A Highly Decreased Binding of Cyclic Adenosine Monophosphate to Protein Kinase A in Erythrocyte Membranes is Specific for Active Psoriasis

A cyclic adenosine monophosphate binding abnormality in psoriatic erythrocytes that could be corrected by retinoid treatment has been reported. It was tested whether this binding abnormality is specific for psoriasis and the effects of treatment were compared with etretinate, cyclosporine A, or anthralin on 2-3H-8-N3-cyclic adenosine monophosphate binding to the regulatory subunit of protein kinase A in erythrocyte membranes. One hundred and fifteen individuals were evaluated, including: (i) 34 healthy persons; (ii) 15 patients with nonatopic inflammatory skin diseases (eczema, erythroderma, tinea, Grover's disease, erysipelas, urticaria); (iii) eight with other dermatoses mediated by immune mechanisms (systemic lupus erythematosus, lichen planus, necrotizing vasculitis, erythema nodosum, systemic sclerosis); (iv) 14 with generalized atopic dermatitis; and (v) 44 with psoriasis vulgaris clinically assessed by Psoriasis Area and Severity Index. In psoriasis, the course of the binding of 2-3H-8-N3-cyclic adenosine monophosphate to erythrocytes was measured in nine patients during a 10 wk treatment with etretinate, in 21 patients during a 10 wk treatment with cyclosporine A, and one patient under topical treatment with anthralin for 4 wk. We found the following femtomolar binding per mg protein: (i) healthy persons (1064 ± 124, mean ± SD); (ii) nonatopic inflammatory skin diseases (995 ± 103); (iii) immune dermatoses (961 ± 92); (iv) atopic dermatitis (960 ± 110); and (v) psoriasis (645 ± 159; p <0.0001 compared with nonpsoriatics, Mann–Whitney U test). Treatment of psoriasis with etretinate, cyclosporine A, or anthralin normalized the binding of cyclic adenosine monophosphate, which was inversely correlated to the Psoriasis Area and Severity Index score. It was concluded that the decreased binding of cyclic adenosine monophosphate to protein kinase A in erythrocytes is specific for psoriasis and normalizes after successful treatment

Social reinforcement learning and its neuronal modulation by oxytocin in healthy young adults

Background: Currently, no pharmacological treatment of the social symptoms of Autism Spectrum Disorder (ASD) is available and behavioral interventions only show modest effects. Recently, oxytocin (OXT) has been shown to enhance motivation and attention to social stimuli, by modulating the brain reward circuitry in social situations. Likely, these effects have the potential to enhance social reinforcement learning, the core mechanism of behavioral interventions. However, it is unclear whether these effects are mediated by an OXT-induced increase in saliency towards social stimuli per se or whether they are due to a modulation of the brains’ reward circuitry, which is specific for social feedback. This question plays an important role for the design of future interventions aiming to combine OXT and behavioral treatments in ASD.Objectives: We investigated the influence of OXT on socially reinforced learning and its underlying neural mechanisms in a social learning task, which allowed for the differentiation of social feedback stimuli and social stimuli as the target of learning. Methods: Using functional Magnetic Resonance Imaging we assessed brain activation during performance of a probabilistic reinforcement learning task in 24 typically developing controls (18-25 years). We used a double-blind placebo-controlled cross-over design. Participants indicated whether social or non-social stimuli belong to category A or B. After a jittered delay, social or non-social feedback (either rewarding or neutral) with non-100% contingencies was provided. Data were analyzed using computational modeling of reinforcement learning, according to the Q-learning model. From the behavioral choice data, individual model parameters were estimated and used to calculate trial-by-trial reward-prediction error values. We assessed the correlation of brain activation with reward-prediction error values during feedback as well as brain activation related to the anticipation of reward during choice. Results were significant at p<.05 (cluster-level corrected, p<.001 voxel level).Results: Analyses revealed a significant correlation of brain activation in the striatum with the reward prediction error across conditions, confirming that overall learning was mediated by striatal circuitry. During feedback anticipation, OXT selectively enhanced brain activation in the striatum and insular cortex for social feedback conditions despite the learning target being non-social. The learning target being social, however, did not show a modulation by OXT during feedback anticipation. Behaviorally, subjects demonstrated significant learning during the task independent of task or treatment condition. More extensive analyses including data of patients with ASD will follow. Conclusions: Our results demonstrate that in healthy controls, OXT selectively enhances brain activation related to the acquired anticipation of social feedback, but no selectivity was evident for social stimuli as a learning target. This pattern suggests that the modulatory role of OXT during reward processing is tied to the feedback phase being social. Our investigation therefore provides deeper insights into the neural mechanisms of OXT-induced modulation of the reward system and its potential enhancement of socially reinforced learning. Combinations of behavioral interventions with OXT might be particularly effective, if emphasis is put on positive, socially mediated feedback. Further investigations are needed to study this mechanism and its implications for interventions with OXT in ASD