Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.
The extended psychosis phenotype, or the expression of non-clinical positive psychotic experiences, is already prevalent in adolescence, and has a dose-response risk relationship with later psychotic disorder. In two large adolescent general population samples (n=5422 and n=2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor analysis followed by Confirmatory Factor Analysis) in Sample 1 suggested that psychotic experiences were best represented by five underlying dimensions; Confirmatory Factor Analysis in Sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity and Paranormal Beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder.
Research suggests that subclinical psychotic experiences during adolescence represent the behavioral expression of liability for psychosis. Little is known, however, about the longitudinal trajectory of liability in the general population. Growth mixture modeling was used to examine longitudinal trajectories of self-reported positive psychotic experiences in the Youth Self Report, completed three times over a period of six years by the TRAILS general population cohort of adolescents aged 10-11 years at baseline (N=2230). Four groups with distinct developmental trajectories of Low, Decreasing, Increasing and Persistent levels of mild positive psychotic experiences were apparent. The Persistent trajectory was associated strongly with cannabis use, childhood trauma, developmental problems and ethnic minority status, consistently displayed strong associations with factors known to predict transition from subclinical psychotic experience to clinical psychotic disorder (severity of and secondary distress due to psychotic experiences, social and attentional problems and affective dysregulation) as well as with high levels of parental-reported psychotic experiences and use of mental health care at the end of the follow-up period. Progressively weaker associations were apparent for, respectively, the Increasing, Decreasing and Low trajectories. The results suggest that the outcome of early developmental deviation associated with later expression of psychotic experiences is contingent on the degree of later interaction with environmental risks inducing, first, persistence of psychotic experiences and, second, progression to onset of need for care and service use. Insight into the longitudinal dynamics of risk states in representative samples may contribute to the development of targeted early intervention in psychosis.