Our understanding of mental health is constantly evolving, and the need to harness interdisciplinary and translational tools to better understand underlying mechanisms of mental illness is more important than ever. Translational research relies on model systems to bridge the gap between human experiences and systematic investigation of putative mechanisms. The study of emotionality - including negative affective states - has been particularly challenging. The complexity of classification systems for psychiatric diagnosis has led to disciplinary fragmentation, making it difficult to comprehensively and translationally investigate affective dysfunction. Furthermore, there is a disparity in what we know about drivers of sex differences in disorders characterized by negative affect, e.g., anxiety and depression, despite increased prevalence in women. Both clinical (human) and preclinical (model systems) research has historically focused on males, to the detriment of patients and our understanding of how sex may contribute to neural and behavioral outcomes. Therefore, it is imperative that research includes sex as a biological variable in studies of mental health.
To advance translational research within affective (dys)function, we must move past symptom-based diagnoses to those that better delineate affective frameworks across species. The research Domain Criteria (RDoC) project constitutes a translational framework for psychopathology research initiated by the National Institute of Mental Health (NIMH) to overcome limitations emerging from the use of symptom-based diagnostics. Instead, this categorization system is informed by genetics, neurobiology, and behavioral observation vs. clinical diagnoses. NIMH’s RDoC domain of negative valence systems includes five constructs of negative affect that are classified and studied along dimensions of functioning from what is considered normal to abnormal. Specifically, these constructs of negative valence systems include: acute threat (fear), potential threat (anxiety), sustained threat, loss, and frustrative nonreward. Although classified separately, these constructs are largely interrelated. Within the realm of threat (acute, possible, sustained), the organisms must evaluate spatial and temporal proximity of a threatening or aversive stimulus. Loss and frustrative nonreward can be characterized by reactions to situations involving deprivation, withdrawal, devaluation or inability to obtain motivationally significant rewards. All constructs are disrupted in individuals with affective dysfunction.
The goal of this topic is to welcome reviews and groundbreaking original articles addressing negative valence systems at any level(s) of analysis (genes, molecules, cells, circuits, physiology, behavior, novel paradigms) in humans and non-human animals. These studies may inform development of targeted prevention strategies and treatments for disorders that affect negative valence systems and/or provide evidence for innovative translational methodology. Articles must include male and female subjects (all-female studies will be considered), and should investigate outstanding and timely topics/themes including, but not limited to:
- Cross-species investigation of negative valence systems at any analysis level
- Proposal/proof-of-concept of novel translational methodology to study negative valence systems
- Studies aiming to behaviorally/mechanistically differentiate acute, sustained, and/or perceived threat
- Impact of sex on negative valence systems
- Studies aiming to behaviorally or mechanistically differentiate constructs
- Goal-directed behavior under conditions of negative affect
- Addiction/self-medication driven by negative affect
- Environmental contributions of negative valence system

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Frontiers in Systems Neuroscience

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