Risks, correlates, and consequences of the extended psychosis phenotype

Psychotic disorders such as schizophrenia entail substantial suffering for the affected individuals and their networks. Traditionally, these disorders come as diagnosable entities that you either have or have not. However, recent epidemiological research has shown that symptoms of psychotic disorder, i.e., psychotic experiences, are common in the general population, especially during adolescence, and that these experiences are correlated with the development of psychosis. Thus, the traditionally binary psychosis phenotype can be extended to also include psychotic experiences. Despite efforts, little is known about the causes, correlates and consequences of the “extended psychosis phenotype”. Therefore, this thesis aimed to shed new light on these aspects of this broadly defined psychosis phenomenon.

In studies I and II, data from the Child and Adolescent Twin Study in Sweden (CATSS) were used to examine childhood neuropsychiatric problems (here language and mathematical problems, autistic traits, and general neuropsychiatric problems) as risk factors of adolescent psychotic experience (and juvenile mania symptoms). When possible, twin models were additionally used to disentangle the relative contributions of genetic and environmental influences in the observed associations. Results showed that childhood problems with communication, reading and mathematics, but not speech, predicted adolescent psychotic experiences. Further, it was found that the association between childhood autistic traits was explained by general neuropsychiatric problems. The twin models revealed that the same set of genes produce susceptibility for the studied childhood neuropsychiatric problems and adolescent psychotic experiences.

In study III, data from the National Patient Register was used to determine if Darier disease, a rare skin disease, would correlate with schizophrenia or bipolar disorder in the general population. The hypothesis was based on the shared common ectodermal origin of skin and brain. We found that individuals with Darier disease had a 2-fold elevated risk of being diagnosed with schizophrenia, and a 4-fold excess risk of being diagnosed with bipolar disorder, compared with matched comparison subjects.

In study IV, CATSS data was linked to the National Patient Register to examine consequences of adolescent psychotic experiences. Results revealed that adolescents reporting psychotic experiences had elevated risks of being diagnosed with alcohol or substance misuse, or suicide attempt.

In sum, we found that adolescent psychotic experiences are neurodevelopmental phenomena that share genetic etiological factors with childhood neuropsychiatric problems. Further, we demonstrated population associations between Darier disease and schizophrenia, and bipolar disorder. Lastly, we observed that adolescent psychotic experiences are associated with adverse consequences.

These results confirm the neurodevelopmental origin of the extended psychosis phenotype, including psychotic experiences, and highlight the need for cross-professional monitoring of adolescents reporting psychotic experiences.

List of scientific papers

I. Cederlöf, M., Östberg, P., Pettersson, E., Anckarsäter, H., Gumpert, C., Lundström, S., & Lichtenstein, P. (2014). Language and mathematical problems as precursors of psychotic-like experiences and juvenile mania symptoms. Psychological Medicine. 44(06), 1293-1302.
https://doi.org/10.1017/S0033291713002018

II. Cederlöf, M., Pettersson, E., Sariaslan A., Larsson, H., Östberg, P., Kelleher, I., Långström, N., Hellner Gumpert, C., Lundström, S., & Lichtenstein, P. (2015). The association between childhood autistic traits and adolescent psychotic experiences is explained by general neuropsychiatric problems. American Journal of Medical Genetics Part B Neuropsychiatr Genet. [Epub ahead of print]
https://doi.org/10.1002/ajmg.b.32386

III. Cederlöf, M., Bergen, S. E., Långström, N., Larsson, H., Boman, M., Craddock, N., Östberg, P., Lundström, S., Sjölander, A., Nordlind, K., Landén, M., & Lichtenstein, P. (2015). The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population‐based family study. Bipolar Disorders. 17(3), 340-344.
https://doi.org/10.1111/bdi.12257

IV. Cederlöf, M., Kuja-Halkola, R., Larsson, H., Sjölander, A., Östberg, P., Lundström, S., Anckarsäter, H., Kelleher, I., & Lichtenstein, P. A longitudinal study of adolescent psychotic experiences and later drug use disorder and suicide attempt. [Manuscript]