Abstract Background: Social skills develop along with metacognitive abilities from early childhood through young adulthood. Impairment in metacognitive and other social cognitive abilities may contribute to poorer social function in clinical high risk for psychosis (CHR) adolescents. However, it is unclear whether social cognitive impairment represents developmental delay in skill acquisition or, rather, a consequence of emerging symptoms. Furthermore, it is unknown how early pharmacotherapy could influence this developmental trajectory. This study examined the hypotheses that (1) age-related trajectories of social cognition differ between CHR and normally developing youth and (2) age-related trajectories are partially explained by history of symptoms and psychotropic medication. Methods: Emotion perception, social perception, and theory of mind abilities were assessed in 675 CHR and 264 age-matched healthy comparison (HC) participants aged 12–35 (average = 19.0 ± 4.5 years). Linear and nonlinear curves were fit to relationships between social cognitive variables and age. Differences in age effects between CHR and HC were modeled as interaction terms. Duration of a prodromal syndrome prior to baseline and medication history were tested for interactions with age effects. Results: Emotion perception and social perception age trajectories did not differ by group. Theory of mind age trajectory, particularly for sarcasm items, had a lower slope for CHR than HC. CHR diverged from HC from mid-adolescence onward (starting to differ between approximately ages 15 and 17.5), with a minimum observation window of 4 years required to detect correlations with age. Age trajectory for theory of mind was unrelated to the presence or duration of a prior prodromal syndrome but did interact with medication history, wherein participants with an antipsychotic or antidepressant medication history did not differ from HCs. Only antipsychotic- and antidepressant-naive CHR participants showed a smaller slope for theory of mind, with differences from HC increasing with advanced age. Conclusion: In the current study, all social cognitive abilities increased during adolescence, but development of theory of mind appeared blunted for CHR participants starting in mid-adolescence. This difference, however, was only true for participants without an antipsychotic or antidepressant medication history, which could suggest benefits of early treatment or subgroups within CHR for whom social cognition is affected differently. These cross-sectional results require longitudinal replication and further inquiry into the relationships between treatment history and social cognitive development. Current results suggest that factors related to risk for psychosis may moderate adolescent social development, and that interventions targeting social cognition may be particularly helpful at this stage.

Deficits in social cognition are well established in schizophrenia and have been observed prior to the illness onset. Compared to healthy controls (HCs), individuals at clinical high risk of psychosis (CHR) are said to show deficits in social cognition similar to those observed in patients experiencing a first episode of psychosis. These deficits have been observed in several domains of social cognition, such as theory of mind (ToM), emotion perception and social perception. In the current study, the stability of three domains of social cognition (ToM, social perception and facial emotion perception) was assessed over time along and their association with both clinical symptoms and the later development of psychosis. Six hundred and seventy-five CHR individuals and 264 HC participants completed four tests of social cognition at baseline. Of those, 160 CHR and 155 HC participants completed assessments at all three time points (baseline, 1year and 2years) as part of their participation in the North American Prodrome Longitudinal Study. The CHR group performed poorer on all tests of social cognition across all time points compared to HCs. Social cognition was not associated with attenuated positive symptoms at any time point in the study. CHR individuals who developed a psychotic disorder during the course of the study did not differ in social cognition compared to those who did not develop psychosis. This longitudinal study demonstrated mild to moderate, but persistent ToM and social perception impairments in those at CHR for psychosis compared to HCs.

Several studies have demonstrated that youth at clinical high risk (CHR) of developing psychosis have a high prevalence of comorbid psychiatric disorders. Less is known about the impact of comorbid diagnoses on later conversion to psychosis and the change over time. The aim of this study was to determine the frequency and distribution of psychiatric diagnoses at baseline and over time in the North American Prodrome Longitudinal Study (NAPLS 2) and the role of comorbid diagnoses in conversion to psychosis. The NAPLS 2 sample consisted of 744 CHR youth and 276 healthy controls. Only 21% of the CHR group did not have a comorbid diagnosis with many have 2-3 DSM-IV comorbid diagnoses. The most common diagnoses were anxiety and depressive disorders, which did improve over time. The only diagnosis at baseline that differentiated the converters from the non-converters was cannabis misuse. Comorbidity, except for cannabis use, was essentially independent of clinical outcome. It is possible that those with comorbid diagnoses are preferentially the help-seeking individuals that present for help in our clinics and research projects and that those who are at risk but do not have a comorbid diagnosis may not be seeking help in the prodromal phase.

Background

Clinical high risk (CHR) status is characterized by impairments in social cognition, but questions remain concerning their stability over development. In cross-sectional analysis of a large naturalistic sample, the current study examined whether those at CHR status show deviant trajectories for age-related change in social cognitive ability, and whether these trajectories are influenced by treatment history.

Method

Emotion perception (EP) and theory of mind (ToM) were assessed in 675 CHR and 263 healthy comparison (HC) participants aged 12-35. Age effects in CHR were modeled against HC age-expected performance. Prior medication status was tested for interactions with age.

Results

CHR exhibited normal age trajectory for EP, but significantly lower slopes for ToM from age 17 onward. This effect was specific to stimuli exhibiting sarcasm and not to detection of lies. When treatment history was included in the model, age-trajectory appeared normal in CHR subjects previously prescribed both antipsychotics and antidepressant medication, although the blunted trajectory still characterized 80% of the sample.

Discussion

Cross-sectional analyses suggested that blunting of ToM in CHR develops in adolescence, while EP abilities were diminished evenly across the age range. Exploratory analyses of treatment history suggested that ToM was not affected, however, in CHRs with lifetime histories of both antipsychotic and antidepressant medications. Reduction in age-expected ToM ability may impair the ability of individuals at CHR to meet social developmental challenges in adolescence. Medication effects on social cognition deserve further study.