Abstract
The recent sociodevelopmental cognitive model of schizophrenia/psychosis is a highly influential and compelling compendium of research findings. Here, we present logical extensions to this model incorporating ideas drawn from epigenetic mediation of psychiatric disease, and the plausible effects of epigenetics on the emergence of brain network function and dysfunction in adolescence. We discuss how gene–environment interactions, effected by epigenetic mechanisms, might in particular mediate the stress response (itself heavily implicated in the emergence of schizophrenia). Next, we discuss the plausible relevance of this framework for adolescent genetic risk populations, a risk group characterized by vexing and difficult-to-explain heterogeneity. We then discuss how exploring relationships between epigenetics and brain network dysfunction (a strongly validated finding in risk populations) can enhance understanding of the relationship between stress, epigenetics, and functional neurobiology, and the relevance of this relationship for the eventual emergence of schizophrenia/psychosis. We suggest that these considerations can expand the impact of models such as the sociodevelopmental cognitive model, increasing their explanatory reach. Ultimately, integration of these lines of research may enhance efforts of early identification, intervention, and treatment in adolescents at-risk for schizophrenia.
Highlights
Schizophrenia remains the most profoundly debilitating of psychiatric conditions [1, 2]
We attempt an incremental contribution to this synthesis suggesting that an expansion of this model may help elucidate the following: schizophrenia but others with similar genetic vulnerability do not. (b) In this context, the vexing problem of specific genetic at-risk populations is considered
Whereas unexplained neurodevelopmental variation and resilience may explain this [10], we suggest that epigenetic mediation, of genes mediating the stress response in adolescence, may explain some of this uncharacterized variance. (c) we note the vast evidence of functioning brain network disruptions in schizophrenia, and the fact that these disruptions are being characterized in at-risk populations, including children of patients, and suggest that epigenetic effects may mediate the shaping of functioning brain networks in the adolescent risk state, resulting in a highly variable and unpredictable pattern of conversion to psychosis
Summary
Schizophrenia remains the most profoundly debilitating of psychiatric conditions [1, 2]. High-risk subjects with sub-threshold negative symptoms show attenuated responses to rewarding social stimuli, in regions of the limbic system, including the amygdala and the ventral prefrontal cortex [75] This pattern of responses is similar to those seen in patients with frank depression, and suggests additional compelling evidence in support of stress mediating the emergence of negative symptoms that in turn affect functioning brain networks [44, 104,105,106,107]. As evidence accumulates regarding the existence of methQTLs, we note that analyses based on these proposed genes should take these into consideration
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