bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Histamine H1 Antagonism: Novel Hypnotic and Pharmacologic Actions Challenge Classical Notions of Antihistamines
Authors: Stahl Stephen M.
Published: August 2016

Numerous “antihistamines” as well as various psychotropic medications with antihistamine properties are widely utilized to treat insomnia. Over-the-counter sleep aids usually contain an antihistamine and various antidepressants and antipsychotics with antihistamine properties have sedative-hypnotic actions. Although widely used for the treatment of insomnia, many agents that block the histamine H1 receptor are also widely considered to have therapeutic limitations, including the development of next-day carryover sedation, as well as problems with chronic use, such as the development of tolerance to sedative-hypnotic actions and weight gain. Although these clinical actions are classically attributed to blockade of the H1 receptor, recent findings with H1 selective agents and H1 selective dosing of older agents are challenging these notions and suggest that some of the clinical limitations of current H1-blocking agents at their currently utilized doses could be attributable to other properties of these drugs, especially to their simultaneous actions on muscarinic, cholinergic, and adrenergic receptors. Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics.
Anxiety Disorders and Rheumatic Fever: Is There an Association?
Authors: Seixas André Augusto Anderson , Hounie Ana Gabriela , Fossaluza Victor , Curi Mariana , Alvarenga Pedro Gomes , De Mathis Maria Alice , De Mathis Maria Eugênia , Vallada Homero , Pauls David , Pereira Carlos Alberto de Bragança , Miguel Eurípedes Constantino
Published: August 2016

Introduction:

Findings suggest that obsessive-compulsive disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF).

Objectives:

To determine whether RF or Sydenham's chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC.

Methods:

This was a case-control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members.

Results:

Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF, GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family.
Treatment of Severe, Treatment-Refractory Obsessive-Compulsive Disorder: A Study of Inpatient and Community Treatment
Authors: Boschen Mark J. , Drummond Lynne M. , Pillay Anusha
Published: August 2016

Introduction:

This research reports on a prospective outcome study of two cohorts of patients with severe, chronic, resistant obsessive-compulsive disorder (OCD).

Methods:

One cohort consisted of a total of 52 patients treated in an inpatient setting, while the second group comprised 65 patients treated in a community-outpatient setting. Treatment consistent primarily of intensive graded exposure and self-imposed response prevention augmented with cognitive restructuring.

Results:

The groups demonstrated significant improvement over the course of treatment. In the inpatient and community groups, there was significant improvement over the first 12 weeks of treatment, and further improvement between 12 and 24 weeks.

Conclusion:

These results suggest that even for patients who have demonstrated treatment-resistance, there may be benefit in intensive behavioral treatment of OCD. In addition it was found that even for those patients with the most profound refractory OCD and complicating factors inpatient stays of up to 24 weeks were effective in reducing symptoms.
Taking the Next Steps in the Treatment of Alzheimer's Disease: Disease-Modifying Agents
Authors: Salloway Stephen
Published: August 2016

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the United States and the number of AD patients is increasing at an alarming rate. There is no cure for AD and the currently available treatments are symptomatic, providing only limited effects on disease pathophysiology and progression. An overwhelming need exists for therapies that can slow or halt this debilitating disease process. Disease modification in AD has been defined from patient-focused, regulatory, and neurobiological perspectives. The latter two of these perspectives rely largely on an interruption of the disease process and a clear demonstration of this interruption. As defined by Cummings, a disease-modifying treatment is a “pharmacologic treatment that retards the underlying process of AD by intervening in the neurobiological processes that constitute the pathology and pathophysiology of the disease and lead to cell death or dysfunction.” By this definition, the burden of confirmatory study is placed on any new treatment for which the claim of “disease modification” is to be made (Slide 1).
Deep Brain Stimulation or Duodenal Levodopa/Carbidopa Infusion: Choosing the Right Therapy for Individual Patients
Authors: Volkmann Jens
Published: August 2016

Parkinson's disease is a progressive neurodegenerative disorder with prominent motor features. The cardinal motor signs, bradykinesia, rigidity, and tremor, are treated effectively by dopaminergic therapies. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment, and as the disease progresses, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods (when medication effects wear off) and dyskinesia (dystonic or choreatic movements) (Slide 1). Risk factors for motor complications include younger age at disease onset, longer disease duration, higher levodopa dosage, and more severe motor symptoms.
Studies of Anticipation in Bipolar Affective Disorder
Authors: Lange Kezia J. , McInnis Melvin G.
Published: August 2016

Anticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.
Finding Genes for Bipolar Disorder in the Functional Genomics Era: From Convergent Functional Genomics to Phenomics and Back
Authors: Niculescu Alexander B. , Kelsoe John R.
Published: August 2016

Psychiatric genetics, while promising to unravel the mechanisms of psychiatric disorders, has proven to be a challenging field. Psychiatric disorders, like other common genetic traits, are complex and heterogeneous. Psychiatric genetics has also suffered from a lack of quantifiable, biology-based phenotypes. However, the field is currently at an opportune moment. The work of various investigators is on the verge of paying rich dividends. Efforts at positional cloning are being greatly accelerated by the fruits of the Human Genome Project. New tools of functional genomics, such as expression profiling and proteomics, are being applied to animal models. These two methods can complement each other in an approach we have termed convergent functional genomics. Lastly, improvements in the measurement of biologically distinct endophenotypes—or phenomics—will lead to a better understanding of the mapping of genes to phenotypes in both animal and human systems.
A Review of Adult ADHD: A Neuropsychological and Neuroimaging Perspective
Authors: Kaplan Richard F. , Stevens Michael C.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder which effects an estimated 3% to 5% of children. Despite estimates that ADHD persists in 30% to 70% of adults having had the disorder in childhood, ADHD in adulthood remains controversial. This report summarizes current thinking in the diagnosis and etiology of adult ADHD. Most theories posit that ADHD is related to anomalies in frontal lobe function and dopaminergic transmission. However, there is debate as to whether ADHD is a unitary disorder with different manifestations, a syndrome, or multiple disorders. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classifies ADHD into inattention, hyperactivity-impulsivity, and combined subtypes. Although problems with cognition are core ADHD symptoms, self reporting has not been a reliable predictor of neuropsychological test performance. Nevertheless, we suggest that a performance-based diagnosis, including empirically derived, age-sensitive neuropsychological tests, provides the best hope of dissociating ADHD from psychiatric disorders with similar symptoms. We also describe the promise of new neuroimaging technologies, such as functional magnetic resonance imaging, in elucidating the pathophysiology of ADHD and similar psychiatric disorders.
Inferring Structural and Architectural Features of Brain Tissue from DT-MRI Measurements
Authors: Pierpaoli Carlo
Published: August 2016

Diffusion tensor magnetic resonance imaging is an imaging modality that measures the diffusion properties of water molecules in tissues noninvasively. Water diffusion is affected by tissue constituents, such as macromolecules, membranes, organelles, as well as by tissue microstructure, architecture, and organization. From the quantities measured with diffusion tensor-magnetic resonance imaging, one can infer information about brain tissue that cannot be obtained using conventional, compositional-based (eg, proton density and chemical spectroscopy), or relaxometry-based (eg, magnetization transfer, T1, T2, and T2*) magnetic resonance imaging methods. Understanding the relationship between a measured water diffusion pattern and the underlying histological features of the tissue, however, is not simple. In the absence of a robust and comprehensive model of water diffusivity in biological tissues, the biological interpretation of diffusion measurements relies on empirical evidence. Herein, the properties of several diffusion tensor-derived quantities are reviewed, together with the experimental evidence that helps clarify their relationship with the underlying properties of brain tissue.
Quantitative DT-MRI Investigations of the Human Cingulum Bundle
Authors: Makris Nikos , Pandya Deepak N. , Normandin Joseph J. , Papadimitriou George M. , Rauch Scott L. , Caviness Verne S. , Kennedy David N.
Published: August 2016

White matter fiber pathways are key structural components of the brain and its functional organization. The limbic system carries a great deal of its anatomic connectivity via the cingulum bundle. By allowing the in vivo delineation of the stem of the major fiber pathway systems, diffusion tensor magnetic resonance imaging has opened a new window into the detailed structure of the white matter in health and disease. Topographic, biophysical, and volumetric information about fiber tracts will provide a more complete understanding of the brain. By appreciating its interconnections, the precise anatomical knowledge of the cingulum bundle will improve our understanding of the limbic system and may enable improvements in the assessment and treatment of neuropsychiatric disorders. In this study, the stem of the cingulum bundle was investigated and defined in terms of its trajectory, anisotropy, and volume, in four normal human subjects, using diffusion tensor imaging.
How Well Does Cognitive-Behavioral Therapy Treat Symptoms of Complex PTSD? An Examination of Child Sexual Abuse Survivors Within A Clinical Trial
Authors: Resick Patricia A. , Nishith Pallavi , Griffin Michael G.
Published: August 2016

Are brief cognitive-behavioral treatments for posttraumatic stress disorder (PTSD) also effective for the wider range of symptoms conceptualized as complex PTSD? Female rape victims, most of whom had extensive histories of trauma, were randomly assigned to cognitive-processing therapy, prolonged exposure, or a delayed-treatment waiting-list condition. After determining that both types of treatment were equally effective for treating complex PTSD symptoms, we divided the sample of 121 participants into two groups depending upon whether they had a history of child sexual abuse. Both groups improved significantly over the course of treatment with regard to PTSD, depression, and the symptoms of complex PTSD as measured by the Trauma Symptom Inventory. Improvements were maintained for at least 9 months. Although there were group main effects on the Self and Trauma factors, there were no differences between the two groups at posttreatment once pretreatment scores were covaried. These findings indicate that cognitive-behavioral therapies are effective for patients with complex trauma histories and symptoms patterns.
Cognitive-Behavioral Therapy for Panic Disorder: A Review of Treatment Elements, Strategies, and Outcomes
Authors: Rayburn Nadine Recker , Otto Michael W.
Published: August 2016

This article provides an overview of cognitive-behavioral therapy (CBT) for panic disorder. CBT is currently considered a first-line treatment for panic disorder. It offers benefit after short-term intervention, typically consisting of 12–15 sessions conducted in either an individual or a group format. The treatment focuses on the elimination of the patterns that underlie and perpetuate the disorder. Through CBT, patients learn about the nature of the disorder and acquire a set of strategies that counter the fears of panic attacks themselves, and break the recurring cycle of anticipatory anxiety, panic, and agoraphobic avoidance. The collaborative format of treatment, and a focus on elimination of core fears may be factors in enhancing longer-term outcome. In this article, we review the efficacy of CBT as a first-line treatment, a strategy for medication nonresponders, a replacement strategy for patients who wish to discontinue pharmacotherapy, and a potential preventive strategy for at-risk individuals. We also discuss some of the complex issues involved with combination-treatment strategies.
Topiramate in the Preventive Treatment of Episodic Migraine: A Combined Analysis From Pilot, Double-Blind, Placebo-Controlled Trials
Authors: Edwards Keith R. , Potter Doreen L. , Wu Shu-Chen , Kamin Marc , Hulihan Joseph
Published: August 2016

The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6—8 week titration, and 8–12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.
Restless Legs Syndrome and Drug-Induced Akathisia in Headache Patients
Authors: Young William B. , Piovesan Elcio J. , Biglan Kevin M.
Published: August 2016

The purpose of the research presented in this article was to characterize restless legs syndrome (RLS) in a headache population and correlate treatment induced risks with dopamine blockers. Fifty patients with severe headache who were admitted to an outpatient infusion center were enrolled. The diagnosis of RLS was established using the International Restless Legs Syndrome Study Group criteria. Patients were screened for baseline akathisia using an akathisia scale and reexamined for akathisia after receiving intravenous infusion with one of four dopamine receptor blocking agents as treatment for their headaches. A change from baseline to post-infusion assessment of two points on a global assessment of akathisia was considered positive for drug-induced akathisia. Our results indicated that 41 (82%) of patients had episodic or chronic migraine. The rest had new daily persistent headache, cluster, or posttraumatic headache. Seventeen subjects (34%) met the criteria for RLS. Nineteen (38%) of the subjects developed drug-induced akathisia. Thirteen (76.5%) of the subjects with RLS developed akathisia compared with only 6 of the 33 (18.2%) without RLS (P<.0001). Finally, we concluded that headache patients with RLS are at a greatly increased risk of developing drug-induced akathisia when treated with intravenous dopamine receptor blocking agents.
Putative Common Pathways in Therapeutic Brain Stimulation for Affective Disorders
Authors: Bolwig Tom G.
Published: August 2016

Brain stimulation methods in the treatment of affective disorder are electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Clinically, ECT is considered the strongest remedy in the treatment of severe depression, especially depression with psychotic features, and in the elderly. TMS, despite positive reports, is somewhat more controversial. VNS has, so far, only been used in treatment-resistant depression with limited results. DBS may be of potential use in rare cases of treatment-resistant cases of affective disorder. This article highlights the similarities and differences between the four stimulation methods. The main difference is the seizures necessary in ECT. A stronger involvement of the hippocampus following experimental seizures compared with effects in that region induced by TMS and VNS might explain the consistent findings of the superiority of ECT in the most severe cases of affective disorder.
Norepinephrine Function in Personality Disorder: Plasma Free MHPG Correlates Inversely With Life History of Aggression
Authors: Coccaro Emil F. , Lee Royce , McCloskey Michael
Published: August 2016

Objective:

Clinical and pre-clinical data suggest the possibility of a facilitory role for norepinephrine (NE) in impulsive-aggressive behavior. While clinical studies have focused on putative central measures of NE activity, few studies have been published using peripheral measures. In this study, the relationship between plasma free NE metabolite, plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG), and impulsive aggression was explored in subjects with personality disorder.

Methods:

Subjects were 30 male subjects with personality disorder in whom basal plasma free MHPG concentrations were obtained. Aggression was assessed using the Life History of Aggression (LHA) assessment and the Buss-Durkee Aggression scales; impulsivity was assessed using the Barratt Impulsiveness and the Eysenck Personality Questionnaire Impulsivity scales.

Results:

A significant inverse correlation was found between LHA-Aggression and pMHPG in these subjects. Correlations with other behavioral measures were not statistically significant. pMHPG was significantly lower among subjects with borderline personality disorder but not significantly lower after controlling for LHA-Aggression scores.

Conclusion:

These data suggest that pMHPG is inversely correlated with life history of aggression in subjects with personality disorder and that central and/or peripheral NE may play a role in modulating aggressive behavior in these subjects.
The Role of Childhood Trauma in Differences in Affective Instability in Those With Personality Disorders
Authors: Goodman Marianne , Weiss Daniel S. , Koenigsberg Harold , Kotlyarevsky Vladimir , New Antonia S. , Mitropoulou Vivian , Silverman Jeremy M. , O'Flynn Karen , Siever Larry J.
Published: August 2016

Background:

This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174).

Methods:

Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure.

Results:

A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21–.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores.

Conclusion:

This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder.
Stroke-Associated Acquired Stuttering
Authors: Fawcett Robert G.
Published: August 2016

In this case report, the syndrome of acquired stuttering is described including its etiology, common presenting features, and differences from developmental stuttering. A case is described in an elderly female patient with sudden acquired stuttering associated with ischemic infarct near the left basal ganglia.
The Impact of Comorbidity on the Management of Pathological Gambling
Authors: Dell'Osso Bernardo , Hollander Eric
Published: August 2016

A 30-year-old woman with severe pathological gambling and cyclothymia presented to our program with no previous history of pharmacologic or psychotherapeutic treatment. Pathological gambling is an impulse-control disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) in which comorbidity is common, particularly with substance abuse, obsessive-compulsive disorder and mood disorders. As described in this case, pathological gamblers with bipolar comorbidity may be effectively treated with mood stabilizers such as lithium. After receiving 10 weeks of lithium treatment, the patient showed improvement in both gambling behavior and affective instability. The identification of specific subtypes among patients with pathological gambling may be relevant to the choice of pharmacologic treatment.
Anxiety and Schizophrenia: The Interaction of Subtypes of Anxiety and Psychotic Symptoms
Authors: Huppert Jonathan D. , Smith Thomas E.
Published: August 2016

Objective

To examine the interaction of specific anxiety subtypes and psychosis.

Introduction

Accumulating evidence suggests that anxiety and its disorders play a significant role in patients with schizophrenia, but few studies have examined multiple types of anxiety and how they interact with different symptoms of schizophrenia.

Methods

Thirty-two patients diagnosed with schizophrenia or schizoaffective disorder were assessed through self-report measures and interviewer rating scales to examine symptoms of psychosis and anxiety.

Results

A majority of patients (62%) were diagnosed with at least one comorbid anxiety disorder. Obsessive-compulsive symptoms and social anxiety symptoms were related to positive symptoms, bizarre behavior, and quality of life (QOL). Furthermore, panic and social anxiety were related to suspiciousness/paranoia. No consistent relationship was found with negative symptoms. Finally, severity of anxiety disorders was negatively correlated with the severity of formal thought disorder.

Discussion

This is one of the first studies to simultaneously examine the interrelationships of different types of anxiety symptoms and psychotic symptoms. The present findings are consistent with the studies that have suggested relationships between panic and paranoia and comorbid anxiety disorders and impaired QOL. These data suggest that further research into anxiety in schizophrenia, including the cognitive and neurobiological correlates, may help elucidate the mechanisms involved in the manifestation of these psychopathologies

Conclusion

Anxiety disorders are common in patients with schizophrenia. The presence of such symptoms may influence the presence of core psychotic symptoms and QOL. More information is needed in terms of the relationship between treatment of these symptoms and changes in psychotic symptoms and/or relapse prevention.
Pain Perception in Irritable Bowel Syndrome
Authors: Tillisch Kirsten , Mayer Emeran A.
Published: August 2016

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal discomfort or pain in the absence of detectable organic disease. IBS is common and is associated with a significant impairment in health-related quality of life. Enhanced perception of visceral stimuli (“visceral hypersensitivity”) appears to be an important patho-physiological mechanism. Early IBS studies using functional brain imaging techniques suggest an alteration in central pain modulation circuits, rather than an increased sensitivity of peripheral visceral pain pathways. The frequent comorbidity with psychiatric disorders suggests the possibility of shared pathophysiological mechanisms and etiologic factors.
An Integrated Analysis of the Efficacy of Desvenlafaxine Compared with Placebo in Patients with Major Depressive Disorder
Authors: Thase Michael E. , Kornstein Susan G. , Germain Jean-Michel , Jiang Qin , Guico-Pabia Christine , Ninan Philip T.
Published: August 2016

Introduction: To assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) in outpatients with major depressive disorder.

Methods: A meta-analysis of individual patient data was performed on the complete set of registration trials (nine randomized, double-blind, placebo-controlled 8-week studies) of desvenlafaxine. Patients received fixed (50, 100, 200, or 400 mg/day; n = 1,342) or flexible doses (100–400 mg/day; n = 463) of desvenlafaxine or placebo (n = 1,108). The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression (HAM-D17); the primary intent to treat analyses used the last-observation-carried-forward method.

Results: Significantly greater improvement with desvenlafaxine versus placebo on the HAM-D17 total score was observed for the full data set (difference in adjusted means: −1.9; P<.001), each fixed-dose group (all P<.001), and the flexible-dose group (P=.024). Overall rates of HAM-D17 response (≥50% decrease from baseline score: 53% vs 41%) and remission (HAM-D17 ≤7: 32% vs 23%) were significantly greater for desvenlafaxine versus placebo (all P<.001). Discontinuation rates due to adverse events increased with dose (4% to 18%; placebo: 3%).

Conclusion: Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed.
Extended Release Quetiapine Fumarate Monotherapy for Major Depressive Disorder: Results of a Double-Blind, Randomized, Placebo-Controlled Study
Authors: Weisler Richard , Joyce J. Mark , McGill Lora , Lazarus Arthur , Szamosi Johan , Eriksson Hans ,   Moonstone Study Group
Published: August 2016

Introduction: Once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy was evaluated in major depressive disorder (MDD).

Method: This was an 8-week (6-week randomized-phase; 2-week drug-discontinuation/tapering phase), double-blind, parallel-group, placebo-controlled study. The primary outcome measure was Montgomery-Åsberg Depression Rating Scale (MADRS) total score randomization-to-Week 6 change. Other assessments included the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and adverse events (AEs).

Results: 723 patients were randomized: 182, 178, 179, and 184 to quetiapine XR 50, 150, 300 mg/day, and placebo, respectively. At Week 6, significant reductions occurred in MADRS score with quetiapine XR 50 mg/day (−13.56; P<.05), 150 mg/day (−14.50; P<.01) and 300 mg/day (−14.18; P<.01) versus placebo (−11.07); at Day 4, reductions for quetiapine XR (titrated to 50 or 150 mg/day according to dose group) versus placebo (−2.9) were: −4.7 (P<.01), −5.2 (P<.001), and −5.1 (P<.001), respectively. At endpoint, MADRS response (≥50% reduction in score) was 42.7% (P<.01), 51.2% (P<.001), and 44.9% (P≤.001) for quetiapine XR 50, 150, and 300 mg/day, respectively; 30.3% for placebo. Overall, quetiapine XR 150 mg/day provided consistently more positive secondary efficacy results than 50 mg/day and 300 mg/day versus placebo. The most common AEs in quetiapine XR-treated patients were dry mouth, sedation, somnolence, headache, and dizziness.

Conclusion: In patients with MDD, quetiapine XR monotherapy (50/150/300 mg/day) is effective in reducing depressive symptoms, with improvement from Day 4 onwards. Safety and tolerability were consistent with the known profile of quetiapine.
Effects of a Tyramine-Enriched Meal on Blood Pressure Response in Healthy Male Volunteers Treated with Selegiline Transdermal System 6 mg/24 Hour
Authors: Blob Lawrence F. , Sharoky Melvin , Campbell Bryan J. , Kemper Eva M. , Gilmor Michelle , VanDenBerg Chad M. , Azzaro Albert J.
Published: August 2016

Background:

Monoamine oxidase inhibitors are well recognized as effective antidepressant agents but are rarely used due, in part, to the risk of hypertensive crisis following the ingestion of foods high in tyramine (“cheese reaction”). A selegiline transdermal system (STS) was developed to provide antidepressant concentrations of selegiline in the brain, while preserving the gastrointestinal monoamine oxidase A (MAO-A) barrier. The present study was conducted to determine the effect of the STS 6 mg/24 hour on cardiovascular safety following the ingestion of ∼400 mg of tyramine consumed as a component of aged cheeses.

Methods:

In this open-label, single-center phase I study, cardiovascular vital signs were recorded following tyramine challenges during placebo and STS 6 mg/24 hr treatment. Subjects were observed for clinical signs and symptoms of a pressor response and/or potential hypertensive crisis during and following the challenges.

Results:

Ingestion of tyramine-enriched meals following 13 consecutive days of treatment with the STS 6 mg/24 hr (pharmacokinetic steady-state) produced no clinically significant changes in cardiovascular vital signs in 12 healthy adult male subjects. No evidence of a tyramine pressor effect on systolic blood pressure or evidence of hypertensive crisis occurred during the STS treatment.

Conclusion:

These results suggest that STS 6 mg/24 hr may be administered without concern for dietary tyramine consumption.
Hyperperfusion Syndromes: Insight into the Pathophysiology and Treatment of Hypertensive Encephalopathy
Authors: Gardner Craig J. , Lee Kiwon
Published: August 2016

Hypertensive encephalopathy is one of the manifestations of a hypertensive crisis. It is not the absolute value of the blood pressure that causes the encephalopathy, rather the presence of an abrupt rise in pressure. In terms of clinical and radiographic findings, there are many similarities among a group of entities, including hypertensive encephalopathy, eclampsia, and immunosuppressant neurotoxicity. Hyperperfusion syndromes may represent these clinical disease states that may share the same pathophysiology. Magnetic resonance imaging fluid attenuated inversion recovery sequences have recognized the prominent cortical involvement of the disease that had been previously missed on computed tomography. Studies have found cortical involvement in 94% of their patients, particularly in mild cases. Animal models demonstrate endothelial damage and enhanced pinocytosis in the cortex as reasons why edema may begin in that region of the brain. Patients diagnosed with hypertensive encephalopathy should be diagnosed and treated promptly in order to avoid further neurological complications. The mean arterial pressure should be lowered by 20% to 25% within the first hour of patient presentation, followed by further gradual reduction in blood pressure over the following 24 hours. Hypertensive emergency in acute ischemic stroke should be managed with more caution. According to the 2003 American Stroke Association treatment guidelines, for patients with ischemic stroke not eligible for thrombolytic therapy, target blood pressures are a diastolic blood pressure <120 mmHg and systolic blood pressure <220 mmHg. The systolic pressure must be <185 mmHg and diastolic pressure <110 mmHg at all times if eligible for thrombolytic therapy.
Alzheimer's Disease:Progress in the Development of Anti-amyloid Disease-Modifying Therapies
Authors: Christensen Daniel D.
Published: August 2016

The amyloid hypothesis—the leading mechanistic theory of Alzheimer's disease—states that an imbalance in production or clearance of amyloid β (Aβ) results in accumulation of Aβ and triggers a cascade of events leading to neurodegeneration and dementia. The number of persons with Alzheimer's disease is expected to triple by mid-century. If steps are not taken to delay the onset or slow the progression of Alzheimer's disease, the economic and personal tolls will be immense. Different classes of potentially disease-modifying treatments that interrupt early pathological events (ie, decreasing production or aggregation of Aβ or increasing its clearance) and potentially prevent downstream events are in phase II or III clinical studies. These include immunotherapies; secretase inhibitors; selective Aβ42-lowering agents; statins; anti-Aβ aggregation agents; peroxisome proliferator-activated receptor-gamma agonists; and others. Safety and serious adverse events have been a concern with immunotherapy and γ-secretase inhibitors, though both continue in clinical trials. Anti-amyloid disease-modifying drugs that seem promising and have reached phase III clinical trials include those that selectively target Aβ42production (eg, tarenflurbil), enhance the activity of α-secretase (eg, statins), and block Aβ aggregation (eg, transiposate).
Pure Mutism Due To Simultaneous Bilateral Lenticulostriate Artery Territory Infarction
Authors: Akkus Dilek Evyapan
Published: August 2016

A case of pure mutism without pseudobulbar palsy and other neurological findings resulting from simultaneous bilateral lenticulostriate artery territory infarction is presented. A 45-year-old woman suffered a transient ischemic attack with nonfluent aphasia and right hemiparesis. Six months later, she developed pure mutism without oral apraxia, pseudobulbar signs, and motor deficits. Magnetic resonance imaging revealed bilateral infarction in the lentiform nucleus regions. In the available data, there is only one report of simultaneous bilateral lenticulostriate infarction.To date, in all reported cases of mutism of subcortical vascular origin there are also various degrees of pseudobulbar signs and motor deficits and the responsible lesions are mostly consecutive.The case presented here is the first to show pure vascular mutism without other neurological findings.
Advances in Magnetic Resonance Imaging Methods for the Evaluation of Bipolar Disorder
Authors: Lyoo In Kyoon , Hwang Jaeuk , Sim Minyoung , Dunn Brian J. , Renshaw Perry F.
Published: August 2016

This article reviews the current state of magnetic resonance imaging techniques as applied to bipolar disorder. Addressed are conventional methods of structural neuroimaging and recently developed techniques. This latter group comprises volumetric analysis, voxel-based morphometry, the assessment of T2 white matter hyperintensities, shape analysis, cortical surface-based analysis, and diffusion tensor imaging. Structural analysis methods used in magnetic resonance imaging develop exponentially, and now present opportunities to identify disease-specific neuroanatomic alterations. Greater acuity and complementarity in measuring these alterations has led to the generation of further hypotheses regarding the pathophysiology of bipolar disorder. Included in the summary of findings is consideration of a resulting neuroanatomic model. Integrative issues and future directions in this relatively young field, including multi-modal approaches enabling us to produce more comprehensive results, are discussed.
Level of Insight and Clinical Features of Obsessive-Compulsive Disorder with and Without Body Dysmorphic Disorder
Authors: Nakata Ana Cristina Gargano , Diniz Juliana B. , Torres Albina R. , de Mathis Maria Alice , Fossaluza Victor , Braganças Carlos Alberto , Ferrão Ygor , Miguel Euripedes C.
Published: August 2016

Introduction: Body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) have several similarities and are included among the obsessive-compulsive spectrum of disorders. However, the content of preoccupations and level of insight of BDD patients differ from OCD patients.

Objective: To compare the level of insight regarding obsessive-compulsive symptoms (OCS) and other clinical features in OCD patients with and without comorbid BDD.

Methods: We evaluated 103 OCD patients (n=25, comorbid BDD), according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria using the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive-Compulsive Scale, the University of São Paulo Sensory Phenomena Scale, the Beck Depression and Anxiety Inventories, and the Brown Assessment of Beliefs Scale.

Results: The study groups differed significantly on several clinical features, including level of insight. A worse level of insight regarding OCS was independently associated with the presence of comorbid BDD. Lower educational level, more psychiatric comorbidities, presence of somatic and hoarding obsessions, and presence of intrusive images were associated with BDD comorbidity, even after adjusting for possible confounders.

Conclusion: The presence of BDD in OCD patients is associated with poorer insight into obsessional beliefs and higher morbidity, reflected by lower educational levels and higher number of psychiatric comorbid disorders in general.
Obsessive-Compulsive Disorder:An Open-Label Pilot Trial of Escitalopram
Authors: Almeida Amanda Galvão-de , Quarantini Lucas C. , Góis Cristianne R. , Santos-Jesus Rogério , Miranda-Scippa Ângela M.A. , de Oliveira Irismar R. , Prado Helena da Silva , Leckman James F. , Rosário Maria C.
Published: August 2016

Introduction:Selective serotonin reuptake inhibitors are considered the most effective and well-established pharmacotherapy for the treatment of obsessive-compulsive disorder (OCD), a chronic and disabling condition. However, ~40% of patients do not have a significant improvement, suggesting that new medications are needed. This study was designed to investigate the treatment response to escitalopram in OCD patients.

Methods:This open-label study involved 11 adult OCD outpatients diagnosed with the Structured Clinical Interview forDiagnostic and Statistical Manual of Mental Disorders, Fourth EditionAxis I Disorders. Data were collected and the treatment response was assessed by an experienced psychiatrist by using the Yale-Brown Obsessive-Compulsive Scale. Subjects received escitalopram 30 mg/day for 12 weeks starting at 10 mg/day. Dosage adjustments were made within 2 weeks, depending on the tolerability of the patient.

Results:Six of the 11 patients (54.5%) presented a reduction of at least 40% in the baseline total Yale-Brown Obsessive-Compulsive Scale scores.

Conclusion:Despite the small sample size and the open-label nature of this trial, these data suggest that escitalopram may be a useful option for patients with OCD.
The Genetics of Schizophrenia Converge Upon the NMDA Glutamate Receptor
Authors: Stahl Stephen M.
Published: August 2016

Recent research shows that single genes do not cause schizophrenia, but that multiple “susceptibility” genes each provide a genetic “bias” towards schizophrenia. Each susceptibility gene codes for a subtle molecular abnormality that hypothetically causes inefficient information processing in brain circuits that mediate the symptoms of this disorder. It is therefore not surprising that many of the susceptibility genes that have been identified for schizophrenia are known to regulate neuronal connectivity, synaptogenesis, and N-methyl-D-aspartate (NMDA) glutamate receptor functions. This includes genes for brain-derived neurotrophic factor (BDNF), dysbindin, also known as dystrobrevin-binding protein 1, neuregulin, disrupted in schizophrenia-1 (DISC-1), D-amino acid oxidase activator (DAOA), and regulator of G-protein signaling (RGS4). Hypothetically, converging molecular abnormalities expressed by defective versions of these genes could cause dysregulation of NMDA receptors and NMDA synapses, leading to vulnerability for schizophrenia due to inefficient information processing at glutamate synapses.
Serotonin Syndrome in Elderly Patients Treated for Psychotic Depression with Atypical Antipsychotics and Antidepressants: Two Case Reports
Authors: Kohen Izchak , Gordon Marc L. , Manu Peter
Published: August 2016

We report two cases of serotonin syndrome in elderly patients during treatment of psychotic depression with atypical antipsychotics and antidepressants. The first case is a 69-year-old man who was admitted for depression with psychosis and treated with trazodone, risperidone, and sertraline. Subsequently, he developed myoclonus, tremor, cogwheel rigidity, and diaphoresis. The second case is a 72-year-old female initially admitted to a medical inpatient unit for a change in mental status that presented as increased confusion, lethargy, slurred speech, and a fever of 101.5°. She had been on phenelzine and quetiapine. In both cases, all symptoms resolved within 24 hours of the psychotropics being stopped. In both cases, we believe that serotonin syndrome was produced by a combination of an antidepressant and an atypical antipsychotic. There have been several case reports of serotonin syndrome from similar combinations of antidepressant and atypical antipsychotic treatment. Clinicians treating elderly patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome.
Selective Unilateral Autonomic Activation: Implications for Psychiatry
Authors: Shannahoff-Khalsa David S.
Published: August 2016

Research advances have led to three methods for selectively activating one half of the autonomic nervous system in humans.The first method is an ancient yogic technique called unilateral forced nostril breathing (UFNB) that employs forced breathing through only one nostril while closing off the other. The second method works by stimulation of an autonomic reflex point on the fifth intercostal space near the axilla. The most recent method employs unilateral vagus nerve stimulation (VNS) via the mid-inferior cervical branch and requires surgical implantation of a wire and pacemaker. UFNB is non-invasive and seems to selectively activate the ipsilateral branch of the sympathetic nervous system with a possible compensation effect leading to contralateral VNS. UFNB and VNS have been employed to treat psychiatric disorders. While UFNB has been studied for its potential effects on the endogenous ultradian rhythms of the autonomic and central nervous system, and their tightly coupled correlates, VNS has yet to be studied in this regard. This article reviews these three methods and discusses their similarities, putative mechanisms, their studied effects on the endogenous autonomic nervous system and central nervous system rhythms, and their implications for the treatment of psychiatric disorders.
Findings with 0.25 mg Dexamethasone Suppression Test in Eating Disorders: Association with Childhood Trauma
Authors: Díaz-Marsá Marina , Carrasco José L. , Basurte Elena , Pastrana José I. , Sáiz-Ruiz Jerónimo , López-lbor Juan J.
Published: August 2016

Introduction: While both blunted and enhanced cortisol suppression following a dexamethasone suppression test (DST) are described in eating disorders, some evidence suggests that enhanced cortisol suppression might be associated with the presence of trauma history. The objective of this study is to investigate hypothalamic-pituitary-adrenal axis response to a modified DST in eating disorders and its relationship with childhood trauma.

Methods: Fifty-two patients with eating disorders were studied with a 0.25 mg DST and with measures of childhood trauma.

Conclusion: Patients with bulimia symptoms had significantly greater cortisol suppression than controls and restrictive anorexia patients (F=8.2, P<.05). Cortisol suppression was significantly correlated with intensity of childhood traumatic events (F=0.32, P<.05). Hypersensitive hypothalamic-pituitary-adrenal axis response to DST in eating disorders may be related with a history of childhood trauma and suggests some biological similarities with posttraumatic syndromes that should be further explored.
Depression and Huntington's Disease: Prevalence, Clinical Manifestations, Etiology, and Treatment
Authors: Slaughter James R. , Martens Matthew P. , Slaughter Kathleen A.
Published: August 2016

In order to determine the extent to which depression complicates Huntington's disease (HD), we have analyzed the existing literature on depression in HD in order to report the prevalence, clinical manifestations, and treatment of HD depression. By means of MEDLINE literature searches and reviews of HD articles' bibliographies, we identified for our analysis 16 HD depression studies. Our results indicate that the prevalence of depression is 30% for all HD patients. Clinical manifestations of HD depression include a marked increased risk for suicide. The etiology of HD depression is unclear, but may be due to a number of factors, such as dysfunction in the caudate nucleus, dysfunction in the ventral striatum, and various genetic factors that are discussed in this review. Case reports and case series support the efficacy of standard antidepressant interventions in resolving symptoms of depression. Efficacious treatments reported in the literature include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and electro-convulsive therapy. In this study, the successful anecdotal treatment of seven consecutive HD depressed patients with sertraline suggests that sertraline may be a safe and efficacious treatment of HD depression.