The aim of the current study was to use fMRI to examine the neural correlates of engaging in rumination among a sample of remitted depressed adolescents, a population at high risk for future depressive relapse. A rumination induction task was used to assess differences in patterns of neural activation during rumination as compared with a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and 15 healthy control adolescents. Self-report depression and rumination as well as clinician-rated depression were also assessed among all participants. All participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), inferior parietal lobe (IPL), and medial temporal gyrus (MTG) during rumination. Increased activation in these regions during rumination was correlated with increased self-report rumination and symptoms of depression across all participants. Adolescents with rMDD also exhibited greater activation in regions involved in visual, somatosensory, and emotion processing when compared to healthy peers. The current findings suggest that during ruminative thought, adolescents with rMDD are characterized by increased recruitment of regions within the DMN and in areas involved in visual, somatosensory, and emotion processing.

Background Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Methods Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. Results The majority of the sample (68%; 35 of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. Conclusions CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward processing deficits prior to treatment.

Vulnerability models of depression posit that individual differences in trait-like vulnerabilities emerge early in life and increase risk for the later development of depression. In this review, we summarize advances from affective neuroscience using neural measures to assess vulnerabilities in youth at high risk for depression due to parental history of depression or temperament style, as well as prospective designs evaluating the predictive validity of these vulnerabilities for symptoms and diagnoses of depression across development. Evidence from multiple levels of analysis indicates that healthy youth at high risk for depression exhibit abnormalities in components of the Research Domain Criteria (RDoC) positive valence systems, including blunted activation in the striatum during reward anticipation and feedback, and that some of these measures can be used to predict later symptoms. In addition, alterations in components of RDoC’s negative valence systems, including neural processing of sadness, loss, and threat, have been observed in risk for depression, though effects appear to be more task and method dependent. Within the social processes domain, preliminary evidence indicates that neural processing of social feedback, including heightened reactivity to exclusion and blunted response to social reward, may be related to depression vulnerability. These studies indicate that affective neuroscience can inform understanding of developmental pathways to depression and identify altered emotional processing among youth at high risk. We provide an integrated summary of consistent findings from this literature, along with recommendations for future directions and implications for early intervention.

Background The primary aim of the current study was to examine differences in physiological reactivity (measured via pupillometry) to emotional stimuli between children of depressed vs. nondepressed mothers. A second goal was to examine differences in pupil dilation to emotional stimuli between children of anxious vs. nonanxious mothers. Method Participants included 117 mother-child pairs drawn from the community. Children were between the ages of 8 and 14. Pupil dilation was assessed using an eye-tracker while participants viewed angry, happy, or sad faces. Results Children of mothers with a history of major depression (MDD) exhibited increased pupil dilation to sad, but not happy or angry, faces compared to children of nondepressed mothers. Second, we found that children of anxious mothers exhibited increased pupil dilation to angry, but not happy or sad, faces compared to youth of nonanxious mothers. Conclusions The current findings add to the growing body of research suggesting that differences in physiological reactivity to depression- and anxiety-relevant cues may represent an important mechanism in the intergenerational transmission of MDD and anxiety.

The primary aim of the current study was to examine whether physiological reactivity to depression-relevant stimuli, measured via pupil dilation, serves as a biomarker of depression risk among children of depressed mothers. Participants included 47 mother-child dyads. All mothers had a history of major depressive disorder (MDD). Pupil dilation was recorded while children viewed angry, happy, and sad faces. Follow-up assessments occurred 6, 12, 18, and 24 months after the initial assessment, during which structured interviews were used to assess for children’s levels of depressive symptoms as well as the onset of depressive diagnoses. Children exhibiting relatively greater pupil dilation to sad faces experienced elevated trajectories of depressive symptoms across the follow up as well as a shorter time to depression onset. These findings were not observed for children’s pupillary reactivity to angry or happy faces. The current findings suggest that physiological reactivity to sad stimuli, assessed using pupillometry, serves as one potential biomarker of depression risk among children of depressed mothers. Notably, pupillometry is an inexpensive tool that could be administered in clinical settings, such as pediatricians’ offices, to help identify which children of depressed mothers are at highest risk for developing depression themselves.

This study aimed to characterize affective functioning in families of youth at high familial risk for depression, with particular attention to features of affective functioning that appear to be critical to adaptive functioning but have been underrepresented in prior research including: positive and negative affect across multiple contexts, individual and transactional processes, and affective flexibility. Interactions among early adolescents (ages 9-14) and their mothers were coded for affective behaviors across both positive and negative contexts. Primary analyses compared never-depressed youth at high (n=44) and low (n=57) familial risk for depression. The high risk group showed a relatively consistent pattern for low positive affect across negative and positive contexts at both the individual and transactional level. In contrast to prior studies focusing on negative affect that did not support disruptions in negative affect, the data from this study suggest variability by context: (i.e. increased negativity in a positive, but not negative, context) and individual vs. transactional processes (e.g., negative escalation). Findings are discussed in concert with attention to affect flexibility, contextual and transactional factors.

ClinicalTrials.gov identifier: NCT01903447.

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