bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enrolling Decisionally Incapacitated Subjects in Neuropsychiatric Research
Authors: Fins Joseph J. , Miller Franklin G. 
Published: August 2016

AbstractThis paper discusses the National Bioethics Advisory Commissions (NBAC's) report on research involving persons with mental disorders that may affect decisionmaking capacity. After placing the NBAC recommendations into their historic context, the authors propose a strategy to enroll decisionally incapacitated subjects into neuropsychiatric research. The authors maintained that their proposed consensus model for research authorization, utilizing subject advocates, fosters valuable clinical research while protecting potentially vulnerable subjects.
Pharmacotherapeutic Options in the Treatment of Comorbid Depression and Anxiety
Authors: Pollack Mark H. , Marzol Patricia C. 
Published: August 2016

AbstractAlthough anxiety and mood disorders are listed as separate disorders in theDiagnostic and Statistical Manual of Mental Disorders,Fourth Edition, they frequently coexist. They may be expressed phenotypically as comorbidities or as the provisional entity mixed anxiety-depressive disorder. Patients with both anxiety and depression are more symptomatic, use more health care resources, and have a worse prognosis than those with a single disorder. Recognizing and treating these patients are challenges for physicians because the symptoms of the two disorders often overlap. Administration of effective treatment, comprising both anxiolytic and antidepressant effects, can reduce patient distress and disability, as well as inappropriate utilization of medical services. Medications such as tricyclic antidepressants, selective serotonin reuptake inhibitors, nefazodone, venlafaxine XR (extended release) and mirtazapine, are highly effective in treating comorbid depression and anxiety. These newer agents now represent the pharmacotherapeutic treatments of choice for the comorbid conditions.
The Science of Antipsychotics: Mechanistic Insight
Authors: Tamminga Carol A. 
Published: August 2016

ABSTRACTWith the introduction of conventional antipsychotics in the 1950s, clinicians began to expect effective treatment of positive symptoms of schizophrenia. However, these drugs do not resolve negative and cognitive symptoms of schizophrenia and are also associated with serious side effects, including extrapyramidal side effects (EPS) and tardive dyskinesia. In 1989, clozapine was introduced and labeled the first new antipsychotic owing to its improved efficacy and side-effect profile. Clozapine proved effective in alleviating many of the positive, negative, and cognitive symptoms of schizophrenia, without causing inevitable EPS or tardive dyskinesia. Over the past decade, a number of different new antipsychotics have been developed. These drugs have an affinity for multiple dopamine-receptor subtypes as well as serotonin, norepinephrine, and glutamate receptors, allowing for better treatment outcomes. The antagonism of the 5-HT2A receptor may be responsible for improvement in negative symptoms and decrease in EPS. In addition to providing enhanced efficacy, the affinity of the new drugs for multiple receptors introduces new side effects not seen with the conventional agents, including weight gain. Each new antipsychotic has a unique receptor-binding profile that corresponds to its pharmacologic and side-effect profile. Understanding the differences in mechanisms of action of new antipsychotics will allow physicians to better choose treatment that meets the needs of each individual patient.
Management of Acute Psychosis: From Emergency to Stabilization
Authors: Zimbroff Dan L. 
Published: August 2016

ABSTRACTIn treating and managing acute psychosis in patients with schizophrenia, early intervention may be valuable. The need to quickly control severe symptoms, however, must be balanced with a treatment algorithm that is both safe and effective. The present management of acute psychotic agitation varies among clinicians. Key treatment goals have been to calm the agitated, assaultive, violent, or disruptive patient, minimize the danger to self and others, and achieve a smooth transition from intramuscular to oral maintenance. For many years, intramuscular treatment with benzodiazepines and/or conventional antipsychotics, such as haloperidol, has been the mainstay of treatment for acute psychosis. Unfortunately, the poor tolerability of conventional antipsychotics compromises their usefulness for both short- and long-term treatment. Although new antipsychotics have a more favorable side-effect profile, the transition from an intramuscular formulation has been problematic. Fortunately, the development of intramuscular formulations of olanzapine and ziprasidone offer new treatment options for patients experiencing acute psychotic episodes. This article will review the use of intramuscular agents, standard antipsychotics, and new antipsychotics in the emergency room setting. The strengths and limitations of each will be discussed.
The Goal of Epilepsy Therapy: No Seizures, No Side Effects, as Soon as Possible
Authors: Engel Jerome 
Published: August 2016

Epilepsy is a significant health problem. Ten percent of people living a normal lifespan will experience at least one epileptic seizure and one third will develop a chronic epileptic condition. At any given time, 0.5% to 1% of the world's population has active epilepsy, amounting to over 40 million people. A World Health Organization-sponsored study determined that epilepsy accounts for 1% of the global burden of disease, measured as disability-adjusted life years equivalent to the global burden of lung cancer in men and to breast cancer in women. Disability-adjusted life years measure years of productivity lost as a result of disability or death, which is relatively high for epilepsy because this condition often begins in childhood. The cost of epilepsy in the United States has been estimated at $12.5 billion/year, and 80% of this cost is borne by the 30% of patients whose seizures are not controlled.The cost of uncontrolled epileptic seizures to society, and to individuals with epilepsy and their families, is measured not only in economic terms, but also in terms of human suffering. In this month's first article, Michael R. Sperling, MD, who has authored seminal papers on consequences of epilepsy, provides evidence that epilepsy is not a benign disorder; that early control of epileptic seizures is important to avoid irreversible disability due to the development of psychological and social disturbances and progressive cerebral dysfunction, as well as epilepsy-related death. The burden imposed on society and on individuals by uncontrolled epileptic seizures is all the more tragic because many suffer needlessly. For a significant number of adults who have had recurrent seizures since infancy, childhood, or adolescence, more aggressive early intervention might have rescued them from a lifetime of disability. Consequently, the goal of therapy today should be no seizures and no side effects, as soon as possible.
Genetics of Posttraumatic Stress Disorder
Authors: Segman Ronnen H. , Shalev Arieh Y. 
Published: August 2016

ABSTRACTPosttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. PTSD is disabling and commonly follows a chronic course. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. A twin study of Vietnam veterans has shown significant genetic contribution to PTSD. The fact that PTSD's underlying genotypic vulnerability is only expressed following trauma exposure limits the usefulness of family-based linkage approaches. In contrast to the other major psychiatric disorders, large studies for the search of underlying genes have not been described in PTSD to date. Complementary approaches for locating involved genes include association-based studies employing case-control or parental genotypes for transmission dysequilibrium analysis and quantitative trait loci studies in animal models. Identification of susceptibility genes will increase our understanding of traumatic stress disorders and help to elucidate their molecular basis. The current review provides an up-to-date outline of progress in the field of PTSD.
Mental Symptoms and Disorders During Pregnancy
Authors: Halbreich Uriel , Kornstein Susan G. 
Published: August 2016

Pregnancy is a period of substantial neuroendocrine changes. These changes are not limited to the hypothalamic-pituitary-gonadal hormones, but also involve the placenta and its secreted hormones, especially the corticotropin releasing hormone that is a major component of the stress axis. These hormonal changes are also associated with changes in the immune/inflammatory and cardiovascular systems. The cumulative evidence that dysregulation in this multifactorial interactional field may cause deleterious effects on the fetus and its future development emphasizes the importance and clinical relevance of this line of research. When vulnerability and genetic predisposition to gestational stress and its adverse effects are added to the equation, the importance of adequate treatments and possible preventive interventions is underscored.Pregnancy is usually perceived as a happy period. However, as demonstrated by Uriel Halbreich, MD, severe mood, behavior, and cognitive symptoms are quite prevalent during pregnancy. The magnitude of the problem is probably not reflected by the reported prevalence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or International Classification of Diseases, Ninth Edition major mental disorders. A closer evaluation and treatment of symptoms, especially when they are associated with impairment, stress, and distress, may improve the mental health of the mother and the expected baby.
Patterns of Neural Response to Emotive Stimuli Distinguish the Different Symptom Dimensions of Obsessive-Compulsive Disorder
Authors: Phillips Mary L. , Mataix-Cols David 
Published: August 2016

ABSTRACTDespite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.
Effects of Low-Dose Risperidone and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic Patients
Authors: Fagerlund Birgitte , Mackeprang Torben , Gade Anders , Hemmingsen Ralf , Glenthøj Birte Y. 
Published: August 2016

AbstractBackground: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogenous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal.Objective: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogenous group of drug-naïve first-episode schizophrenic patients in a longitudinal setting.Methods: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N-25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naïve, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time.Results: The patients showed considerable cognitive deficits when drug-naïve. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls.Conclusion: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naïve schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.
Management of Overactive Bladder
Authors: Romanzi Lauri J. 
Published: August 2016

At least 80% of urology patients are taking several medications for any variety of other medical conditions. However, regarding treatment of overactive bladder (OAB) specifically, there are several antimuscarinic drugs available. Tolterodine and trospium chloride are, in essence, nonspecific in terms of muscarinic receptor selectivity. Solifenacin and oxybutynin show selectivity for the M1, and darifenacin is significantly M3 receptor specific (Slide 17).The potential benefit for selective antimuscarinic agents is that they might target the bladder more specifically and avoid anticholinergic side effects in other organ systems, specifically the brain and heart. We do know that M3 receptors are also present in the intestines and in the salivary glands; thus, we might not expect organ selectivity with an M3-specific receptor because that receptor would also potentially affect the salivary gland and the intestinal tract as well.There is a growing body of data regarding M3 activity specificity and decreased cognitive impairment in patients of various ages. This, as well as the reduction of cardiac side effects, are the major benefits of using an M3-selective anticholinergic medication rather than a nonselective agent for the treatment of OAB.
The Neurobiology of Postpartum Depression
Authors: Zonana Jessica , Gorman Jack M. 
Published: August 2016

AbstractPostpartum psychiatric changes can range from maternity blues to psychosis. Causality is still undetermined, but explanations for these disturbances often focus on hormonal changes and dysregulation. Researchers have begun the process of delineating what neurobiological factors may be associated with depressive disorders in pregnancy and the postpartum. This article reviews the current literature on the roles of gonadal and pituitary hormones in the psychopathophysiology of postpartum mood disorders. Other biological factors, such as biogenic amines, neuroactive steroids, cholesterol, and fatty acids, are also discussed. The potential benefits of neuroimaging to aid in understanding neuropsychiatric changes that occur in the context of postpartum depression are also considered.
Integrating Neurobiology and Psychopathology into Evidence-Based Treatment of Social Anxiety Disorder
Authors: Liebowitz Michael R. , Ginsberg David L. , Ninan Philip T. , Schneier Franklin R. , Blanco Carlos 
Published: August 2016

AbstractSocial anxiety disorder (SAD) is a common, chronic psychiatric disorder characterized by a persistent fear of social or performance situations in which embarrassment can occur. This disorder typically appears during the mid-adolescent years and is unremitting throughout life if not properly treated. SAD presents as two subtypes: the more common and debilitating generalized form, and the nongeneralized form, which consists predominantly of performance anxiety. The majority of patients with SAD have comorbid mental disorders, including mood, anxiety, and substance abuse. No single development theory has been proposed to account for the origins of SAD, although current understanding of the etiology of SAD posits an interaction between psychological and biological factors. Risk factors include environmental and parenting influences and dysfunctional cognitive and conditioning events in early childhood. The neurobiology of SAD appears to involve neurochemical dysfunction, as evidenced by studies of neuroreceptor imaging, neuroendocrine function, and profiles of response to specific medications. Clinical trials have demonstrated that benzodiazepines and antidepressants are effective in the treatment of SAD. The selective serotonin reuptake inhibitors are emerging as the first-line treatment for SAD, based on their proven safety, tolerability, and efficacy. Goals for ongoing future research include development of approaches to achieve remission, to convert nonresponders and partial responders to full responders, and to prevent relapse and maintain long-term efficacy.This monograph explores the epidemiology, clinical presentation, and differential diagnosis of SAD, with a focus on neural circuitry of social relationships and neurochemical dysfunction. The prevalence, rates of recognition and treatment, patterns of comorbidity, quality-of-life issues, and natural history of SAD are discussed as well as pharmacologic and psychosocial treatment strategies for SAD.
Posttraumatic Stress Disorder in Posttransplant Children: Creating a Clinical Program to Address Their Needs
Authors: Emre Sukru 
Published: August 2016

AbstractPosttraumatic stress symptoms have been shown to occur in pediatric and adult solid-organ transplant recipients. The presence of these symptoms is associated with non-adherence to medications, increased distress, and poor outcome. Because posttraumatic stress disorder is treatable and because a transplant operation usually is an “anticipated trauma,” it is possible to address posttraumatic stress disorder symptoms in transplant recipients and attempt to prevent their development. Under my direction, the pediatric liver transplant program at Mount Sinai Medical Center in NewYork City created research and clinical programs to address posttraumatic stress symptoms and their consequences. Specifically, the focus on non-adherence to immunosuppressive medications in transplant recipients who are distressed and their parents. This article begins with a review of the data that led to the decision to start these programs. I then present the basic elements that are in place, in this particular program, to address patients' needs. I end this review with preliminary outcome data that illustrate the potential impact of such an integrated approach to patient care on medical outcomes.
Brain Reward Circuits in Alcoholism
Authors: Koob George F. , Roberts Amanda J. 
Published: August 2016

AbstractThis article discusses the neurocircuitry and the neurochemical systems, as well as the molecular elements within these systems, that are believed to be important in the etiology of alcoholism. Alcoholism is a complex behavioral disorder characterized by excessive consumption of alcohol; a narrowing of the behavioral repertoire toward excessive consumption; the development of tolerance and dependence; and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome.Recent work has begun to define the neurocircuits responsible for the major sources of positive and negative reinforcement that are key to animal models of excessive alcohol intake. Alcohol appears to interact with alcohol-sensitive elements within neuronal membranes that convey the specificity of neurochemical actions. Positive reinforcement appears to be mediated by an activation γ-aminobutyric acid A receptors, release of opioid peptides and dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic alcohol administration. This is reflected by their exhibiting opposite effects during acute alcohol withdrawal, and by the recruitment of other neurotransmitter systems, such as the stress neuropeptide corticotropin-releasing factor. These neuropharmacologic actions are believed to produce allostatic changes in set-point, which set up the vulnerability to relapse that is so characteristic of alcoholism. Future challenges include a focus on understanding exactly how these neuroadaptive changes convey vulnerability to relapse in animals with a history of alcohol dependence.
Investigating Tourette Syndrome as a Neurologic Sequela of Rheumatic Fever
Authors: Kurlan Roger 
Published: August 2016

AbstractSydenham's chorea is currently recognized as the only neurologic sequela of rheumatic fever. Recent evidence suggests that there may be a spectrum of neurobehavioral disturbances, particularly including tics and obsessive-compulsive disorder, that develops following streptococcal infection by the process of molecular mimicry, whereby antibodies directed against bacterial antigens cross-react with brain targets. This proposed postinfectious, immune-mediated condition has been termed “pediatric autoimmune neuropsychiatric disorders after streptococcal infection” (PANDAS). This article reviews research evidence in favor and also against the PANDAS concept and discusses the implications of the hypothesis.
Eating Disorders and Tourette Syndrome: A Case Series of Comorbidity and Associated Obsessive-Compulsive Symptomatology
Authors: Guarda Angela S. , Treasure Janet , Robertson Mary M. 
Published: August 2016

AbstractThere is a well-established overlap in phenomenology between anorexia nervosa and obsessive-compulsive disorder, and between obsessive-compulsive symptoms and Tourette syndrome (TS). Five cases of eating disorders in patients with obsessive-compulsive symptoms and TS are presented. The identification of four similar cases in the literature putatively marks a subset of eating disorders with a link to TS and to obsessive-compulsive symptomatology. This association may reflect a common underlying neurobiologic imbalance.