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The role of learning and conditioning varies across human anxiety disorders, and distinguishing between fear and panic is important to guide investigation in panic disorder. By reminding that some psychological and psychobiological theories view panic attacks as false alarms of unconditioned biological origin, we suggest that employing endophenotypes of biological and evolutionary relevance—such as the respiratory responses to suffocative stimuli—can be fruitful for both human research and animal models of panic, and can help keeping unconditioned components of the clinical picture separate from the conditioned components in the experimental setting. We present a review of a model of panic disorder by which idiosyncratic environmental adverse events can promote unconditioned and unexpected spells of physical alarm. Along the proposed causal pathway the alternative splicing expression of …