A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.
IMPORTANCEAlcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. OBJECTIVE To examine whether lockdown measures are associated with AC and consumptionrelated temporal and psychological within-person mechanisms.
<b><i>Introduction:</i></b> The emergence of Pavlovian-to-instrumental transfer (PIT) research in the human neurobehavioral domain has been met with increased interest over the past two decades. A variety of PIT tasks were developed during this time; while successful in demonstrating transfer phenomena, existing tasks have limitations that should be addressed. Herein, we introduce two PIT paradigms designed to assess outcome-specific and general PIT within the context of addiction. <b><i>Materials and Methods:</i></b> The single-lever PIT task, based on an established paradigm, replaced button presses with joystick motion to better assess avoidance behavior. The full transfer task uses alcohol and nonalcohol rewards associated with Pavlovian cues and instrumental responses, along with other gustatory and monetary rewards. We constructed mixed-effects models with the addition of other statistical analyses as needed to interpret various behavioral measures. <b><i>Results:</i></b> Single-lever PIT: both versions were successful in eliciting a PIT effect (joystick: <i>p</i> < 0.001, η<sub>p</sub><sup>2</sup> = 0.36, button-box: <i>p</i> < 0.001, η<sub>p</sub><sup>2</sup> = 0.30). Full transfer task: it was determined that the alcohol and nonalcoholic reward cues selectively primed their respective reward-associated responses (gustatory version: <i>p</i> < 0.001, <i>r</i> = 0.59, and monetary version: <i>p</i> < 0.001, <i>r</i> = 0.84). The appetitive/aversive cues resulted in a general transfer effect (gustatory: <i>p</i> < 0.001, η<sub>p</sub><sup>2</sup> = 0.09, and monetary: <i>p</i> < 0.001, η<sub>p</sub><sup>2</sup> = 0.17). <b><i>Discussion/Conclusion:</i></b> Single-lever PIT: PIT was observed in both task versions. We posit that the use of a joystick is more advantageous for the analysis of avoidance behavior. It evenly distributes movement between approach and avoid trials, which is relevant to analyzing fMRI data. Full transfer task: While gustatory conditioning has been used in the past to elicit transfer effects, we present the first paradigm that successfully elicits both specific and general transfers in humans with gustatory alcohol rewards.
Self-regulation, the ability to guide behavior according to one’s goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test–retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures’ construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks.
Background: Alcohol use disorder (AUD) is a critical public health issue with sex-specific characteristics and the need for a better mechanistic understanding. Initial evidence suggests that progesterone can reduce alcohol intake, while estradiol leads to an increase. However, we lack knowledge about how progesterone relative to estradiol influences alcohol use patterns in females and males with AUD. Methods: This multicenter within-subject study analyzed data on real-life alcohol use (21,438 intensively-sampled smartphone entries), menstrual cycle, and serum progesterone/estradiol ratios (677 blood samples) gathered during a 12-month follow-up in 74 naturally cycling females and 285 males with AUD (mean age: 29.7 and 37.8 years, respectively; data collection: 2020-2022). We used multilevel modelling to identify changes in alcohol use and progesterone/estradiol ratios across the menstrual cycle in females and associations between progesterone/estradiol ratios and alcohol use in males. Results: During the late luteal phase, females showed 0.6- to 0.8-fold lower (predicted) probabilities of binge drinking and 2.8- to 5.6-fold higher mean progesterone/estradiol ratios compared to the menstrual, follicular, and ovulatory phases. Similarly, in males, an increase of 10 units in the progesterone/estradiol ratio was related to 8 and 9% lower probabilities of binge drinking and any alcohol use, respectively. Conclusions: Based on ecologically valid results, this study reveals that higher progesterone/estradiol ratios can protect against problematic alcohol use in females and males with AUD. Therefore, the progesterone/estradiol ratio is a promising treatment target. Translated into clinical practice, our results also indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.
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