bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual Dysfunction in Major Depression
Authors: Williams Katherine , Reynolds Margaret F. 
Published: August 2016

AbstractLittle is known about the prevalence, typology, and natural course of non—drug-induced sexual dysfunction in patients with depression. Loss of libido has been reported in various studies to affect from 25% to 75% of patients with unipolar depression, and its prevalence appears to be correlated with the severity of depression. Disorders of arousal also appear to be relatively common in both men and women with major depression, of whom ~25% may experience problems with erection or lubrication. The scant available data regarding orgasmic difficulties in patients with depression who have not yet taken antidepressant medication suggest that they are more common than in the general population. The potential causes of sexual dysfunction in patients with depression are complex and little investigated, and future research must distinguish and explore the various biological, psychological, and psychosocial factors that are likely to be involved.
Fibromyalgia Syndrome: New Developments in Pathophysiology and Management
Authors: Russell I. Jon 
Published: August 2016

Fibromyalgia syndrome (FMS) is a common, chronically painful condition that is still seeking a home among the clinical professions. It is characterized by moderately severe soft-tissue pain and allodynia, which suggests a role for one group of specialists, but its pathogenesis is in the nociceptive machinery of the central nervous system, which defines the territory of other specialties. Comorbidities such as insomnia, cognitive dysfunction, depression, anxiety, recurrent headaches, dizziness, fatigue, morning stiffness, dysesthesia, irritable bowel syndrome, and irritable urethra logically invoke input from practitioners from almost every field of medicine.The precipitating causes of FMS may vary among individuals, but a mechanism underlying the painful symptoms involves central sensitization leading to an amplified perception of pain. As a result, this condition is recognized as the human model for chronic widespread allodynia. Biological abnormalities that are detected in most patients by objective methods include dysfunctional sleep (polysomnography), central sensitization (functional magnetic resonance imaging), temporal summation (windup, second pain), and facilitation of nociception (elevated spinal fluid levels of substance P, deficient biogenic amines that fail to maintain descending inhibition, and, in primary FMS, elevated spinal fluid levels of nerve growth factor).Treatment of FMS is symptomatic and multimodal, including education, physical modalities, and medications that target central neural pathways. Rehabilitation goals include improved physical function, social adaptation, emotional balance, and a better quality of life. Several series of placebo-controlled clinical trials have made available new medications with unique therapeutic mechanisms. Thus, it can be predicted that the next 10 years will see validation of a clinical case definition, more interest in the underlying pathogenesis, a better understanding of how medical care should be adapted to subgroup variations, new medications with specific domain indications, mechanism-directed polypharmacy, characterization of the genetic predisposition, and more emphasis on preventable inciting events.
Use of Magnetic Resonance Imaging to Identify Mild Cognitive Impairment: Who Should Be Imaged?
Authors: Apostolova Liana G. 
Published: August 2016

Problems with memory are a very common complaint in the elderly and are not synonymous with dementia. Some degree of cognitive decline, manifested as greater difficulty in learning and retrieving new information for instance, develops with normal aging. Thus many older patients do not perform at the same level they did when they were younger but they do perform well when compared to their peers. For many, cognitive change ends at this stage and they proceed to lead normal, healthy, dementia-free lives.The cohort that has cognitive changes beyond what is expected in normal aging but does not yet meet criteria for dementia concerns clinicians greatly as many of these patients eventually become demented. These patients usually go through a latent stage in which neurodegenerative pathology silently spreads in the brain. Once there is enough pathological burden, cognitive decline beyond what is expected for normal aging can be detected by formal neuropsychological testing. Frequently such patients go through a state called mild cognitive impairment (MCI). In this state patients are still functionally intact and live independently, but show cognitive impairment relative to the age- and education-adjusted norms.The MCI state in itself is a prominent risk factor for developing dementia. Most patients with amnestic MCI develop Alzheimer’s disease (AD) dementia over time. At six years, as many as 80% progress to AD. Thus, MCI is a very important topic of research and an increasingly important topic of clinical care.
FDG and Amyloid Positron Emission Tomography
Authors: Mintun Mark A. 
Published: August 2016

For over 20 years, researchers have used the tracer [18F]fluorodeoxyglucose (FDG) in positron emission tomography (PET) imaging. FDG PET imaging has been utilized to study the characteristic metabolic changes in Alzheimer’s disease (AD), and as more molecular imaging tracers become available for human research, PET will likely assume many new roles for investigating more specific abnormalities, such as amyloid deposition, in the future.FDG is a glucose analog that images glucose metabolism and also illustrates neural firing. Different synapse activity, particularly excitatory activity from glutamate release, appears to change FDG uptake. AD will affect both brain infrastructure by decreasing the amount of cell bodies and synapses as well as decreasing synaptic activity, which are both changes that decrease the amount of FDG. AD is not a perfectly uniform process, and this is reflected by distinct progressive patterns of decreased FDG and decreased metabolism across different regions of the brain.FDG enters the brain via blood flow, and then into brain tissue by both diffusion and facilitated transport. Once it enters the glia and neurons, FDG can be phosphorylated, a step that is essentially irreversible, but then cannot be processed further by the cells, effectively trapping the FDG in situ. The amount of trapping that occurs in the brain over the first 10–20 minutes is very high and constitutes over 80% of the uptake. Thus, after the first 10–20 minutes uptake phase, a pattern of FDG emerges that mirrors the distribution of glucose metabolism in all subcortical and cortical structures.
Treatment of Bipolar Mania
Authors: Post Robert M. , Janicak Philip G. , DelBello Melissa P. , Ginsberg David L. 
Published: August 2016

AbstractWhile severity of manic episodes can be successfully reduced, repeated recurrences are common with ~40% of patients meeting criteria for rapid cycling after aggressive treatment. Manic episodes present much earlier in children of bipolars and due to unique presentation physicians often mistakenly diagnose such children with attention-deficit/hyperactivity disorder. Differential symptoms include suicidal thoughts, grandiosity, hallucinations, and depressive withdrawal. Such children may require the usual combination treatment with a mood stabilizer and an antipsychotic, with the addition of a stimulant as well. Treatment of adults and children often includes second-generation antipsychotics, which have increasingly shown efficacy both as monotherapy and adjunctive treatments of acute mania. Most recently, some anticonvulsants have demonstrated acute antimanic properties as well and more studies of their role in bipolar disorder are underway.
The Expanding Role of Antipsychotics
Authors: Janicak Philip G. 
Published: August 2016

Antipsychotics have been utilized in the treatment of bipolar disorder for many decades and were the mainstay of treatment before lithium was reintroduced in the late 1960s. Today, many bipolar patients who present with psychotic features are misdiagnosed and prescribed an antipsychotic for another disorder. Estimates of psychotic symptoms in bipolar disorder, particularly during a manic episode, are ≥50% by clinical assessment and even higher by individual reports. Thus, antipsychotics are frequently used: as first treatment for psychosis not recognized as bipolar disorder, and as an adjunct to a mood-stabilizing agent in bipolars with psychotic symptoms.Most recently, antipsychotics have been examined for their mood-stabilizing properties as well (Slide 9). One may conceptualize using a selective serotonin reuptake inhibitor (SSRI) antidepressant for disorders such as panic disorder or obsessive-compulsive disorder, and using an antiepileptic as a mood-stabilizing agent; however, it is more difficult to accept that an agent approved for treatment of psychosis can be a primary therapy for bipolar disorder. Data from the monotherapy trials suggest that second-generation antipsychotics (SGAs) are at least as effective as lithium and valproic acid for acute mania. There is a very large database indicating that SGAs can be utilized as monotherapy for acute mania. However, there is limited data on the role of these agents in prevention of relapse and recurrence and in their efficacy for depression in the context of bipolar disorder. More studies will be needed to clarify whether SGAs should be used as monotherapy or whether they would be best used as augmenting agents in severe and psychotically manic or depressed patients.
Prevalence and the Shift in Age of Onset
Authors: DelBello Melissa P. 
Published: August 2016

Bipolar disorder is presenting at a younger age of onset. In the past, many children with bipolar disorder were undiagnosed and ended up in juvenile detention centers. These children were also often misdiagnosed with severe attention-deficit/hyperactivity disorder (ADHD) or conduct disorder. In addition, an increased prevalence rate of substance use disorders and possibly stimulant prescriptions may be responsible for the shift in age of onset of bipolar disorder. The most compelling epidemiological observations have come out of the Netherlands, where they typically treat ADHD behaviorally rather than with stimulants. Childhood bipolar disorder remains unidentified in the Netherlands despite aggressive searching, whereas adolescent and adult bipolar disorder has been found in numbers similar to those in the United States. This provides cross-sectional epidemiological evidence that stimulants may be shifting the age of onset in patients who are presenting with potentially prodromal bipolar symptoms. Lastly, several researchers speculate that trinucleotide repeats in the DNA (deoxyribonucleic acid) may be responsible for so-called genetic anticipation phenomenon, by which expansion of trinucleotide repeats in successive generations may be shifting the age of onset to an earlier age. These are just some of the mechanistic possibilities for why we are seeing a shift in the age of onset of bipolar disorder.Lewinsohn and colleagues found that the lifetime prevalence of adolescent bipolar I and II disorder is ~1%, with a 5% lifetime prevalence rate of subsyndromal bipolar disorder. Many symptomatic children and adolescents do not meet full duration criteria for a hypomanic or manic episode, or they may be one symptom short of meeting criteria for the disorder.
Introduction—Recent Advances in Understanding and Treating the Anxiety Disorders
Authors: Stein Dan J. , Denys Damiaan 
Published: August 2016

Anxiety disorders are the most common of the psychiatric disorders, with an estimated prevalence of 2% to 18% worldwide. Psychiatry is gradually progressing towards a clinical neuroscience with an improved understanding of the pathophysiology of psychiatric disorders, an individualized approach to diagnosis and treatment of patients, and the potential for early disorder detection and prevention. Recently, there has been not only a growing literature on effective interventions for anxiety disorders, but also new proof of principle treatment studies based on laboratory research.Anxiety disorders are frequently discussed at international psychiatric conferences; however, the attention these disorders receive by researchers at large is often minimal compared with their overall contribution to the substantial clinical burden and economic costs of mental disorders. There are potential advantages for clinicians and researchers to convene for the purpose of reviewing recent advances in anxiety disorder research and to exchange ideas about future progress in this field. The Anxiety Disorders Association of America has sponsored highly productive meetings in the United States for many years as well as successful meetings in other countries. Positive outcomes from these meetings encouraged the initiation of an international conference series that centers specifically on anxiety disorders.
Everyday Problems in Treating Depression: Focus on SNRIs
Authors: Kasper Siegfried 
Published: August 2016

Most effective antidepressants directly or indirectly increase the synaptic concentrations of serotonin (5-HT) and/or norepinephrine (NE) by blocking the reuptake of one or both of the neurotransmitters. This property was initially discovered with the tricyclic antidepressants (TCAs). Their various additional interactions at different receptors and ion channels are not required for antidepressant action, but are responsible for the poor tolerability and toxicity in overdose of the early antidepressants.The selective serotonin reuptake inhibitors are effective and well tolerated. Selective norepinephrine reuptake inhibitors, such as reboxetine, also have proven antidepressant activity. A selective action on one or the other of the principal monoamines thus appears to be sufficient for antidepressant activity. The idea that a dual action on both neurotransmitters might produce greater efficacy in certain patients led to the development of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants, which block the reuptake of both 5-HT and NE without the nonspecific, side-effect–inducing interactions of the TCAs. The three SNRIs—venlafaxine, milnacipran, and duloxetine—constitute a new class of antidepressants.Antidepressant response rates rarely exceed 60% to 70% and remission rates are usually <50%. Although SNRIs clearly provide superior efficacy in certain populations, their use has not dramatically changed antidepressant therapy. The search for agents that are more effective, rapidly acting, and better tolerated continues. However, clinicians must find ways to better use the antidepressants that are available today. This supplement, based on a symposium held at the International Forum on Affective Disorders in Budapest in December 2007, discusses several everyday problems in the treatment of depression, with a focus on SNRIs.
Treatment of Comorbid Pain with Serotonin Norepinephrine Reuptake Inhibitors
Authors: Briley Mike , Moret Chantal 
Published: August 2016

AbstractComorbid chronic pain is common in depressed patients. It is predictive of a poor prognosis for depression and is a major risk factor for suicidal behavior. Depression and chronic pain may result from a common neurobiological dysfunction of monoamine cell bodies in the basal ganglia. Amitriptyline, which inhibits both serotonin and norepinephrine reuptake, is a preferred treatment of chronic pain although it is not officially indicated for this condition. Chronic pain can be modeled in animals where amitriptyline has been shown to be highly effective. Similar effects are obtained with the serotonin norepinephrine reuptake inhibitors milnacipran, duloxetine, and venlafaxine, whereas selective serotonin reuptake inhibitors (SSRIs) are only weakly active. Both animal and clinical studies of chronic pain show that dual-acting reuptake inhibitors are more active than selective norepinephrine reuptake inhibitors, which are, in turn, more active than SSRIs. A meta-analysis of placebo-controlled studies confirmed that dual-action antidepressants, but not SSRIs, were effective in reducing chronic lower-back pain. Milnacipran, duloxetine, and venlafaxine, have all been reported to be effective in a number of chronic pain conditions, including the treatment of fibromyalgia where their analgesic effects are independent of comorbid depression.
Assessment and Diagnosis of Excessive Daytime Sleepiness
Authors: Bogan Richard K. 
Published: August 2016

The symptoms of excessive daytime sleepiness (EDS) need to be assessed both clinically and with objective diagnostics. As with any other medical disorder, when patients present with excessive sleepiness, the first step is to determine the chief complaint. The spectrum of clinical presentations for EDS is wide, and patients may complain of fatigue, low energy, laziness, apathy, lethargy, poor memory, reduced concentration, reduced attention, irritability, poor performance in work/school, automatic behavior, frequent accidents, drowsiness, and/or sleep attacks. Oftentimes patients do not recognize their own excessive sleepiness and will not quantify the problem unless they are specifically asked if they are sleepy. Some of these patients only present because they have been referred by their employers due to their excessive sleepiness.After the patient has noted his chief complaint, the clinician should assess the patient's score on the Epworth Sleeping Scale (ESS) on a quantifiable basis. The ESS is a self-administered questionnaire used to rate the severity of EDS. Respondents are asked to use a numeric scale from 0 to 3, corresponding to the likelihood (never, slight, moderate, and high) that they may fall asleep in eight given situations (Slide 1). An ESS score can range from 0 to 24. A score >9 indicates an abnormal level of sleepiness. A score >14 suggests marked sleepiness. Most patients with narcolepsy will score in this range. The normal range varies for different sleep disorders (Slide 2).
Delirium and Isolated Angiitis of the Central Nervous System: A Case Report and Review
Authors: Carandang Carlo G. , Grant Allison L. 
Published: August 2016

ABSTRACTCentral nervous system (CNS) vasculitis is a rare entity, especially when it occurs in isolation; it is seen more commonly as part of a multisystem vasculitis. Common presenting symptoms include persistent headache, encephalopathy, and multifocal signs. We discuss the case of a 68-year-old female who presented twice in 1 month with confusion and choreaform movements. Extensive workup was negative for a connective tissue disease or other conditions in the differential, including neurosarcoidosis, Creutzfeldt-Jakob disease, and neurosyphilis. The only significant findings were elevated erythrocyte sedimentation rate, inflammatory signs in the CNS, and diffuse slowing of the electroencephalogram. A presumptive diagnosis of isolated angiitis of the central nervous system (IACNS) was made and the patient was successfully treated with steroids. She recovered fully with no residual symptoms. The diagnosis of IACNS is often difficult given there are no definitive laboratory investigations or pathognomonic presentation. However, a series of signs, symptoms, and laboratory findings have been proposed that are helpful in making the diagnosis. To our knowledge, IACNS presenting primarily with delirium has not been previously reported in the literature. The diagnosis of IACNS is purely speculative for this case, as the gold standard for diagnosis, a leptomeningeal cortical biopsy, was not performed.
Conclusion: The Future of Single-Isomer Pharmacology
Authors: Rosenbaum Jerrold F. 
Published: August 2016

Taken together, the articles gathered in this supplement underscore the major role in drug development that single-isomer science can play—a role that will undoubtedly take on a greater importance in the future. While the chirality of certain pharmacologically active molecules has been recognized for almost a century, it is only in recent years that drug synthesis and chiral separation techniques have advanced far enough to allow meaningful comparisons among enantiomers. Now that these methods are broadly available, the potential applications of single isomer drug development are considerable.Numerous examples from a range of therapeutic areas confirm that single enantiomers can enhance clinical efficacy, reduce adverse effects, cause fewer interactions with other drugs, and minimize response variations among patients by offering more predictable pharmacokinetics and greater selectivity. In some cases, these advantages are simply due to the removal of an inactive enantiomer, but in other cases, a given dose of a single isomer offers greater benefits when administered alone than when administered as the racemic mixture, suggesting that the opposite enantiomer (the distomer) actually has detracting effects. As the papers by Drs. Gal and Hurt explain, the different activities of a pair of enantiomers are usually traceable to stereochemical differences in the way they interact with chiral macromolecules such as enzymes, transport systems, and receptors.
Bipolar Disorder in Children and Adolescents
Authors: Wolf Dwight V. , Wagner Karen Dineen 
Published: August 2016

AbstractThere is increased recognition that bipolar disorder has an early age of onset. The prevalence of bipolar disorder in prepubertal children has not been determined, however the prevalence in adolescence is ˜1%. Bipolar disorder in children poses a diagnostic challenge since the symptoms may differ from those in late adolescence and adulthood. Comorbid disorders, such as attention-deficit/hyperactivity disorder, further complicate both the diagnosis and course of the disorder. There is increasing evidence of the chronicity and severity of this disorder in youths. Bipolar disorder significantly disrupts a child's psychosocial development including impairments in academic functioning, family functioning, and relationship with peers. Although this disorder has significant morbidity in children and adolescents, there is a paucity of controlled studies to assess the efficacy and safety of mood stabilizers in the treatment of this disorder in youths. The treatment literature consists largely of case studies, retrospective chart reviews, and open-label studies. There is a compelling need for double-blind, placebo-controlled trials to determine whether commonly used medications to treat this disorder are significantly superior to placebo. Since many children in clinical practice require more than one psychotropic medication to adequately manage this disorder, studies of combination treatments are warranted. This review will provide an overview of the literature of bipolar disorder in children and adolescents, including discussion of the prevalence, diagnosis, epidemiology, course of the illness, and treatment issues.