How does psychosis arise (part 2)

In discussing explanatory models for how psychosis arises a key issue, in my view, is that psychosis is not one ‘thing’. Everyone who experiences psychosis does not have the same condition. I would suggest, to the contrary, that each person who experiences psychosis is different and unique. The experiences are different and the evolving causes and conditions are different. Therefore, the explanations will be different.

If you accept the view of individual uniqueness then the kind of explanatory model(s) we are looking for are going to be quite general in nature. They will identify the kinds of causes and conditions that could lead to psychosis. There will be multiple factors that could interact with one another in a variety of ways. Only rarely, if ever, will the models explain what happened to a particular individual.

Perhaps the closest to a simple explanation would be for psychosis that is associated with a particular genetic variant, the 22q11.2 deletion. People who have this relatively rare genetic condition (1 in 2000) have, to varying degrees, a number of abnormalities in development, including the heart, the structure of palate and general intelligence. They also have a high rate of psychosis (as high as 30% compared with 3% in the general population).

In 22q11.2 deletion, a small number of genes on chromosome 22 are missing. One is the COMT gene that guides production of the enzyme COMT, a key enzyme in regulating dopamine metabolism in the brain.

So if we find someone with this genetic condition, and they become psychotic, our explanation would certainly include the gene deletion. But why is it that only 30% of people with the deletion develop psychosis. Why not 100%?

Clearly, when we are talking about causes and conditions leading to psychosis, the story is complex. As well, the 22q11.2 deletion syndrome accounts for a minute percentage of all cases of psychosis. In the other cases the genetics appears to be even more complex.

Years of trying to find ‘the gene for schizophrenia (or psychosis)’ has resulted in identification of a large number of genes that seem to be very weakly associated with psychosis. Researchers have come to call them ‘susceptibility genes’ to emphasize that alterations in any one of these genes cannot, alone, explain psychosis. Instead, the idea is that each gene provides some increased susceptibility, and that a person with a combination of a number of these genes (under particular conditions) becomes highly likely to experience psychosis.

This supports the view of individual uniqueness; each person with psychosis will have a different set of susceptibility genes and encounter different conditions in which those genes are expressed.

Are we getting anywhere in terms of explanatory models? Is recognizing individuality and complexity useful?