Swiss researchers believe they have discovered a method by which prenatal factors coupled with stress during puberty can result in schizophrenia.
Neuroscientists and psychologists have long suspected that adverse environmental factors — in addition or even in the absence of genetic factors — may play an important role in the development of schizophrenia. Experts have questioned if prenatal infections such as toxoplasmosis or influenza, psychological, stress or family history are risk factors for schizophrenia.
Now, in a mouse study, researchers believe for the first time they are able to demonstrate clear evidence that a combination of two environmental factors contributes significantly to the development of schizophrenia-relevant brain changes.
Moreover, investigators feel they have identified the stages in a person’s life when environmental factors must come into play to help induce the disorder.
In the study, published in the journal Science, researchers developed a special mouse model in which they were able to simulate the processes in humans virtually in fast forward.
Investigators discovered the first negative environmental influence that favors schizophrenia is a viral infection of the mother during the first half of the pregnancy. Then, if a child with such a prenatal infectious history is also exposed to major stress during puberty, the probability that he or she will suffer from schizophrenia later increases markedly.
Hence, the mental disorder needs the combination of these two negative environmental influences to develop.
“Only one of the factors — namely an infection or stress — is not enough to develop schizophrenia,” said Urs Meyer, Ph.D., a senior scientist at the Laboratory of Physiology & Behavior at ETH Zurich.
The infection during pregnancy lays the foundation for stress to “take hold” in puberty. The mother’s infection activates certain immune cells of the central nervous system in the brain of the fetus — microglial cells — which produce cytotoxins that alter the brain development of the unborn child.
Researchers believe that once the mother’s infection subsides, the microglial cells lie dormant but have developed a “memory.”
If the adolescent suffers severe, chronic stress during puberty, such as sexual abuse or physical violence, the microglial cells awaken, as it were, and induce changes in certain brain regions.
Ultimately, these neuroimmunological changes do not have a devastating impact until adulthood. The brain seems to react particularly sensitively to negative influences in puberty as this is the period during which it matures.
“Evidently, something goes wrong with the ‘hardware’ that can no longer be healed,” said Sandra Giovanoli, a doctoral student under Meyer. The researchers achieved their ground-breaking results based on sophisticated mouse models, using a special substance to trigger an infection in pregnant mouse mothers to provoke an immune response.
Thirty to 40 days after birth – the age at which the animals become sexually mature, which is the equivalent of puberty – the young animals were exposed to five different stressors which the mice were not expecting. Researchers posit these as the equivalent of chronic psychological stress in humans.
Following the perinatal stress, the researchers tested the animals’ behavior directly after puberty and in adulthood. As a control, the scientists also studied mice with either an infection or stress, as well as animals that were not exposed to either of the two risk factors.
When the researchers examined the behavior of the animals directly after puberty, they were not able to detect any abnormalities. In adulthood, however, the mice that had both the infection and stress behaved abnormally.
The behavior patterns observed in the animals are comparable to those of schizophrenic humans. For instance, the rodents were less receptive to auditory stimuli, which went hand in hand with a diminished filter function in the brain. The mice also responded far more strongly to psychoactive substances such as amphetamine.
“Our result is extremely relevant for human epidemiology,” said Meyer. Even more importance will be attached to environmental influences again in the consideration of human disorders – especially in neuropsychology. “It isn’t all genetics after all,” he said.
Although certain symptoms of schizophrenia can be treated with medication, the disease is not curable. However, the study provides hope that we will at least be able to take preventative action against the disorder in high-risk people.
Researchers stress that the results of their work are no reason for pregnant women to panic.
Many expecting mothers get infections such as herpes, a cold or the flu. And every child goes through stress during puberty, whether it be through bullying at school or quarrelling at home. “A lot has to come together in the ‘right’ time window for the probability of developing schizophrenia to be high,” said Giovanoli.
Ultimately, other factors are also involved in the progress of the disease. Genetics, for instance, which was not taken into consideration in the study, can also play a role. But unlike genes, certain environmental influences can be changed, Giovanoli said; how one responds to and copes with stress is learnable.
Source: ETH Zurich