September 30, 2005

Prenatal Infection Increases Risk of Schizophrenia

Current research suggests that schizophrenia results from abnormal development of the brain. Studies have shown that exposure of pregnant women to environmental challenges, such as psychosocial stressors, obstetric complications, and infection, increase the risk that their children will develop schizophrenia or certain other disorders of the brain at adulthood. Influenza, measles, polio, herpes simplex type 2, diphtheria, and pneumonia, are all risk factors but it is not know if these diseases act directly on the fetal brain or if the developmental abnormalities are a secondary result of the maternal immune response to infection. This experiment, from the journal Molecular Psychiatry, hopes to shed some light on the subject.

One group of pregnant rats was injected with a low dose of a bacterial endotoxin called LPS that, in previous studies performed on pregnant rats, resulted in behavioral changes in offspring that were equivalent to human schizophrenia. After injection, the mothers and fetuses were tested for LPS and molecules called cytokines. Cytokines are a type of regulatory protein that are released by cells of the immune system in response to an infection (such as LPS) and are crucial in the generation of an immune response.

LPS was detected in maternal tissues, including the placenta, but not in fetal tissues. However, abnormal levels of cytokines were observed in both the mother and the fetus. These results suggest that the behavioral changes observed because of maternal infection are due to the immune response caused by LPS rather than any direct action of the pathogen on the fetal brain.

Cytokines have an important role in normal brain development, as well as in the development and function of the placenta. However, cytokines are also implicated in the death and dysfunction of neurons after injury or chronic disease in the adult brain. Elevated levels of cytokines during pregnancy could result in tissue damage to the placenta, which may hinder the delivery of oxygen and nutrients to the developing fetus. Abnormal cytokine expression is also implicated in premature birth, fetal growth restriction, and pre-eclampsia (a condition characterized by high blood pressure, excessive fluid in the body, and excessive protein in the urine, during or directly after pregnancy). All of these prenatal complications are considered risk factors for later development of schizophrenia.

Another hypothesis is that cytokines themselves are not the cause of the observed neurodevelopmental abnormalities but act to influence other key molecules, such as IGF-1, a protein that induces neuronal proliferation and specialization in the fetal rat brain. Cytokines also affect levels of glucocorticoid and thyroid hormones, two types of hormones which, when expressed abnormally during pregnancy, are associated with impaired cognitive and motor functions in children.

Heat stress is one more factor that can result in neurodevelopmental abnormalities. Fever, which is often part of the immune response generated by an infection, is also mediated by cytokines.

It is still not certain which one, or which combination of these possible risk factors is responsible for the development of schizophrenia in adulthood. Clearly, more research is needed. However, this line of research suggests that preventative measures during pregnancy may reduce the risk of later development of schizophrenia. And, the more we understand about the mechanism of action of prenatal infection and the resulting abnormalities of the brain, the more effective those measures will be.

Ashdown, Dumont, Ng, Poole, Boksa, Luheshi. “The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia”. Molecular Psychiatry. ( Sept 27, 2005.

Related news on

Cat Virus Linked to Schizophrenia
Pregnancy, Cats and Schizophrenia
The Role of Infections in Schizophrenia
Flu and Schizophrenia
Risk from Short Birth Intervals
Schizophrenia Probability Model
Single Gene Cause Schizophrenia

For more information on causes of schizophrenia check out these pages under Schizophrenia Information on the main page: Causes and Prevention, Schizophrenia Biology & Genetics


Yes, I had Hong Kong flu in the first part of my pregnaancy in 1958 amd my son does have schizophrenia. He has been on medication for about 16 years now and it was hell getting him to accept his illness and become willing to take his meds. He's doing well now considering how chronic his condition is and I appreciate the fact that I have discovered the websites and supporting links regarding this illness.


Posted by: Gloria at October 1, 2005 05:38 PM

Could someone from this site please give actual proof of how a child in his/her mothers womb can develop schizophrenia from the mother having to deal with environmental, or psychosocial stressors.

Posted by: Shavon at October 5, 2005 10:16 AM

Shavon, that would be difficult, as there is no proof that environmental or psychosocial stressors (by this I think most people mean bad experiences of the mother, such as her being abused, psychologically traumatized, etc), cause the illness. Some people think it does; I don't. I think there is ample evidence to disprove that.

However, scientists who site 'environmental causes' aren't usually indicating what non-scientists would think. 'Environment' means the biochemistry and genetics of the mother while the fetus is in utero, the fetus' own genetics and biochemstry, and various interactions between the two. Suggesting schizophrenia is 'environmental' is strictly speaking very, very vague as 'environment' includes all biology and biochemstry of the mother and fetus, and everything that happens to them.

Evidence is accumulating that schizophrenia does start before birth. the biggest piece of information that convinced me was research on the organization of the brain cells in specific areas of the brain; nearly all these cells migrate into position in the first few months of the fetus' existence. these brain cells show abnormalities but no gliosis (scarring), therefore the differences in organization had to occur very, very eaerly in the life of the fetus.

Genetics don't just govern what traits an individual will have, genes also control the growth process and every single process the cells in the body participate in. Genes turn on and off as the fetus grows - they get expressed and then stop, and can switch on and off over and over. It isn't a simple situation or an easy one to research.

Genes control all cell processes, every day. They control how cells grow, develop, differentiate, and how the brain cells migrate, route, turn, dock and connect to other brain cells.

At crucial times of growth, brain cells actually are deliberately, naturally and normally 'killed off', or 'pruned', and the brain will rapidly select brain cells to nurture, connect to and kill off ones it doesn't need. Schizophrenia and autism begin to be obvious at periods of rapid brain growth and change - autism at 1 1/2 or so, and schizophrenia often in the teen and young adult period, also a time when the brain is rapidly remodeling.

Just a few weeks before schizophrenia symptoms become obvious, something alters the brain - markedly, measurably (now that we have better MRI's). Just before a person starts to 'hear voices', key brain cells in the audio cortex are 'pruned'. It appears that the wrong cells are pruned during heavy brain cells growth and change periods. The brain changes are too rapid for a psychological trauma to cause these, and in fact, very few people have a traumatic event at the time these changes do occur.

Thing is, that isn't the whole story. These same people have abnormal MRI's and brain cells positions that start years before that. Toddlers, decades before they get schizophrenia as adults, are crawling, grasping and gazing abnormally, and showing neurological signs that will surface at a young age, and often disappear for years - until they become 'ill' as adults. These people often will have some symptoms for years before they are diagnosed - many friends recall hallucinations since childhood.

Clearly, to me, the process starts before birth, shows signs decades before it is diagnosed, and clearly, also, to me, despite much research, we still do not know why this process starts, when, or how it continues, or why.


Posted by: slc at October 9, 2005 03:34 PM

I was working and during the Asian flu season of 1958 the company I worked for insisted that all employees take the shot. I took the flu shot with some reservation due to my pregnancy. I then developed a case of the flu.I was in my 3rd mo. of pregnancy.
My daughter was born at term in July of that same year with Downs Syndrome and developed Schizophrenia about the age of 17 years. I have always wondered if there was a connection.
Norma O'Neal

Posted by: Norma O'Neal at October 11, 2005 01:36 PM

Post a comment

Please enter this code to enable your comment -
Remember Me?
(you may use HTML tags for style)
* indicates required