Oxytocin attenuates amygdala responses to emotional faces regardless of valence.

BACKGROUND: Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. METHODS: In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. RESULTS: Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. CONCLUSIONS: Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.     

Penile rehabilitation following treatment for prostate cancer: an analysis of the current state of the art

Despite recent advances in surgical technique using laparoscopic and robotic approaches for the management of early organ-confined prostate cancer, most contemporary reports demonstrate significant rates of erectile dysfunction comparable to standard open approaches. Controversy remains related to many of the pre-and postoperative management strategies, including agents to enhance nerve recovery, erectogenic drugs, antioxidants, vasoactive injectables, vacuum erection devices and nerve grafting procedures. Additionally, the optimal timing of these interventions and their duration, dose, frequency and outcome thresholds remain ill-defined. In our paper, we provide a comprehensive literature review involving both the basic and clinical data surrounding rehabilitative approaches.     

Effects of intranasal oxytocin on pupil dilation indicate increased salience of socioaffective stimuli

To investigate the mechanisms by which oxytocin improves socioaffective processing, we measured behavioral and pupillometric data during a dynamic facial emotion recognition task. In a double‐blind between‐subjects design, 47 men received either 24 IU intranasal oxytocin (OXT) or a placebo (PLC). Participants in the OXT group recognized all facial expressions at lower intensity levels than did participants in the PLC group. Improved performance was accompanied by increased task‐related pupil dilation, indicating an increased recruitment of attentional resources. We also found increased pupil dilation during the processing of female compared with male faces. This gender‐specific stimulus effect diminished in the OXT group, in which pupil size specifically increased for male faces. Results suggest that improved emotion recognition after OXT treatment might be due to an intensified processing of stimuli that usually do not recruit much attention.     

Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang II-induced cardiac hypertrophy and fibrosis

Conflicting results have been reported for the roles of cGMP and cGMP-dependent protein kinase I (cGKI) in various pathological conditions leading to cardiac hypertrophy and fibrosis. A cardioprotective effect of cGMP/cGKI has been reported in whole animals and isolated cardiomyocytes, but recent evidence from a mouse model expressing cGKIβ only in smooth muscle (βRM) but not in cardiomyocytes, endothelial cells, or fibroblasts has forced a reevaluation of the requirement for cGKI activity in the cardiomyocyte antihypertrophic effects of cGMP. In particular, βRM mice developed the same hypertrophy as WT controls when subjected to thoracic aortic constriction or isoproterenol infusion. Here, we challenged βRM and WT (Ctr) littermate control mice with angiotensin II (AII) infusion (7 d; 2 mg⋅kg⁻¹⋅d⁻¹) to induce hypertrophy. Both genotypes developed cardiac hypertrophy, which was more pronounced in Ctr animals. Cardiomyocyte size and interstitial fibrosis were increased equally in both genotypes. Addition of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, in the drinking water had a small effect in reducing myocyte hypertrophy in WT mice and no effect in βRM mice. However, sildenafil substantially blocked the increase in collagen I, fibronectin 1, TGFβ, and CTGF mRNA in Ctr but not in βRM hearts. These data indicate that, for the initial phase of AII-induced cardiac hypertrophy, lack of cardiomyocyte cGKI activity does not worsen hypertrophic growth. However, expression of cGKI in one or more cell types other than smooth muscle is necessary to allow the antifibrotic effect of sildenafil.Cyclic GMP-dependent protein kinase I (cGKI) is expressed in a wide variety of cells including cardiomyocytes (CMs), cardiac myofibroblasts (CMFs), cardiac fibroblasts (CFs), endothelial cells (ECs), and smooth muscle cells (SMCs) (1). Increased cGKI activity has been reported to protect against cardiac hypertrophy induced by pressure overload (2, 3). For example, mice that carry a mutated form of cGKI unable to interact with downstream targets, develop increased pathologic hypertrophy, accelerated mortality, and congestive heart failure when subjected to thoracic aorta constriction (TAC) (4).Hypertrophy induced by angiotensin II (AII) is thought to be attenuated by cGKI, because AII signaling through G_q/11 is abrogated by the regulator of G-protein signaling protein (RGS), a known substrate of cGKI (5). However, selective deletion of the AII receptor 1 (AT-R1) in the kidney ameliorated AII-induced cardiac hypertrophy, suggesting that the cardiac AT-R1 is dispensable for the induction of this response (6), whereas transgenic mice that overexpress the human AT-R1 specifically in CMs develop hypertrophy, fibrosis, dysfunctions, and early death (7). Furthermore, activation of TRPC channels followed by elevated [Ca²⁺]_i may contribute to the induction of the cardiac hypertrophy gene response (8–11). Again, TRPC3 and TRPC6 channels are negatively regulated by cGKI (12–14).It also has been reported that particulate guanylyl cyclase A, the major receptor for atrial natriuretic peptide (ANP) in the heart, couples to and directly activates the TRPC3/C6 channels in chronic cardiac hypertrophy, thus bypassing cGMP and cGKI (15). It was reported that cardiac cGMP can affects cardiac properties by modulating cAMP levels, bypassing again cGKI (16, 17). Thus, the site(s) of action of cGMP/cGKI are not entirely clear (18) and interpretation of cGMP/cGKI effects on cardiac hypertrophy may be quite complicated.Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, elevates cardiac cGMP at high doses (100 mg⋅kg⁻¹⋅d⁻¹), increases cGKI activity, and has been reported to reverse TAC-induced cardiac hypertrophy (2). This effect is postulated to be caused by an increased activity of RGS2 (19), and in part by the direct regulation of TRPC3/6 conductance by cGKI (11, 14) mentioned above. However, two clinical studies did not report positive therapeutic results after prolonged treatment of diastolic dysfunction with sildenafil (20, 21).We (22) and others (23) have tested the hypothesis that CM-cGKI attenuates cardiac hypertrophy by using the cGKIβ rescue mouse line (βRM). These animals express the cGKIβ isozyme under the SM22α promoter, which is active principally in SMCs and activated CMFs, but do not express cGKIβ in other cell types (24). Chronic infusion of isoproterenol or TAC induced in βRM mice a cardiac hypertrophy that was identical to that of WT littermate controls (22), a result that argues against the hypothesis that CM, EC, or CF cGKI is responsible for the antihypertrophic effects of cGMP in the heart. To examine the role(s) of sildenafil to inhibit cardiac hypertrophy and fibrosis, we now extend these experiments using AII-induced hypertrophy and high concentrations of sildenafil (0.6 mM) in the drinking water. Once again, the lack of cGKI in CM and CF did not cause an increased hypertrophic response as predicted (2). Moreover, little or no antihypertrophic effect of sildenafil was observed in the WT mice and no effect was seen in the βRM mice. However, a large effect of sildenafil was observed on fibrosis in WT but not the βRM mice, suggesting that cGKI present in cardiac SMCs or activated CMFs is an important regulator of cardiac fibrosis.     

Oxytocin, vasopressin, and human social behavior

There is substantial evidence from animal research indicating a key role of the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in the regulation of complex social cognition and behavior. As social interaction permeates the whole of human society, and the fundamental ability to form attachment is indispensable for social relationships, studies are beginning to dissect the roles of OT and AVP in human social behavior. New experimental paradigms and technologies in human research allow a more nuanced investigation of the molecular basis of social behavior. In addition, a better understanding of the neurobiology and neurogenetics of human social cognition and behavior has important implications for the current development of novel clinical approaches for mental disorders that are associated with social deficits (e.g., autism spectrum disorder, social anxiety disorder, and borderline personality disorder). This review focuses on our recent knowledge of the behavioral, endocrine, genetic, and neural effects of OT and AVP in humans and provides a synthesis of recent advances made in the effort to implicate the oxytocinergic system in the treatment of psychopathological states.     

Oxytocin improves "mind-reading" in humans.

BACKGROUND: The ability to "read the mind" of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals. METHODS: In a double-blind, placebo-controlled, within-subject design, 30 healthy male volunteers were tested for their ability to infer the affective mental state of others using the Reading the Mind in the Eyes Test (RMET) after intranasal administration of 24 IU oxytocin. RESULTS: Oxytocin improved performance on the RMET compared with placebo. This effect was pronounced for difficult compared with easy items. CONCLUSIONS: Our data suggest that oxytocin improves the ability to infer the mental state of others from social cues of the eye region. Oxytocin might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.     

Autismus und soziale Kognition

Autism spectrum disorders (autism, Asperger's syndrome, high-functioning autism) are characterized by a common pattern of marked impairments in social interactions. Deficits have been described in face processing, facial emotion recognition, and social attribution ("theory of mind") or generally speaking in social cognition. Some studies have shown that these impairments are already detectable in early childhood, leading to the assumption that the underlying cause is an early disruption of neuronal development. Accordingly, neuroimaging data have revealed alterations of structure and function in the brains of autistic children, adolescents, and adults. The present review gives a systematic overview of the existing literature on functional imaging studies using experimental paradigms of social cognition, i.e. face discrimination, facial emotion recognition, and theory of mind in autistic disorders.     

Intranasal oxytocin enhances emotion recognition from dynamic facial expressions and leaves eye-gaze unaffected

Previous studies have shown that oxytocin improves the encoding and recognition of facial expressions, which has been proposed to be mediated by an increased exploration of the eye region during face processing. In the present study, we used eye tracking to assess visual attention to the eye region while participants performed a dynamic facial emotion recognition task. In a double-blind, placebo-controlled between-subjects design participants received 24 IU intranasal oxytocin (n = 23) or a placebo (n = 24). Although oxytocin administration had no effect on participants' visual scanning of emotional faces, it generally enhanced recognition performance, as the oxytocin group recognized emotional expressions at lower intensity levels. These findings suggest that oxytocin-induced improvement of facial emotion recognition is independent of modulations in overt visual attention.