Levels of diagnostic certainty for nonepileptic attack disorder in the neuropsychiatry setting.

Nonepileptic attack disorder (NEAD) is a medical condition commonly seen in neuropsychiatry services, often as a differential diagnosis of other neuropsychiatric conditions. Recommendations by the International League Against Epilepsy (ILAE) Nonepileptic Seizures Task Force propose a four-level hierarchical approach to the diagnosis of NEAD, based on history, witnessed event, and electroencephalographic (EEG) investigation. We set out to provide the first description of the diagnostic levels of patients with NEAD at a specialist neuropsychiatry clinic. Comprehensive clinical data from 148 consecutive patients with NEAD attending the specialist Neuropsychiatry Clinic run by a single Consultant in Behavioral Neurology were retrospectively reviewed. Patients with NEAD were primarily referred to neuropsychiatry by Consultant Neurologists (n = 94; 63.5%). The majority of patients were female (n = 108; 73.0%), with a disease duration of 7.9 years (standard deviation: 10.4). Anxiety was the most common comorbidity (n = 43; 26.7%). Categorization of patients according to the ILAE Nonepileptic Seizures Task Force criteria was mainly based on clinical features and EEG findings, as only 7 (4.7%) patients had attacks witnessed by a specialist. The largest diagnostic categories were 'possible' (n = 54; 36.5%) and 'clinically established' (n = 40; 27.0%), followed by 'documented' (n = 12; 8.1%) and 'probable' (n = 5; 3.4%). In 125 patients (84.4%), EEGs were performed. Selective serotonin reuptake inhibitors were the most frequently prescribed psychotropic medications (n = 48; 32.4%); 89 patients (60.1%) received behavioral therapy. There were no differences in pharmacological or behavioral management strategies across the patients categorized under different diagnostic levels. Patients with NEAD seen within neuropsychiatry settings are mainly assigned 'possible' and 'clinically established' levels of diagnostic certainty. Difficulty in capturing typical clinical events witnessed by an experienced clinician while on video-EEG can limit the clinical application of the 'documented' diagnostic level. If appropriate, active interventions can be implemented irrespective of diagnostic levels to minimize delays in the neuropsychiatric care pathways.

Deep brain stimulation: new possibilities for the treatment of mental disorders. / Gleboka stymulacja mózgu (Deep Brain Stimulation) ­ nowe mozliwosci leczenia zaburzen psychicznych.

Deep brain stimulation (DBS) is a treatment method that is currently getting more and more attention from psychiatrists. It has proven to be efficacious and safe in the treatment of neurological disorders, mainly Parkinson's disease (PD), dystonia and essential tremor. DBS has very often contributed to successful treatment in cases that had proved resistant to all other methods of treatment. Nowadays treatment-resistant obsessive-compulsive disorder (OCD) is the main psychiatric indication for DBS. Many studies have focused on assessing the efficacy and safety of this method in different mental disorders, including depressive disorders, Alzheimer's disease, anorexia nervosa, Tourette syndrome, substance addiction or aggressive behaviors. Single cases of successful treatment in bipolar disorder, schizophrenia and post-traumatic stress disorder have also emerged in recent years. In this review the current state of knowledge on the applicability of DBS in psychiatry is presented, based on the available systematic reviews, clinical trials and case studies, as well as on neurophysiological and neuroimaging data.

[Interest of extrahospital multidisciplinary unit of neuro-psycho-geriatric intervened in nursing home: Analysis of 288 interventions]. / Intérêt d'une unité mobile multidisciplinaire extra-hospitalière de neuro-psychogériatrie intervenant en EHPAD : analyse de 288 interventions.

INTRODUCTION: Geriatrics Mobile Units are a new organisation operating in nursing homes. Their mission is to propose globally oriented neuro-psychiatric and geriatric care. The purpose of the study is to assess their activity and impact over a 21-month period. METHOD: A prospective single center study of UMNPG's data including intervention characteristics, patient characteristics, recommendations and reassessment after intervention. The Neuropsychiatric Inventory Nursing Home version (NPI-NH) was measured during intervention and reassessed after 30 days (Student's t-test). RESULTS: From March 2014 to December 2015, UMNPG conducted 288 interventions mainly for medical advices (81%), clinical assessments (54%) and health care team support (46%). The average age was 84.6±7.3years, 73.3% of whom were women. The patients were dependent (62% of GIR 1 or 2) with dementia (60%) and under several medications (83.7%). The symptoms were mainly agitation/aggression (76.4%), anxiety (75%), depression (66.7%), irritability (60.4%), aberrant motor behaviour (55.9%) and delusions (48.6%). The main proposals of UMNPG were a change in treatment (79.5%), a health care team support (85.4%) and hospitalization (8.4%). The rate of follow-up on recommendation was 83% on the 15th day and 80% on the 30th day. The rate of avoided hospitalizations was 16%. The average NPI-NH decreased (on day 0 NPI=50±19.2; on day 30 NPI=33.9±19.6, p<0.001). CONCLUSION: UMNPG-EHPAD intervenes for frail elderly residents with multiple disorders in crisis situations. Medical recommendations help to support people in nursing homes and decrease NPI-NH. UMNPG-EHPAD is part of geriatric network strengthening the city/hospital connection.

Editorial. / Od Redakcji.

no summary.

Relevance of Rodent Models of Depression in Clinical Practice: Can We Overcome the Obstacles in Translational Neuropsychiatry?

The diagnosis of a mental disorder generally depends on clinical observations and phenomenological symptoms reported by the patient. The definition of a given diagnosis is criteria based and relies on the ability to accurately interpret subjective symptoms and complex behavior. This type of diagnosis comprises a challenge to translate to reliable animal models, and these translational uncertainties hamper the development of new treatments. In this review, we will discuss how depressive-like behavior can be induced in rodents, and the relationship between these models and depression in humans. Specifically, we suggest similarities between triggers of depressive-like behavior in animal models and human conditions known to increase the risk of depression, for example exhaustion and bullying. Although we acknowledge the potential problems in comparing animal findings to human conditions, such comparisons are useful for understanding the complexity of depression, and we highlight the need to develop clinical diagnoses and animal models in parallel to overcome translational uncertainties.

Clinically useful brain imaging for neuropsychiatry: How can we get there?

Despite decades of research, visions of transforming neuropsychiatry through the development of brain imaging-based "growth charts" or "lab tests" have remained out of reach. In recent years, there is renewed enthusiasm about the prospect of achieving clinically useful tools capable of aiding the diagnosis and management of neuropsychiatric disorders. The present work explores the basis for this enthusiasm. We assert that there is no single advance that currently has the potential to drive the field of clinical brain imaging forward. Instead, there has been a constellation of advances that, if combined, could lead to the identification of objective brain imaging-based markers of illness. In particular, we focus on advances that are helping to (1) elucidate the research agenda for biological psychiatry (e.g., neuroscience focus, precision medicine), (2) shift research models for clinical brain imaging (e.g., big data exploration, standardization), (3) break down research silos (e.g., open science, calls for reproducibility and transparency), and (4) improve imaging technologies and methods. Although an arduous road remains ahead, these advances are repositioning the brain imaging community for long-term success.

[The problem of small "n" and big "P" in neuropsycho-pharmacology, or how to keep the rate of false discoveries under control]. / A kis "n", nagy "P" probléma a neuropszichofarmakológiában, avagy hogyan kontrolláljuk a hamis felfedezések arányát.

One of the characteristics of many methods used in neuropsychopharmacology is that a large number of parameters (P) are measured in relatively few subjects (n). Functional magnetic resonance imaging, electroencephalography (EEG) and genomic studies are typical examples. For example one microarray chip can contain thousands of probes. Therefore, in studies using microarray chips, P may be several thousand-fold larger than n. Statistical analysis of such studies is a challenging task and they are refereed to in the statistical literature such as the small "n" big "P" problem. The problem has many facets including the controversies associated with multiple hypothesis testing. A typical scenario in this context is, when two or more groups are compared by the individual attributes. If the increased classification error due to the multiple testing is neglected, then several highly significant differences will be discovered. But in reality, some of these significant differences are coincidental, not reproducible findings. Several methods were proposed to solve this problem. In this review we discuss two of the proposed solutions, algorithms to compare sets and statistical hypothesis tests controlling the false discovery rate.

Editorial: Illuminating the dark matter of developmental neuropsychiatric genetics - strategic focus for future research in child psychology and psychiatry.

Research on genetic factors influencing cognitive and behavioural traits or which are central to the aetiology of neuropsychiatric diseases has been complicated by a furtive discrepancy between high heritability estimates and a scarcity of replicable gene-disorder associations. This 'missing heritability' has been either euphemised as the 'dark matter' of gene-trait association or aggravated as the 'looming crisis in behavioural genetics'. Nevertheless, in recognising the importance of this topic for our understanding of child psychiatric conditions and highlighting its commitment to the field, the Journal of Child Psychology and Psychiatry (JCPP) has for the first time appointed an editor with special responsibility for molecular (epi)genetics.

General overview: biomarkers in neuroscience research.

Biomarkers are in demand for disease diagnosis, treatment response monitoring, and development of novel therapeutics. Biomarker discovery in neuroscience is challenging due to absence of robust molecular correlates and the interpatient heterogeneity that characterizes neuropsychiatric disorders. Because of the complexity of these disorders, a panel of biomarkers derived from different platforms will be required to precisely reflect disease-related alterations. Animal models of psychiatric phenotypes as well as -omics and imaging methodologies are important tools for biomarker discovery. However, the limitations of current research concerning sample handling and collection, candidate biomarker validation, and a lack of interdisciplinary approaches need to be addressed. Ultimately, the coordinated effort of relevant stakeholders including researchers, physicians, and funding organizations together with standardization initiatives will be vital to overcome the present challenges and to advance personalized health care using sensitive and specific biomarkers.

Challenges of introducing new biomarker products for neuropsychiatric disorders into the market.

There are many challenges associated with the discovery and development of serum-based biomarkers for psychiatric disorders such as schizophrenia. Here, we review these challenges from the point of view of psychiatrists, general practitioners, the regulatory agencies, and biomarker scientists. There is a general opinion in psychiatric medicine that improvements over the current subjective tests are essential. Despite this, there is a reluctance to accept that peripheral molecules can do the job any better. In addition, psychiatrists find it difficult to accept that peripheral molecules, such as those found in blood, can reflect what is happening in the brain. However, the regulatory health authorities now consider biomarkers as important for the future of drug development and have called for efforts to modernize methods, tools, and techniques for the purpose of developing more efficient and safer drugs. We also describe here the development of the first ever molecular blood test for schizophrenia, and its reception in the market place, as a case in point.

Changed relative to what? Housekeeping genes and normalization strategies in human brain gene expression studies.

Many studies in biological psychiatry compare the abundance of individual messenger RNAs between cases and control subjects or, more recently, between genotype groups. Most utilize some form of normalization procedure, usually expressing the transcript(s) of interest relative to that of a housekeeping gene or genes (also called reference genes), to overcome various sources of experimental error. Indeed, normalization is such a standard procedure that its purpose, principles, and limitations are sometimes overlooked, and some papers lack sufficient information as to its implementation. Here, we review the rationales for normalization and argue that in well-conducted psychiatric gene expression studies using human brain tissue, it is reducing intersubject variability rather than experimental error that is the major benefit of normalization. We also review the conceptual and empirical basis for the category of housekeeping genes-i.e., genes with a ubiquitous and invariant expression. We conclude that the evidence is against any such simple categorization and that a more pragmatic, less dogmatic, approach to the selection and implementation of reference genes is required, which takes into account the particular issues that pertain to human brain tissue studies. This pragmatism extends to the issue of whether normalization should be to one or multiple reference genes. We end by making several recommendations toward a more flexible, transparent, and comprehensive approach to data presentation and analysis. We illustrate the review with examples from studies of schizophrenia and mood disorder.

Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit.

OBJECTIVE: To validate a diagnostic instrument for pediatric delirium in critically ill children, both ventilated and nonventilated, that uses standardized, developmentally appropriate measurements. DESIGN AND SETTING: A prospective observational cohort study investigating the Pediatric Confusion Assessment Method for Intensive Care Unit (pCAM-ICU) patients in the pediatric medical, surgical, and cardiac intensive care unit of a university-based medical center. PATIENTS: A total of 68 pediatric critically ill patients, at least 5 years of age, were enrolled from July 1, 2008, to March 30, 2009. INTERVENTIONS: None. MEASUREMENTS: Criterion validity including sensitivity and specificity and interrater reliability were determined using daily delirium assessments with the pCAM-ICU by two critical care clinicians compared with delirium diagnosis by pediatric psychiatrists using Diagnostic and Statistical Manual, 4th Edition, Text Revision criteria. RESULTS: A total of 146 paired assessments were completed among 68 enrolled patients with a mean age of 12.2 yrs. Compared with the reference standard for diagnosing delirium, the pCAM-ICU demonstrated a sensitivity of 83% (95% confidence interval, 66-93%), a specificity of 99% (95% confidence interval, 95-100%), and a high interrater reliability (κ = 0.96; 95% confidence interval, 0.74-1.0). CONCLUSIONS: The pCAM-ICU is a highly valid reliable instrument for the diagnosis of pediatric delirium in critically ill children chronologically and developmentally at least 5 yrs of age. Use of the pCAM-ICU may expedite diagnosis and consultation with neuropsychiatry specialists for treatment of pediatric delirium. In addition, the pCAM-ICU may provide a means for delirium monitoring in future epidemiologic and interventional studies in critically ill children.