Alterations in functional networks during working memory (WM), including the salience network, frontoparietal network, dorsal attention network and default-mode network, have been repeatedly reported in schizophrenia. Changes in functional connectivity related to Early-Life Adversity (ELA) have yet to be characterized despite its relevance in schizophrenia and healthy participants. Furthermore, it remains to be tested if different severity levels of ELA are associated with the recruitment of functional networks during working memory.

Data were analyzed from 69 healthy controls (HC) and 26 patients with chronic schizophrenia (SZ) matched for sex, IQ, and handedness as part of the ‘Immune Response and Social Cognition in Schizophrenia’ project. Individuals completed the Childhood Trauma Questionnaire (CTQ) and performed a spatial WM task while undergoing functional MRI in a 3T MRI scanner. We tested for group differences for rescaled total CTQ scores, low ELA severity levels and high ELA severity levels in HC and SZ. Then we compared the impact of ELA severity on the high difficulty level during working memory-related functional connectivity across the whole brain, salience network, frontoparietal network, dorsal attention network and default-mode network, using an a priori region of interest (ROI) to ROI analysis in CONN Toolbox. We report findings that survived p<0.05 FDR threshold at the analysis level and multiple comparisons corrections.

SZ reported significantly greater ELA severity than HC (T(92) = 1.997, P < 0.049), while no significant group difference for a total ELA score was found (T(92) = 1.821, P < 0.072). We identified significant changes in functional connectivity at the whole-brain level across 164 ROIs, driven by increased negative functional connectivity in frontoparietal brain regions in SZ relative to HC across the whole sample (T(92) = -3.65, P < 0.036). For all other task-based networks of the salience network, frontoparietal network and dorsal attention network, only HC with low ELA severity levels showed reduced functional connectivity in parts of the networks (salience network, F(43) = 2.76, P < 0.041; frontoparietal network, T(46) = 3.28, P < 0.039; dorsal attention network, F(46) = 4.55, P < 0.015), but not in HC with high ELA severity levels or SZ. Conversely for the task-negative network of the default-mode network, only SZ with high ELA severity levels showed significantly reduced functional connectivity in parts of the network (T(12) = -3.72, P < 0.09), but not in SZ with low ELA levels or HC.

These preliminary results suggest that reduced functional connectivity across networks during WM is a correlate of ELA experience in both HC and SZ, rather than an illness-effect in SZ only. Low ELA severity levels in HC appear to lead to deactivation of task-based networks during WM. In contrast, high ELA severity levels in SZ seem to be related to deactivation in the task-negative network during the WM task. We speculate that these deactivations of networks may reflect a biomarker of ELA experience in healthy participants and patients with schizophrenia.