Classification of anxiety disorders from a neuroscience perspective: Implications for the assessment and treatment and anxiety disorders

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The hypothesis guiding the proposed research is that anxiety disorder diagnoses vary along a continuum of fear/defense circuit function. At one end of the continuum are patients whose motivational circuitry is normal but exaggerated in reactivity for whom the pathology is mainly defined by the inappropriateness of the fear reaction´s target (i.e., it is not realistically minatory) – as in single-diagnosis specific phobia or circumscribed social phobia; the next step is to disorders in which the hyperreactivity is generalized, in which fear reactions are prompted by multiple stimuli or unpredictable aversive events and the fear state is increasingly sustained; the final step is found in anxiety patients characterized by long-enduring dysfunction (disorder chronicity), intense symptom severity, high comorbidity, and high “negative affectivity”. In this latter group of patients, the fear circuit appears to be compromised, functionally dysregulated, and fails to mediate defensive reflexes (e.g., startle potentiation) that normally occur in the context of threat. The proposed examination of this emotion and neuroscience based conception of psychopathology is novel and breaks important new ground of major clinical significance, going beyond current diagnostic categorizations that are mainly based on patient´s symptom reports. Although there have been many studies of startle potentiation to fear cues in anxiety patients, using a variety of paradigms, issues of chronicity, severity, and comorbidity remain unsresolved. The proposed research strategy is to examine reflex and brain measures of hyperactivity/hypoactivity in the full spectrum of anxiety disorders (including patients with comorbid depression and multiple anxiety comorbidities), thus assessing at different stages on the hypothesized continuum of fear/defense circuit function, using a multiple measurement approach.