful of how misleading the concept of heritability can be in some contexts (McGrath and Selten, 2008), this paper reminds us how optimal versus suboptimal environments can alter the expression of a massively polygenic surface level phenotype like “IQ.”

3. It is critical that we progress our understanding of migrant status as a risk factor. Can we unravel the...  Read more

View all comments by John McGrath

Comment by:  Kathryn Abel
Submitted 4 March 2009 Posted 6 March 2009

The concept of “social environment” should include maternal environment, i.e., maternal effects on early programming of development.


Abel KM (2004) Fetal Origins of Schizophrenia: testable hypotheses of genetic and environmental influences. British Journal of Psychiatry 184: 383-386. Abstract

St Clair, D., Xu, M., Wang, P., Yu, Y., Fang, Y., Zhang, F., Zheng, X., Gu, N., Feng, G., Sham, P., He, L. (2005). Rates of Adult Schizophrenia Following Prenatal Exposure to the Chinese Famine of 1959-1961. JAMA 294: 557-562. Abstract

McClellan, J. M., Susser, E., King, M.-C. (2006). Maternal famine, de novo mutations, and schizophrenia.. JAMA 296: 582-584. Abstract

Khashan A, Abel KM., McNamee R, Goertz M, Baker PN, Webb RT, Kenny L and Mortensen PB. (2008) Higher risk of offspring schizophrenia following prenatal exposure to severe life events. Archives of General Psychiatry; 65:146-152. Abstract

Khashan AS, McNamee R, Abel KM, Pedersen MG, Webb RT, Kenny L, Mortensen PB, Baker PM. (2008) Reduced infant birthweight consequent upon maternal exposure to severe life events Psychosomatic Medicine 70:688-694. Abstract

View all comments by Kathryn Abel

Comment by:  Paul Fearon
Submitted 5 March 2009 Posted 9 March 2009

Important and complex questions! The markedly raised rates observed in the vast majority of studies of ethnic minority/migrant groups in several countries are striking. There are two findings that may provide clues to unraveling the likely complex etiology of these phenomena:

1. South Asians in the U.K. have much lower rates of psychosis than Black Caribbeans, Black Africans, and those of mixed race (Fearon et al., 2006; Coid et al., 2008), yet migrated at broadly similar times and are both visible members of ethnic minority groups. Why is this?

2. I'm not sure if it’s published yet, but hasn't Ezra Susser's group found that “migrant” groups in Israel do not have the raised rates seen in migrants to other countries?

If the two points above are true, one possible explanation is the importance of one's expectations and experiences (whether first- or second-generation) in the host country. Unraveling the exact nature of this is the challenge.

As the discussion will be...  Read more

View all comments by Paul Fearon

Comment by:  Erika Cilengir
Submitted 4 March 2009 Posted 13 March 2009

Regarding immigrant populations, are you looking at the occurrence of early-onset schizophrenia vs. late-onset schizophrenia? I am wondering whether a person who may be predisposed genetically to developing schizophrenia might actually develop the illness once he/she immigrates to a new country and is faced with some of the challenges you describe above.

View all comments by Erika Cilengir

Comment by:  Jan Golembiewski
Submitted 4 March 2009 Posted 13 March 2009

E.T. Hall, supported by Dr. H. Searles, posits that psychotic episodes are more likely to occur and are more intense when perceptual systems are under stress, particularly because of lack of stimulus. Osmond (1957) and others point out that we all are prone to psychotic episodes if out perceptual systems are sufficiently blinkered.

Architecture itself can assist in maintaining normal perceptual functions. Salutogenics (Aaron Antonovsky, 1987) provides clues. Whilst this theory is useful for architecture, it is probably even better suited for the addressing questions about psychosocial implications of urban settlement patterns and urban design.


Antonovsky, A. (1987) Unravelling the Mystery of Health, San Francisco, Jossey-Bass Inc.

Hall, E. T. (1975) Mental Health Research and out of Awareness Cultural Systems. IN MARETZKI, T. W. & NADER, L. (Eds.) Cultural Illness and Health. Washington DC, American Anthropological Association.

HALL, E. T. (1990) The hidden dimension, New York, Anchor Books.

OSMOND, D. H. (1958) The Seclusion Room-Cell or Sanctuary? Ment Hosp, 9, 18-19.

SEARLES, Dr. H. F. (1960) The Non-human Environment, New York, International Universities Press.

SEARLES, Dr. H. F. (1965) Collected Papers on Schizophrenia and Related Subjects, London, Maresfield Library.

View all comments by Jan Golembiewski

Comment by:  David Yates
Submitted 5 March 2009 Posted 13 March 2009

Is selective migration not accepted anymore? Is it not the case that families that migrate are unsettled where they were, and that a reason for some having a bigger proportion of schizophrenia, might be that they are people who do not—cannot—fit in and are therefore more likely to be families that are affected by schizophrenia, and selected for to be more likely to develop the condition when in unfamiliar surroundings, and continue the susceptibility in the progeny?

The same will apply to those moving from rural to urban environments. Their progeny will carry a higher genetic risk than the indigenous around them.

The parental lack of the cultural experience and familiarity with the local mores and customs in their new placements will continue to have upbringing difficulties which their progeny will be influenced by, and will make the progeny more prone to suffer social ”sensitivity,” less likely to enter or accept local services, and more likely to end up with the more florid and recognizable expressions of schizophrenia.

View all comments by David Yates

Comment by:  Jan Golembiewski
Submitted 14 March 2009 Posted 16 March 2009

John McGrath’s observation that a “generation of researchers has been inoculated with false beliefs, which has led to an ideological resistance to data….” (2006) is significant because there has been a tendency to disregard social and environmental patterns when looking at schizophrenia, but this politically correct blindness has not been ubiquitous. David Halpern wrote a very worthy book on mental illness in the community (1995) and the introduction of this book includes a literature review on variation in mental illness generally. Halpern reviews a number of papers on the question raised by David Yates about the effect of drift (migration) vs. environmental and social causation and finds that there can be little doubt that both effects are true to some extent. He also points out that migration isn’t a one-way flow. Just as people will move to city cores to find cheaper and more anonymous accommodation, people will also move out of the cities to find respite from the stresses of city life (Halpern, 1995).

Having said this, skeptics should note that all psychosis is even...  Read more

View all comments by Jan Golembiewski

Comment by:  Amresh Shrivastava
Submitted 16 March 2009 Posted 16 March 2009

Health inequalities and social environment are closely interlinked (Warr et al., 2009). It clearly influences not only nature and size of pathology but also the treatment outcomes.

That social environment modifies the effect of genes has long been known and is being repeatedly replicated, e.g., 5-HTTLPR genotype on PTSD risk (Wille et al., 2008). It has become widely accepted that the psychotic disorders are endpoints of atypical developmental trajectories indexed by abnormal emotional and cognitive development early in life. However, the role of environmental factors in determining these trajectories has received relatively little attention (Bentall and Fernyhough, 2008).

Research in mental health has shown a biopsychosocial model for understanding development of mental disorders. The questions today, though, remain

1. Why do people in similar situations not develop the illness?

2. Why do people in diverse situations...  Read more

View all comments by Amresh Shrivastava

Comment by:  Jean-Paul Selten
Submitted 16 March 2009 Posted 16 March 2009

Excellent background document and interesting comments. The most important reason for the neglect of environmental factors is the so-called heritability index (Schwartz and Susser, 2006). According to textbooks, the "heritability" of schizophrenia is 85 percent. This figure is severely misleading, but makes geneticists rich. They will not address this fraud; we will have to do it.


Schwartz M and Susser E. The myth of the heritability index. In Beyond Nature and Nurture in Psychiatry: Genes, Environment and Their Interplay. Eds. James MacCabe, Robin Murray, Peter McGuffin, Padraig Wright, Owen O'Daly. Taylor & Francis, Inc., 2006, pp 223.

View all comments by Jean-Paul Selten

Comment by:  Alberto Arregui
Submitted 16 March 2009 Posted 16 March 2009

Hoping someone has an answer to these two questions:
1. Is early onset schizophrenia (i.e. between 15-24 years of age) still considered a distinct clinical entity? Is it still true that males have a higher prevalence in this age group?

2. When I participated in postmortem studies in Cambridge 1979 thru 1981)I was curious as to why the date of birth of schizophrenia patients (as opposed to schizophrenia-like) clustered between November and February. Is this still just an impression or does someone have better data?

View all comments by Alberto Arregui

Comment by:  Brian Chiko
Submitted 16 March 2009 Posted 17 March 2009

Stress/demethylation/choline and schizophrenia prevention
It increasingly seems that stress and DNA demethylation may be a key pathway that links many of the social and psychological factors identified in the summary with increased risk of psychosis. New research also suggests that a diet rich in methyl donors during pregnancy and early childhood may eliminate or greatly reduce risk of schizophrenia and psychosis. I'd appreciate other people's thoughts on this recent research and theories and if others see this as a potentially fruitful path of research.

The supporting research includes recent research by J. David Sweatt’s group at the University of Alabama at Birmingham which has found that with the BDNF gene, demethylation happens rapidly under certain conditions, such as when people experience stress. This demethylation seems to upregulate gene expression.

Prenatal supplementation with vitamins rich in methyl donors such as choline is seems to mitigate the effect of prenatal stress on brain development, and greatly lower risk of schizophrenia (tested in...  Read more

View all comments by Brian Chiko

Comment by:  German TorresDiana AyubchaSherry M. Zakhary
Submitted 16 March 2009 Posted 17 March 2009

As indicated by March, Kirkbride, and Veling, several studies suggest that people born in urban areas are more susceptible to develop psychoses than individuals born in less densely populated areas. Urbanicity may just be a risk factor that when combined with a particular genetic predisposition, triggers a striking transformation in behavior. It is conceivable that susceptible individuals to psychoses are born with a "social" phenotype of inconspicuous solitary preference, including avoidance behavior and nighttime spatial living. This "social" preference would work relatively well under a solitary phase or low population density. However, when this particular "social" phenotype is placed in a high population density, frequent social contact (e.g., mechanical/touch, olfactory, and/or visual) would elicit the release of abnormal levels of dopamine, serotonin, and/or NPY in specific brain circuits. It should be noted that the above neurochemicals have already been associated with promoting gregarious behavior and aggregation (e.g., socialization) in invertebrate animals (  Read more

View all comments by German Torres
View all comments by Diana Ayubcha
View all comments by Sherry M. Zakhary

Comment by:  Vera A. Morgan
Submitted 16 March 2009 Posted 17 March 2009

Critical to our understanding of the role of adverse social environments as a risk factor for schizophrenia is our capacity to operationalize the concept. This means both identifying specific and valid proxies for adversity exposure, as well as including the timing of the exposure into our studies, whether they be clinical or register-based studies. It also requires some thought on the question of resilience. Who is vulnerable and who is not—and why? Discussions such as this play an important role in developing our understanding of the concepts.

View all comments by Vera A. Morgan

Comment by:  Kiumars Lalezarzadeh
Submitted 17 March 2009 Posted 17 March 2009

The social environment of many immigrants can entail sociopolitical trauma affecting both national identification and mental well-being. Muldoon, Schmid, and Downes (2008) showed that the negative impact of direct political violence or conflict on mental well-being is mediated by national identification. When immigrants perceive discrimination they can lose their national identification to the new nation to which they have immigrated and develop hostile attitude towards the members of dominant out-group. There is gradual effect of discrimination and perceived discrimination on mental well-being (Jasinskaja-Lahti et al., 2008).

1. To what extent is the above gradual effect on mental well-being transmitted to the second-generation immigrants?

Adjustment to immigration has stages going from over-identifying and conforming to the dominant out-group to then returning to one's own in-group up to 28 years after immigration. In the conflict between going from the out-group identification back to in-group identification, the second-generation is developing or being...  Read more

View all comments by Kiumars Lalezarzadeh

Comment by:  Karl-Ludvig Reichelt (Disclosure)
Submitted 12 March 2009 Posted 17 March 2009

Immigrants and nutrition as possible cause for increase in schizophrenia
Most immigrants to Europe come from countries where rice and maize are staple foods. Usually very little milk is used, and many Asiatic and African peoples lack lactase after the age of six or seven. Quite a number suffer from intestinal, endocrine, and behavioral problems (Wändell and Gåfvels, 2007; Meyer et al., 2004; McKenzie et al., 2003; Thabit et al., 2008). Immigrants generally move to obtain better living possibilities, and with low incomes are dependent on grains (bread) and milk products.

Since we have found peptides derived from food proteins increased in schizophrenia and autism (Reichelt et al., 1996; Reichelt and Knivsberg, 2003) with confirmed relevant bioactivities (  Read more

View all comments by Karl-Ludvig Reichelt

Comment by:  Peter Jones
Submitted 18 March 2009 Posted 19 March 2009

I enjoyed the discussion and am sorry I missed the live interaction yesterday. I'm left with a couple of questions:

Why and how are stressful environments (of the type that are relevant to the urbanicity and migrant:host increased risk) stressful? More to the point, how and why are these social environments stressful to some people and not to others? This may be the relevant diathesis rather than anything proximally related to psychosis. It is true that the vast majority of people who are exposed to these "environments" don't develop psychosis—but do they find them as stressful as people who do? If they don't, then presumably they are incorrectly classified as having been exposed.

We need to understand more about the afferent arm of the stress response and GxE mechanisms, rather than the efferent genetic component. The methylation comments were relevant here, but how do social environments lead to such changes?

I was at a wonderful Keystone Symposium on schizophrenia and BPD genetics recently where the topical question from the multi-millionaire GWAS...  Read more

View all comments by Peter Jones
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