Increased pericardial adipose tissue and cardiometabolic risk in patients with schizophrenia versus healthy controls.

Patients with schizophrenia are at increased risk of diabetes, cardiovascular disease (CVD) and associated mortality versus the general population. Increased intra-abdominal and pericardial adipose tissue are associated with elevated CVD and mortality in the general population, but little is known about these in patients with schizophrenia. This study examined pericardial and intra-abdominal adipose tissue in schizophrenia and compared this to healthy controls. Thirty-one patients with schizophrenia (mean age 41.2 years, 76% males) and 30 healthy volunteers (CTRL) were examined in this study. The primary outcomes were the volumes of pericardial adipose tissue and intra-abdominal adipose tissue, measured using magnetic resonance imaging. Secondary outcomes included diabetes and cardiac event risk assessed by established instruments. Volumes of pericardial adipose tissue were increased in male and female patients with schizophrenia compared to healthy controls after the adjustment of age, sex and body mass index (P < 0.005). The 10-year risk of a cardiac event was significantly higher in patients with schizophrenia. Furthermore, the risk for developing type-2 diabetes mellitus was slightly increased in schizophrenia. Volumes of intra-abdominal adipose tissue were slightly increased in male and female patients with schizophrenia, albeit not statistically significant. This study demonstrates that patients with schizophrenia have increased pericardial adipose tissue versus controls. This increased fat deposit around the heart is highly relevant for understanding the comorbidity between heart disease and schizophrenia. Interventions aiming to reduce pericardial and intra-abdominal adipose tissue, such as exercise, may be essential to reduce the burden of heart disease in schizophrenia.

[Neurobiological foundations underlying normal and disturbed sexuality]. / Neurobiologische Grundlagen der Sexualität und ihrer Probleme.

BACKGROUND: Sexual functions are regulated by hormonal and neurochemical factors as well as neuronal networks. An understanding of these basic principles is necessary for the diagnostics, counselling and treatment of sexual problems. OBJECTIVE: Description of essential mechanisms of sexual function on a neurochemical and neuronal level. MATERIAL AND METHODS: Literature search, selection and discussion of relevant studies. RESULTS: Analogous to the dual control model there are primary inhibitory (e. g. serotonin) and excitatory neurotransmitter systems (e.g. sex steroids and dopamine). Moreover, neuronal structures have been identified that are responsible for processing sexual stimuli. These networks are altered in subjects with sexual disorders or by pharmacological treatment, e. g. antiandrogens and selective serotonin reuptake inhibitors (SSRI) CONCLUSION: Knowledge of the neurobiology of sexuality forms the foundations for the treatment of sexual dysfunctions in psychiatry and other disciplines.

Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials.

INTRODUCTION: Botulinum toxin A (BTA) injection into the glabellar region is currently being studied as a treatment for major depressive disorder (MDD). Here we explore efficacy data of this novel approach in a pooled analysis. METHODS: A literature search revealed 3 RCTs on this topic. Individual patient data and clinical end points shared by these 3 trials were pooled and analyzed as one study (n=134) using multiple regression models with random effects. RESULTS: In the pooled sample, the BTA (n=59) and the placebo group (n=75) did not differ in the baseline variables. Efficacy outcomes revealed BTA superiority over placebo: Improvement in the Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale 6 weeks after baseline was 45.7% for BTA vs. 14.6% for placebo (p<0.0001), corresponding to a BTA response rate of 54.2% (vs. 10.7%) and a BTA remission rate of 30.5% (vs. 6.7%). DISCUSSION: Equalling the status of a meta-analysis, this study increases evidence that a single treatment of BTA into the glabellar region can reduce symptoms of MDD. Further studies are needed to better understand how BTA exerts its mood-lifting effect.

Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study.

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

Sexual cues alter working memory performance and brain processing in men with compulsive sexual behavior.

Pornography has been repeatedly at the centre of public attention and has been controversially discussed for a long time. However, little is known about the connection between pornographic stimuli and individual (neuronal) processing of attention and memory. Here, the impact and neural underpinnings of pornographic pictures on working memory processes in a sample of subjects with compulsive sexual behaviour was investigated. Therefore, whilst using functional magnetic resonance imaging (fMRI), a letter n-back task with neutral or pornographic pictures in the background was employed in 38 patients and 31 healthy controls. On the behavioural level, patients were slowed down by pornographic material depending on their pornography consumption in the last week, which was reflected by a higher activation in the lingual gyrus. In addition, the lingual gyrus showed a higher functional connectivity to the insula during processing of pornographic stimuli in the patient group. In contrast, healthy subjects showed faster responses when confronted with pornographic pictures only with high cognitive load. Also, patients showed a better memory for pornographic pictures in a surprise recognition task compared to controls, speaking for a higher relevance of pornographic material in the patient group. These findings are in line with the incentive salience theory of addiction, especially the higher functional connectivity to the salience network with the insula as a key hub and the higher lingual activity during processing of pornographic pictures depending on recent pornography consumption.

An Exploratory Study on the Central Nervous Correlates of Sexual Excitation and Sexual Inhibition.

The Sexual Inhibition/Sexual Excitation Scales (SIS/SES) measure sexual excitation and sexual inhibition proneness. We used SIS and SES scores of 62 heterosexual teleiophilic men (Mage 34.3, SD = 9.9) to predict brain activation levels during the presentation of male and female visual sexual stimuli in a magnetic resonance imaging (MRI) scanner. Statistical analyses revealed significant correlations. SES and SIS1 scores were positively associated with brain activation in various brain regions during the presentation of both male and female stimuli. SIS2 turned out to be a weaker predictor of brain activation, still revealing one significant correlation in the right lateral orbitofrontal cortex. Significant regions for SES and SIS1 were, among others, primary and supplementary motor areas, the caudate nucleus, the dorsal anterior cingulate cortex, anterior insula, and prefrontal areas. Our study can be seen as an exploratory investigation of SIS and SES with means of functional brain imaging. The results provide a promising contribution to the assertion of neurophysiological systems of sexual inhibition and excitation proneness.

Pericardial adipose tissue and the metabolic syndrome is increased in patients with chronic major depressive disorder compared to acute depression and controls.

OBJECTIVE: Major depressive disorder (MDD) is associated with an estimated fourfold risk for premature death, largely attributed to cardiovascular disorders. Pericardial adipose tissue (PAT), a fat compartment surrounding the heart, has been implicated in the development of coronary artery disease. An unanswered question is whether people with chronic MDD are more likely to have elevated PAT volumes versus acute MDD and controls (CTRL). METHODS: The study group consists of sixteen patients with chronic MDD, thirty-four patients with acute MDD, and twenty-five CTRL. PAT and adrenal gland volume were measured by magnetic resonance tomography. Additional measures comprised factors of the metabolic syndrome, cortisol, relative insulin resistance, and pro-inflammatory cytokines (interleukin-6; IL-6 and tumor necrosis factor-α, TNF-α). RESULTS: PAT volumes were significantly increased in patients with chronic MDD>patients with acute MDD>CTRL. Adrenal gland volume was slightly enlarged in patients with chronic MDD>acute MDD>CTRL, although this difference failed to reach significance. The PAT volume was correlated with adrenal gland volume, and cortisol concentrations were correlated with depression severity, measured by BDI-2 and MADRS. Group differences were found concerning the rate of the metabolic syndrome, being most frequent in chronic MDD>acute MDD>CTRL. Further findings comprised increased fasting cortisol, increased TNF-α concentration, and decreased physical activity level in MDD compared to CTRL. CONCLUSION: Our results extend the existing literature in demonstrating that patients with chronic MDD have the highest risk for developing cardiovascular disorders, indicated by the highest PAT volume and prevalence of metabolic syndrome. The correlation of PAT with adrenal gland volume underscores the role of the hypothalamus-pituitary-adrenal system as mediator for body-composition changes. Metabolic monitoring, health advices and motivation for the improvement of physical fitness may be recommended in depressed patients, in particular in chronic depression.

Gray matter anomalies in pedophiles with and without a history of child sexual offending.

Pedophilia is a psychiatric disorder that is inter-related with but distinct from child sexual offending (CSO). Neural alterations reportedly contribute to both pedophilia and CSO, but until now, no study has distinguished the brain structural anomalies associated with pedophilia from those specifically associated with CSO in pedophilic men. Using high-resolution T1-weighted brain images and voxel-based morphometry, we analyzed the gray matter (GM) volume of the following 219 men recruited at four acquisition sites in Germany: 58 pedophiles with a history of CSO, 60 pedophiles without any history of CSO and 101 non-pedophilic, non-offending controls to control for the effects of age, education level, verbal IQ, sexual orientation and the acquisition site. Although there were no differences in the relative GM volume of the brain specifically associated with pedophilia, statistical parametric maps revealed a highly significant and CSO-related pattern of above vs below the 'normal' GM volume in the right temporal pole, with non-offending pedophiles exhibiting larger volumes than offending pedophiles. Moreover, regression analysis revealed that the lower GM volume of the dorsomedial prefrontal or anterior cingulate cortex was associated with a higher risk of re-offending in pedophilic child molesters. We believe our data provide the first evidence that CSO in pedophilia rather than pedophilia alone is associated with GM anomalies and thus shed new light on the results of previous studies on this topic. These results indicate the need for new neurobehavioral theories on pedophilia and CSO and may be potentially useful for treatment or prevention approaches that aim to reduce the risk of (re)offending in pedophilia.

Effects of acute prolactin manipulation on sexual drive and function in males.

The neuroendocrine response to sexual activity in humans is characterized by a pronounced orgasm-dependent increase of plasma levels of prolactin. In contrast to the well-known inhibitory effects of chronic hyperprolactinemia on sexual drive and function, the impact of acute prolactin alterations on human sexual physiology is unknown. Therefore, this study was designed to investigate the effects of acute manipulation of plasma prolactin on sexual behavior. Ten healthy males participated in a single-blind, placebo-controlled, balanced cross-over design. Prolactin levels were pharmacologically increased to high levels (protirelin, 50 micro g i.v.) or reduced to low physiological concentrations (cabergoline, 0.5 mg p.o.). Sexual arousal and orgasm were then induced by an erotic film and masturbation. In addition to continuous neuroendocrine and cardiovascular recordings, the quality and intensity of the acute sexual drive, arousal, orgasm and refractory period were assessed by extensive psychometric measures. Administration of cabergoline decreased prolactin levels and significantly enhanced all parameters of sexual drive (P<0.05), function (P<0.01) and positive perception of the refractory period (P<0.01). Administration of protirelin increased prolactin concentrations and produced small, but not significant reductions of sexual parameters. The sexual effects observed from cabergoline were completely abrogated by coadministration of protirelin. Although different pharmacological sites of action of prolactin-altering drugs have to be considered, these data demonstrate that acute changes in prolactin plasma levels may be one factor modulating sexual drive and function. Therefore, besides a neuroendocrine reproductive reflex, a post-orgasmic prolactin increase may represent one factor modulating central nervous system centers controlling sexual drive and behavior. These findings may offer a new pharmacological approach for the treatment of sexual disorders.

Specificity of the neuroendocrine response to orgasm during sexual arousal in men.

We have demonstrated that sexual activity produces transient sympathoadrenal activation and a pronounced, long-lasting increase in prolactin in men and women. However, by analyzing endocrine alterations at 10-min intervals, a precise assignment of these changes to the pre-, peri- and postorgasmic periods was not possible. Thus, the current study aimed to accurately differentiate the endocrine response to sexual arousal and orgasm in men using an automatic blood collection technique with 2-min sampling intervals. Blood was drawn continuously before, during and after orgasm over a total period of 40 min in 10 healthy subjects and were compared with samples obtained under a control condition. Sexual activity induced transient increases of plasma epinephrine and norepinephrine levels during orgasm with a rapid decline thereafter. In contrast, prolactin levels increased immediately after orgasm and remained elevated throughout the experiment. Although oxytocin was acutely increased after orgasm, these changes were not consistent and did not reach statistical significance. Vasopressin, LH, FSH and testosterone plasma concentrations remained unaltered during sexual arousal and orgasm. These data confirm that prolactin is secreted after orgasm and, compared with oxytocin, seems to represent a more reliable and sustained marker for orgasm in man. The results further reinforce a role for prolactin either as a neuroendocrine reproductive reflex or as a feedback mechanism modulating dopaminergic systems in the central nervous system that are responsible for appetitive behavior.

Cognitive and partner-related factors in rapid ejaculation: differences between dysfunctional and functional men.

Despite the high prevalence of rapid ejaculation in community samples, there is still a paucity of data on cognitive and other relevant aspects of the subjective experience of premature ejaculation (PE) patients and their functional counterparts. Therefore, the main aim of this study was to expand our understanding of the complex nature of rapid ejaculation disorders by providing a detailed characterization of ejaculatory patterns, behavioral aspects, cognitive, and partner-related factors in a sample of unselected PE patients compared to a group of functional men. To explore the areas that might differentiate PE men from their sexually functional counterparts, a multidimensional self-administered questionnaire, the PEQuest, was created. This 36-item instrument addresses a number of domains relevant to ejaculatory function and dysfunction such as ejaculatory latencies and ejaculatory control, cognitions and feelings during sexual intercourse, factors interfering with ejaculatory control, techniques to delay ejaculation, and partnership factors. A total of 45 PE patients (mean age: 41.8 years) and 72 non-patients (mean age: 37.1 years) were included. The results show significant group differences in the majority of PEQuest domains. In the functional group, an average intravaginal latency time of 12.8 min (median: 10 min) was reported compared to 3.7 min (median: 2 min) in the patient group with 87% of PE patients ejaculating within 2 min and 100% within 5 min after penetration. In their subjective experience in sexual situations, PE patients were totally preoccupied with thoughts about controlling their orgasm, with the anxious anticipation of a possible failure, and thoughts about keeping their erection while the inner experience of functional men is focused on sexual arousal and sexual satisfaction. The factors that maximally impede the control of ejaculation are similar for both groups, but functional men normally succeed in adapting their sexual behavior to these factors whereas PE men fail in their efforts. Regarding partner-related factors, PE patients felt less secure and experienced with respect to female sexuality than their functional counterparts, and more often reported a discrepancy between their own limited experience and the more extensive sexual experience of their partner. In conclusion, a number of salient differences in ejaculatory behavior, cognitive-affective patterns, and partner-related factors between PE patients and functional men could be delineated in this study, indicating that chronic rapid ejaculation is a serious disorder with a profound impact on the man's life and his partnership.