Abstract
Patients with schizophrenia spectrum disorders show disturbances in self-referential processing and associated neural circuits including the default mode network (DMN). These disturbances may precede the onset of psychosis and may underlie early social and emotional problems. In this study, we examined self-referential processing in a group of children (7–12 years) at familial high risk (FHR) for psychosis (N = 17), compared to an age and sex-matched group of healthy control (HC) children (N = 20). The participants were presented with a list of adjectives and asked to indicate whether or not the adjectives described them (self-reference condition) and whether the adjectives described a good or bad trait (semantic condition). Three participants were excluded due to chance-level performance on the semantic task, leaving N = 15 FHR and N = 19 HC for final analysis. Functional MRI (fMRI) was used to measure brain activation during self-referential vs. semantic processing. Internalizing and externalizing problems were assessed with the Child Behavior Checklist (CBCL). Evaluating main effects of task (self > semantic) showed activation of medial prefrontal cortex in HC and precuneus/posterior cingulate cortex (PCC) in FHR. Group-comparison yielded significant results for the FHR > HC contrast, showing two clusters of hyperactivation in precuneus/ PCC (p = 0.004) and anterior cerebellum / temporo-occipital cortex (p = 0.009). Greater precuneus/PCC activation was found to correlate with greater CBCL internalizing (r = 0.60, p = 0.032) and total (r = 0.69, p = 0.009) problems. In all, this study shows hyperactivity of posterior DMN during self-referential processing in pre-adolescent FHR children. This finding posits DMN-related disturbances in self-processing as a developmental brain abnormality associated with familial risk factors that predates not just psychosis, but also the prodromal stage. Moreover, our results suggest that early disturbances in self-referential processing may be related to internalizing problems in at-risk children.
Highlights
Schizophrenia spectrum disorders are widely considered to be disorders of brain development, even though their most characteristics symptoms do not appear until the first manifestation of psychosis, typically in adolescence or early adulthood [1, 2]
We examined functional brain activation related to self-referential processing in children with a familial risk for psychosis
The current results are highly consistent with previous literature showing a pattern of anterior default-mode network (DMN) (MPFC) hypoactivation and posterior DMN hyperactivation during self-related processing in patients with schizophrenia [8,9,10, 16, 40, 41] and their unaffected relatives [16, 17]
Summary
Schizophrenia spectrum disorders are widely considered to be disorders of brain development, even though their most characteristics symptoms do not appear until the first manifestation of psychosis, typically in adolescence or early adulthood [1, 2]. There are various theories as to why psychotic symptoms take so long to manifest when the underlying etiology is likely neurodevelopmental in nature On such theory is the “two-hit” hypothesis, which posits that early genetic and environmental risk factors may disrupt certain aspects of brain development, but only to the extent that they render an individual vulnerable to a “second hit.”. This second hit, such as exposure to trauma or substance abuse, would be the catalyst for the actual manifestation of the illness [6]. Early dendritic spine deficits may be aggravated by (in itself normal) synaptic pruning in adolescence and only become detrimental to brain and cognitive functioning
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