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Meta-analysis identifies brain abnormalities that may explain disparities of MDD in youth

A meta-analysis identified reliable neural abnormalities among youth with major depressive disorder that may explain seemingly disparate symptoms of the disorder.

“Advances in neuroimaging techniques have led to a growing interest in investigating abnormalities in the brain structure and function in individuals diagnosed as having [major depressive disorder]. These advances provide promising opportunities to advance our understanding of the underlying pathophysiological effects of [major depressive disorder] and generate novel treatment targets for emerging technologies and more conventional pharmacotherapy and psychotherapy,” Chris H. Miller, BS, of Stanford University, and colleagues wrote.

Researchers evaluated relevant functional MRI studies published from November 2006 through February 2015 to identify the most reliable neural abnormalities among youth diagnosed with major depressive disorder (MDD) and characterize their associations with specific psychological dysfunctions. Study participants were aged 4 to 24 years and included 246 individuals with MDD and 276 healthy controls.

Youth with MDD exhibited reliable patterns of abnormal activation compared with healthy controls. These included task-general and task-specific effects of hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05), and hypoactivation in caudate (P < .01) during aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05) and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks.

“Although MDD is defined diagnostically as a clinical syndrome of co-occurring symptoms, clinical researchers are moving toward a biologically driven dimensional system based on neural models of psychological dysfunction capable of linking together seemingly disparate symptoms to a coherent neural explanation. Accordingly, in this meta-analysis, we identified several brain regions in which youth with MDD reliably exhibited abnormal activations compared with age-matched healthy control participants during affective processing and executive functioning tasks,” Miller and colleagues wrote. “Based on these findings and the existing neuroscience literature, we propose that altered activation of several distributed brain networks described previously may help explain seemingly disparate symptoms in this population as well as develop targeted interventions for prevention and treatment.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.