Adolescents at risk of psychosis: a comparison of the "At risk mental state" and Multiple Complex Developmental Disorder

Abstract

Comparing vulnerability markers for psychosis in different high-risk populations will ultimately lead to more insight into the causes of the syndrome and a more accurate identification of at-risk individuals. This dissertation concentrated on the comparison of two groups of adolescents that are at high risk of developing a first psychotic episode: 1) 80 help-seeking adolescents presenting with prodromal-like symptoms that met the research criteria for At Risk Mental State (ARMS), and 2) 32 adolescents diagnosed with the Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) subtype Multiple Complex Developmental Disorder (MCDD). The main aims are to compare potential neurocognitive and behavioral vulnerability markers for psychosis in these two high-risk groups, and to explore social-cognitive impairments as potential vulnerability markers for psychosis. As expected, the two high-risk groups could be distinguished by early-childhood behavior and autism traits. The ARMS group showed higher levels of positive and negative high-risk symptoms than the MCDD group, which we suggest to be possibly explained by the fact that the former was older. However, the groups did not differ regarding schizotypal personality traits and basic symptoms, as well as disorganized and general high-risk symptoms. Interestingly, 78% of the MCDD adolescents met the ARMS criteria. While both high-risk groups experienced significant social difficulties, they showed normal functioning on most of the assessed neurocognitive domains. Both high-risk groups only showed poorer performances on tasks assessing attention/working memory and verbal output generation, with small effect sizes. Psychomotor speed was also reduced in both high-risk groups, with a small effect size in the ARMS group, and a medium effect size in the MCDD group. Neither of the two high-risk groups had overall impairments in the accuracy of recognizing facial expressions. However, the MCDD group showed specific deficits in the accuracy of recognizing fear, and an overall reduced speed of processing complex visual information, with small to medium effect sizes. Reported studies in individuals with PDD suggest that these impairments may be associated with the PDD-spectrum, rather than only with the MCDD subtype of PDD-NOS. Our meta-analysis on the association between schizophrenia and another measure of social cognition, i.e. mentalizing or Theory of Mind, revealed a significant and stable mentalizing impairment in individuals diagnosed with schizophrenia, with a large overall effect size. The finding that remitted schizophrenia patients also show mentalizing impairment suggests that it represents a possible trait marker for schizophrenia. This is further corroborated by evidence that mentalizing is also impaired in individuals at genetic risk for schizophrenia, and that mentalizing impairment is positively associated with schizotypal traits. In conclusion, both high-risk groups report a broad range of high-risk traits and symptoms, as well as social impairment. However, they show a relatively intact functioning on most of the assessed neurocognitive domains, although their psychomotor speed, attention/working memory, and verbal output generation are somewhat poorer compared to non-psychiatric controls. Dysfunctions of these neurocognitive domains thus represent potential vulnerability markers for psychosis. Our findings further indicate that of the social cognitive domains, impairment of mentalizing may represent a vulnerability marker for psychosis