[Cohort studies in child and adolescent psychiatry]. / Kohortenstudien in der Kinder- und Jugendpsychiatrie.

BACKGROUND: Longitudinal cohort studies with early start and life span perspectives are increasingly recognized as being crucial to uncover developmental trajectories as well as risk and resilience factors of psychiatric disorders. OBJECTIVE: The importance of longitudinal studies is presented and the main findings of the Mannheim study of children at risk (MARS), the adolescent brain cognitive development (ABCD), the pediatric and adolescent health survey (Kinder- und Jugendgesundheitssurvey, KiGGS) and the AIMS longitudinal European autism project (LEAP) cohort studies are described. MATERIAL AND METHODS: A literature search was carried out in MEDLINE. RESULTS: The MARS followed participants with psychosocial and organic risks over more than 30 years starting from birth and showed the importance of early risk factors (prenatal period up to early childhood) for neuropsychosocial development. The ABCD cohort study (start 9-10 years old) underlined the developmental significance of early socioemotional and prenatal risks as well as toxin exposure. The KiGGS cohort followed children and adolescents from age 0-17 years up to the ages of 10-28 years. Main findings underline the importance of the socioeconomic status and gender-specific effects with respect to sensitive periods for the onset and trajectories of psychiatric disorders. The AIMS cohort followed patients with and without autism spectrum disorders aged between 6 and 30 years and first results revealed small effects regarding group differences. Further, cohort studies starting prenatally along with deep phenotyping are warranted to uncover the complex etiology of mental disorders. CONCLUSION: Existing cohort studies on early mental development have shown specific focal points. To identify general and specific risk and resilience factors for psychiatric disorders and to model trajectories, there is a need for multimodal integration of data sets.

Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls.

Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.

The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders.

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.

[Wearables for context-triggered assessment in psychiatry]. / Wearables zum kontextgesteuerten Assessment in der Psychiatrie.

The breathtaking technological progress in the field of mobile computing, smartphones and wearables offers new opportunities for psychiatric research and therapy. Wearables enable not only the objective assessment of psychiatric symptoms in real time and everyday life but using continuous monitoring and analysis of relevant parameters can also define important situations, contexts and timing during which extended assessment strategies and real-life interventions can be implemented. The momentary effect of inner city green space exposure on well-being, motivational behavior feedback and geofencing for the detection of drinking episodes are used as examples to illustrate the core benefits of real-time analyses and feedback from wearables for psychiatric research and therapy.

Anti-Muellerian hormone concentration in bitches with histopathologically diagnosed ovarian tumours and cysts.

Increased concentrations of Anti-Muellerian hormone (AMH) can indicate a granulosa cell tumour as shown in women, mares and cows. To investigate AMH to differentiate canine granulosa cell tumour from other ovarian pathologies, we evaluated the ovaries of 63 bitches. Blood serum samples were collected before surgery for AMH analysis. Ovaries were submitted for histopathological examination. Fourteen bitches showed normal ovaries. These bitches had AMH values between 0.12 and 0.99 ng/ml. In 20 bitches ovarian cysts i.e., follicular cysts (n = 8), corpora lutea cysts (n = 7), subsurface cysts (n = 5) were diagnosed. These dogs had AMH values of 0.11-2.09 ng/ml. Bitches with small luteinized follicular cysts had slightly higher AMH values than those without ovarian alteration. In 29 cases ovarian neoplasms i.e., granulosa cell tumour (n = 9), epithelial tumours (n = 16), dysgerminomas (n = 3) and one sarcoma were identified. Anti-Muellerian hormone values of bitches with an ovarian neoplasm except granulosa cell tumour ranged from 0.18 to 1.18 ng/ml. The AMH values of bitches with granulosa cell tumour ranged from 1.12 to ≤23 ng/ml and were significantly higher (p < .05) than in all of the other bitches. The cut-off of 0.99 ng/ml gave a sensitivity of 100% and a specificity of 94.44% to diagnose granulosa cell tumour. In conclusion, markedly elevated AMH concentrations in bitches are indicative for a granulosa cell tumour. However, negative testing does not rule out the existence of small one. Differentiation of GCT from luteinized follicular cysts may especially be difficult.

[A selective review of recent research results in biological psychiatry]. / Aktuelle Forschungsergebnisse aus dem Bereich der biologischen Psychiatrie.

In accordance with the motto of this year's German Society for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) conference, this article surveys very recent developments in biological psychiatry and neurosciences that have the potential to open up new vistas for the psychiatry and psychotherapy of the future. The work reported includes progress in genome-wide association studies, the implications of these findings for psychiatric nosology and gene-environment interactions, new methods to characterize mechanisms of altered brain function in animal models and humans and the translation of these findings into new therapies. As a core methodology for the psychiatry of the future, biological and applied neuroscience approaches should benefit from sustained structural funding to ensure that these advances impact real-world patient care.

[Artificial intelligence in psychiatry-an overview]. / Künstliche Intelligenz in der Psychiatrie ­ ein Überblick.

Artificial intelligence and the underlying methods of machine learning and neuronal networks (NN) have made dramatic progress in recent years and have allowed computers to reach superhuman performance in domains that used to be thought of as uniquely human. In this overview, the underlying methodological developments that made this possible are briefly delineated and then the applications to psychiatry in three domains are discussed: precision medicine and biomarkers, natural language processing and artificial intelligence-based psychotherapeutic interventions. In conclusion, some of the risks of this new technology are mentioned.

Histomorphometric evaluation of MMP-9 and CD31 expression during healing under Negative Pressure Wound Therapy in dogs.

INTRODUCTION: The aim of the study was to evaluate the molecular and histological effects of negative pressure wound therapy (NPWT) on vascularisation in clinical cases of open wound treatment in dogs. Open wounds (n=10) were randomly assigned to one of two groups: NPWT treatment (n=5) or foam treatment (polyurethane-foam dressing, n=5). Wounds were matched based on age and underlying cause and analysed with respect to neovascularisation (CD31) and matrix proteinase changes (MMP-9). Histological slides were blinded and analysis was performed using automated histomorphometric software. Values determined at day zero after debridement were used as a reference and wound development at day six was evaluated using linear mixed models. Signalment, pre-treatment time and underlying cause were similar between groups. NPWT resulted in a highly significant increase of vascularisation (p.

INTRODUCTION: Le but de ce travail était de relever les effets moléculaires et histologiques de la thérapie des plaies par pression négative (NPWT) au cours du traitement de plaies ouvertes en clinique chez le chien. Des plaies ouvertes (n=10) ont été répartie de manière randomisée en deux groupes : NPWT (n=5) ou recouvrement au moyen d'un pansement en polyuréthane (n=5). Les plaies ont été appariées en tenant compte de leur âge ainsi que de leur cause et examinées quant à leur néo vascularisation (CD31) et aux variations de l'activité des métalloprotéases matricielles (MMP-9). L'appréciation des divers échantillons histologiques a été faite à l'aveugle, au moyen d'un logiciel d'histomorphométrie automatisé. Les valeurs obtenues au jour 0 après débridement servaient de référence pour l'évolution des plaies au jour 6, évolution analysée avec un modèle mixte. Le signalement, la durée du traitement préalable ainsi que les causes étaient comparables entre les groupes. La NPWT amenait, comparativement au contrôle, à une augmentation significative de la vascularisation (p.

[DGPPN recommendations on quality indicators for schizophrenia]. / Aktuelle Empfehlungen der DGPPN für Schizophrenie-Qualitätsindikatoren.

BACKGROUND: In Germany, several quality indicators have been proposed for the measurement of quality of mental healthcare. Some of these quality indicators have been tested in feasibility studies. The German Association for Psychiatry and Psychotherapy (DGPPN) established the "Task Force Quality Indicators (QI)" that, based on previous experience in the development and pilot testing of indicators, considered the further development and practical realization of QI for schizophrenia. AIM: The aim was to select a set of QI for schizophrenia that can also be applied to other diagnoses or used in generic measurements. Another goal was to focus on high feasibility of indicators. METHODS: In a multistage selection process, the DGPPN Task Force selected QI that focus on essential quality aspects from an inventory of 161 existing QI developed by national and international research groups. Indicators were adapted in consultation with the "trialogic forum" of the DGPPN. RESULTS: The DGPPN proposes the following ten indicators for quality measurement in mental healthcare for schizophrenia: QI1 Long-term treatment/Monitoring of side effects, QI2 Seclusion and restraint, QI3 Number of suicides, QI4 Psychoeducational-oriented intervention for significant others, QI5 Timely beginning of outpatient treatment after discharge from inpatient treatment, QI6 Aggression management - inpatient treatment, QI7 Diagnostic procedures/Physical examination, QI8 Antipsychotic polypharmacy, QI9 Rehabilitation/Vocational rehabilitation, QI10 Diagnostic procedures/Psychosocial functioning. DISCUSSION: Most of our proposed QI have to be measured by means of additional data documentation. Based on prior experience in the pilot testing of QI, the DGPPN estimates that the additional efforts in data documentation would be manageable, but have to be refinanced. The indicators will be tested in feasibility studies in different mental healthcare hospitals in Germany.

Forty years of structural imaging in psychosis: promises and truth.

OBJECTIVE: Since the first study published in the Lancet in 1976, structural neuroimaging has been used in psychosis with the promise of imminent clinical utility. The actual impact of structural neuroimaging in psychosis is still unclear. METHOD: We present here a critical review of studies involving structural magnetic resonance imaging techniques in patients with psychosis published between 1976 and 2015 in selected journals of relevance for the field. For each study, we extracted summary descriptive variables. Additionally, we qualitatively described the main structural findings of each article in summary notes and we employed a biomarker rating system based on quality of evidence (scored 1-4) and effect size (scored 1-4). RESULTS: Eighty studies meeting the inclusion criteria were retrieved. The number of studies increased over time, reflecting an increased structural imaging research in psychosis. However, quality of evidence was generally impaired by small samples and unclear biomarker definitions. In particular, there was little attempt of replication of previous findings. The effect sizes ranged from small to modest. No diagnostic or prognostic biomarker for clinical use was identified. CONCLUSIONS: Structural neuroimaging in psychosis research has not yet delivered on the clinical applications that were envisioned.

[The German research network for mental disorders]. / Das deutsche Forschungsnetz zu psychischen Erkrankungen.

Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.

[DSM-5: What is new and what is relevant to forensic psychiatric assessment?]. / DSM 5: Was ist neu und was ist für die Begutachtung relevant?

DSM-5 lists a number of new diagnostic categories and also major changes in diagnoses that have previously been in use. The diagnostic sections of the DSM-5 and certain fundamental changes are presented. Some of the implications with respect to expert opinions are discussed. Certain aspects of the DSM-5 section on somatic symptom disorder will be discussed in more detail, since complaints of physical symptoms without an adequate medical explanation are very frequently encountered in the general population.

Investigation of metamemory functioning in the at-risk mental state for psychosis.

BACKGROUND: Metamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis. METHOD: Patients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings. RESULTS: FEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance. CONCLUSIONS: These data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.

Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.

Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10(-5), odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.

[Practice relevant research in biological psychiatry]. / Praxisrelevante Forschung in der biologischen Psychiatrie.

The practice of psychiatry would be unthinkable without modern psychopharmacology. Drug treatment, especially of severe psychiatric disorders, is often a precondition of community participation, societal reintegration and recovery. Seen in this context it is understandable that biological psychiatry has long been primarily defined by its close interconnection with psychopharmacology and has been perceived this way by practicing physicians. In recent years, however, the concept of what is "biological" has markedly expanded and so has the outreach of this approach into the practice of psychiatry. This article discusses examples showing that biological research methods provide new impulses for individualized medicine, psychotherapy and understanding environmental risks and therefore provide the basis for a preemptive and preventive approach that will be the key to master the challenges posed by the severe burden of mental illness.

Preventive incisional negative pressure wound therapy (Prevena) for an at-risk-surgical closure in a female Rottweiler.

This case report describes a combination of negative pressure-wound-therapy (NPWT) and NPWT assisted incision management after resection of an abscess located at the right thoracic wall in a Rottweiler. The patient had a history of severe incisional complications after surgical interventions performed in the past, including repeated episodes of wound dehiscence, major skin necrosis and infection with and without a multiresistant strain of Staphylococcus aureus and several episodes of open wound management with healing rates between months and a year. Wound closure after resection of the mass was performed as a staged procedure. After two days of open NPWT the wound was primarily closed and a preventive incisional vacuum assisted therapy (CI-NPWT) was started for 7 days. The patient was discharged during therapy with the portable device in place. The Unit was removed at day 7 post wound closure, suture removal followed at day 10. Wound healing was uneventful and no major complications occurred at a follow up time of 8 months. This is the first description of closed incisional negative pressure wound therapy in the dog.

[Difficulties in the assessment of trauma-related disorders]. / Begutachtung von Traumafolgestörungen.

Assessment of trauma disorders is becoming increasingly important. A major problem here is that trauma disorders are extremely heterogeneous. Moreover, they are often associated with comorbid disorders, such as borderline personality disorder. The valid diagnostic systems ICD-10 and DSM-5 poorly represent trauma disorders. The so-called complex post-traumatic stress disorder or DESNOS (disorders of extreme stress not otherwise specified) are listed .in either of the ICD-10 or DSM-5. The distinctiveness is not generally scientifically accepted. In addition, the assessment of trauma disorders is complicated because there are often multiple traumas of varying degrees of severity.

Effect of casozepine administration on stress in dogs during a veterinary examination - A randomized placebo-controlled trial.

The aim of the study was to investigate the stress-reducing effect of a casozepine before a veterinary examination in dogs. It should be examined whether the dogs are less stressed during a standardized veterinary examination after an oral application of casozepine over 2 days and whether the administration has an influence on the salivary concentrations of the stress hormones vasopressin and cortisol. Across the study group (n=36), a significantly lower stress score (P=0.0026) and lower mean (P=0.01) and maximum (P=0.024) pulse rates were seen at follow-up after casozepine administration, in contrast to the placebo group (n=26). Salivary vasopressin concentrations increased during follow-up in the placebo group (P=0.04), whereas they remained the same in the casozepine group. Cortisol concentrations increased during follow-up in the casozepin group (P=0.01). The results indicate that although dogs in both groups remained excited at follow-up, short-term casozepine administration before a veterinary visit had a weak stress-reducing effect in dogs based on subjective stress scoring and pulse rate.