Discovering novel susceptibility pathways for psychosis
Psychosis is a challenging scientific problem that obviously has clinical significance in, for example, severe depression and schizophrenia, and it represents a heavy burden on society. Current medication however often has unwanted side effects. The primary objective of this project is the identification of new targets for drugs attenuating susceptibility to psychosis and thus enhancing the 'resilience' of brain and body.

A central factor in the research is the sensitivity of dopamine receptors to apomorphine. These receptors in psychosis patients show similar features as those in schizophrenia patients. The focus of the research is on genetically caused abnormalities in the brain that are fundamental to the development of psychosis. So far two pathways relevant in the development of psychosis have been identified. The next step will be developing ways to influence these pathways. An improved understanding of the causal factors precipitating this disorder will therefore serve the common good, benefiting not only the patients themselves, but also their family members.

Fast facts
Full project title: Novel susceptibility pathways and drug targets for psychosis
Start date: March 2007
End date: May 2013
Goal: Discover new drug targets for psychosis
Principal investigator: Gerard Martens
Project size: 10 FTE's
Partners: Leiden University, Lundbeck A/S, Radboud University Nijmegen


psychosis is an abnormal condition of the mind and loss with reality. Patients suffering from psychosis may experience hallucinations, delusional beliefs, personality changes and thought disorder accompanying a difficulty with social interaction and common daily activities. More specifically, patients can experience (hear, see, smell or taste) things that are not there, suffer incoherent speech, or become paranoid. These symptoms may occur on a frequent, constant, basis or sporadically. In general an estimated 0.2% of the adults experiences psychosis on a regular basis.

The exact cause of the condition is not known, moreover, it is likely that it has several different causes. Sometimes the psychosis is caused by what can be considered external factors, such as a brain tumor, Parkinson’s or malaria. In general, treatment usually occurs with so-called antipsychotics. Many of these have undesired side effects, such as weight gain, lowered life expectancy, diabetes or, when lowering the doses, psychotic attacks that are much more severe than the original ones. The development of new antipsychotic drugs that are more effective and have less side effects is thus an important ongoing research field.

Jessica E. van Schijndel (project T5-209)
Towards candidate genes for schizophrenia

Nikos Daskalakis (project T5-209)
Nurturing Nature

Niels Speksnijder (project T5-209)
Determinants of Psychosis Vulnerability

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