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The relationship between subjective stress perception and the objective stress response to acute stress stimuli is not sufficiently understood. The aim of the present study was to test the hypothesis that the neuroendocrine response in socially evaluated cold pressor test (CPT) depends on the extent of perceived stressfulness of the stimulus. The test was performed in 24 healthy male volunteers. Subjective stress perception was assessed using nine visual analog scales. The subjects were divided to low and high stress perception groups according to the median split of the scores. Subjects with high stress perception exhibited slightly lower values of systolic blood pressure and lower overall concentrations of salivary cortisol compared to subjects with low stress perception. Salivary alpha-amylase activity did not show significant changes. Salivary aldosterone decreased in time in subjects with low but increased early after the test in subjects with high stress perception. Interestingly, salivary concentrations of the pro-inflammatory cytokine interleukin-1beta were considerably higher in subjects with high stress perception, particularly immediately before the test. The differences in salivary cortisol and interleukin-1beta were confirmed by the analysis with distress as a continuous covariate. Distress scores correlated negatively with salivary cortisol and positively with interleukin-1beta. The rate pressure product, which is a global measure of energy consumption by the heart, was significantly higher immediately before than after the stress exposure. The present findings show that concentrations of interleukin-1beta are a sensitive component of the stress response at the time before the stressful event.Lay summaryIt is generally expected that higher perceived stressfulness of a stimulus is accompanied by higher activation of stress-related systems. This study evaluating a combined psychosocial and physical stress situation in healthy men provides evidence that individual parameters of the stress response are differently related to perceived stress intensity. Subjects with high stress perception exhibited lower systolic blood pressure and salivary cortisol, higher interleukin-1beta, marginal differences in alpha amylase and aldosterone compared to subjects with low stress perception, which might be important for stress coping.

The neural mechanisms underpinning empathy for pain are still a matter of debate. One of the major questions is whether empathy-related pain responses indicate domain-general vs. pain-specific affective responses. Using fMRI and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them to the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiate the role of shared representations in empathy.

Social isolation deprives rodents of social interactions that are critical for normal development of brain and behavior. Several studies have indicated that postweaning isolation rearing may affect nitric oxide (NO) production. The aim of this study was to compare selected behavioral and biochemical changes related to NO production in the brain of rats reared in social isolation for different duration. At the age of 21 days, male Sprague Dawley rats were randomly assigned into four groups reared in isolation or socially for 10 or 29 weeks. At the end of the rearing, open-field and prepulse inhibition (PPI) tests were carried out. Furthermore, in several brain areas we assessed NO synthase (NOS) activity, protein expression of nNOS and iNOS isoforms and the concentration of conjugated dienes (CD), a marker of oxidative damage and lipid peroxidation. Social isolation for 10 weeks resulted in a significant decrease in PPI, which was accompanied by a decrease in NOS activity in the cerebral cortex and the cerebellum, an increase in iNOS in the hippocampus and an increase in CD concentration in cortex homogenate. On the other hand, a 29 week isolation had an opposite effect on NOS activity, which increased in the cerebral cortex and the cerebellum in animals reared in social isolation, accompanied by a decrease in CD concentration. The decrease in NOS activity after 10 weeks of isolation might have been caused by chronic stress induced by social isolation, which has been documented in previous studies. The increased oxidative state might result in the depleted NO bioavailability, as NO reacts with superoxide radical creating peroxynitrite. After 29 weeks of isolation, this loss of NO might be compensated by the subsequent increase in NOS activity.

Post-weaning social isolation has been shown to be a relevant animal model for studying the mechanisms underlying psychopathological states induced by early-life stressful experiences. Besides extensively studied brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) receptor, increasing attention is being given to a neuropeptide precursor VGF (non-acronymic). Several lines of evidence indicate an interplay between the neurotrophins and nitric oxide signaling. This study investigated the long-term consequences of post-weaning social isolation on behavior, VGF/BDNF/TrkB pathway and two isoforms of nitric oxide synthase (NOS) in the hippocampus and examined whether these effects were sex-specific. Male and female Sprague-Dawley rats were reared either in social isolation or social groups from postnatal day 21 for 9 weeks (n = 12–15/group and sex). Post-weaning social isolation induced impairments in sensorimotor gating and increased anxiety-like behavior in rats of both sexes. These behavioral alterations were accompanied by attenuated gene expression of VGF and TrkB receptor in the hippocampus. Isolation-induced reduction in VGF gene expression was more evident in male isolates. Similar changes were found in neuronal NOS (nNOS) gene expression with reduced mRNA levels in male isolates. Gene expression of BDNF and inducible NOS was not influenced by isolation rearing or sex. In addition, sex-specific patterns of VGF and nNOS gene expression in the hippocampus with higher mRNA levels in males than in females were revealed. The present study demonstrates a relationship between nNOS, VGF, BDNF, and TrkB confirming a link between nitric oxide and neurotrophins signaling pathways. Our findings indicate that long-term post-weaning social isolation alters signaling via VGF/BDNF/TrkB and nNOS that could interfere with neurodevelopmental processes which may contribute to pathological behavioral symptoms in adulthood. Future studies are needed to support this suggestion since the direct mechanistic link has not been approached in this study.

The role of vascular endothelial growth factor (VEGF) in chronic stress and neurodevelopmental disorders is of growing research interest. Here we show that post-weaning isolation rearing of rats decreased gene expression of VEGF in the hippocampus. Gene expression of VEGF upstream regulator fibroblast growth factor-2 (FGF-2) or its downstream mediator endothelial nitric oxide synthase (eNOS) was unchanged. Other signaling pathways appear to be involved in isolation-induced reduction in VEGF gene expression. Sex differences in VEGF and eNOS gene expression with significantly higher mRNA levels in females than males were revealed.

Background: TMS has high potential as smoking cessation treatment. However, the neural mechanisms underlying TMS induced reduction of tobacco craving remain unclear. Electroencephalographic (EEG) delta frequency has been associated with the activity of the dopaminergic brain reward system, which is crucial for nicotine induced effects, and decreases after nicotine admission in smokers. Objective: The aim of this study was to investigate EEG delta power changes induced by hf rTMS of the left dorsolateral prefrontal cortex (DLPFC) in nicotine deprived smokers and it’s relation to cue-induced nicotine craving. Methods: Fourteen healthy smokers meeting ICD-10 criteria for tobacco addiction participated in this within-subject sham controlled study. Participants had to abstain from smoking 6 h before the experiment. Effects of high-frequency repetitive TMS (hf rTMS) (10 Hz) for verum (left DLPFC) and sham (vertex) stimulations on cue-induced nicotine craving and resting state EEG delta power were assessed before and three times within 40 min after rTMS. Results: Both craving (P ¼ 0.046) and EEG delta power (P ¼ 0.048) were significantly lower after verum stimulation compared to sham stimulation across the whole post stimulation time period assessed. However, changes of craving ratings and delta power did not correlate. Conclusion: Hf rTMS applied to the left DLPFC reduces nicotine craving in short-term abstinent smokers. Changes in delta activity support the idea that stimulation induced effects are mediated by the dopaminergic brain reward system, which presumably plays a prominent, but probably not exclusive, role in this stimulation induced behavioral modulation, making this method a promising smoking cessation treatment candidate.

The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10–15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that followed. The following report is a composite of these reviews. It is hoped that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

In the last decade, a number of functional neuroimaging studies have identified a set of neural structures that are involved in empathy for another person’s pain. Bilateral anterior insular cortex and medial/anterior cingulate cortex seem to play a crucial role, but several other brain regions are also co-activated; this includes structures associated mostly with “Theory of Mind” or “mentalizing”, including precuneus, ventral prefrontal cortex, superior temporal cortex, and temporo-parietal junction. Electrophysiological pain-empathy responses have been analyzed to investigate the temporal dynamics of neural activity underlying this process. To the best of our knowledge, however, this has been performed with scalp recordings only; pain empathy-related brain potentials have not recorded using intracranial electrodes until now. In the present study, we investigated intracranial event-related brain potentials (ERPs) from three intractable epileptic patients who underwent preoperatively diagnostic invasive video-EEG monitoring. During the experiment, patients watched 3-second dynamic visual stimuli depicting needle injections into a left hand (N = 42), or the same left hand touched by a cue tip (N = 42). Intracranial EEGs were recorded using intracerebral and subdural electrodes, investigating in total more than 300 brain sites. The ERPs in each condition (needle and cue tip) were averaged separately off-line, and statistical differences in response amplitudes after painful vs. non-painful stimuli were detected. In all three subjects, significantly different event-related responses to painful vs. non-painful stimuli were observed in some investigated neural structures, including left-hemispheric temporo-parietal junction, right-sided temporo-occipital junction, and right-sided lateral occipital cortex. In these brain sites, painful needle stimuli evoked more prominent ERPs compared to cue-tip touch. The latency of these intracranial ERPs can be used for direct measurement of local activation with millisecond temporal resolution, and can be compared across different brain structures as well as with the scalp ERPs. Our pilot data demonstrate the ability of intracranial ERP recordings to contribute to our understanding of pain empathy. More generally, these data provide important insights into more complex social phenomena, and complement widely available functional neuroimaging data which are limited by their reliance on hemodynamic rather than direct neural measurements.

In the first study we have tried to test usefulness of ANP and BNP in the timing of aortic valve surgery. 23 patients were examined and compared to 20 controls. Echocardiography and 6-minute walk test were performed and pre-, peak- and post-exercise samples were taken from each patient. ANP and BNP plasma concentrations were measured by immuno-radiometric assay.

The aim of the present study was to evaluate the antihypertensive efficacy of the highly beta(1)-selective adrenergic antagonist nebivolol in comparison with bisoprolol in the treatment of mild to moderate essential hypertension.This multicenter, single-blind, randomized, parallel-group 16-week study involved a 4-week placebo run-in, followed by a 12-week treatment period (5 mg nebivolol or 5 mg bisoprolol). Patients (n = 273) eligible for the study had a sitting diastolic blood pressure (DBP) between 95 and 110 mm Hg and a systolic blood pressure (SBP)/=180 mm Hg at the end of the placebo run-in period. The primary endpoint of the study was the percentage of responders achieving DBP normalization (/=90 mm Hg) or a DBP reduction of at least 10 mm Hg.The baseline SBP and DBP were similar in the two groups. Both SBP and DBP decreased gradually and significantly upon treatment. The two treatments had similar effects on the mean change from the baseline for both DBP (nebivolol -15.7 +/- 6.4 mm Hg vs. bisoprolol -16.0 +/- 6.8 mm Hg) and SBP. A high proportion of responders was noted in both groups (nebivolol 92.0% vs. bisoprolol 89.6%) and there was no significant difference between the treatments. The overall number and incidence of spontaneously reported adverse events were slightly, but not significantly lower for nebivolol (8 events; 5.8%) than for bisoprolol (12 events; 8.9%).The findings of the present trial indicate that 5 mg nebivolol once daily is an effective antihypertensive agent. It can therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate essential hypertension.

LUKAC, P., et al.: Determination of Repetitive Slow Pathway Conduction for Evaluation of the Efficacy of Radiofrequency Ablation in AVNRT.Aims: To determine whether the loss of repetitive slow pathway conduction identifies a successful radiofrequency ablation of atrioventricular nodal reentry tachycardia (AVNRT). Methods and results: Thirty nine consecutive patients undergoing ablation of AVNRT using the slow pathway approach were included. At baseline and after each radiofrequency application with an episode of junctional rhythm, repetitive slow pathway conduction was assessed as follows: Effective refractory period of the fast pathway was determined. The coupling interval of the first atrial extrastimulus (A2) was set at 30 ms below the effective refractory period of the fast pathway to ensure its conduction via the slow pathway. The second atrial extrastimulus (A3) was introduced at progressively longer coupling intervals starting from 200 ms until: (1) it propagated to the His bundle or (2) an anterogradely blocked AV nodal echo of A2 appeared before a conducted A3 depolarized the atrium in the His bundle electrogram. The response was termed repetitive slow pathway conduction if A3 was conducted with anAH > 200 ms. Application was considered successful if no AVNRT could be induced. Repetitive slow pathway conduction was present after 1 of 39 successful and after 34 of 40 ineffective applications(P < 0.0001). Repetitive slow pathway conduction identified a successful application with 97% sensitivity, 86% specificity, 86% positive predictive value, and 97% negative predictive value. Conclusion: The presence of repetitive slow pathway conduction identifies an unsuccessful application with a clinically meaningful negative predictive value. (PACE 2003; 26[Pt. I]:827–835)