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Maternal Depression, Child Temperament, and Early-Life Stress Predict Never-Depressed Preadolescents’ Functional Connectivity During a Negative-Mood Induction

Understanding the development of depression can inform etiology and prevention/intervention. Maternal depression and maladaptive patterns of temperament (e.g., low positive emotionality [PE] or high negative emotionality, especially sadness) are known to predict depression. Although it is unclear how these risks cause depression, altered functional connectivity (FC) during negative-emotion processing may play an important role. We investigated whether maternal depression and age-3 emotionality predicted FC during negative mood reactivity in never-depressed preadolescents and whether these relationships were augmented by early-life stress. Maternal depression predicted decreased medial prefrontal cortex (mPFC)–amygdala and mPFC–insula FC but increased mPFC–posterior cingulate cortex (PCC) FC. PE predicted increased dorsolateral prefrontal cortex–amygdala FC, whereas sadness predicted increased PCC-based FC in insula, orbitofrontal cortex, and anterior cingulate cortex (ACC). Sadness was more strongly associated with PCC–insula and PCC–ACC FC as early stress increased. Findings indicate that early depression risks may be mediated by FC underlying negative-emotion processing.