Major depression and atrial natriuretic peptide: The role of adverse childhood experiences.

Atrial natriuretic peptide (ANP) exerts anxiolytic effects in animals and humans. Patients with anxiety, trauma-associated and depressive disorders exhibit lower ANP plasma levels compared to healthy individuals. However, the role of ANP in patients with major depressive disorder (MDD) with and without concomitant adverse childhood experiences (ACE) and in healthy individuals with and without ACE is not clear. We recruited a total of 93 women: 23 women with MDD and ACE, 24 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD, and 24 healthy women without ACE. ANP plasma levels were measured with a radioimmunoassay. The four groups did not differ in demographic and clinical variables. We found a positive correlation between age and plasma levels of ANP (r = .39; p < .001). After controlling for age, there was no significant main effect of MDD or ACE on ANP plasma levels, but a significant interaction between MDD and ACE such that ACE was associated with reduced basal ANP levels in the absence of MDD. We assume that low plasma ANP might be a consequence of ACE in the absence of current psychopathology. Therefore, future studies are needed to replicate our findings and to characterize the influencing factors of ACE on ANP more comprehensively, for example by including a comprehensive trauma and comorbidity anamnesis as well as cardiovascular state and risk factors.

Early detection and integrated care for adolescents and young adults with psychotic disorders: the ACCESS III study.

OBJECTIVE: The objective of the study was to investigate whether a combined intervention composed of early detection plus integrated care (EDIC) enhances outcomes in patients with early psychosis compared to standard care (SC). METHODS: ACCESS III is a prospective non-randomized historical control design 1-year study examining the efficacy of EDIC (n = 120) vs. SC (n = 105) in patients aged 12-29 years. Primary outcome was the rate of ≥6 months combined symptomatic and functional remission. Additional outcomes comprised the reduction of DUP and course of psychopathology, functioning, quality of life, and satisfaction with care. RESULTS: In observed cases, 48.9% in the EDIC and 15.2% in the SC group reached the primary endpoint. Remission was predicted by EDIC (OR = 6.8, CI: 3.15-14.53, P < 0.001); younger age predicted non-remission (OR = 1.1, CI: 1.01-1.19, P = 0.038). Linear regressions indicated a reduction of DUP in EDIC (P < 0.001), but not in SC (P = 0.41). MMRMs showed significantly larger improvements in PANSS positive (P < 0.001) and GAF (P < 0.01) scores in EDIC vs. SC, and in EDIC over time in CGI-Severity (P < 0.001) and numerically in Q-LES-Q-18 (P = 0.052). CONCLUSIONS: EDIC lead to significantly higher proportions of patients achieving combined remission. Moderating variables included a reduction of DUP and EDIC, offering psychotherapeutic interventions.

[Staphylococcal Scalded Skin Syndrome in a Very Low Birth Weight Premature Infant]. / Staphylococcal Scalded Skin Syndrome bei einem sehr unreifen Frühgeborenen.

INTRODUCTION: Staphylococcal scalded skin syndrome (SSSS) was often endemic in the past but is nowadays rare. The hematogeneous spread of exfoliative toxins A (ETA) or B (ETB) produced by specific Staphylococcus aureus strains causes a scald-like eruption with disseminated bullous lesions. CASE REPORT: A perioral impetigo lesion occurred on day 14 of life in a preterm male infant (1,065 g, 30 weeks of gestational age). Empiric antibiotic therapy with cefotaxime and vancomycin was given for 6 days and led to complete resolution. A Staphylococcus aureus strain was isolated. After a symptom-free interval a relapse was noted on day 26 of life. Despite restarting the antibiotic therapy immediately the initial lesion expanded, and disseminated flaccid blisters on an erythematous base appeared within a few hours. On histological examination the cleavage was in the level of the granular layer. There was no mucosal involvement, and the Nikolsky I sign was positive. The antibiotic therapy was changed to a combination of cefotaxime, flucloxacillin and clindamycin which rapidly stopped progression of the exfoliation. Supportive therapy included adequate analgesia, parenteral rehydration, and application of local antiseptics. The preterm infant completely recovered. In the primary lesion an ETA-producing Staphylococcus aureus strain was isolated. Nasal microtrauma by a nasogastric tube was assumed to have caused the fulminant disease. At the same time, no other Staphylococcus aureus infections were seen in our Department of Neonatology. DISCUSSION: According to the literature, the incidence of SSSS is higher in premature infants and newborns than in older children. Possible causes include lower antibody levels against exfoliative toxins and renal immaturity. Rapid diagnosis and immediate appropriate antibiotic therapy are essential to prevent secondary infection, dehydration with electrolyte disturbance, death, and endemic spread.

Does Pregnenolone Enhance Exposure Therapy in Obsessive-Compulsive Disorder? - A Pilot, Interim Report of a Randomized, Placebo-Controlled, Double-Blind Study.

Exposure therapy is an effective cognitive-behavioral treatment for patients with obsessive-compulsive disorder (OCD). However, a further amelioration of symptoms by additional drugs that enhance extinction learning is desirable. An interesting candidate is pregnenolone, which positively modulates NMDA and GABAA receptors in preclinical studies and influences amygdala and prefrontal activity in humans. We present pilot data showing high acceptance and good tolerability of pregnenolone given 2 h before exposure sessions in OCD patients. As per our interim analyses, exposure treatment resulted in significantly improved main outcome parameters, but no effects of pregnenolone vs. placebo pretreatment were detectable thus far.

[The significance of depot medication in the long-term-treatment of schizophrenia]. / Stellenwert von Depotformulierungen in der Langzeittherapie der Schizophrenie.

Relapse prevention in schizophrenia is a key aim in therapy. However, it is estimated that approximately 75% of patients with schizophrenia relapse within five years. Each relapse might worsen the disease and increase the risk of psychosocial and work-related disadvantages. A continuous long-term therapy is able to reduce this risk, but medical non-adherence, which is influenced by numerous factors, is a limitation. Naturalistic studies show that depot-antipsychotics compared with oral antipsychotics lead consistently to a better outcome, for example by reducing relapse rates or hospitalisation. Numerous meta-analyses of randomised controlled trials comparing oral versus depot-antipsychotics also show this advantages. However these results are not consistent in all meta-analyses. Results of controlled studies do not appropriately reflect the reality of daily practice. The advantages of depot-antipsychotics are shown more distinctly in naturalistic studies. The following review reflects the current therapy of schizophrenia and discusses adequately a broad application of depot-antipsychotics based on existing data. In addition, concerns and prejudices of physicians and patients against antipsychotic long-term therapy and depot-formulation are discussed and a recommendation is provided.

Intraperitoneal atrial natriuretic peptide attenuates anxiety-related behaviour during alcohol withdrawal in mice.

Converging evidence from both preclinical and clinical studies suggests atrial natriuretic peptide (ANP) as a potential target for treatment of alcohol withdrawal and dependence. Since ANP tightly interacts with hypothalamic-pituitary-adrenocortical (HPA) axis activity, especially the modulation of stress-related anxiety during alcohol withdrawal might mediate these effects. We have now evaluated the anxiolytic activity of intraperitoneal ANP application during alcohol withdrawal in alcohol-habituated mice (C57/Bl6J). Anxiety related behaviour was attenuated during ethanol withdrawal following application of ANP (60 µg/kg) vs. saline. Our results support that anxiolytic effects of ANP mediate ANP-related gene effects with clinical data on withdrawal symptomatology.

[Expression, identification and experience of emotions in mental diseases. An overview]. / Ausdruck, Erkennen und Erleben von Emotion bei psychischen Störungen. Eine Übersicht.

Several studies in clinical neuroscience have focused on the analysis of expression of emotions, identification of emotions and experience of emotions. These empirical studies produced certain insights into emotional competency in different mental diseases, most of them in schizophrenia. The current article gives a description of the scientific data about alterations in emotional competency in several mental diseases (e.g. schizophrenia, depression, bipolar and borderline diseases) and links the data, if possible, with clinical relevance with a special focus on emotional competency in prodromal schizophrenia.

Association between cortisol awakening response and memory function in major depression.

BACKGROUND: While impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in each group. METHOD: We examined 21 patients with major depression without medication, 20 depressed patients on antidepressant treatment, and 41 age-, sex- and education-matched healthy subjects. We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured CAR on two consecutive days. RESULTS: Patient groups did not differ in severity of depression. We found a significant effect of group (p = 0.03) for CAR. Unmedicated patients exhibited a greater CAR compared with medicated patients (p = 0.04) with no differences between patient groups and HC. We found a significant effect of group for verbal (p = 0.03) and non-verbal memory (p = 0.04). Unmedicated patients performed worse compared with medicated patients and HC in both memory domains. Medicated patients and HC did not differ. Regression analyses revealed a negative association between CAR and memory function in depressed patients, but not in HC. CONCLUSIONS: While in unmedicated depressed patients the magnitude of CAR is associated with impaired memory, medicated patients showed a smaller CAR and unimpaired cognitive function compared with HC. Our findings are compatible with the idea that antidepressants reduce CAR and partially restore memory function even if depressive psychopathology is still present.

Biomarkers in development of psychotropic drugs.

Biomarkers have been receiving increasing attention, especially in the field of psychiatry In contrast to the availability of potent therapeutic tools including pharmacotherapy, psychotherapy, and biological therapies, unmet needs remain in terms of onset of action, stability of response, and further improvement of the clinical course. Biomarkers are objectively measured characteristics which serve as indicators of the causes of illnesses, their clinical course, and modification by treatment. There exist a variety of markers: laboratory markers which comprise the determination of genetic and epigenetic markers, neurotransmitters, hormones, cytokines, neuropeptides, enzymes, and others as single measures; electrophysiological markers which usually comprise electroencephalography (EEG) measures, and in particular sleep EEG and evoked potentials, magnetic encephalography, electrocardiogram, facial electromyography, skin conductance, and others; brain imaging techniques such as cranial computed tomography, magnetic resonance imaging, functional MRI, magnetic resonance spectroscopy, positron emission tomography, and single photon emission computed tomography; and behavioral approaches such as cue exposure and challenge tests which can be used to induce especially emotional processes in anxiety and depression. Examples for each of these domains are provided in this review. With a view to developing more individually tailored therapeutic strategies, the characterization of patients and the courses of different types of treatment will become even more important in the future.

Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate.

In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.

Cigarette craving increases after a psychosocial stress test and is related to cortisol stress response but not to dependence scores in daily smokers.

Stress is known to induce cigarette craving in smokers, but the underlying mechanisms are widely unknown. We investigated how dependence severity, smoking habits and stress-induced cortisol secretion are associated with increased cigarette craving after a standardised laboratory stressor. Hundred and six healthy participants (50 men, age 18-19 years) underwent a standardised public speaking stress task. In all, 35 smoked daily (DS), 13 smoked occasionally (OS), and 58 never smoked (NS). Smoking was unrestricted until 2 h before stress onset. Plasma cortisol was measured before and up to 95 min after the stressor. All current smokers rated intensity of cigarette craving immediately before and immediately after the stressor using the Brief Questionnaire of Smoking Urges (BQSU). Cortisol levels significantly increased in response to stress in all groups. The magnitude of this stress response was significantly lower in DS compared with OS and NS but did not differ between OS and NS. Baseline BQSU scores were significantly higher in DS than OS. BQSU scores increased significantly during the stress period and were positively correlated to the cortisol response in the DS but were unrelated to their nicotine dependence scores. In OS, no change in cigarette craving could be observed. In daily smokers, cigarette craving is increased after compared with before stress exposure and is related to the magnitude of cortisol stress response rather than to severity of nicotine dependence. This result supports, but does not prove, the concept that hypothalamus-pituitary-adrenal stimulation is one of the mechanisms how stress can elicit cigarette craving.

Coherent contributions to isospin mixing in the mirror pair 67As and 67Se.

Isospin symmetry breaking has been investigated in mass A=67 mirror nuclei through the experimental determination of the E1 strengths of analog electromagnetic transitions. Lifetimes of excited states have been measured in (67)Se and (67)As with the centroid shift method. Through the comparison of the B(E1) strengths of the mirror 9/2(+)-->7/2(-) transitions, the isovector and the isoscalar components of the electromagnetic transition amplitude were extracted. The presence of a large isoscalar component provides evidence for coherent contributions to isospin mixing, probably involving the isovector giant monopole resonance.

[Persistent pharyngeocutaneous fistula after transcervical resection of a diverticulum of the hypopharynx]. / Persistierende pharyngokutane Fistel nach Resektion eines Hypopharynxdivertikels.

CASE: A 26-year-old white male patient had undergone resection of a diverticulum of the hypopharynx and myotomy of the cricopharyngeal muscle elsewhere. A transcervical approach had been chosen owing to the presence of an arteria lusoria and the associated risk of vessel injury. The patient had subsequently had recurrent fistulas through the skin incision, which had not resolved despite four further operations. He presented in our department with significant weight loss and persistent retrosternal pain. Esophageal manometry revealed that resting muscle tone in the upper esophageal sphincter was still significantly elevated. Assuming that the earlier myotomy had not been completely successful, we decided to complete this operation as revision surgery. The pharynx was closed with a running suture using the Conley technique. The fistula healed, and there were no further recurrences. CONCLUSION: Complete and careful dissection of all muscle fibers back to the mucosa is essential, as well as complete removal of the diverticulum if this operation is to be successful when performed by the transcutaneous approach. Recurrent diverticula are not the only possible complication; persistent pharyngeocutaneous fistulas can also arise.

Gender-specific effects in the treatment of acute schizophrenia with risperidone.

INTRODUCTION: Gender-related effects play a role in antipsychotic treatment. We recently published a study demonstrating the efficacy of the atypical antipsychotic risperidone in the management of acute psychotic decompensations. We have now reanalysed the clinical data to assess the effects of gender on treatment and outcome. METHODS: High-dose treatment with risperidone (6-8 mg/d) was administered to 23 male and 25 female acutely psychotic schizophrenic admissions. PANSS- and CGI-ratings were obtained for four weeks. RESULTS: Males and females did not differ significantly in age, duration of treatment, dose of risperidone or clinical ratings. Females were treated with a significantly higher maximum dose of risperidone per kg body-weight. Significantly more females (n=14) than males (n=8) discontinued the use of risperidone. CONCLUSION: Although the reasons for the lower drop-out rate in males are not clear, gender differences in the clinical presentation may have contributed. High-dose treatment with risperidone may be more beneficial in males for the treatment of acute schizophrenia.

A neuroendocrinological hypothesis on gender effects of naltrexone in relapse prevention treatment.

The ability of naltrexone to increase hypothalamo-pituitary-adrenocortical (HPA)-axis activity was recently reported to be associated with its effects on the reduction of craving for alcohol. We now present data showing naltrexone to be more efficacious in female alcoholics. Since HPA-axis might be interpreted as a key mechanism of action that could explain the observed gender differences in the abstinence maintenance treatment of alcohol addiction.

[Airway management for one-lung ventilation]. / Atemwegsmanagement bei der Ein-Lungen-Ventilation.

The progress in sophisticated and complex operating methods for intrathoracic procedures demands reliable lung separation with the possibility of one-lung ventilation. Patients with thoracic traumas and pulmonary emergencies can confront any anaesthesiologist with the need for lung separating procedures. This review describes the contemporary procedures for lung separation. The special aspects of difficult airway management during one-lung ventilation and the indications for one-lung ventilation are described in detail. The pathophysiological changes during one-lung ventilation and strategies to avoid hypoxemia and to preserve adequate oxygenation are discussed.

Neuroendocrine pathways of addictive behaviour.

Alcohol intake is known to modulate plasma concentrations of neuroendocrine peptides. However, recent results suggest that the endocrine system may not only respond passively to alcohol intake but that, vice versa, it also actively modulates alcohol intake behaviour. The most coherent body of data concerns the hypothalamo-pituitary-adrenocortical (HPA) axis, with low corticotrophin-releasing hormone (CRH) being associated with more intense craving and increased probability of relapse after acute detoxification. Leptin, beta-endorphin and atrial natriuretic peptide (ANP), which indirectly regulate the HPA system, also may modulate the intensity of craving or the intensity of the alcohol withdrawal syndrome. Although most of the currently available data demonstrate association rather than causality between neuroendocrine changes and alcohol-related behaviours, they do provide testable hypotheses and open up perspectives of treating alcohol dependence via manipulation of the neuroendocrine axis.