Brain functional connectivities that mediate the association between childhood traumatic events, and adult mental health and cognition

BACKGROUND: Childhood traumatic events are risk factors for psychopathology, but large-scale studies of how childhood traumatic events relate to mental health and cognition in adulthood, and how the brain is involved, are needed. METHODS: The associations between childhood traumatic events (such as abuse and neglect, and defined by the ‘Childhood Trauma’ questions in the UK Biobank database) and brain functional connectivity, mental health problems, and cognitive performance were investigated by a univariate correlation analysis with 19,535 participants aged 45–79 from the UK Biobank dataset. The results were replicated with 17,747 independent participants in the second release from the same dataset. FINDINGS: Childhood traumatic events were significantly associated with mental health problems in adulthood including anxiety (r=0.19, p<1.0 × 10(−323)), depression (r=0.21, p<1.0 × 10(−323)), and self-harm (r=0.24, p<1.0 × 10(−323)), and with adult cognitive performance including fluid intelligence (r=−0.05, p=2.8 × 10(−10)) and prospective memory (r=−0.04, p=6.8 × 10(−8)). Functional connectivities of the medial and lateral temporal cortex, the precuneus, the medial orbitofrontal cortex; and the superior, middle and inferior prefrontal cortex extending back to precentral regions were negatively correlated with the childhood traumatic events (FDR corrected, p<0.01). These lower functional connectivities significantly mediated the associations between childhood traumatic events and addiction, anxiety, depression and well-being (all p<1.0 × 10(−3)), and cognitive performance. The association between childhood traumatic events and behavioural measures and functional connectivity were confirmed in a replication with different participants in the second release of the UK Biobank dataset. INTERPRETATION: Childhood traumatic events are strongly associated with adult mental health problems mediated by brain functional connectivities in brain areas involved in executive function, emotion, face processing, and memory. This understanding may help with prevention and treatment. FUNDING: Funding was provided by the National Key R&D Program of China (No. 2018YFC1312900 and No. 2019YFA0709502).