BackgroundChildhood depression is a highly distinct and prevalent condition with an unknown neurobiological basis. We wish to explore the resting state fMRI data in children for potential associations between neural connectivity and childhood depressive symptoms. MethodsA longitudinal birth cohort study with neuroimaging data obtained at 4.5, 6.0 and 7.5 years of age and the Children Depression Inventory 2 (CDI) administered between 8.5 and 10.5 years was used. The CDI score was used as the dependent variable and tested for correlation, both simple Pearson and network based statistic, with the functional connectivity values obtained from the resting state fMRI. Cross-validated permutation testing with a general linear model was used to validate that the identified functional connections were indeed implicated in childhood depression. ResultsTen functional connections and four brain regions (Somatomotor Area B, Temporoparietal Junction, Orbitofrontal Cortex and Insula) were identified as significantly associated with childhood depressive symptoms for girls at 6.0 and 7.5 years. No significant functional connections were found in girls at 4.5 years or for boys at any timepoint. Network based statistic and permutation testing confirmed these findings. ConclusionsThis study revealed significant sex-dependent associations of neural connectivity and childhood depressive symptoms. The regions identified are implicated in speech/language, social cognition and information integration and suggest unique pathways to childhood depressive symptoms.