Understanding the neural substrates of specific symptoms may provide important information about mechanisms underlying depression vulnerability. A growing body of research under the umbrella term ‘network approach’ has recently received considerable attention; the approach understands and aims to model mental disorders as systems of causally interacting symptoms. So far, network studies have been based on symptoms and environmental factors, ignoring relevant neurobiological factors. Here, we address this knowledge gap by modelling a joint network of depression-related brain structures and individual depression symptoms, using 21 symptoms and five regional brain measures. The sample is a mixed group of individuals that previously have been treated for one or more major depressive episodes (MDE) and never depressed individuals, with the goal to model a continuum of depression severity. Hippocampus was negatively associated with changes in appetite and sadness, and positively associated with loss of interest and irritability. Insula was negatively associated with loss of interest in sex and sadness. Cingulate had a negative association with sadness, and positive associations with crying and worthlessness. Fusiform gyrus had positive associations with crying and irritability.