Schizophrenia might be correlated with poor sleep.

http://medicalxpress.com/news/2012-11-poor-contribute-symptoms-schizophrenia.html

http://medicalxpress.com/news/2011-12-problems-important-schizophrenia.html

http://phys.org/news/2010-11-schizophrenia-revealed-distinctive-pattern.html

Other:

http://www.eurekalert.org/pub_releases/2013-03/ez-mec030113.php

http://www.eurekalert.org/pub_releases/2012-04/uol-rlc041912.php

http://www.eurekalert.org/pub_releases/2013-07/uobc-ivs072613.php

http://www.eurekalert.org/pub_releases/2012-02/cp-rrt021612.php

http://idw-online.de/pages/de/news469550

http://www.eurekalert.org/pub_releases/2013-04/cumc-hlo041813.php

http://www.futurity.org/lefties-likely-schizophrenic/

Regards,

Joachim

Not only many resources can be found at the website of The International Society for Psychological and Social Approaches to Psychosis, but there next conference is exactly about this topic: "From DNA to Neighborhood: Relationship and Experience in Psychosis - An International Dialogue"

http://www.isps.org

A very interesting question and discussion thread. Understanding the advances and limitations on current research related to mental health and epigenetics is crucial to all who work with adolescents and adults with mental health disorders such as schizophrenia.

As discussed above, there are numerous resources. I have a particular interest in the transfer of knowledge from research into practice and with individuals and families and suggest that translating the relevance of epigenetic research into everyday practice and experience is a key focus for future research. Engaging in participative research with individuals suffering from schizophrenia and with their families provides a way to discover the developmental trajectories as well as ways to transfer knowledge and skills. Although there is a great deal of research done with individuals and families, there is a paucity of research related to the application and sharing of epigenetic research and the possible impact on attitudes and outcome.

As discussed there are many risks that can increase the probability of the emergence of schizophrenia - notably childhood trauma as well cannabis use. Another key factor which can impact on the outcome is the social stigma associated with severe mental illness. It thus seems important to understand the role of epigenetic research within the wider biopsychosocial model of mental illness . As well as understanding the risks, it is critical to discover the protective factors which can mediate the probability of the emergence of schizophrenia in conditions of adversity. There is a wealth of research on the risk and protective factors at an individual, family and community level in child and adolescent mental health e.g. Cincetti, Rutter . Discovering the epigenetic underpinning of these factors may prove fruitful in understanding the complex biopsychosocial interactions involved in schizophrenia.

Aleksandar Dimitrijevic makes the point that there is soon to be a conference focused on developing an international dialogue and this is an opportunity to air the polarised debates suggested by Davis Boyda and to take a step in developing a diathesis of individualised, client focused interventions and environmental and societal responses.

I would be very interested in your ideas on the application of epigenetic research and in developing a biopsychosocial model of mental illness.

Thank you for the debate so far.

"We know from twin and adoption studies that the expression of schizophrenia is not 100% genetic"

So, for MZ twins, genetics accounts for about half the variability. The other half could be due common environmental variables (social class, parental neglect, etc); specific environmental factors affecting just one twin (measles, having an accident, etc); or chance/error/randomness. Common environment will usually act equally on both MZ twins, and in any case has surpringly little long-term effect on mental, physical and psychological makeup. Very little is known about specific environmental factors, since psychologists have been fixated on common environmental variables. As for epigenetics, I think it is a case of wait and see.

"In addition, being raped by more than one perpetrator increased the risk of developing psychosis or a spectrum disorder by 15 times."

Schizophrenics come from families with a high incidence of all sorts of mental illness, just the sort of families that cannot protect their children from this sort of abuse, so it is not at all clear that even this strong correlation is causal.

Dear Neil

Twin studies have show us a concordance of disease between monozygotic twins only of 50%, indicating the concomitant role of environmental factors in the pathogenesis of schizophrenia. Environmental factors, that can cause epigenetic modifications, are important in its pathogenesis, acting on a biological inheritable vulnerability (compare Review of Fabi et al. 2013).

I have added different literature to this issue.

Pishva E, Kenis G, van den Hove D, Lesch KP, Boks MP, van Os J, Rutten BP. The

epigenome and postnatal environmental influences in psychotic disorders. Soc

Psychiatry Psychiatr Epidemiol. 2014 Mar;49(3):337-48. doi:

10.1007/s00127-014-0831-2. Epub 2014 Feb 19. PubMed PMID: 24549836.

Wockner LF, Noble EP, Lawford BR, Young RM, Morris CP, Whitehall VL, Voisey J.

Genome-wide DNA methylation analysis of human brain tissue from schizophrenia

patients. Transl Psychiatry. 2014 Jan 7;4:e339. doi: 10.1038/tp.2013.111. PubMed

PMID: 24399042; PubMed Central PMCID: PMC3905221.

Fabi E, Fusco A, Valiante M, Celli R. [Genetics and epigenetics of

schizophrenia]. Clin Ter. 2013;164(4):e319-24. doi: 10.7417/CT.2013.1596.

Italian. PubMed PMID: 24045531.

Nishioka M, Bundo M, Kasai K, Iwamoto K. [Current status of epigenetics of

schizophrenia]. Nihon Rinsho. 2013 Apr;71(4):605-9. Review. Japanese. PubMed

PMID: 23678586.

Monhonval P, Lotstra F. [Epigenetics of early interactions, depression and

schizophrenia]. Rev Med Brux. 2012 Nov-Dec;33(6):532-9. Review. French. PubMed

PMID: 23373124.

Greetings

Egon

"Environmental factors, that can cause epigenetic modifications, are important in its pathogenesis, acting on a biological inheritable vulnerability"

Yes, but it is only a very limited and generally unknown subset of environmental factors that could be involved. Most of the usual suspects (eg social class, childhood diet, parental death or illness, etc) can be ruled out at the outset, since it is those that act on only one of an MZ twin pair that are relevant.

Dear Anthony

I aggree. For example; Schmitt et al. (2014) demonstrated the differential impact of environmental factors. Infection, obestric complication, stress periods, parental loss before the age of 7 cannabis abuse to cause differential epigenetic modifications among momonozygotic twins, bicygotic twins, children, silblings, parents, grand children and general population.

Schmitt A, Malchow B, Hasan A, Falkai P. The impact of environmental factors

in severe psychiatric disorders. Front Neurosci. 2014 Feb 11;8:19. eCollection

2014. Review. PubMed PMID: 24574956; PubMed Central PMCID: PMC3920481.

greetings

Egon

Hi,

Take a look at the research done by Suzanne King of McGill University. You'll find here her publications: http://www.mcgill.ca/tcpsych/faculty/suzanneking.

Also see:

Selected Articles

Brenner, K., St-Hilaire, A., Liu, A., Laplante D. P., & King, S. (2011). Cortisol response and coping style predict quality of life in schizophrenia. Schizophrenia Research. Advance online publication. doi:10.1016/j.schres.2011.01.016

King, S., St-Hilaire, A., & Heidkamp, D. (2010). A review of prenatal factors in schizophrenia. Current Directions in Psychological Science, 19(4), 209–213.

Charil, A., Laplante D. P., Vaillancourt, C., & King, S. (2010). Prenatal maternal stress and brain development. Brain Research Reviews, 65, 56-79.

King, S., Mancini-Marïe, A., Brunet, A., Walker, E. F., Meaney, M. J., & Laplante, D. P. (2009). Prenatal maternal stress from a natural disaster predicts dermatoglyphic asymmetry in humans. Development & Psychopathology, 21, 343-353.

Brenner, K , Liu, A., Laplante, D. P., Lupien, S., Pruessner, J. C., Ciampi, A., Joober, R., King, S. (2009). Cortisol response to a psychosocial stressor in schizophrenia: Blunted, delayed or normal? Psychoneuroendocrinology, 34, 859-868.

Laplante, D. P., Brunet, A., Schmitz, N., Ciampi, A. & King, S., (2008). Project ice storm: Prenatal maternal stress affects cognitive and linguistic functioning in 5 ½ year old children. Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), 47(9), 1063 - 1072.

Laplante, D. P., Zelazo, P. R., Brunet, A., Barr, R. G., Galbaud du Fort, G., Meaney, M. J., Saucier, J.-F., Ciampi, A., & King, S. (2007). Functional play at 2 years of age: Effects of prenatal maternal stress. Infancy, 12(1), 69-93.

Brenner, K., Schmitz, N., Pawliuk, N., Fathalli, F., Joober, R., Ciampi, A., & King, S. (2007). Validation of the CAPE with a Montreal community sample. Schizophrenia Research, 95(1-3), 86-95.

St-Hilaire, A., Holowka, D., Cunningham, H., Champagne, F., Pukall, M., & King, S. (2005). Explaining variation in the premorbid adjustment of schizophrenia patients: The role of season of birth and family history. Schizophrenia Research, 73(1), 39-48.

King, S., Laplante, D. P..(2005). The effects of prenatal maternal stress on children’s cognitive development: Project ice storm. Stress, 8(1), 35-45.

King, S., Joober, R., & Laplante, D. P. (2005). Understanding putative risk factors for schizophrenia: Retrospective and prospective studies. Journal of Psychiatry and Neuroscience, 30(5), 342-348.

"In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons and may contribute to the pathophysiology of affective disorders"

From the abstract supplied by Egon:

2014. Review. PubMed PMID: 24574956

In my experience and observations this has been a strong factor in the development of schizo-affective disorder.

The abstract goes on to say:

"Epigenetic mechanisms altering the chromatin structure such as histone acetylation and DNA methylation may mediate effects of environmental factors to transcriptional regulation of specific genes and be a prominent factor in gene-environmental interaction. In animal models, gene-environmental interaction should be investigated more intensely to unravel pathophysiological mechanisms. These findings may lead to new therapeutic strategies influencing epigenetic targets in severe psychiatric disorders"

My observations also support gene-environmental interaction as a viable animal model for fruitful pursuit in understanding psychotic disorders and in the development of successful genetic and pharmacological approaches to this family of disease.

"In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons..."

But what relevance have these experiments to the crucial question, Why do half of schizophrenic MZ twins have non-schizophrenic cotwins?

Anthony,

"But what relevance have these experiments to the crucial question, Why do half of schizophrenic MZ twins have non-schizophrenic cotwins?"

What if it is more stressful to be born second. What if complications or more stress during birth impact expression of schizophrenia.

"A study in 2013 involving 106 participating centers in 25 countries came to the conclusion that, in a twin pregnancy of a gestational age between 32 weeks 0 days and 38 weeks 6 days, and the first twin is in cephalic presentation, planned Cesarean section does not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal disability, as compared with planned vaginal delivery.[21] In this study, 44% of the women planned for vaginal delivery still ended up having Cesarean section for unplanned reasons such as pregnancy complications."

It turns out that a study was done showing that prolonged labor indeed had an effect on the size of the bilateral hippocampi and cerebral ventricles (monozygotic twin pairs discordant for schizophrenia). See the following abstract:

REGULAR ARTICLE | February 01, 2000

Relationship of Obstetric Complications and Differences in Size of Brain Structures in Monozygotic Twin Pairs Discordant for Schizophrenia

Thomas F. McNeil, Ph.D.; Elizabeth Cantor-Graae, Ph.D.; Daniel R. Weinberger, M.D.

Am J Psychiatry 2000;157:203-212. doi:10.1176/appi.ajp.157.2.203

Article

Tables

References

text A A A

Abstract

Abstract | METHOD | RESULTS | DISCUSSION | References

OBJECTIVE: The aim of the study was to determine whether a history of obstetric complications and congenital minor physical anomalies are related to differences in the characteristics of brain structures observed within monozygotic twin pairs discordant for schizophrenia. METHOD: The size of the bilateral hippocampi and cerebral ventricles was studied by magnetic resonance imaging in 22 monozygotic twin pairs discordant for schizophrenia. Obstetric complications and minor physical anomalies were independently assessed through parental report and examination, respectively.

RESULTS: Compared with the well co-twins, the ill twins consistently had smaller left and right hippocampi as well as larger left lateral ventricles and third ventricles. Relatively small left and right hippocampi were each significantly related to labor-delivery complications and to prolonged labor per se. Relatively large right lateral ventricle size and large total ventricle size were significantly related to labor-delivery complications, prolonged labor, neonatal complications, and total complications for the entire reproductive sequence. In contrast, these brain size differences were not significantly associated with pregnancy complications or minor physical anomalies.

CONCLUSIONS: Trauma at the time of labor and delivery and especially prolonged labor appear to be of importance for brain structure anomalies associated with schizophrenia.

So I do believe this experiment and its results:

"In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons..."

are relevant to the crucial question of why do half of schizophrenic MZ twins have non-schizophrenic cotwins?

Maybe the concordant monozygotic schizophrenic twins have no chance of being well, while the discordant monozygotic schizophrenic twin is pushed over the edge to express the schizophrenic phenotype by being overstressed (and having enough of the maladjusted genes to make that difference)

Or:

From Wikipedia:

"Zygosity is the degree of identity in the genome of twins. There are five common variations of twinning."

"The three most common variations are all dizygotic (fraternal):[14]

Male–female twins are the most common result, 50 percent of dizygotic twins and the most common grouping of twins.

Female–female dizygotic twins (sometimes called "sororal twins")

Male–male dizygotic twins"

"The other two variations are monozygotic ("identical") twins:[14]

Female–female monozygotic twins

Male–male monozygotic twins (less common)"

"Monozygotic twins always have different phenotypes. Normally due to an environmental factor or the deactivation of different X chromosomes in female monozygotic twins"

So, since the majority of monozygotic twins are female, and deactivation of different X chromosomes occurs in monozygotic twin girls approximately 50 percent of the time maybe this could explain your crucial question

A 15-year German study[57] of 8,220 vaginally delivered twins (that is, 4,110 pregnancies) in Hesse yielded a mean delivery time interval of 13.5 minutes.[58] The delivery interval between the twins was measured as follows:

Within 15 minutes: 75.8%

16-30 minutes: 16.4%

31-45 minutes: 4.3%

46-60 minutes: 1.7%

Over 60 minutes: 1.8% (72 instances)

The number of monozygotic twins per 1000 live births is constant at 4 twins, while there was an average of 26 fraternal twins per 1000 live births prior to 1980 in the North America/Europe, so about a 6.5 to 1 ratio of fraternal to identical twins in a population of twins.

So out of the 8220 twins vaginally delivered, 1264 would have been monozygotic. 1% of those or 12 of those monozygotic twins would be schizophrenic, and so 8, or 4 pairs should be concordant for schizophrenia while 4, or 4 pairs should be discordant for schizophrenia.

It would be interesting to know if that pattern was due to the deactivation of different X chromosomes in female monozygotic twin girls, and whether male monozygotic twins ever had discordant presentation.

"What if it is more stressful to be born second. What if complications or more stress during birth impact expression of schizophrenia."

If so, schizophrenia should be commoner in twins, which I do not think is so. In addition, no birth order effect was found in the AJP (2000) article linked above. See this extract:

"In contrast, the signs of brain abnormality in the ill twin, such as especially small hippocampi and especially large ventricles, were not significantly related to rates of pregnancy complications (t2) or to rates of minor physical anomalies (t4). Furthermore, birth order in itself was not significantly related to small hippocampi or large ventricles in the ill twin versus the well twin (results available from authors on request)."

Also, is being born second being proposed to explain the greater MZ concordance for schizophrenia, or the greater DZ discordance?

I suspect obstetric abnormalites are due to fetal abnomalities, most likely defective labyrinthine reflexes. There is no known case (see my RG question) of a viable newborn with total bilateral absence of a peripheral vestibular system -- it is a lethal defect.

"Monozygotic twins always have different phenotypes...So, since the majority of monozygotic twins are female..."

This may be technically correct, but only in a trivial sense, since MZ twins are often very hard to tell apart, hence their common name, identical twins.

This table from James (2010) shows that it is not possible to derive any simple conclusion about sex ratio differences:

"The Sexes, Sex Ratios and Their Standard Errors of Monozygotic Twin Pairs: Data of James (1980)

Male Female Sex Ratio

Dichorionic 76 57 .571

Monochorionic diamniotic 694 717 .492

Monochorionic monoamniotic 126 177 .416

Conjoined 22 74 .229"

"What if it is more stressful to be born second. What if complications or more stress during birth impact expression of schizophrenia."

Your answer,

"If so, schizophrenia should be commoner in twins, which I do not think is so. In addition, no birth order effect was found in the AJP (2000) article linked above. "

First of all this is an opinion, not a fact.

The frequency on monozygotic twins in the population is only 0.001 % and since the frequency of schizophrenia in the population is 0.01 % so the percent of schizophrenic patients in the population that are monozygotic twins would be 0.0001 %. This would not be a frequent event. The incidence of schizophrenia in monozygotic twins having one twin being 'normal' and one twin being schizophrenic would only be one third greater, so 0.000033% in the total population and so may be missed if it is not being looked for (out of monozygotic twin pairs that are schizophrenic 0.5 % would have both twins being schizophrenic and 0.5 % would show one pair resulting in having only one of the twins being schizophrenic, so 1/3 of schizophrenic twin pairs where only one twin is schizophrenic would emerge, obviously a very, very, very infrequent event.)

"Also, is being born second being proposed to explain the greater MZ concordance for schizophrenia, or the greater DZ discordance?"

Being born second is an explanation for having discordant schizophrenia in monozygotic twins having some level of predisposition genetically to schizophrenia subject to stress. (such as stress or complications during delivery leading to schizophrenia. "A study in 2013 involving 106 participating centers in 25 countries came to the conclusion that, in a twin pregnancy of a gestational age between 32 weeks 0 days and 38 weeks 6 days, and the first twin is in cephalic presentation, planned Cesarean section does not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal disability, as compared with planned vaginal delivery.[21] In this study, 44% of the women planned for vaginal delivery still ended up having Cesarean section for unplanned reasons such as pregnancy complications." This suggests that complications in multiple births is quite common.)

"no birth order effect was found in the AJP (2000) article linked above."

'birth order in itself was not significantly related to small hippocampi or large ventricles in the ill twin versus the well twin'

This extract does not comment on whether the the schizophrenia was related to birth order. It says 'birth order in itself was not significantly related to "changes" in the ill twin versus the well twin'. It merely suggests it was not the only factor related to the changes as I read it. Please explain if you find my interpretation incorrect.

"I suspect obstetric abnormalites are due to fetal abnomalities, most likely defective labyrinthine reflexes. There is no known case (see my RG question) of a viable newborn with total bilateral absence of a peripheral vestibular system -- it is a lethal defect."

Why wouldn't both twins in a monozygotic pair of twins suffer from this condition, and at what point in the pregnancy does this condition become a lethal defect? I am not familiar with this condition but it smells of a smoke screen to me. Could you explain why this quote was used as an argument. I may be being dense, but I fail to see the relevance in the subject being discussed.

""I suspect obstetric abnormalites are due to fetal abnomalities, most likely defective labyrinthine reflexes. There is no known case (see my RG question) of a viable newborn with total bilateral absence of a peripheral vestibular system -- it is a lethal defect."

Why wouldn't both twins in a monozygotic pair of twins suffer from this condition, and at what point in the pregnancy does this condition become a lethal defect? I am not familiar with this condition but it smells of a smoke screen to me. Could you explain why this quote was used as an argument. I may be being dense, but I fail to see the relevance in the subject being discussed."

This is relevant to the persistent possibility of reverse causation. Obstetric and birth abnormalities could indeed cause conditions like schizophrenia and autism, but it is possible (and in my opinion based on all the evidence, more likely), that fetal abnormalities, especially of the vestibular system, whether of genetic or environmental origin, cause primitive reflex abnormalities, abnormal fetal and intrauterine development and difficult births.

Anthony,

This comment following my comment below:

"What if it is more stressful to be born second. What if complications or more stress during birth impact expression of schizophrenia."

If so, schizophrenia should be commoner in twins, which I do not think is so. In addition, no birth order effect was found in the AJP (2000) article linked above.

This is faulty logic.  Schizophrenia should be common in twins with a predisposition or constellation of genes potentially leading to schizophrenia.  Prolonged stress at the time of labor could play a role in turning on the expression of these genes (more stressful in the case of  the second twin borne) when complications occur) that can lead to schizophrenia.