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Abstract
The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral–emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.
Highlights
The diagnoses of psychiatric disorders are based on the Diagnostic and Statistical Manual of Mental Disorders (DSM),[1] which specifies the minimum number and duration of symptoms that must be present for a particular diagnosis
The present study bridges this gap by applying the same stimulus, that is, CO2, and obtaining a quantitative comparison of the same physiological outcome parameters in addition to commonly used behavioral phenotypes in three samples: in mice, healthy volunteers and panic disorder (PD) patients
The use of a CO2 inhalation in form of a single vital capacity breath of 35% CO2 as human experimental model for panic was first established in PD patients.[38]
Summary
The diagnoses of psychiatric disorders are based on the Diagnostic and Statistical Manual of Mental Disorders (DSM),[1] which specifies the minimum number and duration of symptoms that must be present for a particular diagnosis. A new framework toward a novel dimensional classification based on integrating behavior and neurobiological measures has been initiated by the US National Institute of Mental Health, the research domain criteria.[2] It is expected that combining selfreports with assessment of behavior, genetics and neural circuitry will lead to a more etiology-based diagnosis rather than a mainly symptom-driven one, leading to improved treatments in the long term. A vast proportion of research into the basic neurobiology of human psychiatric conditions is carried out in other species, making use of animal (mainly rodent) models of psychopathology. A major challenge in this respect is the translation of data from research in animals to humans and, patients with a psychiatric disorder. To maximize the efficacy of translation, the rodent model should resemble the aspects of the disorder in humans as much as possible
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