NIH/NIMH – Emotion Regulation, Aging and Mental Disorder (R01, R21 Clinical Trial Not Allowed)

December 3, 2018 by School of Medicine Webmaster

The following description was taken from the R01 version of this FOA.

This  FOA is intended to support studies aligned with Strategy 2.1 of the NIMH Strategic Plan ( ), which calls for research to “characterize the developmental trajectories of brain maturation and dimensions of behavior to understand the roots of mental illnesses across diverse populations.” In the context of research on emotional processes and their relation to mental illness, the developmental dimension of age-related differences occurring across the lifespan is to be understood as a major aspect of population diversity.


Research suggests that, for many adults, normal aging is associated with general trends toward improvements in emotional function, including emotion regulation (e.g., as evidenced by increasing positive and decreasing negative affect, greater emotional stability, higher life satisfaction, a “positivity effect” in information-processing). As compared with younger adults, older adults often show superior emotion regulation capacities, employ different strategies for executive control of emotional information, and recruit different neural networks in performing affective tasks. Such patterns have been variously hypothesized to stem from increased motivation to maintain emotional well-being, learning of more skillful and efficient emotion processing strategies, or compensatory adaptations to age-related brain changes. However, for the most part, such hypotheses remain minimally examined and unconfirmed.  Although not all adults demonstrate positive emotion regulation changes in association with aging, the factors that account for individual differences in showing the general maturational shifts remain poorly understood.  For example, even though men and women are observed to process emotions differently, to date, evidence remains scarce regarding whether and how sex differences may be modulated during the aging process.

Although mood and anxiety disorders are considered examples of affect dysregulation, knowledge tends to be limited about the specific emotion processing deficits involved. To date, there have been few mechanistic studies employing affective neuroscience methods that have examined how adult maturational changes in emotion regulation may relate to mental disorder in later life. There has been little scientific investigation of the extent to which adults with affective disorders manifest or fail to show the normative maturational shifts, or at what point(s) during the adult lifespan they may begin to show divergent trajectories with respect to their emotion regulation.

In addition, significant gaps remain in our understanding of how age-related cognitive changes may impinge on emotion regulation in adults who experience mental disorders in later life. In the general older adult population, it is considered paradoxical that many aspects of emotional function improve with age even though the cognitive control capacities on which these functions are thought to depend normatively decline with age. Numerous questions remain regarding the role of changes in cognitive control or executive functioning in emotional processes with age, the capacity of older adults to employ alternative strategies to regulate emotion, and the degree to which cognitive changes influence affective dysregulation in those who experience mental disorders with age.

Research Objectives

This FOA is intended to support research designed to clarify the patterns of emotion processing, at neurobiological as well as behavioral levels of analysis, that are characteristic of middle-aged and older adults who experience affective disorders or manifest other forms of obvious and persistent emotional dysregulation, and to deepen our understanding of the mechanisms and contextual factors involved in their emotion dysregulation. Studies leveraging the concepts, methods, and findings emerging from research on normative adult emotional development, including environmental and life course factors, are of particular interest, so as to investigate variation in emotion processing across a spectrum of older adults, ranging from those with mood and anxiety disorders to adults without such psychopathology. Research is encouraged that assesses emotional processes dimensionally, integrating across multiple levels of analysis, including brain-level measurements, and employing cutting-edge methodology from such fields as cognitive and affective neuroscience, neuroimaging, neurophysiology, neuroendocrinology, and lifespan developmental psychology. Research is sought that uses psychometrically sound assessment approaches and directly observes emotion processes, such as in response to emotion-evoking stimuli, situations, scenarios or the like. Applicants are encouraged to propose studies that will examine multiple domains of emotion processing so as to address, in aging adults, the key developmental concept of dynamic interactions among differentially maturing brain systems that support successful (or less successful) emotion regulation.

Varied research paradigms may be useful for pursuing the goals outlined above. Use of constructs from NIMH’s Research Domain Criteria (RDoC) initiative (, or of RDoC-compatible approaches, in assessing emotion processing, other component aspects of mental disorder, and/or related domains of brain function dimensionally is encouraged.  The RDoC initiative has defined a set of constructs that may be useful in this research. These constructs are organized according to five domains of brain functioning (negative valence systems, positive valence systems, cognitive systems, arousal/regulatory systems, and systems for social processes). Research on RDoC constructs should employ assessment methods appropriate for each construct of interest and the assessment methods are expected to converge on the construct from at least two levels of analysis. RDoC units of analysis (potential levels of measurement) include genes, molecules, cells, circuits, physiology, behavior, and self-report. Details about RDoC constructs and units of analysis can be found here. Although the structure of the RDoC matrix suggests boundaries among constructs, given the densely integrated and interconnected nature of the brain’s circuits, it is understood that the constructs function interactively and that promising empirical approaches to an RDoC-based analysis of emotional functioning and its relationship to psychopathology may involve examining intersections among constructs.

Applicants may propose to examine dimensional constructs that do not appear in the NIMH RDoC matrices as long as there is strong theoretical support for their relevance to a mechanistic understanding of emotional processing. Applicants should be able to cite substantial evidence for the validity of such constructs, and to indicate strong theoretical support that the construct maps onto a specific biological system, such as a brain circuit or physiological pathway, thought to be involved in emotion processing or regulation.

With respect to assessing psychopathology or mental disorder, likewise, an RDoC approach encourages taking a dimensional perspective, and concentrating on aspects of behavior and brain function that span a range from intact to gradations of impairment, independent of diagnosis. Thus, in such an approach, recruitment and eligibility of study participants need not be determined on the basis of traditional diagnostic categories, but should instead be based on criteria that result in a sample that is optimized to study the clinical phenomena of interest over their full range of variability. Such an emphasis on understanding the full dimensionality of neurobehavioral functioning generally precludes simple, dichotomous designs comparing patients versus controls. Under this FOA, if an RDoC or other dimensional construct is proposed to serve as the primary variable representing psychopathology (as opposed to using a diagnostic characterization), the study design and sampling plan must be such as to assure that an adequate number of individuals assessed as falling within the more severely impaired ranges of that dimension will be included in the study.

If the proposed research involves neuroimaging methods, applicants are encouraged to incorporate use of protocols from the Human Connectome Project, assuming that the research addresses constructs that have been previously examined in the Human Connectome Project and that such protocols are available to the investigator.

The particular adult age ranges over which differences in emotion processes (and in maturational changes in them) may be examined are not prespecified and should be determined to fit the specific research questions posed. Applicants are expected to provide compelling rationales for their selections in this regard, such as prior evidence that particular age ranges may represent periods in the life cycle especially critical for observing changes in emotion processing that may, in turn, be associated with the development or recurrence of mental disorder in middle or old age.

Regardless of other variations in sampling and experimental approach, it will be considered scientifically essential that the proposed research attend to sex differences as a central issue. As previously noted, age-related changes in cognitive functioning, particularly with respect to cognitive control or executive functioning, are likely to be an important contributory factor to changes in emotion regulation. Inasmuch as cognitive changes and comorbid medical conditions become increasingly common with advancing age, it will also be critical that the research plans adequately assess or control for differences in cognitive functioning and in medical comorbidity as potential confounding influences on emotional experience in middle-aged and older adults.

Applicants are also strongly encouraged to review the Notice on enhancing the reproducibility of NIH-supported research through rigor and transparency (NOT-OD-15-103), and to incorporate appropriate features into the proposed research plans. NIMH has published guidelines for reporting elements of rigor in experimental design in applications (NOT-MH-14-004), and examples of critical elements for a well-designed study are summarized on the NIMH website (

Specific Areas of Research Interest

Areas of interest include, but are not limited to:

  • Research clarifying specific emotion processing irregularities, and their brain-level correlates, characteristic of aging individuals with affective disorders;
  • Investigations of whether or to what degree individuals aging with chronic or recurrent affective disorders manifest normative maturational shifts in their patterns of emotion regulation, particularly with respect to the underlying mechanistic factors involved;
  • Studies identifying trajectories of change in adult affective regulation and associated neurobiological and neurobehavioral factors, and clarifying points in the adult life course at which trajectories may diverge for affectively dysregulated subgroups;
  • Studies evaluating differences in the brain circuits or cortical areas recruited during emotional challenge or task performance as a function of age, sex, and mental disorder, and whether such differences predict resilience against onset or deterioration of course in mental disorders;
  • Studies that examine the impact of early-life adversity, trauma or stress on affect regulation as a central factor in the development of mental disorder in middle or old age;
  • Studies employing efficient multi-cohort designs to estimate adult neurodevelopmental changes relevant to emotion regulation processes and relate these to the risk of developing mental disorders; and,
  • Hypothesis driven research to test putative neural circuits via multiple biological measures.

Examples of studies that will not be supported under this FOA include the following:

  • Applications that characterize adults’ emotional status solely in terms of diffuse mood states (e.g., only via depression, anxiety or other such scales), lacking assessment of specific emotion processing and/or contextual components essential for a mechanistic understanding of changes or differences in emotion regulation;
  • Applications that assess emotion processes and emotion regulatory strategies or processes at only a single level of observation and analysis (i.e., without combining multiple levels/methods such as genetic, cellular, brain circuit, physiological, behavioral, self-report);
  • Applications that fail to analyze emotion processing by sex, or if limited to a single sex, that fail to provide justification for how the proposed single-sex approach will be critical to advancing overall understanding of unique aspects of emotion regulation in relationship to mental disorder in middle or old age;
  • Applications that propose clinical trials of potential therapies for mental disorders, including tests of interventions intended to impact mental disorders by influencing emotion processing or use of emotion regulation strategies.

Investigators interested in proposing research involving a clinical trial are referred to the  NIMH Clinical Trials website and to the FOAs indicated there for submitting applications containing clinical trial components.

Deadlines:  standard dates apply


Filed Under: Funding Opportunities