Early Variations in White Matter Microstructure and Depression Outcome in Adolescents With Subthreshold Depression.

OBJECTIVE: White matter microstructure alterations have recently been associated with depressive episodes during adolescence, but it is unknown whether they predate depression. The authors investigated whether subthreshold depression in adolescence is associated with white matter microstructure variations and whether they relate to depression outcome. METHOD: Adolescents with subthreshold depression (N=96) and healthy control subjects (N=336) drawn from a community-based cohort were compared using diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followed up at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines spreading from the regions identified in the TBSS analysis and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. The authors searched for mediating effects of white matter microstructure on the relationship between baseline subthreshold depression and depression at follow-up, and then explored the specificity of the findings. RESULTS: Lower fractional anisotropy (FA) and higher radial diffusivity were found in the anterior corpus callosum in the adolescents with subthreshold depression. Tractography analysis showed that they also had lower FA in the right cingulum streamlines, along with lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. The relation between subthreshold depression at baseline and depression at follow-up was mediated by FA values in the latter tracts, and lower FA values in those tracts distinctively predicted higher individual risk for depression. CONCLUSIONS: Early FA variations in tracts projecting from the corpus callosum to the anterior cingulate cortex may denote a higher risk of transition to depression in adolescents.

Exploring adolescent cognitive control in a combined interference switching task.

Cognitive control enables individuals to flexibly adapt to environmental challenges. In the present functional magnetic resonance imaging (fMRI) study, we investigated 185 adolescents at the age of 14 with a combined response interference switching task measuring behavioral responses (reaction time, RT and error rate, ER) and brain activity during the task. This task comprises two types of conflict which are co-occurring, namely, task switching and stimulus-response incongruence. Data indicated that already in adolescents an overlapping cognitive control network comprising the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), pre-supplementary motor area (preSMA) and posterior parietal cortex (PPC) is recruited by conflicts arising from task switching and response incongruence. Furthermore our study revealed higher blood oxygenation level dependent (BOLD) responses elicited by incongruent stimuli in participants with a pronounced incongruence effect, calculated as the RT difference between incongruent and congruent trials. No such correlation was observed for switch costs. Furthermore, increased activation of the default mode network (DMN) was only observed in congruent trials compared to incongruent trials, but not in task repetition relative to task switch trials. These findings suggest that even though the two processes of task switching and response incongruence share a common cognitive control network they might be processed differentially within the cognitive control network. Results are discussed in the context of a novel hypothesis concerning antagonistic relations between the DMN and the cognitive control network.

Amygdala-function perturbations in healthy mid-adolescents with familial liability for depression.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies have identified increased amygdala responses to negative stimuli as a risk marker of depression in adults, and as a state marker of depression in adults and adolescents. Hyperreactivity of the amygdala has been linked to negatively biased emotional processing in depression. However, no study has elucidated whether similar amygdala perturbations can be found in healthy mid-adolescents with familial liability for depression. We hypothesized that healthy 14-year-olds with relatives with depression would demonstrate increased amygdala responses to negative stimuli, as compared with their peers with no family history of mental disorders. METHOD: We investigated a community-based sample of 164 typically developing 14-year-olds without record of past or current mental disorders. Of these individuals, 28 fulfilled criteria for family history of depression, and 136 served as controls. Groups did not differ with regard to cognitive ability, depressive symptomatology, and anxiety. During fMRI they performed a perceptual discrimination task in which visual target and distractor stimuli varied systematically with regard to emotional valence. RESULTS: Both a hypothesis-driven region-of-interest analysis and a whole-brain analysis of variance revealed that negative distractors elicited greater amygdala activation in adolescents with a family history of depression compared to controls. Amygdala responses also differed during the processing of negative target stimuli, but effects were reversed. CONCLUSION: Our study demonstrates that familial liability for depression is associated with correlates of negatively biased emotional processing in healthy adolescents. Amygdala perturbations during the processing of negative stimuli might reflect an early and subtle risk marker for depression.

Interindividual differences in mid-adolescents in error monitoring and post-error adjustment.

A number of studies have concluded that cognitive control is not fully established until late adolescence. The precise differences in brain function between adults and adolescents with respect to cognitive control, however, remain unclear. To address this issue, we conducted a study in which 185 adolescents (mean age (SD) 14.6 (0.3) years) and 28 adults (mean age (SD) 25.2 (6.3) years) performed a single task that included both a stimulus-response (S-R) interference component and a task-switching component. Behavioural responses (i.e. reaction time, RT; error rate, ER) and brain activity during correct, error and post-error trials, detected by functional magnetic resonance imaging (fMRI), were measured. Behaviourally, RT and ER were significantly higher in incongruent than in congruent trials and in switch than in repeat trials. The two groups did not differ in RT during correct trials, but adolescents had a significantly higher ER than adults. In line with similar RTs, brain responses during correct trials did not differ between groups, indicating that adolescents and adults engage the same cognitive control network to successfully overcome S-R interference or task switches. Interestingly, adolescents with stronger brain activation in the bilateral insulae during error trials and in fronto-parietal regions of the cognitive control network during post-error trials did have lower ERs. This indicates that those mid-adolescents who commit fewer errors are better at monitoring their performance, and after detecting errors are more capable of flexibly allocating further cognitive control resources. Although we did not detect a convincing neural correlate of the observed behavioural differences between adolescents and adults, the revealed interindividual differences in adolescents might at least in part be due to brain development.

Reward processing and intertemporal decision making in adults and adolescents: the role of impulsivity and decision consistency.

Several studies report differences between adults and adolescents in reward processing and impulsivity. Consistently, adolescents are more impulsive in their decision making, as measured by intertemporal choice tasks. Since impulsivity affects an individual's perception and neural processing of rewards, it is unclear whether previously reported differences in brain activation between adults and adolescents are primarily due to maturation of the brain reward system or differences in impulsivity (i.e. discounting behaviour). To disentangle this, we analysed data from 235 adolescents and 29 adults who performed an intertemporal choice task in which monetary rewards were adapted to individual impulsivity. Using functional magnetic resonance imaging (fMRI), we measured brain activity and assessed impulsivity and consistency of choices at the behavioural level. Although adolescents discounted delayed rewards more steeply than adults, when controlling for impulsivity, neural processing of reward value did not differ between groups. However, more impulsive subjects showed a lower brain response to delayed rewards, independent of age. Concerning decision making, adolescents exhibited a lower consistency of choices and less brain activity in the parietal network than adults. We conclude that processing of the value of prospective delayed rewards is more sensitive to discounting behaviour than to chronological age. Lower consistency of intertemporal choices might indicate ongoing maturation of parietal brain areas in adolescents.