According to classical conditioning, when a conditioned stimulus (CS) is repeatedly paired with a unconditioned stimulus (US), it acquires predictive value and produce a conditioned response (CR). Preclinical evidence suggests, however, that there is considerable individual variation in the extent to which a CS acquires incentive salience, with some animals producing a response toward the reward cue (sign trackers; STs), while others showing more attraction for the location in which the reward is going to be presented (goal trackers; GTs). Notably, STs seem to be characterized by psychological features that are considered as risk factors for psychopathologies linked to difficulties in the control of the impulses. The present study aims to translate the ST/GT paradigm to humans, by using a Pavlovian Conditioning Task combined with autonomic and eye movement assessment to derive the two endophenotypes. Then, we will test whether individuals categorized as STs and GTs differ in terms of decision making (based on signal detection theory parameters), and daily attractiveness (assessed by self-report and heart rate variability; HRV) to signs (the smell of the morning coffee) and rewards (e.g., drinking it). We hypothesize that ST will be more likely to engage in model-free decisions. Given that Pavlovian processes are likely to occur outside conscious awareness, we expect increased HRV to the CS compared to the reward in STs, without differences in momentary self-reports. Lastly, we expect STs to be characterized by higher scores on questionnaires assessing difficulties in impulse control (e.g., obsessive-compulsive symptoms, substance use). If replicated in humans, the ST/GT paradigm has the potential to allow the early identification of those who are vulnerable to develop addictive disorders, in line with the call of precision psychiatry of increasing our understanding of mental health to ultimately reduce the gap between scientific innovation and clinical application.
Mental health disorders exert an enormous socioeconomic burden, even greater than cardiovascular disease or cancer, and yet there have been very few therapeutic advances in recent years in the form of novel effective drug treatments in psychiatry. The nosological heterogeneity of psychiatric disorders together with the unavailability of predictive animal models, are two of the reasons for such failure in advances. Moreover, the use of clinical scales depending on subjective impressions rather than objectively measured behavioral or cognitive signs, queries whether similar behavioral or cognitive questions can be asked across species. Whereas more accurate transdiagnostic neurobehavioral measurement ¿ according to the RDoC approach ¿ may help addressing the heterogeneity in Psychiatry, the ¿translational gap¿ between animal models and human studies remains an issue. In rodents, the individual variation in the attraction towards reward cues ¿ as in the ST/GT model ¿ shares neurobehavioral aspects with impulsivity and vulnerability to develop addictions, as well as to some cue-triggered behaviors which are typical of obsessive-compulsive disorder. ST behavior is not dysfunctional per se, but it is extremely sensitive to those motivational mechanisms that may favor the emergence and maintenance of repetitive behaviors, which over time, may become dysfunctional, assuming the form of impulse control disorders. Thus, the ST/GT phenotypical variation has the potential to be an endophenotype of vulnerability to psychiatric disorders. Despite its clinical relevance, whether a distinction between these two phenotypes can be replicated in humans has not been confirmed, yet. Two studies attempted to disentangle this issue but were limited by lack of translational and ecological validity. We aim at overcoming these issues being the first to combine the behavioral paradigm resembling that used in preclinical models, with an ecological assessment and a peripheral physiology index. Overall, the interdisciplinary proposed research offers the chance of a major breakthrough with an impact on both clinical psychology and neuroscience.