Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives.

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

Wearable devices for seizure detection: Is it time to translate into our clinical practice?

With the exponential development of mobile health technologies over the past ten years, there has been a growing interest in the potential applications in the field of epilepsy, and specifically for seizure detection. Better detection of seizures is probably one of the best ways to improve patient safety. Overall, we are observing an exponential increase in the number of non-EEG based seizure detection systems and a progressive homogenization of their evaluation procedures. Most importantly, the properties of these devices for detection of tonic-clonic seizures are now very interesting, both in terms of sensitivity and in terms of false-alarm rates. Accordingly, we might expect that these be used in clinical practice in the near future, especially in patients at high risk of seizure-related injuries or sudden unexpected death in epilepsy (SUDEP).

Frank Beach Award Winner - The future of mental health research: Examining the interactions of the immune, endocrine and nervous systems between mother and infant and how they affect mental health.

Pregnancy and the postpartum period are periods of significant change in the immune and endocrine systems. This period of life is also associated with an increased risk of mental health disorders in the mother, and an increased risk of developmental and neuropsychiatric disorders in her infant. The collective data described here supports the idea that peripartum mood disorders in mother and developmental disorders in her infant likely reflects multiple pathogeneses, stemming from various interactions between the immune, endocrine and nervous systems, thereby resulting in various symptom constellations. In this case, testing the mechanisms underlying specific symptoms of these disorders (e.g. deficits in specific types of learning or anhedonia) may provide a better understanding of the various physiological interactions and multiple etiologies that most likely underlie the risk of mental health disorders during this unique time in life. The goal here is to summarize the current understanding of how immune and endocrine factors contribute to maternal mental health, while simultaneously understanding the impact these unique interactions have on the developing brain of her infant.

Placental programming of neuropsychiatric disease.

The placenta is vital for fetal growth, and compromised function is associated with abnormal development, especially of the brain. Linking placental function to brain development is a new field we have dubbed neuroplacentology. Approximately 380,000 infants in the United States each year abruptly lose placental support upon premature birth, and more than 10% of pregnancies are affected by more insidious placental dysfunction such as preeclampsia or infection. Abnormal fetal brain development or injury can lead to life-long neurological impairments, including psychiatric disorders. The majority of research connecting placental compromise to fetal brain injury has focused on gas exchange or nutritional programming, neglecting the placenta's essential neuroendocrine role. We will review the current evidence that placental dysfunction, particularly endocrine dysfunction, secretion of pro-inflammatory cytokines, or barrier breakdown may place many thousands of fetuses at risk for life-long neurodevelopmental impairments each year. Understanding how specific placental factors shape brain development and increase the risk for later psychiatric disorders, including autism, attention deficit disorder, and schizophrenia, paves the way for novel treatment strategies to maintain the normal developmental milieu and protect from further injury.

Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications.

In this review, we outline the role of orexin receptor antagonists in disorders of sleep/wake and other potential neuropsychiatric conditions, with a focus on suvorexant, which is currently the only approved agent in this class. The efficacy of suvorexant was established in Phase 2-3 trials with treatment durations ranging from 1 to 12 months in patients with insomnia. Suvorexant is effective at improving sleep assessed by patient self-report and by polysomnography, with generally little effect on underlying sleep architecture. The main side-effect is next day somnolence. With the growing realization of the important connections between sleep and other disorders, studies are ongoing to explore this novel mechanism in other disorders such as Alzheimer's disease and depression.

Assessment of Cognitive Training & Social Interaction in People with Mild to Moderate Dementia: A Pilot Study.

Objectives: To evaluate the cognitive, neuropsychiatric, and quality of life outcomes of computer-based cognitive training and social interaction on people with mild to moderate dementia. Methods: Ten individuals with dementia were recruited to complete a cognitive training regimen. They were randomly assigned to a high social interaction (HSI) group (n = 5) and low social interaction (LSI) group (n = 5). Eight of the original 10 participants completed the cognitive training and were evaluated on cognitive abilities, neuropsychiatric symptoms (NPS), and quality of life (QoL). Results: Mean scores for the HSI group increased on cognitive assessments, where mean scores for the LSI group saw decline, or stability. There was an overall reduction in the frequency and severity of NPS presentation in both the HSI and LSI group. Mixed results were found for mean changes in QoL. Discussion: These results support the idea of social interaction influencing cognitive outcomes, cognitive training influencing NPS, and both social interaction and cognitive training influencing QoL. The findings illustrate the feasibility and importance of incorporating social activity to computerized cognitive training for people with dementia. Clinical Implications: Cognitive training that incorporates social interaction may be a promising intervention for individuals with dementia experiencing NPS.

Research Trends in the Neuropsychiatry Literature Since the New Millennium.

The authors examined current research trends in neuropsychiatry by analyzing original research studies published since the new millennium. A total of 14,587 articles published between 2000 and 2013 were systematically screened from 10 neuropsychiatry journals, which were selected based on impact factor ranking. Clinical studies accounted for the highest proportion of neuropsychiatry research articles published since the new millennium (N=5,097; 68.9%), followed by laboratory studies (N=1,824; 24.7%) and service evaluation, classification, and historical studies (N=474; 6.4%). This study confirms that neuropsychiatry is a quintessentially clinical discipline with a continuing focus on phenomenological aspects, possibly reflecting the centrality of clinical observations to the diagnostic process.

[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.

The science of neuropsychiatry: past, present, and future.

The field of neuropsychiatry aims to overcome the separation of neurology and psychiatry, which is reflected in a gap between the neurologist, searching for the underlying neuroanatomical basis of a disorder, and the psychiatrist, dipping into its phenomenology and underlying genetics. This gap becomes slighter in our day, as recent research in clinical neurosciences enables us to better investigate the neural basis of neuropsychiatric disorders. This article reviews the history and development of neuropsychiatry in the occidental world, suggesting that the science of neuropsychiatry could optimize for the diagnosis, monitoring, and treatment of behavioral, cognitive, and so-called mental disorders.

Brain images, babies, and bathwater: critiquing critiques of functional neuroimaging.

Since the mid-1980s, psychologists and neuroscientists have used brain imaging to test hypotheses about human thought processes and their neural instantiation. In just three decades, functional neuroimaging has been transformed from a crude clinical tool to a widely used research method for understanding the human brain and mind. Such rapidly achieved success is bound to evoke skepticism. A degree of skepticism toward new methods and ideas is both inevitable and useful in any field. It is especially valuable in a science as young as cognitive neuroscience and its even younger siblings, social and affective neuroscience. Healthy skepticism encourages us to check our assumptions, recognize the limitations of our methods, and proceed thoughtfully. Skepticism itself, however, also must be examined. In this article, I review the most commonly voiced criticisms of functional neuroimaging. In the spirit of healthy skepticism, I will critically examine these criticisms themselves. Each contains at least a kernel of truth, although I will argue that in some cases the kernel has been over extended in ways that are inaccurate or misleading.

Neuroimaging and psychiatry: the long road from bench to bedside.

Advances in neuroscience have revolutionized our understanding of the central nervous system. Neuroimaging technologies, in particular, have begun to reveal the complex anatomical, physiological, biochemical, genetic, and molecular organizational structure of the organ at the center of that system: the human brain. More recently, neuroimaging technologies have enabled the investigation of normal brain function and are being used to gain important new insights into the mechanisms behind many neuropsychiatric disorders. This research has implications for psychiatric diagnosis, treatment, and risk assessment. However, with some exceptions, neuroimaging is still a research tool, not ready for use in clinical psychiatry.

Neuroimaging: beginning to appreciate its complexities.

For over a century, scientists have sought to see through the protective shield of the human skull and into the living brain. Today, an array of technologies allows researchers and clinicians to create astonishingly detailed images of our brain's structure as well as colorful depictions of the electrical and physiological changes that occur within it when we see, hear, think and feel. These technologies-and the images they generate-are an increasingly important tool in medicine and science. Given the role that neuroimaging technologies now play in biomedical research, both neuroscientists and nonexperts should aim to be as clear as possible about how neuroimages are made and what they can-and cannot-tell us. Add to this that neuroimages have begun to be used in courtrooms at both the determination of guilt and sentencing stages, that they are being employed by marketers to refine advertisements and develop new products, that they are being sold to consumers for the diagnosis of mental disorders and for the detection of lies, and that they are being employed in arguments about the nature (or absence) of powerful concepts like free will and personhood, and the need for citizens to have a basic understanding of how this technology works and what it can and cannot tell us becomes even more pressing.

[Stem cell research and its growing impact on contemporary psychiatry]. / Badania nad komórkami macierzystymi i ich rosnacy wplyw na wspólczesna psychiatrie

The expanding field of stem cell research is now beginning to help with the problems of modern psychiatry. On the one hand, induced pluripotent stem cells (iPSCs) can now be used to generate neural cell lines from patients suffering from psychiatric disorders, which can then serve as models for studying changes in gene expression pattern involved in the pathogenesis of these diseases. These artificially generated neural cells are also employed in studying the efficacy of newly developed antipsychotic treatments. On the other hand, evidence has accumulated that not only monocytes, which can be microglia precursors, but also certain other adult bone marrow-derived cells may cross the blood-brain barrier and affect biological processes in brain tissue. Along with evidence of circulating and brain-infiltrating cells, there are well-studied factors (e.g., chemokines, phosphosphingolipids, and complement-cleavage fragments) that modulate trafficking of these cells between bone marrow and neural tissue. These observations may help to shed new light on the pathogenesis of psychotic disorders and, in the future, perhaps help to develop more effective treatments.

Why we essentialize mental disorders.

Essentialism is one of the most pervasive problems in mental health research. Many psychiatrists still hold the view that their nosologies will enable them, sooner or later, to carve nature at its joints and to identify and chart the essence of mental disorders. Moreover, according to recent research in social psychology, some laypeople tend to think along similar essentialist lines. The main aim of this article is to highlight a number of processes that possibly explain the persistent presence and popularity of essentialist conceptions of mental disorders. One such process is the general tendency of laypeople to essentialize conceptual structures, including biological, social, and psychiatric categories. Another process involves the allure of biological psychiatry. Advocating a categorical and biological approach, this strand of psychiatry probably reinforced the already existing lay essentialism about mental disorders. As such, the question regarding why we essentialize mental disorders is a salient example of how cultural trends zero in on natural tendencies, and vice versa, and how both can boost each other.

[Biomarker research in neuropsychiatry: challenges and potential]. / Biomarkerforschung in der Neuropsychiatrie: Herausforderung und Potenzial.

The introduction of blood-based biomarkers for psychiatric disorders faces numerous challenges. The goal of research efforts is the improvement of the current more or less subjective diagnosis, treatment and patient management. So far attempts to introduce molecular analyses have faced considerable resistance. There is an urgent need for a paradigm shift so that peripheral markers may also deliver insights into pathological states of the brain. Health regulators have called for a reform of research and development approaches, with the goal to enhance the safety and efficiency of future antipsychotic drugs using biomarker-based methods. Here we discuss the potential of the biomarker sector in this context, as exemplified by the recent introduction of Veripsych™, the first blood test aiding the diagnosis of schizophrenia.

Annual Research Review: The promise of stem cell research for neuropsychiatric disorders.

The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders, attention deficit hyperactivity disorder, obsessive compulsive disorder and many other neurodevelopmental conditions. However, precisely how genes may function in human brain development and how they interact with each other leading to psychiatric disorders is unknown. Because of an increasing understanding of neural stem cells and how the nervous system subsequently develops from these cells, we have now the ability to study disorders of the nervous system in a new way - by rewinding and reviewing the development of human neural cells. Induced pluripotent stem cells (iPSCs), developed from mature somatic cells, have allowed the development of specific cells in patients to be observed in real time. Moreover, they have allowed some neuronal-specific abnormalities to be corrected with pharmacological intervention in tissue culture. These exciting advances based on the use of iPSCs hold great promise for understanding, diagnosing and, possibly, treating psychiatric disorders. Specifically, examination of iPSCs from typically developing individuals will reveal how basic cellular processes and genetic differences contribute to individually unique nervous systems. Moreover, by comparing iPSCs from typically developing individuals and patients, differences at stem cell stages, through neural differentiation, and into the development of functional neurons may be identified that will reveal opportunities for intervention. The application of such techniques to early onset neuropsychiatric disorders is still on the horizon but has become a reality of current research efforts as a consequence of the revelations of many years of basic developmental neurobiological science.