bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Neurophysiology of Childhood and Adolescent Bipolar Disorder
Authors: DelBello Melissa P. , Adler Caleb M. , Strakowski Stephen M. 
Published: August 2016

ABSTRACTIntroduction:Children and adolescents with bipolar disorder often present with higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear whether the differences in clinical presentation between youth and adults with bipolar disorder are due to differences in underlying etiologies or developmental differences in symptom manifestation. Neuroimaging studies of children and adolescents with bipolar disorder may clarify whether neurobiological abnormalities associated with early-and adult-onset bipolar disorder are distinct. Moreover, children and adolescents with bipolar disorder are typically closer to their illness onset than bipolar adults, providing a window of opportunity for identifying core neurobiological characteristics of the illness (ie, disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course.Methods:Peer-reviewed publications of neuroimaging studies of bipolar children and adolescents were reviewed.Results:Structural, neurochemical, and neurofunctional abnormalities in prefrontal and medical temporal and subcortical limbic structures, including the striatum, amygdala, and possibly hippocampus, are present in children and adolescents with bipolar disorder.Conclusion:Differences between neurobiological abnormalities in bipolar youth and adults as well as recommendations for future research directions are discussed.
Brain Network Dysfunction in Bipolar Disorder
Authors: Adler Caleb M. , DelBello Melissa P. , Strakowski Stephen M. 
Published: August 2016

ABSTRACTBipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.
Balancing Short-Term Symptom Control and Long-Term Functional Outcomes in Patients with Parkinson's Disease
Authors: Tetrud James W. 
Published: August 2016

ABSTRACTLevodopa has played a central role in the treatment of Parkinson's disease for nearly 40 years and remains the single most effective symptomatic treatment for the disease. However, the response to levodopa therapy changes over time, and its long-term use is commonly associated with disabling motor complications. For this reason, the appropriate role of levodopa in the treatment of Parkinson's disease—in particular, the question of when to initiate therapy with the drug—has been a matter of controversy. Because levodopa is the most effective treatment for Parkinson's disease, the management of this disease becomes a matter of balancing short-term symptom control with long-term functional outcomes. This article provides an overview of the basis for levodopa-associated motor complications and their impact on patients' clinical function and quality of life, followed by a discussion of strategies for managing these complications to achieve optimum symptom control while minimizing the adverse effects of long-term therapy.
Obsessive-Compulsive Disorder:Boundary Issues
Authors: Fineberg Naomi A. , Saxena Sanjaya , Zohar Joseph , Craig Kevin J. 
Published: August 2016

ABSTRACTThe boundaries between obsessive-compulsive disorder (OCD) and other neuropsychiatric disorders remain unresolved and may well differ from one disorder to another. Endophenotypes are heritable, quantitative traits hypothesized to more closely represent genetic risk for complex polygenic mental disorders than overt symptoms and behaviors. They may have a role in identifying how closely these disorders are associated with another and with other mental disorders with which they share major comorbidity. This review maps the nosological relationships of OCD to other neuropsychiatric disorders, using OCD as the prototype disorder and endophenotype markers, such as cognitive, imaging, and molecular data as well as results from demographic, comorbidity, family, and treatment studies. Despite high comorbidity rates, emerging evidence suggests substantial endophenotypic differences between OCD and anxiety disorders, depression, schizophrenia, and addictions, though comparative data is lacking and the picture is far from clear. On the other hand, strong relationships between OCD, Tourette syndrome, body dysmorphic disorder, hypochondriasis, grooming disorders, obsessive-compulsive personality disorder, and pediatric autoimmune neuropsychiatric disorders associated with streptococcus are likely. Studies designed to delineate the cause, consequences, and common factors are a challenging but essential goal for future research in this area.
Symptom Dimensions in Obsessive-Compulsive Disorder:Implications for theDSM-V
Authors: Leckman James F. , Rauch Scott L. , Mataix-Cols David 
Published: August 2016

ABSTRACTIn the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation.The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with “normal” worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's “tic-related” status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.
D-cycloserine Inhibits Amygdala Responses During Repeated Presentations of Faces
Authors: Britton Jennifer C. , Gold Andrea L. , Feczko Eric J. , Rauch Scott L. , Williams Danielle , Wright Christopher I. 
Published: August 2016

ABSTRACTIntroduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined.Methods: The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0±8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks.Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected.Conclusion: This finding may have relevance for testing treatments of anxiety and depression.
An Abbreviated Review of Immune Abnormalities in Schizophrenia
Authors: Rapaport Mark H. , Delrahim Katia K. 
Published: August 2016

AbstractInitial investigations of the possible interaction between schizophrenia and the immune system began in the early 1900s and have proceeded in a rather halting fashion because of the methodological challenges faced by investigators. However, a confluence of recent data suggests that activation of the inflammatory response system, the cellular immune system, and the humoral immune system may be present in some patients with schizophrenia. Some of the most compelling data support the hypothesis that minor levels of immune activation may be associated with acute psychotic exacerbations. However, a second body of evidence suggests that some individuals with schizophrenia may have chronic, evolving autoimmune processes. This article is an overview of the history, rationale, and some of the recent findings on the interaction between schizophrenia and the immune system.
Stiff-Person Syndrome: Autoimmunity and the Central Nervous System
Authors: Murinson Beth Brianna , Vincent Angela 
Published: August 2016

AbstractStiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.
Implications of the cAMP Signaling Pathway in Psychiatric Disorders: A Systematic Review of the Evidence
Authors: Perez Jorge , Tardito Daniela 
Published: August 2016

ABSTRACTThe last decade has seen a shift in the theoretical framework addressing the pathophysiology of psychiatric disorders. During this period, research endeavors have been directed toward investigating the biochemical mechanisms involved in the transduction of information from the cell surface to the cell interior. The emerging picture, supported by growing evidence, is that in addition to neurotransmitters and their receptors, various signal transduction pathways may be linked to the pathophysiology of major psychiatric disorders. In this review, the role of one such pathway—the cyclic adenosine monophosphate (cAMP) signaling pathway—will be highlighted. We review data suggesting the involvement of the upstream and downstream components of this system in the pathophysiology of psychiatric disorders.
An Unusual Case of Motor and Vocal Tics With Obsessive-Compulsive Symptoms in a Young Adult With Behçet's Disease
Authors: Budman Cathy , Sarcevic Adnan 
Published: August 2016

ABSTRACTBehçet's disease is a chronic relapsing-remitting, multi-system inflammatory disorder of unknown etiology, characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. The most common central nervous system findings are demyelization and perivascular cell infiltration; menin-goencephalitis, cerebral atrophy, and vascular thrombosis may also occur. Neuropsychiatric symptoms may include: paroxysmal dystonia, parkinsonism, delirium, hallucinations, and behavioral disturbances. We report an unusual case of explosive onset of motor and vocal tics with obsessive-compulsive symptoms in a 22-year-old male with Behçet's disease. The putative roles of infection and autoimmune mechanisms in the pathogenesis of tics and obsessive-compulsive symptoms are explored.
Global Benefit-risk Evaluation of Antidepressant Action: Comparison of Pooled Data for Venlafaxine, SSRIs, and Placebo
Authors: Entsuah Richard , Gao Bo 
Published: August 2016

ABSTRACTDo antidepressants have an equivalent risk-benefit ratio? Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is an effective antidepressant for treating major depression. The results of some clinical studies have suggested that venlafaxine may have more potent efficacy in sustaining remission in patients with major depression. Comparative clinical studies, however, lack suitable power to discern treatment differences in safety and also lack a quantitative basis for comparing risk and benefit. A global benefit-risk analysis of pooled data from eight randomized, double-blind, clinical trials of the safety and efficacy of venlafaxine and selective serotonin reuptake inhibitors (SSRIs) was performed. By using the ratio measure of risk-benefit, patients treated with venlafaxine (n=851) for 6–8 weeks experienced a relative gain of 1.57 compared with SSRI-treated patients (n=743) and a relative gain of 2.27 compared with placebo-treated patients (n=439). Subgroup analyses showed a relative gain of 1.35 for venlafaxine-treated patients (n=538) compared with fluoxetine-treated patients (n=549) and a relative gain of 2.53 compared with placebo-treated patients (n=357). A dose-response relationship was apparent between low (<75 mg/day), medium (75–150 mg/day), and high (>150 mg/day) dosages of venlafaxine; r values were 0.758, 0.822, and 1.181, respectively (P=.023, high dosage versus placebo; P=.030, medium dosage versus placebo). Important differences in risk and benefit exist between venlafaxine and SSRIs as a group compared with fluoxetine alone. A significant gain in benefit-risk in the treatment of major depression was observed with an increase in venlafaxine dosage from 75–>150 mg/day.
Axons, Cells, and Depression: The Nexus of Neurology and Psychiatry in Multiple Sclerosis
Authors: Gorman Jack M. , Finkel Jennifer 
Published: August 2016

In many ways, multiple sclerosis (MS) is among the most frustrating and vicious of human diseases. Although we can readily see the demyelinating effect of MS lesions on postmortem examination, the diagnosis during life is fraught with difficulty. Advances in cerebrospinal fluid analysis and neuroimaging techniques have contributed to a recent revision of diagnostic criteria for MS, yet the majority of patients still wait for years until a definitive diagnosis is reached. They then face a disease that is both highly unpredictable and, in most cases, severely debilitating.The unpredictable nature of MS is particularly distressing and many patients exist in a persistent state of fear and anxiety about their next MS exacerbation. Despite improved treatments, MS leaves some of the most severely affected patients wheelchair-bound by their early twenties. The more fortunate ones learn to deal with sporadic functional impairments for the rest of their lives. The unpredictable nature of MS leaves its victims always wondering about the next phase of their illness. For some, a more negative but definitive prognosis would be easier to accept than one for which the outcome is so unclear.To make matters worse, the cause of MS remains an elusive one. Research points to an infectious and/or autoimmune etiology. The disorder is more common among those living in northern hemispheres, afflicts women more often than men, and has a partial genetic basis as evidenced by a greater concordance rate for monozygotic than dizygotic twins that nevertheless, falls far short of what would be expected of an autosomal, Mendelian disease. Drugs that modulate the immune system, from steroids to interferons, are somewhat helpful. Yet despite this, the long-term prognosis for MS has not changed much in recent decades and no therapy exists that addresses the root pathophysiology of the disease—demyelination.
Detecting Cognitive Dysfunction in Multiple Sclerosis with a Magnetic Resonance Imaging Rating Scale: A Pilot Study
Authors: Chamelian Laury , Bocti Christian , Gao Fu-Qiang , Black Sandra E. , Feinstein Anthony 
Published: August 2016

AbstractObjective: In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction.Methods: Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. “Low” and “High” lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve.Results: Despite a similar demographic profile, subjects with a “High” lesion score performed significantly worse than the “Low” lesion score group on verbal (P=.007) and visuospatial (P=.02) memory, and on a global index of cognitive functioning (P=.001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (σ=0.82, P<.0001).Conclusion: CHIPS is helpful in clinically predicting cognitive impairment in MS.
Sex Steroids and Human Behavior: Implications for Developmental Psychopathology
Authors: Alexander Gerianne M. , Peterson Bradley S. 
Published: August 2016

AbstractIn a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.
Introduction The Transition from Reproductive Age to Menopause: Implications for Mental Health
Authors: Halbreich Uriel , Kornstein Susan 
Published: August 2016

The transition from reproductive age to menopause is a major milestone in the female lifecycle. It is a hormonal process with a very clear end result: a menopausal state—though its commencement is gradual and vague. It is unavoidable and perfectly normal. The age of the transition varies widely, a fact that hints at the possibility that the reproductive clock is individualized, ticking at a diversified pace. Therefore, the study of the menopausal transition may actually be a derivative of the study of reproduction because it marks the closing of that chapter in a woman's life.In a sequential approach, the period of transition is defined as perimenopause, or the menopausal transition, the beginning of the second phase in the life of the adult woman, characterized by a stable, low level of gonadal steroids, as opposed to the cyclic fluctuations during the reproductive phase. This imposed, though anticipated, closing of the reproductive chapter of life is often associated with mixed feelings.As reviewed by Andrea Riccardo Genazzani, MD, PhD, and colleagues, gonadal steroids exercise a profound effect on many body systems, including the brain, in which they have specific receptors, influencing neurotransmitters and other central nervous system (CNS) mechanisms that are considered to be involved in the regulation of mood, cognition, and behavior. Therefore, it would be anticipated that the menopausal decrease in activity levels of female gonadal hormones, ie, estrogen and progesterone, resulting in substantial changes in mood, cognition, and behavior of menopausal women—but this is not the case. This fact illuminates two issues of social and clinical significance: Menopause, per sé, is a normal healthy situation, and even though it is normal it is characterized by age-related processes that may be slowed down or delayed by gonadal steroids.
The Impact of Mood Stabilizers on Suicide in Bipolar Disorder: A Comparative Analysis
Authors: Goodwin Frederick K. , Ghaemi S. Nassir 
Published: August 2016

AbstractWhich mood stabilizers are the most effective in reducing suicide rates in patients with bipolar disorder? This paper reviews the literature and compares the data on two types of mood-stabilizing agents, lithium and anticonvulsants. Compared with the large amount of data on lithium, there is surprising little information available on the effects of anticonvulsants on mortality in manic-depressive illness. Each was also assessed in terms of suicide risk factors such as depression and mixed episodes, rapid cycling, substance abuse, anxiety and panic, and central serotonergic function. Only two studies that provide data demonstrating anticonvulsant efficacy in preventing suicide in bipolar disorder are available, and the data are incomplete at best. Further research in this area should include an emphasis on the outcome of mortality in patients treated with any of the anticonvulsants or with lithium-anticonvulsant combinations.
Current and Emerging Treatments for Cervical Dystonia
Authors: Factor Stewart A. , Lew Mark F. , Trosch Richard M. 
Published: August 2016

ABSTRACTCervical dystonia (CD), also known as spasmodic torticollis, is the most common of the focal dystonias. Muscle hypertrophy is present in nearly all patients, and neck pain is associated with CD in about 80% of patients. Remissions can occur in about 20% of patients, though most last under a year.Medical therapies have not generally worked well for patients with CD, and are typically associated with many side effects. Botulinum toxin (BT), which causes fewer side effects, has been considered the treatment of choice. Beyond medical therapy, various surgeries for CD have been performed for many decades. Of surgical treatments now in use, selective peripheral denervation is the most common.In CD, botulinum toxin type A (BT-A) targets pain, dystonic posturing, limited range of motion, and tremor. BT type B (BT-B) is a serotype of BT that is ontogenetically distinct from the type A toxin. There have been three randomized, multicenter, double-blind, placebo-controlled trials of BT-B. It appears that BT-B is a safe and effective treatment for patients with CD who are responsive or resistant to BT-A.