Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition.

BACKGROUND: Individuals with Major Depressive Disorder (MDD) are characterized by biases in attention to negative emotional material. While there is evidence that anomalous functioning in frontocingulate regions may underlie these biases, we know little about the neural correlates of negative emotional biases in depressed adolescents. METHODS: Eighteen adolescents diagnosed with MDD and 21 matched healthy control (CTL) adolescents underwent fMRI while performing an emotional distractor task. On each trial participants were presented with task-relevant house pairs and task-irrelevant face pairs. Participants indicated whether the house pairs were identical while ignoring the face pairs, which were either fearful, sad, or neutral. RESULTS: Despite equivalent behavioral performance (response time and accuracy) between groups, adolescents with MDD exhibited greater activation in frontocingulate regions, including dorsal anterior cingulate cortex (dACC) and inferior frontal gyrus/middle frontal gyrus (IFG/MFG), and occipitoparietal regions, including lateral occipital cortex and superior parietal lobule when ignoring fearful versus neutral faces. Response times to these trial conditions also correlated negatively with activation in IFG/MFG and lateral occipital cortex suggesting these regions are recruited in order to effectively ignore emotional distractors. Groups did not differ when ignoring sad versus neutral faces or fearful versus sad faces. CONCLUSIONS: Adolescents with MDD recruit both cognitive control and visual attention regions to a greater degree than do CTL adolescents, reflecting greater cognitive demand when downregulating threat-related stimuli.

Depressed adolescents are characterized by negative interpretation biases. Although investigators have used cognitive bias modification for interpretation (CBM-I) to experimentally manipulate interpretation biases in depressed adults, the near- and far-transfer effects are not well understood in adolescents diagnosed with Major Depressive Disorder (MDD). In this study, we extend previous research by investigating the near- and far-transfer effects of 6 sessions of Positive versus Neutral CBM-I on independent measures of interpretation bias (near-transfer effects) and on attention biases and clinical symptoms (far-transfer effects) in a sample of adolescents with MDD (n = 46). At post-training, adolescents who received Positive CBM-I interpreted ambiguous scenarios more positively than did participants who received Neutral CBM-I, providing evidence of training effectiveness. There was no evidence, however, of near- or far-transfer effects. These findings raise concerns about the malleability of interpretation biases in adolescent depression and suggest that further work is needed to establish the clinical utility of CBM-I for adolescents with MDD.