fMRI responses to emotional faces in children and adolescents at genetic risk for psychiatric illness share some of the features of depression

Abstract

Background: Fronto-limbic regions of the brain including the sub-genual (sgPFC) and medial prefrontal (mPFC) cortices are central to processing emotionally salient and hedonic stimuli (Mayberg, 2009) and implicated in depression. The relevance of cortico-limbic models of emotion and reward processing in children with genetic risk for psychiatric disorders has not been assessed.

Methods: Here we studied adolescents at risk for schizophrenia (HRS) and controls (HC) using an event-related fMRI continuous affective appraisal task. HRS were divided into sub-groups based on the presence or absence of negative symptoms (Miller et al., 2003), HRS_NS+ and HRS_NS- respectively. Brain responses to positive, negative and neutral emotional stimuli were estimated.

Results: Consistent with observations in the depressive phenotype, for positively valenced stimuli, HRS_NS+ (relative to HC and HRS_NS-) were characterized by hypo-responsivity of the sgPFC and the mPFC, but hyper-responsivity of the mid-brain. sgPFC and mPFC signals were coupled across groups.

Limitations: Such studies can benefit from larger sample sizes, though our observed effect sizes were in the moderate to large range.

Conclusions: Children and adolescents at risk for psychiatric illness and who evince reliably present negative symptoms show brain responses to socially rewarding stimuli similar to those observed in depression. Studies in at-risk children and adolescents may be important in understanding how early manifestations of depression-like characteristics impact brain function.

Figure 1

(a) Pie-chart shows group membership across each of the HC, HRS_NS− and HRS_NS+ groups in the analyzed data. (b) As seen, sensitivity to task (assessed with d’) did not differ across groups (p>.5) indicating that groups remained on-task and inter-group differences were not driven by differences in cognitive performance.

Figure 2

Significant clusters under the overall main effect of group are depicted for responses to positively valenced stimuli. Clusters are projected to the dorsal surface for the medial prefrontal cortex (a), the medial surface for the mid-brain (b) and the ventral surface for the sub-genual prefrontal cortex (c)(see Table 1 for significance). Adjoining graphs depict estimated BOLD (% signal change) under the clusters of significance for each of the groups and each of the main effects (error bars are ± sem). As indicated, significant effects were observed in analyses of signal change data (See Results). Post-hoc comparisons (Sidak, 1967)(p<.05) revealed significant differences between HRS_NS+ and HC (mPFC, mid-brain and sgPFC; * in the Figure) and HRS_NS+ and HRS_NS− (mPFC and mid-brain; † in the Figure).

Figure 3

fMRI response (across all subjects) in each of the mPFC and sgPFC (a) and mPFC and the midbrain (b) are plotted in scatterplots. As seen, across groups, the mPFC-sgPFC response is highly coupled (confirmed by significant parametric regression). Across groups, the mPFC-midbrain response is not statistically coupled. Within HRS, a marginally significant negative coupling was observed suggesting that within the risk group, decreases in the mPFC response were associated with increases in the midbrain response. The overlaid density ellipses denote the density of data within each group. The dotted lines represent the results of spline interpolation (see Methods).