Abstract
Tremendous progress has been made in basic neuroscience in recent decades. One area that has been especially successful is research on how the brain detects and responds to threats. Such studies have demonstrated comparable patterns of brain-behavior relationships underlying threat processing across a range of mammalian species, including humans. This would seem to be an ideal body of information for advancing our understanding of disorders in which altered threat processing is a key factor, namely, fear and anxiety disorders. But research on threat processing has not led to significant improvements in clinical practice. The authors propose that in order to take advantage of this progress for clinical gain, a conceptual reframing is needed. Key to this conceptual change is recognition of a distinction between circuits underlying two classes of responses elicited by threats: 1) behavioral responses and accompanying physiological changes in the brain and body and 2) conscious feeling states reflected in self-reports of fear and anxiety. This distinction leads to a "two systems" view of fear and anxiety. The authors argue that failure to recognize and consistently emphasize this distinction has impeded progress in understanding fear and anxiety disorders and hindered attempts to develop more effective pharmaceutical and psychological treatments. The two-system view suggests a new way forward.
Keywords: Antianxiety Agents; Cognitive Neuroscience; Emotion; Models/Theories Of Psychiatry; Other Aspects Of Psychopharmacology.
Introduction
Recent events in psychiatry highlight a growing chasm between basic science and the clinic (1). Progress in understanding the brain has not been mirrored in improved clinical outcomes. Most current therapies with some efficacy emerged decades ago. Promising new treatments either have not turned out to be useful when tested with patients or exhibit potential adverse effects that limit their applicability to severe, treatment-refractory disorders.
Research on brain mechanisms engaged during confrontations with threats—stimuli with the potential to inflict harm to the organism—has shown high degrees of conservation across mammals, likely reflecting evolutionary advantages of an efficiently functioning threat-processing circuitry. This work provides a unique opportunity for developing novel treatments for conditions involving alterations in threat processing, especially the so called anxiety disorders. Nevertheless, research in this area has
been disappointing as a source of novel treatments (2). We argue that this state of affairs reflects how fear and anxiety have been conceived, andwe offer a new framework to address the problem.
It has long been assumed that an innate “fear system” exists in the mammalian brain and that this system, in the presence of a threat, generates both the conscious feeling of “fear” and the behavioral and physiological responses typical of such experiences (Figure 1A). We propose instead a “two systems” framework, with one set of circuits for generating conscious feelings and a second set for controlling behavioral and physiological responses to threats (Figure 1B). The first systemprimarily involves cortical areas, and the second mostly involves subcortical regions, such as the amygdala, although certain cortical areas interact with and regulate processing in these regions. While the first system generates conscious feelings, the second largely operates nonconsciously. Conflation of these circuits and their functions has hampered clinical
extension of basic research. While the actual circuitry is considerably more complex than implied by the two-system label, the framework represents a useful heuristic around which to restructure translational efforts to achieve a deeper, more nuanced understanding than currently exists about how brain mechanisms give rise to normal and pathological feelings of fear and anxiety and the behavioral and physiological symptoms that accompany these subjective experiences.
CONCLUSIONS
Progress has stalled in treatment development for mental disorders. Cross-species conservation of brain-behavior relationships occurring in the presence of threats provides unique opportunities and creates the potential for mutually informative basic and clinical research in the service of treatment development for anxiety disorders. However, current approaches fail to recognize adequately the distinctions between neural circuitry supporting subjective feeling states as opposed to defensive responding. Failure to do so prevents the field from leveraging cross-species conservation of threat processing circuits. The two-system framework we propose distinguishes neural circuitry supporting defensive responding from circuitry supporting feeling states and provides a new heuristic for basic, clinical, and translational research on anxiety disorders.