Stress from neglect plays role in schizophrenia

Stress at a very young age, caused for instance by neglect or social isolation, increases the risk of developing symptoms of schizophrenia in rats with a genetic predisposition. This is the conclusion of the research of Nikos Daskalakis of the Medical Pharmacology Department of the Leiden/Amsterdam Centre for Drug Research (LACDR).

Three-stage rocket

‘It is a three-stage rocket,’ concludes Daskalakis on the basis of his research on genetically selected rats. ‘If you have a genetic predisposition, and you are exposed to a lot of stress in the first phase of your life, as well as at a later stage, then the chances of developing schizophrenia increase dramatically.’ Examples involve neglect of a very young rat by the mother in combination with social isolation during puberty. ‘All these negative stimuli reinforce one another,’ says Daskalakis.


Dealing better with stress

If, on the other hand, you have a genetic predisposition to schizophrenia (more sensitive dopamine receptors), but in the first phase of your life you grow up protected and are well cared for, then you will be able to handle stress much better at a later stage. ‘The specific genes which make you more sensitive to schizophrenia can under certain circumstances work to your advantage,’ says the researcher.

Programming fear

Daskalakis also studied the consequences of exposure to neglect and isolation for the development of the fear circuit in the rat brain. ‘If rats are separated from their mother, anger becomes programmed for a lifetime,’ says Daskalakis. In his view, this can provide important information, for instance with respect to babies who experience various kinds of stressful situations in the first days of their lives. The expectation is that the results hold not only for rats, but also for people, because of their similar stress system.

Early life experiences

Thesis supervisor Prof. Ron de Kloet is enthusiastic about the results of the research, which was made possible as a result of a subsidy from TI Pharma. ‘This is a proof of concept, which makes it incredibly important for the further development of medication for treating schizophrenia. We can now concretely look at what exactly is going on in the brain that causes the natural predisposition to be reinforced by early life experiences.’ The three-step rocket model is currently being verified using schizophrenia patients. This research fits in with the priority medicines programme of the World Health Organization (WHO). This programme is dedicated to medication which the WHO sees as having top priority. The study involved Leiden University, Radboud University in Nijmegen and the Danish pharmaceutical company Lundbeck.

Delusions, hallucinations and thinking disorders

Schizophrenia is a serious psychiatric disease, where patients may suffer from delusions, hallucinations and thinking disorders. In the Netherlands, 60,000 to 80,000 people suffer from schizophrenia. Researchers have known for some time that the disease may have a variety of causes, but the PhD research carried out by Daskalakis shows how factors such as stress and genetic predisposition reinforce one other.

(6 December 2011/Source: LUMC)

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Last Modified: 09-12-2011