TY - JOUR
T1 - Hyperactivation of Posterior Default Mode Network During Self-Referential Processing in Children at Familial High-Risk for Psychosis
AU - Collin, Guusje
AU - Bauer, Clemens C.C.
AU - Anteraper, Sheeba Arnold
AU - Gabrieli, John D.E.
AU - Molokotos, Elena
AU - Mesholam-Gately, Raquelle
AU - Thermenos, Heidi W.
AU - Seidman, Larry J.
AU - Keshavan, Matcheri S.
AU - Shenton, Martha E.
AU - Whitfield-Gabrieli, Susan
N1 - Funding Information:
Funding. This work was supported by the National Institute of Mental Health (R21 MH 092840) and the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 749201.
Publisher Copyright:
© Copyright © 2021 Collin, Bauer, Anteraper, Gabrieli, Molokotos, Mesholam-Gately, Thermenos, Seidman, Keshavan, Shenton and Whitfield-Gabrieli.
PY - 2021/2/9
Y1 - 2021/2/9
N2 - 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.
AB - 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.
KW - default mode network
KW - familial high-risk
KW - psychosis
KW - schizophrenia
KW - self-referential processing
UR - http://www.scopus.com/inward/record.url?scp=85101579572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101579572&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2021.613142
DO - 10.3389/fpsyt.2021.613142
M3 - Article
C2 - 33633608
AN - SCOPUS:85101579572
SN - 1664-0640
VL - 12
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
M1 - 613142
ER -