The NIMH Research Domain Criteria (RDoC) initiative grew out of the agency’s goal to develop “new ways of classifying mental disorders based on behavioral dimensions and neurobiological measures” (NIMH, 2008). In this article, we review how depression research can be meaningfully conducted within an RDoC framework, with a particular focus on the negative valence systems construct of Loss. New efforts to understand depression within the context of RDoC must seek an integrative understanding of the disorder across multiple units of analysis from genes to neural circuits to behavior. In addition, the constructs or processes must be understood within the context of specific environmental and developmental influences. Key concepts are discussed and we end by highlighting research on rumination as a prime example of research that is consistent with RDoC.

Background The family environment plays an important role in the intergenerational transmission of MDD, but less is known about how day-to-day mother-child interactions may be disrupted in families with a history of MDD. Disruptions in mother-child synchrony, the dynamic and convergent exchange of physiological and behavioral cues during interactions, may be one important risk factor. Although maternal MDD is associated with a lack of mother-child synchrony at the behavioral level, no studies have examined the impact of maternal MDD on physiological synchrony. Therefore, the current study examined whether maternal history of MDD moderates mother-child physiological synchrony (measured via RSA) during positive and negative discussions. Method Children ages 7–11 and mothers with either a history of MDD during the child’s lifetime (n=44) or no lifetime diagnosis of any mood disorder (n=50) completed positive and negative discussion tasks while RSA was continuously recorded for both child and mother. Results Results indicated significant between-dyad and within-dyad group differences in physiological synchrony during positive and negative discussions. Between-dyad analyses revealed evidence of synchrony only among never depressed dyads, among whom higher average mother RSA during both discussions was associated with higher average child RSA. Within-dyad analyses revealed that never depressed dyads displayed positive synchrony (RSA concordance) whereas dyads with a history of maternal MDD displayed negative synchrony (RSA discordance) during the negative discussion and that the degree of negative synchrony exhibited during the negative discussion was associated with mothers’ and children’s levels of sadness. Conclusions These results provide preliminary evidence that physiological synchrony is disrupted in families with a history of maternal MDD and may be a potential risk factor for the intergenerational transmission of depression.

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.

There is growing evidence that rumination, perhaps specifically brooding rumination, is a core feature of depression and that it contributes to the development and maintenance of the disorder. A separate line of research has highlighted the role played by heart rate variability (HRV). Importantly, both appear to be driven by disruption in the same neural circuit, heightened amygdala reactivity combined with decreased prefrontal control, and both are highlighted in different units of analysis as reflecting the Research Domain Criteria (RDoC) construct of Loss. However, little is known about the relation among these variables. In the current study, we predicted that lower levels of HRV would be associated with higher levels of brooding rumination and that women at high risk for future depression (i.e., those with a history of past major depressive disorder [MDD]) would exhibit lower levels of HRV and higher levels of brooding. We also examined genetic influences on the variables in this model. We predicted that COMT Val158Met genotype, which has been linked to heightened amygdala reactivity and deficits in prefrontal functioning, would be associated with HRV and brooding rumination, particularly among women with a history of MDD. The results largely supported our hypotheses, providing additional support for relations among the different units of analysis for the Loss construct.

The current study examined the role of cognitive factors in the development and maintenance of depressive symptoms from pregnancy into the postpartum period. One hundred and one women were assessed for levels of rumination (brooding and reflection), negative inferential styles, and depressive symptoms in their third trimester of pregnancy and depressive symptom levels again at four and eight weeks postpartum. We found that, although none of the three cognitive variables predicted women’s initial depressive reactions following childbirth (from pregnancy to one month postpartum), brooding rumination and negative inferential styles predicted longer-term depressive symptom changes (from pregnancy to two months postpartum). However, the predictive validity of women’s negative inferential styles was limited to women already exhibiting relatively high depressive symptom levels during pregnancy, suggesting that it was more strongly related to the maintenance of depressive symptoms into the postpartum period rather than increases in depressive symptoms following childbirth. Modifying cognitive risk factors, therefore, may be an important focus of intervention for depression during pregnancy.