Resting-state functional connectivity disruption between the left and right pallidum as a biomarker for subthreshold depression

Although the identification of late adolescents with subthreshold depression (StD) may provide a basis for developing effective interventions that could lead to a reduction in the prevalence of StD and prevent the development of major depressive disorder, knowledge about the neural basis of StD remains limited. The purpose of this study was to develop a generalizable classifier for StD and to shed light on the underlying neural mechanisms of StD in late adolescents. Resting-state functional magnetic resonance imaging data of 91 individuals (30 StD subjects, 61 healthy controls) were included to build an StD classifier, and eight functional connections were selected by using the combination of two machine learning algorithms. We applied this biomarker to an independent cohort (n = 43) and confirmed that it showed generalization performance (area under the curve = 0.84/0.75 for the training/test datasets). Moreover, the most important functional connection was between the left and right pallidum, which may be related to clinically important dysfunctions in subjects with StD such as anhedonia and hyposensitivity to rewards. Investigation of whether modulation of the identified functional connections can be an effective treatment for StD may be an important topic of future research.