BACKGROUND: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear. METHODS: We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14-25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization. RESULTS: Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate-corrected ps , .05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive "hubs" such as parvalbumin and calmodulin. CONCLUSIONS: Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia.

Low self-esteem is a risk factor for a range of psychiatric disorders. From a cognitive perspective a negative self-image can be maintained through aberrant learning about self-worth derived from social feedback. We previously showed that neural teaching signals that represent the difference between expected and actual social feedback (i.e., social prediction errors) drive fluctuations in self-worth. Here, we used model-based functional magnetic resonance imaging (fMRI) to characterize learning from social prediction errors in 61 participants drawn from a population-based sample (n = 2402) who were recruited on the basis of being in the bottom or top 10% of self-esteem scores. Participants performed a social evaluation task during fMRI scanning, which entailed predicting whether other people liked them as well as the repeated provision of reported feelings of self-worth. Computational modeling results showed that low self-esteem participants had persistent expectations that others would dislike them, and a reduced propensity to update these expectations in response to social prediction errors. Low self-esteem subjects also displayed an enhanced volatility in reported feelings of self-worth, and this was linked to an increased tendency for social prediction errors to determine momentary self-worth. Canonical correlation analysis revealed that individual differences in self-esteem related to several interconnected psychiatric symptoms organized around a single dimension of interpersonal vulnerability. Such interpersonal vulnerability was associated with an attenuated social value signal in ventromedial prefrontal cortex when making predictions about being liked, and enhanced dorsal prefrontal cortex activity upon receipt of social feedback. We suggest these computational signatures of low selfesteem and their associated neural underpinnings might represent vulnerability for development of psychiatric disorder.

Adolescents are prone to social influence from peers, with implications for development, both adaptive and maladaptive. Here, using a computer-based paradigm, we replicate a cross-sectional effect of more susceptibility to peer influence in a large dataset of adolescents 14 to 24 years old. Crucially, we extend this finding by adopting a longitudinal perspective, showing that a within-person susceptibility to social influence decreases over a 1.5 year follow-up time period. Exploiting this longitudinal design, we show that susceptibility to social influences at baseline predicts an improvement in peer relations over the follow-up period. Using a Bayesian computational model, we demonstrate that in younger adolescents a greater tendency to adopt others’ preferences arises out of a higher uncertainty about their own preferences in the paradigmatic case of delay discounting (a phenomenon called ‘preference uncertainty’). This preference uncertainty decreases over time and, in turn, leads to a reduced susceptibility of one’s own behaviour to an influence from others. Neuro-developmentally, we show that a measure of myelination within medial prefrontal cortex, estimated at baseline, predicts a developmental decrease in preference uncertainty at follow-up. Thus, using computational and neural evidence, we reveal adaptive mechanisms underpinning susceptibility to social influence during adolescence.