Neuroimaging Studies of Major Depressive Disorder in Youth Offer Inconsistent Conclusions

Chinese radiographer in her 30s, waist up operating medical scanner
Although neuroimaging studies of major depressive disorder in youth were largely inconsistent, blunted reward-related activity was noted as a potential biological marker for both disorder onset and course.

Results from a systematic review published in Developmental Cognitive Neuroscience suggest an association between blunted reward-related activity and major depressive disorder (MDD) onset among children and adolescents. However, many limitations were encountered during review, including between-study inconsistencies regarding structural brain measures, limited sample sizes, and failure to account for confounding factors such as sex and pubertal development.

Investigators conducted a systematic review of the PubMed and MEDLINE databases from inception to February 1, 2019, for studies examining associations between neuroimaging markers and pediatric MDD. Studies with longitudinal design that included at least two clinical assessments of depression and one neuroimaging assessment were eligible for inclusion. To capture data regarding pediatric MDD, studies that did not include a sample of patients aged 5 to 25 years were excluded. Various imaging modalities were relevant to review, including structural magnetic resonance imaging (MRI), diffusion tensor imaging, functional MRI (fMRI), and electroencephalography (EEG).

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A total of 68 longitudinal neuroimaging studies, including 34 distinct samples, were selected for review. Among these studies, 26 examined structural brain measures and 39 examined functional brain measures, including fMRI and EEG. Multiple studies reported an association between blunted reward-related activity during adolescence and subsequent onset of clinical depression. Specifically, blunted activity in the ventral striatum and increased functional connectivity between the ventral striatum and medial prefrontal cortex were observed in both EEG and fMRI studies.

Regarding other functional and structural brain measures, data varied significantly between studies. Some studies examined the effects of environmental and genetic factors on MDD, but results were inconsistent, likely as a result of small sample sizes with insufficient statistical power. Moreover, few studies considered the impact of hormone level changes during puberty, or the differences associated with age group and sex.

Although this systematic review identified blunted reward activity as a potential neuroimaging marker of MDD in adolescence, associations between MDD and structural brain measures were highly inconsistent. Investigators emphasized the need for further study in larger samples and suggested a whole-brain approach over a region-of-interest approach to increase reproducibility. The potential confounding effects of environmental and genetic factors on brain development and MDD also warrant additional research.


Toenders YJ, van Velzen LS, Heideman IZ, Harrison BJ, Davey CG, Schmaal L. Neuroimaging predictors of onset and course of depression in childhood and adolescence: a systematic review of longitudinal studies [published online August 8, 2019]. Dev Cogn Neurosci. doi:10.1016/j.dcn.2019.100700