Serum BDNF levels correlate with regional cortical thickness in minor depression: a pilot study.

Serum brain-derived neurotrophic factor (BDNF) reflects state changes in mood disorders. But its relation to brain changes in depression has rarely been investigated in humans. We assessed the association between serum BDNF, cortical thickness, or gray matter volume in 20 subjects with a minor depressive episode and 40 matched healthy subjects. Serum BDNF positively correlated with cortical thickness and volume in multiple brain regions in the minor depression group: the bilateral medial orbitofrontal cortex and rostral anterior cingulate cortex, left insula, and cingulum, right superior frontal gyrus, and other regions-regions typically affected by major depression. Interestingly, these correlations were driven by subjects with first episode depression. There was no significant association between these imaging parameters and serum BDNF in the healthy control group. Interaction analyses supported this finding. Our findings point to a specific association between serum BDNF and magnetic resonance imaging parameters in first-episode minor depression in a region- and condition-dependent manner. A positive correlation between serum BDNF and structural gray matter estimates was most consistently observed for cortical thickness. We discuss why cortical thickness should be preferred to volumetric estimates for such analyses in future studies. Results of our pilot study have to be proven in future larger-scale studies yielding higher statistical power.

The age-dependent relationship between resting heart rate variability and functional brain connectivity.

Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain - mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0 ±â€¯4.2 years, 119 middle-aged: 46.3 ±â€¯6.2 years, 129 older: 66.9 ±â€¯4.7 years), gray matter volume (GMV, voxel-based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed-based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV-related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole-brain functional connectivity analyses, we found an age-dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed-based functional connectivity analysis using the vmPFC cluster revealed an HRV-related cortico-cerebellar network in younger but not in middle-aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain-body interactions and their changes over the lifespan.

The role of microRNAs in Anopheles biology-an emerging research field.

In the last years, microRNAs (miRNAs) have been established as important post-transcriptional regulators of critical physiological processes in animals and plants. Here, we summarize what is known about miRNA biosynthesis, expression and function in the malaria vector mosquito Anopheles gambiae with a particular emphasis on the mosquito-parasite interactions. We discuss the important gaps in the current knowledge, including the potential of miRNA manipulation for future vector control strategies.

Investigation of the confounding effects of vasculature and metabolism on computational anatomy studies.

Computational anatomy studies typically use T1-weighted magnetic resonance imaging contrast to look at local differences in cortical thickness or grey matter volume across time or subjects. This type of analysis is a powerful and non-invasive tool to probe anatomical changes associated with neurodevelopment, aging, disease or experience-induced plasticity. However, these comparisons could suffer from biases arising from vascular and metabolic subject- or time-dependent differences. Differences in blood flow and volume could be caused by vasodilation or differences in vascular density, and result in a larger signal contribution of the blood compartment within grey matter voxels. Metabolic changes could lead to differences in dissolved oxygen in brain tissue, leading to T1 shortening. Here, we analyze T1 maps and T1-weighted images acquired during different breathing conditions (ambient air, hypercapnia (increased CO2) and hyperoxia (increased O2)) to evaluate the effect size that can be expected from changes in blood flow, volume and dissolved O2 concentration in computational anatomy studies. Results show that increased blood volume from vasodilation during hypercapnia is associated with an overestimation of cortical thickness (1.85%) and grey matter volume (3.32%), and that both changes in O2 concentration and blood volume lead to changes in the T1 value of tissue. These results should be taken into consideration when interpreting existing morphometry studies and in future study design. Furthermore, this study highlights the overlap in structural and physiological MRI, which are conventionally interpreted as two independent modalities.

Getting depression clinical practice guidelines right: time for change?

OBJECTIVE: As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013;128(Suppl. 444):2-15; and 'It's time we managed depression: The emerging role of chronobiology' Malhi et al. Acta Psychiatr Scand 2013;128(Suppl. 444):1] examining chronobiology in the context of depression, this article examines recent western clinical practice guidelines (CPGs) for the treatment of depression with respect to the recommendations they make, in particular as regards chronobiological treatments, and briefly considers the implications of their methodology and approach. METHOD: Five international treatment guidelines, which had been published in the past 5 years, were identified, representing North American and European views. Chosen guidelines were reviewed by the authors, and the relevant recommendations were distributed for discussion and subsequent synthesis. RESULTS: Most current guidelines do not address chronobiology in detail. Chronotherapeutic recommendations are tentative, although agomelatine is considered as an option for major depression and bright light therapy for seasonal affective disorder. Sleep deprivation is not routinely recommended. CONCLUSION: Recommendations are limited by the lack of reliable therapeutic markers for chronotherapeutics. Current evidence supports use of light therapy in seasonal depression, but in non-seasonal depression there is insufficient evidence to support reliance on chronotherapeutics over existing treatment modalities.

Psychological management of unipolar depression.

OBJECTIVE: To be used in conjunction with 'Pharmacological management of unipolar depression' [Malhi et al. Acta Psychiatr Scand 2013;127(Suppl. 443):6-23] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of psychological treatments in depression derived from a literature review. METHOD: Medical databases including MEDLINE and PubMed were searched for pertinent literature, with an emphasis on recent publications. RESULTS: Structured psychological treatments such as cognitive behaviour therapy and interpersonal therapy (IPT) have a robust evidence base for efficacy in treating depression, even in severe cases of depression. However, they may not offer benefit as quickly as antidepressants, and maximal efficacy requires well-trained and experienced therapists. These therapies are effective across the lifespan and may be preferred where it is desired to avoid pharmacotherapy. In some instances, combination with pharmacotherapy may enhance outcome. Psychological therapy may have more enduring protective effects than medication and be effective in relapse prevention. Newer structured psychological therapies such as mindfulness-based cognitive therapy and acceptance and commitment therapy lack an extensive outcome literature, but the few published studies yielding positive outcomes suggest they should be considered options for treatment. CONCLUSION: Cognitive behaviour therapy and IPT can be effective in alleviating acute depression for all levels of severity and in maintaining improvement. Psychological treatments for depression have demonstrated efficacy across the lifespan and may present a preferred treatment option in some groups, for example, children and adolescents and women who are pregnant or postnatal.

Clinical practice recommendations for depression.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.

Clinical practice recommendations for bipolar disorder.

OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.

[Relevance of a performance capacity model for uniform and standardized performance diagnostics]. / Die Relevanz eines Leistungsfähigkeitsmodells für eine einheitliche und standardisierte Leistungsdiagnostik.

To obtain a standardized method for performance capacity assessment in social medicine reference to a generally accepted model of performance capacity is necessary. Further, such a model enables description of the effects of chronic disease on performance capacity. This article describes how the term "performance capacity" can be reduced to operational basal parameters by a hierarchic breakdown, with the domain "physical performance capacity" having the most complex structure. Furthermore the construction of a graduation according to work-load taxonomies for every parameter is shown. The collection of data on the level of basal parameters is essential to assess the concrete performance capacity. To apply the model as a basis for estimating the effects of chronic disease, graduated disease features have to be created. The benefit of the procedure described lies in increased transparency of the decision process. Hence, performance capacity assessment will gain reliability and objectivity.

Social phobia in the Australian National Survey of Mental Health and Well-Being (NSMHWB).

BACKGROUND: This article reports data on social phobia from the first large scale Australian epidemiological study. Prevalence rates, demographic correlates and co-morbidity in the sample that met criteria for social phobia are reported and gender differences examined. METHOD: Data were obtained from a stratified sample of 10641 participants as part of the Australian National Survey of Mental Health and Well-Being (NSMHWB). A modified version of the Composite International Diagnostic Interview (CIDI) was used to determine the presence of social phobia, as well as other DSM-IV anxiety, affective and substance use disorders. The interview also screened for the presence of nine ICD-10 personality disorders, including anxious personality disorder, the equivalent of DSM-IV avoidant personality disorder (APD). RESULTS: The estimated 12 month prevalence of social phobia was 2.3%, lower than rates reported in several recent nationally representative epidemiological surveys and closer to those reported in the Epidemiological Catchment Area study (ECA) and other DSM-III studies. Considerable co-morbidity was identified. Data indicated that the co-morbidity with depression and alcohol abuse and dependence were generally subsequent to onset of social phobia and that the additional diagnosis of APD was associated with a greater burden of affective disorder. Social phobia most often preceded major depression, alcohol abuse and generalized anxiety disorder. CONCLUSIONS: Social phobia is a highly prevalent, highly co-morbid disorder in the Australian community. Individuals with social phobia who also screen positively for APD appear to be at greater risk of co-morbidity with all surveyed disorders except alcohol abuse or dependence.

[Open heart surgery with extracorporeal circulation during pregnancy]. / Szívmútét extracorporalis keringéssel és terhesség.

The incidence of heart disease in pregnancy has been gradually falling during the last three decades. Cardiopathy still remains a prominent cause of maternal and fetal morbidity and mortality. Most patients know about their heart disease long before conception, even though the potential risk factors of deteriorating cardiac function during pregnancy are generally not emphasized. These women when pregnant may develop heart failure due to the increased cardiorespiratory requirements. When medical therapy proves insufficient heart surgery becomes mandatory to save the patient's life. The pregnant state is not optimal for cardiac surgery as the principle interest of the mother and the fetus is different. We report on two pregnant patients who underwent unavoidable heart surgery with cardiopulmonary bypass and review the literature regarding the optimal management of open-heart operation in pregnancy aiming to decrease the feto-maternal mortality. The successful outcome of the cardiac surgery on pregnant women is determined by the severity of the preexisting disease, the surgical techniques, and the circumstances of the cardiopulmonary bypass. The best possible results can be achieved by providing preconceptional counseling for the cardiopathic patients regarding the relation between the preexisting risk factors and the adverse maternal and neonatal outcome. When heart surgery is mandatory in pregnancy the careful technical precautions and the continuous cardiotocography help to minimize fetal complications during the cardiopulmonary bypass (CPB).

The role of preoperative brachytherapy as an adjunct to surgery and postoperative radiotherapy in the treatment of stage I endometrial carcinoma.

PURPOSE: Between 1978 and 1993, 817 cases of endometrial carcinoma were treated with simple hysterectomy with bilateral salpingo-oophorectomy. Five hundred and twenty-six cases had preoperative brachytherapy (Preo), and 291 cases underwent surgery without preoperative radiotherapy (Nopre). The aim of the study was to compare disease-free survival of the two groups. METHODS AND MATERIALS: Survival comparison of the two groups was controlled for postoperative treatment type, according to stage, histological type, degree of differentiation, depth of myometrial invasion and age. The life-table method was used for survival analysis. Cumulative disease-free survival probabilities were calculated as a function of the proportion of normal remaining life elapsed from the time of diagnosis. RESULTS: Five-year disease-free survival of patients with and without preoperative brachytherapy in stage IA, IB and IC was 93 and 93.6%, 93 and 94%, and 80 and 65%, respectively. In well differentiated tumors and poorly differentiated tumors, there was no difference in disease-free survival between patients with and without preoperative brachytherapy. Patients with moderately differentiated tumor treated with preoperative brachytherapy had significantly better disease-free survival than those without preoperative radiotherapy, however, this was confounded by uneven distribution of invasion depth. CONCLUSION: Preoperative brachytherapy plays a limited role in the treatment of early stage endometrial carcinoma.

Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.

[The diagnostic report as an aid for determination of referral to inpatient rehabilitation]. / Der Befundbericht als Entscheidungshilfe für den Zugang zur stationären Rehabilitation.

The investigation analyzes some 206 standardized diagnostic reports submitted by office-practice physicians, demonstrating the role of diagnostic reports in determining access to medical rehabilitation. It is found that the practitioners added no further information about their patients' health status in half of the diagnostic reports given, and no further medical documents in one third. On the other hand, diagnostic reports that included details about the patients' ability to work as well as information about previous treatments resulted to a greater degree in direct award of a medical rehabilitation measure.

Avoidant personality disorder: empirical support for DSM-IV revisions.

This article attempts to answer three questions about avoidant personality disorder (AVPD): (a) Is it a coherent unidimensional entity, (b) Is the requirement that four or more of the criteria be met in order to make the diagnosis justified, and (c) Are the changes made in DSM-IV supported? Four hundred thirty-four people presenting for treatment for anxiety were assessed with the Personality Disorder Examination. The criteria met were factor analyzed to indicate the unidimensionality of the diagnosis. Measures of internal consistency were calculated to validate the instruction to diagnose AVPD if four or more criteria were observed. Confirmatory factor analysis showed that a single factor was the best fit to the observed pattern of relationships between the seven AVPD criteria. The internal consistency of the seven criteria was moderate (Cronbach's alpha = .76) with a median intercriterion correlation of .29. The data provided good support for the hypothesis that the seven DSM-III-R AVPD criteria assess a single dimension. Three of the criteria did not reflect this factor as highly as the remaining four and these three have either been dropped in DSM-IV or substantially revised.

[Surgical management of masculine trassexualism]. / Transsexualismus masculinus mütéte.

The authors report on the first Hungarian case of sex-transforming operation. They present details of the social history and management of their case leading up the decision for surgery. Preoperative assessment and medication, operation technique and postoperative care are also described in detail. The case report highlights the difficult ethical and legal issues which have to be considered when such surgery is requested. Following a series of in-depth psychological, gynaecological, urological and forensic consultations that had been carried out in order to be convinced about the patients's determination for undergoing sex-transforming operation, the authors were granted legal and professional license by the Hungarian Medical Research Council to carry out the procedure. Two years after the operation, the patient commented on her full satisfaction with the care he had received.

A management approach to anxiety.

A planned, structured and systematic approach is likely to optimise the management of anxiety disorders. Accurate diagnosis is essential to select the specific cognitive behavioural and pharmacological treatments available for certain anxiety disorders. However, many effective management strategies can be applied in general practice, using a prioritised, problem focused approach.

Simultaneous multipolar radiofrequency ablation in the monopolar mode increases lesion size.

Delivery of radiofrequency (RF) energy from the distal tip of electrophysiology catheters produces lesions that may be too small to ablate arrhythmogenic sites during a single application of RF energy. To produce larger lesions, we delivered RF energy via a quadripolar catheter in which all four electrodes were connected in unipolar fashion. The catheter (Webster Labs) had a 4-mm tip, 2-mm ring electrodes, and 2-mm interelectrode distance. Lesion size was compared using RF energy delivered in a multipolar configuration with that delivered only to the distal tip using fresh bovine ventricular tissue. In vivo, RF lesions were made in dogs using the distal tip as well as all four poles of the same catheter inserted percutaneously. RF energy was delivered using a constant voltage at a frequency of 400 kHz. Preliminary experiments were conducted to determine the maximum power deliverable without coagulation using each electrode configuration. The use of simultaneous multipolar RF ablation produced significantly larger lesions both in vitro and in vivo. The length of the lesion was increased by a factor of approximately 2 in both the in vitro and in vivo experiments. There was a trend toward an increasing depth of the lesion by simultaneously applying RF energy to all four electrodes. Lesion width was significantly increased in the in vivo studies. We concluded that simultaneous multipolar delivery of RF energy produces larger lesions than can be obtained with delivery of RF energy to the distal tip alone. This technique may offer a means of increasing lesion size, leading to a decrease in the number of applications of RF energy necessary for ablation of arrhythmias.

Indications for induction of labour.

Induction of labour is an important prophylactic procedure in the obstetric practice. Two major types of indications developed: induction because of advanced relevant obstetric complication, and the so called elective induction.

Ovarian malignancies in childhood and adolescence.

We retrospectively reviewed all cases of ovarian malignancies during a 10-year period at the Department of Obstetrics and Gynecology, University Medical School of Debrecen, Hungary. The experience with 16 cases: three epithelial tumors, one granulosa cell tumor, 11 germ cell tumors (six dysgerminoma, four teratoma, one endodermal sinus tumor), and one metastatic ovarian cancer is discussed. Malignant ovarian tumors can best be treated with conservative surgery, followed by adjuvant chemotherapy. Survival mainly depends on tumor type and stage at the time of diagnosis.