The interplay between an infection during pregnancy and stress in puberty plays a key role in the development of schizophrenia, as behaviourists from ETH Zurich demonstrate in a mouse model. However, there is no need to panic.
Around one per cent of the population suffers from schizophrenia, a serious mental disorder that usually does not develop until adulthood and is incurable. Psychiatrists and neuroscientsist have long suspected that adverse enviromental factors may play an important role in the development of schizophrenia. Prenatal infections such as toxoplasmosis or influenza, psychological, stress or family history have all come into question as risk factors. Nevertheless, until now researchers were unable to identify the interplay of the individual factors linked to this serious mental disease.
However, a research group headed by Urs Meyer, a senior scientist at the Laboratory of Physiology & Behaviour at ETH Zurich, has now made a breakthrough: for the first time, they were able to find clear evidence that the combination of two environmental factors contributes significantly to the development of schizophrenia-relevant brain changes and at which stages in a person's life they need to come into play for the disorder to break out. The researchers developed a special mouse model, with which they were able to simulate the processes in humans virtually in fast forward. The study has just been published in the journal Science.
Interplay between infection and stress
The first negative environmental influence that favours schizophrenia is a viral infection of the mother during the first half of the pregnancy. 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," underscores Meyer.
The infection during pregnancy lays the foundation for stress to "take hold" in puberty. After all, the mother's infection activates certain immune cells of the central nervous system in the brain of the foetus: microglial cells, which produce cytotoxins that alter the brain development of the unborn child.
Mouse model provides important clue
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 awake and induce changes in certain brain regions through this adverse postnatal stimulus. 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," says Sandra Giovanoli, who, as a doctoral student under Urs Meyer, did the lion's share of the work on this study.
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 forty 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. This stress is the equivalent of chronic psychological stress in humans.
Diminished filter function