Pregnancy, Flu and Schizophrenia [Archive]

fls

16th July 2007, 09:52 AM

The news article mentions women, the abstract of the actual study only mentions mice. So. maybe time for more studies.

The association with women is based on prior studies. Here is a reference (http://archpsyc.ama-assn.org/cgi/content/full/61/8/774) for that association. Since the studies in women are not experimental, but observational and subject to bias, it cannot be assumed that a causal link has been established. The positive result in a mouse model (if the model is valid?) is interesting, though.

Linda

Psi Baba

16th July 2007, 10:29 AM

Is it really possible to positively diagnose schizophrenia in mice?

kellyb

16th July 2007, 10:35 AM

Is it really possible to positively diagnose schizophrenia in mice?

When they tell you they're hearing voices and are clearly suffering from delusions of grandeur, it's pretty obvious.

casebro

16th July 2007, 10:38 AM

The association with women is based on prior studies. Here is a reference (http://archpsyc.ama-assn.org/cgi/content/full/61/8/774) for that association.
Linda

From that study's results:
" It should be noted, however, that this finding did not achieve statistical significance (P = .08) and is based on a small sample."

But it is good to know that things like this are being studied.

kellyb

16th July 2007, 12:51 PM

There might be a leukemia association there, too.

http://www.medscape.com/viewarticle/550702

TobiasTheViking

16th July 2007, 01:14 PM

While i will admit that i haven't investigated the pregnant with flu link to autism, i have heard from a credible source(one that i trust a lot) that it is on the up and up...

skeptigirl

16th July 2007, 01:18 PM

I haven't had time to listen to this (http://scitalks.com/index.php?category=search&search=patterson) (and I'm not sure it will run on my computer), but it looks to explain how Patterson supports his use of the mouse model for human schizophrenia.

This news account had a tiny bit more info. I can't open the link of Linda's in RTF. I'd like to know if the actual research considered any viral infection or specifically influenza. Reporters never seem to properly distinguish the two.

Professor Paul Patterson from the California Institute of Technology (http://www.abc.net.au/worldtoday/content/2007/s1979483.htm) has told a neuroscience conference in Melbourne that it's a protein produced by pregnant women to help fight infection that leads to an increased risk of the baby becoming schizophrenic or autistic.

Fellow neuroscientists say the finding is in line with other research being carried out in the field, but stress that genetic factors also play a key role in the development of mental illnesses.

PAUL PATTERSON: It appears from our work that the body's natural mechanism for fighting a virus, which includes producing proteins in the blood, some of those proteins, one in particular called Interleukin Six, is a key for altering foetal brain development that leads to these abnormal behaviours.

PAUL PATTERSON: Well in humans it's not the majority, it's an increase of about three to seven-fold over normal.

Of course not every woman who gets a cold during pregnancy will have a schizophrenic offspring, that's because of… presumably because of the genotype, you have to have a certain set of genes to be susceptible to these environmental insults.

BARBARA MILLER (Interviewer/reporter): Professor Patterson's research has not yet been accepted for publication. But Professor Ian Hickie from the Brain and Mind Research Institute at the University of Sydney says the findings appear to be in line with other work being carried out in the field.

IAN HICKIE (Professor, University of Sydney's Brain and Mind Research Institute.): I think it adds further to the research that has been going on in looking for the specific aspects of the immune response in the mother that may be affecting the brain development in the child.

And that's one of the strong theories in schizophrenia is that there is something in the environment that alters the brain development early on in children who later go on to develop schizophrenia in later life.

kellyb

16th July 2007, 01:23 PM

It was specifically influenza.
Here, Skeptigirl...try one of these:
http://scholar.google.com/scholar?hl=en&lr=&safe=off&cluster=12957543986340287223

ETA:
A couple of mouse studies...

http://www.jneurosci.org/cgi/content/abstract/23/1/297

http://www.springerlink.com/content/tplx4r5e5rvr5fxy/

fls

16th July 2007, 01:25 PM

I haven't had time to listen to this (http://scitalks.com/index.php?category=search&search=patterson) (and I'm not sure it will run on my computer), but it looks to explain how Patterson supports his use of the mouse model for human schizophrenia.

This news account had a tiny bit more info. I can't open the link of Linda's in RTF. I'd like to know if the actual research considered any viral infection or specifically influenza. Reporters never seem to properly distinguish the two.

It was specifically influenza.

Here is the abstract:

ACTIVATING THE MATERNAL IMMUNE SYSTEM CAUSES CHANGES IN THE OFFSPRING RESEMBLING THOSE IN SCHIZOPHRENIA AND AUTISM
Patterson P.H.
California Institute of Technology.
Maternal viral infection is associated with increased risk of schizophrenia and autism in the offspring. In a mouse model based on this risk factor, we found that respiratory infection with influenza virus leads to behavioral abnormalities in the adult offspring. These behaviors are consistent with abnormalities seen in schizophrenia and autism, including enhanced anxiety in the open field (OF), as well as deficits in social interaction (SI), latent inhibition (LI) and prepulse inhibition (PPI). The latter is corrected by anti-psychotic and exacerbated by psychomimetic drugs. The adult offspring display neuropathology in the cortex and hippocampus similar to that found in schizophrenia and a localized deficit in Purkinje cells that resembles that in autism. The cause of these various abnormalities is the maternal response to viral infection, as treatment of uninfected, pregnant mice with the dsRNA, poly(I:C), which evokes an anti-viral-like immune response, also induces OF, SI, PPI and LI deficits and the Purkinje cell deficit in the offspring. Exploring potential mediators of these effects revealed that injection of the cytokine IL-6 in normal pregnant mice causes PPI and LI deficits in the offspring, while co-injection of anti-IL-6 antibody with poly(I:C) in pregnant mice blocks the effects of maternal immune activation on the behavior of the offspring. Moreover, the offspring of poly(I:C) treated IL-6 knockout mice do not display behavioral abnormalities. Furthermore, maternal anti-IL-6 blocks the changes in gene expression in the brains of adult offspring that are caused by maternal poly(I:C) treatment. Therefore, IL-6 is a key mediator of the effects of the activated maternal immune response on fetal brain development. Supported by the NIMH, and the McKnight, Autism Speaks, and Cure Autism Now foundations.

Linda

casebro

16th July 2007, 04:05 PM

Next question: What other 'diseases' cause the body to make IL-6?

Off to Google...

ETA: That only took the first hit. From Wiki:

" IL-6 is also a "myokine," a cytokine produced from muscle, and is elevated in response to muscle contraction[2]."

So it looks likely that the mental problems related to mitochondrial disease are only peripherally related. Bad muscles could be the cause, not mitochondrial function in nerve/brain cells.

kellyb

16th July 2007, 04:32 PM

But it might be IgG, too...

http://archpsyc.ama-assn.org/cgi/content/full/61/8/774

Since influenza is believed to only rarely cross the placenta, an indirect effect on fetal brain development is the most plausible pathogenic mechanism linking it to an increased risk of schizophrenia.24 One such mechanism, previously considered, is that maternal IgG antibodies elicited by influenza traverse the placenta and cross-react with fetal brain antigens by molecular mimicry, thereby disturbing fetal brain development and increasing vulnerability to schizophrenia.

king catfish

16th July 2007, 06:17 PM

I know this is only anecdotal, but my grandmother had the flu and rubella when pregnant with my mother. My mother has severe paranoid-type schizophrenia, and is deaf as well.

Edited to add:
When they tell you they're hearing voices and are clearly suffering from delusions of grandeur, it's pretty obvious.

That isn't even remotely funny.

articulett

16th July 2007, 07:16 PM

They've known of the link between second trimester flu and schizophrenia for some time.

Rubella during pregnancy is known to produce a constellation of symptoms including deafness, blindness, and mental retardation to varying degrees--but I don't think it increases the risk for schizophrenia.

The autism link is provocative. The mother's immune system is implicated in a finding that later born brothers are more likely to be gay than their old male sibliings. There are noticeable brain differences in people with some types of autism and in schizophrenia, so I think they are able to identify some of these changes in mice brains as well.

skeptigirl

17th July 2007, 12:06 AM

I know this is only anecdotal, but my grandmother had the flu and rubella when pregnant with my mother. My mother has severe paranoid-type schizophrenia, and is deaf as well.

Edited to add:

That isn't even remotely funny.I thought it was funny. I'm sure kelly meant no harm by it. But I'm sorry about your mother. That must be incredibly difficult. My situation is different but I can imagine how hard yours must be. My mother is developing Alzheimer's and it is quite depressing. I find myself grieving because I miss her company regardless that her physical presence is still here.

There was a lot of research on the Net discussing how the mouse model is correlated with human schizophrenia.

Just because Rubella hasn't been connected with schizophrenia doesn't mean the connection isn't there. The research abstract also saysThe cause of these various abnormalities is the maternal response to viral infection, as treatment of uninfected, pregnant mice with the dsRNA, poly(I:C), which evokes an anti-viral-like immune response, also induces OF, SI, PPI and LI deficits and the Purkinje cell deficit in the offspring.suggesting it is the body's response to something more general in the viral infection rather than specific damage by the influenza virus. I've recently been reading some research into the viral mechanisms of pathology and the discussion of the mechanism which rubella causes arthritis was pretty interesting. In that case the pathology was specifically being initiated by the rubella virus.

The case in the OP discusses something initiated by the body's response instead. It might be sort of a chicken and egg argument though. I'll have to re-read the viral mechanisms involved in the arthritis now to get a more clear picture in my mind.

kellyb

17th July 2007, 12:39 AM

With influenza, since the virus doesn't (usually) cause viremia, but rather stays in the lungs, nose, etc....it would have to be the immune response, wouldn't it?

~~~~~~~~~~~~~~~~~~

By the way, catfish, I am sorry if I offended you. If it makes you feel any better, I'm epileptic, and my first reading about rodents being used as models for psychological issues was when I stumbled across a paper called "Paranoia in Rats with Temporal Lobe Epilepsy"....which brought to mind some rather funny mental images at the time. Turned out to be an interesting study, though, where the researchers initially set out to see if a series of gran mal seizures cognitively impaired the rats enough to show up on maze tests, but they never found out, because the epileptic rats just started climbing the walls in an attempt to escape, not at all worried about finding the cheese.
Anyway, I do think using mice and rats for models of complex psychological disorders has a lot of room for error, but I guess its all we've got sometimes. Or is at least a start.

The Great Hairy One

17th July 2007, 12:56 AM

This is fascinating science. Thanks for the links, everyone, I will tag them for perusal and digestion.

Thanks all. :)

Cheers,
TGHO

Dancing David

17th July 2007, 06:47 AM

Pregnant women who get respiratory infections in the second trimester are up to seven times more likely to have a child with schizophrenia. There is also an increased risk of autism...

http://www.news.com.au/heraldsun/story/0,21985,22079262-24331,00.html

Cool, that also goes back to the Danish studies after WWII, where malnutrition and severe fever in the second trimester are associated with a higher incidence of scizophrenia.

casebro

17th July 2007, 09:17 AM

tabitha

17th July 2007, 09:32 AM

So women of child bearing age should all take Flu vaccine. Every year.But what are the chances of a child being schizo? .1%? so seven times amongst those who got the infection during a three month span does not amount to .7% of babies. Only .7% of those who got the infection. So, what is that in real numbers? nearly nil, I suspect.

I guess another study needs to be done- What percentage of shizo babies WERE exposed?

Likewise, what other causes of IL6 were schizo babies exposed to? Flu, physical stress,....

:eek: Surely that's a really bad idea? If the damage to the fetus is as a result of the mother's immune response to influenza, then that would be the same whether it is the real virus or a vaccine!

Flu shots are pretty ineffective anyway!

I know you are talking about schizophrenia in your post but I think flu shots when pregnant are a really bad idea, for many reasons.

Dymanic

17th July 2007, 09:45 AM

Surely that's a really bad idea? If the damage to the fetus is as a result of the mother's immune response to influenza, then that would be the same whether it is the real virus or a vaccine!
Surely not, and especially not if it's a result of a cell-mediated maternal immune response.

I think flu shots when pregnant are a really bad idea, for many reasons.Among the reasons why it might be considered a good idea is the fact that rates of morbidity and mortality among pregnant women infected with influenza are similar to what's seen in the over-65 age group.

casebro

17th July 2007, 01:11 PM

:eek: Surely that's a really bad idea? If the damage to the fetus is as a result of the mother's immune response to influenza, then that would be the same whether it is the real virus or a vaccine!

I did say "child bearing age", not pregnant. Like all other vaccinations, I meant for it to be taken before it is needed.

But then, since the shizo link only holds for exposure during the second trimester, then a mother-to-be ought to have plenty of time to safely take the vaccine. Think you may be late? get the vaccine.

king catfish

17th July 2007, 02:03 PM

By the way, catfish, I am sorry if I offended you. If it makes you feel any better, I'm epileptic, and my first reading about rodents being used as models for psychological issues was when I stumbled across a paper called "Paranoia in Rats with Temporal Lobe Epilepsy"....which brought to mind some rather funny mental images at the time. Turned out to be an interesting study, though, where the researchers initially set out to see if a series of gran mal seizures cognitively impaired the rats enough to show up on maze tests, but they never found out, because the epileptic rats just started climbing the walls in an attempt to escape, not at all worried about finding the cheese.
Anyway, I do think using mice and rats for models of complex psychological disorders has a lot of room for error, but I guess its all we've got sometimes. Or is at least a start.

No worries. I'm not offended. I just didn't think it was funny. I do not have a problem with your thinking it's funny. Again, no worries. It's just difficult for me to laugh about schizophrenia because of the horror of being raised by someone afflicted with it. I should have held my tongue... the point of my post really was merely to add some anecdotal support to the idea of this affliction being correlated with sickness during pregnancy.

fls

17th July 2007, 02:06 PM

I did say "child bearing age", not pregnant. Like all other vaccinations, I meant for it to be taken before it is needed.

But then, since the shizo link only holds for exposure during the second trimester, then a mother-to-be ought to have plenty of time to safely take the vaccine. Think you may be late? get the vaccine.

Not to throw a wrench into this, but the reference I provided earlier found the strongest association in the first trimester. On the other hand, the response to influenza infection that was relevant in the mouse model depends upon cell-mediated hypersensitivity, which is not the mechanism stimulated by vaccination. I don't think we can say, yet, what can be recommended and what can be considered safe on this issue.*

Linda

*By "this issue" I mean the use of influenza vaccine to prevent influenza in pregnant women to reduce schizophrenia.

kellyb

17th July 2007, 02:32 PM

I have an opinion about the ACIP recommendations, but I'm just going to let it go. :)

skeptigirl

18th July 2007, 05:15 AM

:eek: Surely that's a really bad idea? If the damage to the fetus is as a result of the mother's immune response to influenza, then that would be the same whether it is the real virus or a vaccine!

Flu shots are pretty ineffective anyway!

I know you are talking about schizophrenia in your post but I think flu shots when pregnant are a really bad idea, for many reasons.No it is not a bad idea and the flu vaccine is more effective in some populations than in others.

First, pregnant women are one group for which the flu vaccine has been recommended for a number of years. Women who contract influenza during their second trimester have a higher fatality rate than the non-pregnant population.

Second, you develop antibodies to influenza from the vaccine but you don't have the full reaction one gets with the actual infection. Just the fever alone can damage the fetus. It's a myth that people get flu symptoms from flu shots. Very young children occasionally get a little fever, but it is almost unheard of in adults.

And if you were to get the vaccination before getting pregnant that would be even better. But there is no reason to risk disease over vaccine if one is already pregnant when the vaccine is due.

It is worth doing some research to make sure the vaccine doesn't increase rates of schizophrenia, and it is a problem that we may not know for 20+ years, but there is enough evidence currently to say pregnant women are safer getting the flu vaccine until the research is done rather than the other way around. Unless that is you have some other way of preventing the flu in pregnancy. Because if you get the flu we know it is bad. Right now there is no reason to think the vaccine causes the same problems.

Dancing David

18th July 2007, 02:15 PM

So women of child bearing age should all take Flu vaccine. Every year.

But what are the chances of a child being schizo? .1%? so seven times amongst those who got the infection during a three month span does not amount to .7% of babies. Only .7% of those who got the infection. So, what is that in real numbers? nearly nil, I suspect.

I guess another study needs to be done- What percentage of shizo babies WERE exposed?

Likewise, what other causes of IL6 were schizo babies exposed to? Flu, physical stress,....

1% is the incidence of schizophrenia in the general population. It is like cancer and there has to be the conjunction of multiple factors. There is also a biological predisposition. I agree that there are likely to be multiple routes to a critical tauma.

This is a good discussion of some danish twin studies.

casebro

19th July 2007, 08:37 AM

One concept we have missed in this discussion do far. That is that the fact that IL-6 can cause problems ought to lead to a better understanding of the mechanism by which these illnesses happen. That understanding should enable better treatment for the sufferer. Not just the obvious prevention via vaccination.

I guess my friend was right. He marches to a different drummer. Not schizo, just unique. He always claimed it was because his mother had shock treatments while pregnant with him. Perhaps the muscle spasms did it to him? People in "mental distress" do go into physical umm... "spasm"? Perhaps it is the muscle stress/myokine output of IL6 that could cause some of the heritability of these mental diseases?

Hey, this muscle angle could tie into some of those old superstitions about how stressing a pregnant woman could bewitch her child.

skeptigirl

20th July 2007, 11:17 PM

1% is the incidence of schizophrenia in the general population. It is like cancer and there has to be the conjunction of multiple factors. There is also a biological predisposition. I agree that there are likely to be multiple routes to a critical tauma.

This is a good discussion of some danish twin studies.Pretty much all of the researchers conclude there are genetic factors acted on by environmental factors either just in the womb, or in the womb and then even later additional factors are needed to trigger the illness. There is a chicken and egg question or maybe both when looking at childhood factors such as growing up socially isolated. No one is quite sure why the illness really manifests itself in young adulthood give or take a few years.

Dancing David

21st July 2007, 06:32 AM

Pretty much all of the researchers conclude there are genetic factors acted on by environmental factors either just in the womb, or in the womb and then even later additional factors are needed to trigger the illness. There is a chicken and egg question or maybe both when looking at childhood factors such as growing up socially isolated. No one is quite sure why the illness really manifests itself in young adulthood give or take a few years.

BTW you can have child hood onset and late onset as well.

skeptigirl

23rd July 2007, 12:15 AM

How young, DD? I thought teenage was the youngest. But I've never looked into it.

articulett

23rd July 2007, 01:00 AM

I know that CMV and toxoplasmosis can lead to flu like symptoms... most people get it and never know they've had it... but if you get it during pregnancy it can lead to mental retardation--

Despite the warnings from March of Dimes etc., the worst things that can happen to a baby tend to be out of the mother's control. I remember worrying about things like bus fumes and microwaves when I was pregnant... and then I became a genetic counselor... chromosome abnormalities and viruses happen to everybody. Whenever babies are born with a problem the mother always wonder if it's something she did wrong...like the pot she smoked in college. But even heroin addicted babies turn out just fine for the most part.

I know it sounds crazy... but what you can't control is more likely to lead to the big problems than what you can. The one big thing people can control is fetal alcohol syndrome. An alcoholic who continues to get drunk while pregnant will have kids with notable abnormalities and retardation.

kellyb

23rd July 2007, 01:07 AM

It's also looking like toxoplasmosis when gotten before becoming pregnant can also lead to a threefold increased chance of having a male baby.

Toxoplasmosis is weird, weird stuff...

articulett

23rd July 2007, 01:41 AM

It's also looking like toxoplasmosis when gotten before becoming pregnant can also lead to a threefold increased chance of having a male baby.

Toxoplasmosis is weird, weird stuff...

Males across the board are more prone to mental disorders and defects because of a couple genes on the X chromosome expressed in the brain-- guys only have a single copy, and no back up... which is one of the reasons why there is a disproportionate amount of men in mental hospitals and group homes.

I wonder if Toxo aborts female fetuses... or if people are more likely to know that they contracted it because of noticeable sequalea...

I've never had CMV, and most people have... so it makes me a good blood donor for babies and pregnant women.

I think schizophrenia has got to be one of the worst illnesses a parent can imagine. Your child seems normal... and then... and they often hate the people who try to help them the most-- It's tough for all involved.

kellyb

23rd July 2007, 01:55 AM

I don't know if I've had CMV or not. I asked my OB if my bloodwork showed if I was immune or not at my last appointment, but she said they don't test for it around here, which was surprising. I know the CDC is trying to do national CMV surveillance right now on seroconversion during pregnancy.

I wonder if Toxo aborts female fetuses...

It could work a few different ways. One theory mentioned here is that toxo infection turns "off" the maternal immune response that aborts male fetuses so often (the whole 'there are more male pregnancies, but many end in miscarriage, evening out the m/f pregnancy ratio' thing).
The idea is that since toxo is primarily adapted to rodent/cat transmission, and male rodents take greater risks and are more likely to be eaten by a cat, more male offspring is beneficial to the toxo.

http://www.natur.cuni.cz/~flegr/MANUSCRI/toxosons.pdf