The associative learning roots of affect-driven impulsivity and its role in problem gambling: A replication attempt and extension of Quintero et al. (2020).

Background and aims: Negative/positive urgency (NU/PU) refers to the proneness to act rashly under negative/positive emotions. These traits are proxies to generalized emotion dysregulation, and are well-established predictors of gambling-related problems. We aimed to replicate a previous work (Quintero et al., 2020) showing NU to be related to faulty extinction of conditioned stimuli in an emotional conditioning task, to extend these findings to PU, and to clarify the role of urgency in the development of gambling-related craving and problems. Methods: 81 gamblers performed an acquisition-extinction task in which neutral, disgusting, erotic and gambling-related images were used as unconditioned stimuli (US), and color patches as conditioned stimuli (CS). Trial-by-trial predictive responses were analyzed using generalized linear mixed-effects models (GLME). Results: PU was more strongly related than NU to craving and severity of gambling problems. PU did not influence acquisition in the associative task, whereas NU slightly slowed it. Extinction was hampered in individuals with high PU, and a follow-up analysis showed this effect to depend on relative preference for skill-based and casino games. Discussion and conclusions: Results suggest that resistance to extinction of emotionally conditioned cues is a sign of malfunctioning emotion regulation in problematic gambling. In our work, the key effect was driven by PU (instead of NU), and gambling craving and symptoms were also more closely predicted by it. Future research should compare the involvement of PU and NU in emotion regulation and gambling problems, for gamblers with preference for different gambling modalities (e.g., pure chance vs skill games).

How to pin a compulsive behavior down: A systematic review and conceptual synthesis of compulsivity-sensitive items in measures of behavioral addiction.

Experimental models identify the transition from choice to compulsivity as the main mechanism underlying addiction. In behavioral addictions research, however, the adjective compulsive is used to describe virtually any kind of excessive or dysregulated behavior, which hinders the connection between experimental and clinical models. In this systematic review, we adopted a preliminary definition of compulsive behavior based on previous theoretical work. Subsequently, a systematic review following PRISMA guidelines was conducted (a) to identify the validated instruments, currently used in behavioral addictions research, that include items that are sensitive (intendedly or not) to compulsivity, and (b) to categorize those items into differentiable operationalizations of compulsivity. Six operationalizations of compulsivity emerged from item content analysis: 1. Automatic or habitual behavior occurring in absence of conscious instrumental goals; 2. Behavior insensitive to negative consequences despite conscious awareness of them; 3. Overwhelming urge or desire that impels the individual to initiate the activity and jeopardizes control attempts; 4. Bingeing, or inability to stop or interrupt the activity once initiated, resulting in an episode substantially longer or more intense than intended; 5. Attentional capture and cognitive hijacking; and 6. Inflexible rules, stereotyped behaviors, and rituals related to task completion or execution. Subsequently, a list of 15 representative items per operationalization was elaborated for independent assessment and identification of delimitation problems. A high degree of agreement was reached in assessing them as instantiating compulsivity, as well as in their assignment to the corresponding categories. However, many of them were also considered overinclusive, i.e., uncapable of distinguishing compulsivity from value-based momentary choice. To increase their discriminative value, items in future compulsivity scales should be refined to explicitly mention disconnection between behavior and declarative goals. Further research on factorial structure of a pool of items derived from these operational definitions is warranted. Such a factorial structure could be used as an intermediate link between specific behavioral items and explanatory psychobiological, learning, and cognitive mechanisms.

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. RESULTS: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. CONCLUSIONS: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

Helical computed tomographic angiography of the normal canine pancreas.

Helical abdominal computed tomography (CT) was performed in nine normal beagle-mix dogs. Following cephalic vein injection of ionic iodinated contrast medium via power injector (rate 5 ml/s) dual-phase CT was performed in all dogs. A delayed scan was performed in five dogs between 5 and 13 min after the contrast medium injection. The median time of appearance of contrast medium in the aorta and gastroduodenal artery was 6.3 and 7 s, post start injection and 12 and 12.2 s in the gastroduodenal and portal vein, resulting in a purely arterial pancreatic time window of 5-6s. Pancreatic veins and parenchyma remained enhanced until the end of the dynamic scan (40s). The pancreatic parenchyma showed heterogeneous arterial and homogenous venous contrast enhancement which was slightly hypoattenuating compared to the liver. Delayed scans provided best delineation of the pancreas from the liver. The common bile duct could be identified ventral and to the right of the portal vein joining the dorsomedial aspect of proximal duodenum. Because of the very short time window and variable onset of pure arterial enhancement careful planning of dual-phase studies with previous dynamic CT is recommended. Dual-phase CT angiography enables assessment of the arterial supply, parenchymal perfusion and venous drainage of the canine pancreas.