Despite the absence of positive clinical manifestations, there may be neurofunctional signatures of genetic vulnerability in the relatives of patients with mood disorders. We performed a meta-analysis integrating task-based fMRI studies comparing unaffected relatives of patients with mood disorders and healthy controls. Hyper-activation in the insula, as well as hypo-activation in the inferior parietal cortex and precuneus were identified in the high-risk relatives. Functional decoding further suggested emotion-related dysfunction might be primarily associated with abnormal activation pattern among deficits in multiple behavioral domains. These neurofunctional correlates may serve as high-risk biomarkers underlying illness onset and development in mood disorders.