Background: Depression in adolescents is more heterogeneous and less often diagnosed than depression in adults. At present, reliable approaches to differentiating between adolescents who are and are not affected by depression are lacking. This study was designed to assess voxel-level whole-brain functional connectivity changes associated with adolescent depression in an effort to define an imaging-based biomarker associated with this condition.

Materials and methods: In total, 71 adolescents affected by major depressive disorder (MDD) and 71 age-, sex-, and education level-matched healthy controls were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) based analyses of brain voxel-wise degree centrality (DC), with a support vector machine (SVM) being used for pattern classification analyses.

Results: DC patterns derived from 16-min rs-fMRI analyses were able to effectively differentiate between adolescent MDD patients and healthy controls with 95.1% accuracy (136/143), and with respective sensitivity and specificity values of 92.1% (70/76) and 98.5% (66/67) based upon DC abnormalities detected in the right cerebellum. Specifically, increased DC was evident in the bilateral insula and left lingual area of MDD patients, together with reductions in the DC values in the right cerebellum and bilateral superior parietal lobe. DC values were not significantly correlated with disease severity or duration in these patients following correction for multiple comparisons.

Conclusion: These results suggest that whole-brain network centrality abnormalities may be present in many brain regions in adolescent depression patients. Accordingly, these DC maps may hold value as candidate neuroimaging biomarkers capable of differentiating between adolescents who are and are not affected by MDD, although further validation of these results will be critical.

Suicidal ideation increases precipitously in patients with depression, contributing to the risk of suicidal attempts. Despite the recent advancement in transcranial magnetic stimulation, its effectiveness in depression disorder and its wide acceptance, the network mechanisms of the clinical response to suicidal ideation in major depressive disorder remain unclear. Independent component analysis for neuroimaging data allows the identification of functional network connectivity which may help to explore the neural basis of suicidal ideation in major depressive disorder. Resting-state functional magnetic resonance imaging data and clinical scales were collected from 30 participants (15 major depressive patients with suicidal ideation and 15 healthy subjects). Individual target-transcranial magnetic stimulation (IT-TMS) was then used to decrease the subgenual anterior cingulate cortex activity through the left dorsolateral prefrontal cortex. Thirty days post IT-TMS therapy, seven of 15 patients (46.67%) met suicidal remission criteria, and 12 patients (80.00%) met depression remission criteria. We found that IT-TMS could restore the abnormal functional network connectivity between default mode network and precuneus network, left executive control network and sensory-motor network. Furthermore, the changes in functional network connectivity between the default mode network and precuneus network were associated with suicidal ideation, and depressive symptoms were related to connectivity between left executive control network and sensory-motor network. These findings illustrate that IT-TMS is an effective protocol for the accurate restoration of impaired brain networks, which is consistent with clinical symptoms.