Changes in Default-Mode Network Associated With Childhood Trauma in Schizophrenia

Abstract

Background: There is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated.

Methods: CT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations.

Results: Seed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM.

Conclusions: These findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance.

Keywords: childhood trauma; default-mode network; functional connectivity; resting-state functional magnetic resonance imaging; schizophrenia.

Fig. 1.

Group differences in functional connectivity of the default-mode network. (A) Greater reduced functional connectivity between the left Lateral Parietal seed and the precuneus, right parietal operculum, right superior frontal gyrus, and left postcentral gyrus (Healthy participants < Patients with schizophrenia). (B) Greater reduced functional connectivity between the right Lateral Parietal seed and the precuneus and left parietal operculum (Healthy participants < Patients with schizophrenia). All results thresholded at cluster-level corrected P_FWE < .05 and P_FWE < .05 height threshold). LP, Lateral Parietal Lobe.

Fig. 2.

Functional connectivity and childhood trauma across all participants. (A) For the medial PFC seed, we found a negative association between childhood trauma and reduced functional connectivity with the precuneus across all participants. Results thresholded at cluster-level corrected (P_FWE < .05 and P_FWE < .05 height threshold). (B) For the right Lateral Parietal seed, we found a negative association between childhood trauma and reduced functional connectivity with the precuneus across all participants. Results thresholded at cluster-level corrected (P_FWE < .05 and P_FWE < .05 height threshold). (C) Functional connectivity between the medial PFC seed and precuneus inversely correlated with the total CTQ score across all participants (r = −.342, P < .001). (D) Functional connectivity between the right Lateral Parietal seed and precuneus was negatively correlated with the total CTQ score across all participants (r = −.358, P < .001). CTQ, Childhood Trauma Questionnaire; LP, Lateral Parietal Lobe; PFC, Prefrontal Cortex.

Fig. 3.

Functional connectivity and childhood trauma in patients with schizophrenia. (A) For the medial PFC seed, we found a positive association between childhood trauma and increased functional connectivity with the cerebellum in patients with schizophrenia. Results thresholded at cluster-level corrected P_FWE < .05 and P_FWE < .05 height threshold). (B) Functional connectivity between the right medial PFC seed and cerebellum was positively correlated with the total CTQ score in patients with schizophrenia (r = .562, P < .001). CTQ, Childhood Trauma Questionnaire; PFC, Prefrontal Cortex.

Fig. 4.

Moderated mediation analysis of CTQ, DMN activation, and Theory of Mind performance, with diagnosis as moderator.