bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Risperidone in Psychogenic Stiff Neck
Authors: Marazziti Donatella , Dell'Osso Bernardo
Published: August 2016

A 48-year-old woman suffering from treatment-resistant psychogenic stiff neck and severe depression had been treated with a varied regimen of medications, including antidepressants, neuroleptics, and antiepileptics. These treatments did not result in improvement. Therefore, she was treated with a combination of sertraline and risperidone. Depressive symptoms decreased within a few weeks of treatment initiation. The psychogenic stiff neck, which had begun to improve within the first 2 weeks, had disappeared completely after 6 months of treatment with risperidone alone. This case report suggests that risperidone may be effective in some neurological motor disorders comorbid with mood disorders.
Reduction of Caregiver Burden in Alzheimer's Disease by Treatment with Galantamine
Authors: Kaufer Daniel I. , Borson Soo , Kershaw Paul , Sadik Kay
Published: August 2016

Alzheimer's disease is a progressive condition characterized by a loss of cognition, altered behavior, and a loss of functional ability, such as bathing, dressing, toileting, and organizing finances. Family and friends provide nearly three quarters of all care for patients with Alzheimer's disease. This informal care results in significant burden to caregivers. Caregiver burden is the set of physical, psychological or emotional, social, and financial problems that family members may experience when caring for impaired older adults. Caregivers of Alzheimer's disease patients report higher rates of physical symptoms, mortality, depression, and fatigue, as well as adverse effects on employment compared with those who are not caregivers for Alzheimer's disease patients. In many cases, the same family members are responsible for both out-of-pocket expenditures and caregiving duties. For this article, a MEDLINE search using the key words “caregiver and Alzheimer's disease” and “cost and Alzheimer's disease” was performed. The purpose of this article is to review the literature on caregiver burden, the components of caregiver burden, effects of caregiving on the health of caregivers, the cost of Alzheimer's disease on the caregiver and society, and the benefits attainable with treatment.
Long-Term Safety and Effectiveness of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder
Authors: Weisler Richard , Young Joel , Mattingly Greg , Gao Joseph , Squires Liza , Adler Lenard ,   304 Study Group
Published: August 2016

Objective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.

Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P<.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P<.0001).

Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.
Using fMRI to Study the Neural Correlates of Virtual Reality Analgesia
Authors: Hoffman Hunter G. , Richards Todd L. , Bills Aric R. , Van Oostrom Trevor , Magula Jeff , Seibel Eric J. , Sharar Sam R.
Published: August 2016

Excessive pain during medical procedures, such as burn wound dressing changes, is a widespread medical problem and is especially challenging for children. This article describes the rationale behind virtual reality (VR) pain distraction, a new non-pharmacologic adjunctive analgesia, and gives a brief summary of empirical studies exploring whether VR reduces clinical procedural pain. Results indicate that patients using VR during painful medical procedures report large reductions in subjective pain. A neuroimaging study measuring the neural correlates of VR analgesia is described in detail. This functional magnetic resonance imaging pain study in healthy volunteers shows that the large drops in subjective pain ratings during VR are accompanied by large drops in pain-related brain activity. Together the clinical and laboratory studies provide converging evidence that VR distraction is a promising new non-pharmacologic pain control technique.
Anxiety Disorders in Late Life: An Evolving Picture
Authors: Lenze Eric J. , Shear M. Katherine , Mulsant Benoit H. , Reynolds Charles F.
Published: August 2016

Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.
Neurochemical Aspects of the Sexual Response Cycle
Authors: Halaris Angelos
Published: August 2016

What drives the human sexual response cycle? The human sexual response cycle is a highly complex phenomenon that encompasses many transmitters and transmitter systems centrally and peripherally. The endocrine system is also intricately involved in the brain and in the periphery organs. Integration of these systems is a function of the nervous system that ultimately produces a vast array of cognitive, emotional, physiological, and behavioral responses. Therefore, it is not surprising that a disturbance in even a single system will lead to dysfunction in one or more phases of the sexual response cycle. This article highlights the complex roles the aminergic system plays along with key hormones that are equally involved. The article also points out how rudimentary and fragmented our knowledge is in this field and how few controlled studies are available. The potential for development of specific agents that target selective sexual dysfunctions is exemplified in sildenafil, the first such agent ever to be brought to market.
Collaborative Care: Evidence-Based Models that Improve Primary Care Depressive Outcomes
Authors: Katon Wayne J.
Published: August 2016

The 2001 Institute of Medicine Report “Crossing the Quality Chasm,” summarized the current care of chronic illness in the United States by emphasizing “Between the health care we have and the health care we could have lies not just a gap, but a chasm.” Across multiple chronic illnesses within primary and specialty care systems, this summary statement illustrates that clinicians and other health professionals are not adequately providing patients guideline levels of treatment–levels that can lower the risk for complications of those illnesses.
Understanding the Latest Advances in Pharmacologic Interventions for Alzheimer's Disease
Authors: van Dyck Christopher H.
Published: August 2016

Alzheimer's disease (AD) is a complex medical condition involving abnormalities in multiple biological and environmental domains. Current knowledge suggests that simultaneous intervention in these domains may be the most effective way to help AD patients and their families. Treatments for AD are centered on the inhibition of enzymes responsible for the degradation of acetylcholine—a neurotransmitter that is reduced in AD patients. Four cholinesterase inhibitors have been approved by the United States Food and Drug Administration, three of which are routinely used for the symptomatic treatment of mild-to-moderate AD. Strategies will be reviewed with regard to cognitive, functional, and behavioral domains. Providing a different treatment option for patients with AD, memantine is a low-to-moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been approved for the treatment of moderate-to-severe AD. The clinical efficacy and tolerability of memantine monotherapy and combination therapy in patients with AD will be presented. Finally, the role of non-pharmacologic intervention will be discussed.
Role of Mitochondria in Neurodegenerative Diseases: Mitochondria as a Therapeutic Target in Alzheimer's Disease
Authors: Reddy P. Hemachandra
Published: August 2016

A growing body of evidence suggests that mitochondrial abnormalities are involved in aging and in age-related neurodegenerative diseases as well as cancer, diabetes, and several other diseases known to be affected by mitochondria. Causal factors for most age-related neurodegenerative diseases—including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Friedrich ataxia (FRDA)—are largely unknown. Genetic defects are reported to cause a small number of neurodegenerative diseases (Slide 1), but cellular, molecular, and pathological mechanisms of disease progression and selective neuronal cell death are not understood fully in these diseases. However, based on several cellular, molecular, and animal model studies of Alzheimer's disease, Parkinson's disease, ALS, FRDA, cancer, and diabetes, aging may play a large role in cell death in these diseases. Age-dependent, mitochondrially-generated reactive oxygen species (ROS) have been identified as important factors responsible for disease progression and cell death, particularly in late-onset diseases, in which genetic mutations are not causal factors.
Issues and Strategies in Treating Refractory Obsessive-Compulsive Disorder
Authors: Koran Lorrin M. , Saxena Sanjaya
Published: August 2016

The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).

At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.
Best Clinical Practice With Ziprasidone IM: Update After 2 Years of Experience
Authors: Zimbroff Dan L. , Allen Michael H. , Battaglia John , Citrome Leslie , Fishkind Avrim , Francis Andrew , Herr Daniel L. , Hughes Douglas , Martel Marc , Preval Horacio , Ross Ruth
Published: August 2016

Acute agitation is a common psychiatric emergency often treated with intramuscular (IM) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional IM antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon®) is the first second-generation, or atypical, antipsychotic to become available in an IM formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings.

In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol IM. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from IM to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical settings are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.
Selection of Appropriate Therapy: Valproate and Reproductive Function
Authors: Rasgon Natalie
Published: August 2016

The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.

Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.

Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
Efficacy of Combined Pharmacotherapy and Psychotherapy Versus Monotherapy in the Treatment of Anxiety Disorders
Authors: Black Donald W.
Published: August 2016

Anxiety disorders in the United States are prevalent, widespread, and disabling. These illnesses may account for almost one third of the $148 billion total mental health bill each year. Pharmacologic options include tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and anxiolytics. Psychological treatments include cognitive-behavioral therapy (CBT), cognitive therapy, exposure, and ritual prevention therapies. Despite insufficient evidence, many experts recommend combined treatment, generally medication with CBT. A literature review was conducted to examine studies with random assignment, adequate methods and sample sizes, blind assessments, sufficient dosages and durations of treatment, and satisfactory reporting of data, to determine whether combined treatment was superior to monotherapy. Twenty-six randomized clinical trials were identified; nine met review criteria. A review of relevant studies could not confirm the superiority of combined treatment over monotherapy. In one of four studies of obsessive-compulsive disorder, combined treatment produced better results than monotherapy.  There was no evidence of superiority for combined therapy over monotherapy for the treatment of social phobia or generalized anxiety disorder. There were no studies that met review criteria for either specific phobia or posttraumatic stress disorder (PTSD). With panic disorder, there was evidence that combined treatment might actually lead to worse outcome. Combined treatment is commonly recommended, but empirical support is limited. More research is needed. There are few well-designed studies, and little data regarding PTSD and specific phobias.
The Morbidity of Insomnia
Authors: Krystal Andrew D.
Published: August 2016

Insomnia is a disorder characterized by chronic sleep disturbance associated with daytime disability or distress, such as memory impairment and fatigue, that occurs despite adequate opportunity for sleep. Insomnia may present as difficulty falling/staying asleep or as sleep that is nonrestorative. Studies show a strong correlation between insomnia and impaired quality of life. Pain conditions and depression are commonly associated with insomnia, either as secondary or comorbid conditions. In addition, a greater incidence of anxiety, alcohol and drug dependence, and cardiovascular disease is found in people with insomnia. Data indicate insomnia results from over-engaged arousal systems. Insomnia patients experience increased metabolic rate, body temperature, and heart rate, and elevated levels of norepinephrine and catecholamines. Pharmacologic options for the treatment of insomnia include benzodiazepine hypnotics, a selective melatonin receptor agonist, and sedating antidepressants. However, insomnia may be best treated with cognitive-behavioral therapy and instruction in good sleep hygiene, either alone or in concert with pharmacologic agents. Studies on the effects of insomnia treatment use variable methodologies or do not publish negative results, and there are currently no studies of treatment focusing on morbidity. Further research is necessary to better understand the effects of insomnia therapies on medical and psychiatric disorders.

In this Clinical Information Supplement, Thomas Roth, PhD, describes the nature of insomnia and its pathophysiology. Next, Andrew D. Krystal, MD, MS, reviews morbidities associated with insomnia. Finally, Joseph A. Lieberman III, MD, MPH, provides an overview of therapeutics utilized in patients with insomnia, including behavioral therapies and pharmacologic options.
Metabolic Findings From the CATIE Trial and Their Relation to Tolerability
Authors: Nasrallah Henry A.
Published: August 2016

The overall effectiveness of antipsychotics for the management of schizophrenia is restricted by their side-effect profiles, particularly over an extended treatment period. Intolerable side effects can reduce patient adherence to medication and often lead to treatment discontinuation. Some side effects that result from antipsychotic use are precursors to the metabolic syndrome, which is prevalent among individuals with schizophrenia and represents a significant source of cardiovascular risk. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study assessed the efficacy of the atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone relative to the conventional drug perphenazine. Additional assessments included the metabolic effects of these agents in patients with schizophrenia and the incidence of negative side effects. No significant differences were found between treatment groups for time to discontinuation due to intolerability, but the rates of side effects significantly differed(P=.04).For metabolic parameters, olanzapine was associated with greater and significant adverse effects on weight, lipids, and glucose metabolism versus the other antipsychotics tested. The CATIE results show that important distinctions exist among currently available atypical antipsychotics. Physicians should be aware of the propensity of these drugs to increase the risks of cardiovascular disease and diabetes in treated patients and tailor individual treatment decisions accordingly. This article highlights the metabolic findings from the CATIE schizophrenia study, and explores the differences shown by atypical antipsychotics, with regard to metabolic side effects that increase cardiovascular risk.
Sexual Dysfunction in Patients with Neuropsychiatric Disorders: Challenges and Opportunities
Authors: Gidal Barry , Barry John J.
Published: August 2016

Quality-of-life issues in healthcare have come to be of paramount importance for a population that increasingly expects healthcare not only to treat major illnesses but also to optimize normal levels of physical and psychosocial functioning and overall well-being. Healthcare providers have also increasingly appreciated the impact that adverse effects of treatment can have on quality of life, as well as on compliance with and the effectiveness of treatment.

Many functional impairments and adverse treatment effects take the form of clinical complaints that patients and caregivers typically report to their healthcare providers without prompting. Other adverse effects are not so obviously clinical or treatment-related, and patients may not be inclined or may even be reluctant to bring them up when talking with the provider. Impairment of sexual function is a problem of this kind.

Sexual dysfunction appears to be common and frequently underrecognized in certain patient populations. For example, it has been estimated that 25% to 63% of women and 10% to 52% of men with epilepsy have some form of sexual dysfunction, yet in clinical reviews of sexual disorders, epilepsy is not listed as one of the medical conditions commonly associated with impaired sexual function.
Fibromyalgia Syndrome: Presentation, Diagnosis, Differential Diagnosis, and Vulnerability
Authors: Russell I. Jon , Raphael Karen G.
Published: August 2016

Fibromyalgia syndrome (FMS) presents with widespread soft tissue pain. Common comorbidities include severe insomnia, body stiffness, affective symptoms, irritable bowels, and urethral syndrome. A 1990 research classification depends on a history of widespread pain and prominent tenderness to palpation at 11 or more of 18 specific tender points. It is a criteria-based diagnosis rather than one by exclusion and can accompany other medical conditions. FMS occurs worldwide, and can present any age, but is most common in adult females. Although numerous studies and reviews contend that FMS may be caused by psychological stress such as sexual abuse, a critical epidemiological review fails to support that concept. Existing data suggest that some individuals with FMS may have a dysregulated physiological stress response system that predates the onset of symptoms.
Neurobiology and Genetics of ADHD in Adults
Authors: Spencer Thomas J.
Published: August 2016

Treatment of attention-deficit/hyperactivity disorder (ADHD) may positively impact the neurobiology of adult patients with ADHD. Treatment may also minimize impairment from core symptoms and may alter the course of co-morbid disorders such as depression and substance use disorder. However, much of the information on stimulant use in adult ADHD comes from studies conducted in children, and it remains unclear whether there is a difference between children and adults when it comes to the side effects and tolerability of ADHD treatments. It is known that clinical presentation differs between adults and children, with adults demonstrating a higher percentage of mood disorders. Current treatments for adult ADHD include psychosocial therapies and pharmacologic therapies, the latter of which include the stimulants d-methylphenidate extended release (XR), OROS methylphenidate, lisdexamfetamine, and mixed amphetamine salts XR; and the nonstimulant atomoxetine, a selective norepinephrine reuptake inhibitor. There is need for additional study of treatment strategies for adult ADHD. Although all classes of ADHD medications are approved in adults, there are fewer approved formulations for adults than for children. Efficacy in adults is more subjective than in children, which may affect how efficacy rates for adult treatments are calculated. Adults also present a greater diversion risk than children. In addition, there are several new and emerging medication treatments worth considering.

This Expert Roundtable Supplement represents part 2 of a 3-part supplement series on adult ADHD led by Lenard A. Adler, MD. In this activity, Thomas J. Spencer, MD, discusses the neurobiology and genetics of adult ADHD; Mark A. Stein, PhD, discusses stimulant therapy; and Jeffrey H. Newcorn, MD, reviews nonstimulants and psychosocial treatments.
Neurobiology and Treatment of Compulsive Hoarding
Authors: Saxena Sanjaya
Published: August 2016

Compulsive hoarding is a common and often disabling neuropsychiatric disorder. This article reviews the phenomenology, etiology, neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part of a discrete clinical syndrome that includes difficulty discarding, urges to save, clutter, excessive acquisition, indecisiveness, perfectionism, procrastination, disorganization, and avoidance. Epidemiological and taxometric studies indicate that compulsive hoarding is a separate but related obsessive-compulsive spectrum disorder that is frequently comorbid with obsessive-compulsive disorder (OCD). Compulsive hoarding is a genetically discrete, strongly heritable phenotype. Neuroimaging and neuropsychological studies indicate that compulsive hoarding is neurobiologically distinct from OCD and implicate dysfunction of the anterior cingulate cortex and other ventral and medial prefrontal cortical areas that mediate decision-making, attention, and emotional regulation. Effective treatments for compulsive hoarding include pharmacotherapy and cognitive-behavioral therapy. More research will be required to determine the etiology and pathophysiology of compulsive hoarding, and to develop better treatments for this disorder.
Introduction
Authors: Cummings Jeffrey L.
Published: August 2016

Alzheimer’s disease (AD) research is progressing rapidly and on multiple fronts. Advances are being made in early diagnosis, neuroimaging, and biomarkers; optimal care uses currently available medications and strategies; and new therapies are emerging. Early diagnosis is necessary for optimal patient management. Biomarkers are critical to early diagnosis, and biomarker development is dependent on better understanding of disease pathophysiology (Slide 1). The discussions in this supplement examine how progress in AD research can be translated into clinical care.

Primary care practitioners (PCPs) provide most of the care of patients with AD, and these clinicians are optimally poised to discover new cases emerging among elderly patients. Caregivers are most likely to voice concerns about declining memory in a family member to a PCP before seeking specialty evaluation. PCPs, however, have little time to devote to complex assessments and cannot have specialty-level expertise in all disorders. PCPs must have clinical tools that assist them in rapidly identifying potential problems and triaging them for further evaluation or specialty referral.
New Pharmacotherapeutic Approaches to Obsessive-Compulsive Disorder
Authors: Figee Martijn , Denys Damiaan
Published: August 2016

This article summarizes results of all pharmacotherapy trials for obsessive-compulsive disorder (OCD) published from 2006 to 2008 as well as studies on markers for predicting response to treatment and neurobiological changes induced by pharmacotherapy. Results show that recent developments in the treatment of OCD have been modest and primarily involve evidence for the efficacy of escitalopram and other selective serotonin reuptake inhibitors (SSRIs); augmentation with antipsychotics in treatment-refractory patients and combination treatment with D-cycloserine and cognitive-behavioral therapy has also been effective. The efficacy of serotonin-norepinephrine reuptake inhibitors remains inconclusive. Studies on markers of clinical response have shown inconsistent results, however, duration and severity of OCD and the presence of comorbidities can often identify patients at risk for nonresponse. Lastly, successful treatment with an SSRI results in both serotonergic and dopaminergic changes, but more research is necessary in order to define the biological characteristics of responders and nonresponders.
Fibromyalgia: Key Clinical Domains, Comorbidities, Assessment, And Treatment
Authors: Mease Philip J.
Published: August 2016

In discussion of the best practices for patients with fibromyalgia (FM), it is key to Introduce commentary about what FM is as a clinical condition, how clinicians should assess for FM, and the pharmacologic approaches to management.

The first widely accepted criteria for the classification for FM were published in 1990 as the American College of Rheumatology criteria for FM. However, the condition has long been described in medical history. In the 1800s, a condition similar to FM was labeled “neurasthenia” and was further defined by researchers in the medical literature. During the early 1900s, symptoms associated with FM were labeled “fibrositis,” which was based on the mistaken idea that there were inflammatory changes in peripheral connective tissue. It was not until the mid-1970s when pioneering work by Smythe and Moldofsky defined central nervous system abnormalities, including significant sleep pathology, in patients with this condition that led to the increased recognition by researchers and clinicians that FM was a central pain phenomenon.

Following this critical development, use of the term “fibromyalgia” began and was codified in the 1990 criteria, intended for use in research settings to standardize classification of FM. The 1990 criteria classify the condition as involving chronic widespread pain for at least 3 months. Patients must also exhibit tenderness of at least 11 of 18 tender points.
The Influence of Comorbid Anxiety Disorders on the Selection of Antidepressant Medication in Depressed Patients
Authors: Zimmerman Mark
Published: August 2016

Although there is a wide array of choices of antidepressants, there is little empirical evidence to guide clinicians in their selection. Most reviews of the antidepressant literature, including the American Psychiatric Association's (APA) Practice Guideline for the Treatment of Major Depressive Disorder, conclude that these medications are generally equally effective. Consistent with this, a recent metaanalysis of studies comparing two or more new-generation antidepressants found little evidence that any medication was superior to the others. Although the APA guideline suggests that the choice of antidepressant be based principally on side effects, tolerability, patient preference, and cost, it also reviewed evidence of differential treatment response related to patients' clinical profiles. For patients with nonpsychotic, nonbipolar major depressive disorder (MDD), the guideline indicated that the presence of anxiety symptoms, atypical features, melancholic subtype, symptom severity, and borderline personality disorder may be associated with differential response to antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are recommended for high anxiety, SSRIs and clomipramine for obsessive-compulsive disorder (OCD) symptoms, tricyclic antidepressants (TCAs) for severe depression and melancholia, and SSRIs and monoamine oxidase inhibitors (MAOIs) for atypical depression.

What is most striking in the guideline's review is how limited in scope and utility are the data to guide the outpatient psychiatrist in selecting an antidepressant. Melancholia and severe depression are relatively infrequently encountered in the outpatient setting. The most common comorbidities in depressed outpatients are anxiety disorders, but the guideline simply says that bupropion may be anxiogenic and should be avoided, and that although MAOIs may work well in depressed patients with anxiety, other medications are preferred. It does not discuss the possible influence of specific comorbidities on antidepressant selection.
Comorbid HIV Encephalopathy and Cocaine Use as a Risk Factor for New-onset Seizure Disorders
Authors: Kenedi Christopher A. , Joynt Karen E. , Goforth Harold W.
Published: August 2016

Patients living with human immunodeficiency virus represent a growing population, and an increased number of central nervous system presentations can be expected over the next decade. Emerging data suggests that both HIV-seropositive patients and cocaine-abusing patients may be at special risk of seizure phenomena. This case report discusses the risks of new-onset seizure activity when these two risk factors converge, which is a common occurrence in this population. Data from the fields of neuroanatomy and neurovirology are presented to explain the heightened risk of this patient population and provide the practitioner with an improved understanding of the central nervous system complexities in HIV.
Genetic Linkage in Bipolar Disorder
Authors: Mathews Carol A. , Reus Victor I.
Published: August 2016

Bipolar disorder is an etiologically complex syndrome that is dearly heritable. Multiple, genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the last few decades. However, specific causal genetic mutations for bipolar disorder have not been identified. Both candidate gene studies and complete genome screens have been conducted. They have provided compelling evidence for several potential bipolar disorder susceptibility loci in several regions of the genome. The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21. Other regions of interest, including those on chromosomes 5 and 8, are also under investigation. New approaches, such as the use of genetically isolated populations and the use of endophenotypes for bipolar disorder, hold promise for continued advancement in the search to identify specific bipolar disorder genes.
Treatment of Acute Mania
Authors: Holtzheimer Paul E. , Neumaier John F.
Published: August 2016

Mood stabilizers have evolved considerably over the past decade. Lithium, divalproex, and olanzapine are currently Food and Drug Administration-approved for the treatment of acute mania. A number of new and traditional medications have also been tested and are commonly used in clinical practice. Several strategies for managing treatment-resistant mania have been suggested, but few have been rigorously tested. Emphases on rapid stabilization and fewer side effects have raised the bar for what is expected from mood stabilizers and the successful treatment of mania involves a delicate balance between swiftness, short-term tolerability, and long-term safety.
Antidepressant Effects of Atypical Antipsychotics
Authors: Perlis Roy H.
Published: August 2016

Studies have shown that there is some efficacy for a number of agents, most notably lithium, in treating bipolar depression. However, the studies also highlight the unfortunate reality that many patients fail to respond adequately to first-line therapies and that there is a need to identify additional options for patients and clinicians. The atypical antipsychotics clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and aripiprazole, have been the focus of increased interest in the treatment of bipolar depression.

The use of antipsychotics in the treatment of depressive episodes is not a particularly novel idea. In 1982, Robertson and Trimble reviewed 34 studies examining the use of typical antipsychotics to augment an antidepressant and noticed modest but generally consistent benefits. More widespread use of these agents in the management of depression has been limited, however, because of concerns about the long-term risk of tardive dyskinesia and the induction of extrapyramidal symptoms that often mimic depressive symptoms.

Clozapine, the first of the atypicals, was applied initially in the treatment of schizophrenia and schizoaffective disorder, where antidepressant effects were noted during open treatment. Subsequent case series described some benefit in dysphoric manias in bipolar disorder as well.

Much of the inditect evidence for antidepressant effects of the atypicals came from studies in major depressive disorder (MDD). For example, a series of eight patients with MDD who failed treatment with a selective serotonin reuptake inhibitor (SSRI) achieved marked and rapid response when risperidone was added to the SSRI. All patients remitted within 1 week; Hamilton Rating Scale for Depression score in these patients declined from a mean of 20.5 to a mean of 2.4 (Slide 11). A subsequent series of 30 patients yielded similar results.
Kriminalprognosen in der Praxis
Authors: Rettenberger Martin , Eher Reinhard , Desmarais Sarah L. , Hurducas Cristina , Arbach-Lucioni Karin , Condemarin Carolina , Dean Kimberlie , Doyle Michael , Folino Jorge O. , Godoy-Cervera Verónica , Grann Martin , Ho Robyn Mei Yee , Large Matthew M. , Pham Thierry H. , Nielsen Louise Hjort , Rebocho Maria Francisca , Reeves Kim A. , Ruiter Corine de , Seewald Katharina , Singh Jay P.
Published: August 2016

Zusammenfassung. Einschätzungen über das Risiko zukünftiger Gewalttätigkeit sind ein fester Bestandteil der Arbeit von Psychologinnen und Psychologen, wobei bis heute wenig darüber bekannt ist, in welcher Form kriminalprognostische Einschätzungen in der alltäglichen Berufspraxis vorgenommen werden. Durch die vorliegende Forschungsarbeit wird erstmals ein Einblick in die kriminalprognostische Praxis in Deutschland gegeben. In der vorliegenden Studie werden die Ergebnisse des International Risk Surveys (IRiS; Singh et al., 2014 ) ausgewertet, an der weltweit 2135 Personen aus 44 Ländern teilgenommen haben. Aus Deutschland wurden 97 Psychologinnen und Psychologen sowie Angehörige anderer Berufsgruppen über ihre kriminalprognostischen Tätigkeiten befragt. Die Daten zeigen, dass mittlerweile in der Praxis mehrheitlich auf standardisierte Prognoseinstrumente zurückgegriffen wird. Die Instrumente werden nicht nur für die prognostische Einschätzung über das zukünftige Gewaltrisiko als nützlich eingestuft, sondern auch im Hinblick auf die Therapieindikation sowie die verlaufsdiagnostische Untersuchung von Behandlungs- und Betreuungsfällen als hilfreich beurteilt.
Root microbiota dynamics of perennial Arabis alpina are dependent on soil residence time but independent of flowering time
Authors: Dombrowski Nina , Schlaeppi Klaus , Agler Matthew T , Hacquard Stéphane , Kemen Eric , Garrido-Oter Ruben , Wunder Jörg , Coupland George , Schulze-Lefert Paul
Published: August 2016

Recent field and laboratory experiments with perennial Boechera stricta and annual Arabidopsis thaliana suggest that the root microbiota influences flowering time. Here we examined in long-term time-course experiments the bacterial root microbiota of the arctic-alpine perennial Arabis alpina in natural and controlled environments by 16S rRNA gene profiling. We identified soil type and residence time of plants in soil as major determinants explaining up to 15% of root microbiota variation, whereas environmental conditions and host genotype explain maximally 11% of variation. When grown in the same soil, the root microbiota composition of perennial A. alpina is largely similar to those of its annual relatives A. thaliana and Cardamine hirsuta. Non-flowering wild-type A. alpina and flowering pep1 mutant plants assemble an essentially indistinguishable root microbiota, thereby uncoupling flowering time from plant residence time-dependent microbiota changes. This reveals the robustness of the root microbiota against the onset and perpetual flowering of A. alpina. Together with previous studies, this implies a model in which parts of the root microbiota modulate flowering time, whereas, after microbiota acquisition during vegetative growth, the established root-associated bacterial assemblage is structurally robust to perturbations caused by flowering and drastic changes in plant stature.
Modeling succession of key resource-harvesting traits of mixotrophic plankton
Authors: Berge Terje , Chakraborty Subhendu , Hansen Per Juel , Andersen Ken H
Published: August 2016

Unicellular eukaryotes make up the base of the ocean food web and exist as a continuum in trophic strategy from pure heterotrophy (phagotrophic zooplankton) to pure photoautotrophy (‘phytoplankton’), with a dominance of mixotrophic organisms combining both strategies. Here we formulate a trait-based model for mixotrophy with three key resource-harvesting traits: photosynthesis, phagotrophy and inorganic nutrient uptake, which predicts the trophic strategy of species throughout the seasonal cycle. Assuming that simple carbohydrates from photosynthesis fuel respiration, and feeding primarily provides building blocks for growth, the model reproduces the observed light-dependent ingestion rates and species-specific growth rates with and without prey from the laboratory. The combination of traits yielding the highest growth rate suggests high investments in photosynthesis, and inorganic nutrient uptake in the spring and increased phagotrophy during the summer, reflecting general seasonal succession patterns of temperate waters. Our trait-based model presents a simple and general approach for the inclusion of mixotrophy, succession and evolution in ecosystem models.
Crystal structures of APOBEC3G N-domain alone and its complex with DNA
Authors: Xiao Xiao , Li Shu-Xing , Yang Hanjing , Chen Xiaojiang S.
Published: August 2016

APOBEC3G (A3G) is a potent restriction factor of HIV-1. The N-terminal domain of A3G (A3G-CD1) is responsible for oligomerization and nucleic acid binding, both of which are essential for anti-HIV activity. As a countermeasure, HIV-1 viral infectivity factor (Vif) binds A3G-CD1 to mediate A3G degradation. The structural basis for the functions of A3G-CD1 remains elusive. Here, we report the crystal structures of a primate A3G-CD1 (rA3G-CD1) alone and in complex with single-stranded DNA (ssDNA). rA3G-CD1 shares a conserved core structure with the previously determined catalytic APOBECs, but displays unique features for surface charge, dimerization and nucleic acid binding. Its co-crystal structure with ssDNA reveals how the conformations of loops and residues surrounding the Zn-coordinated centre (Zn-centre) change upon DNA binding. The dimerization interface of rA3G-CD1 is important for oligomerization, nucleic acid binding and Vif-mediated degradation. These findings elucidate the molecular basis of antiviral mechanism and HIV-Vif targeting of A3G.
Increased activity in frontal motor cortex compensates impaired speech perception in older adults
Authors: Du Yi , Buchsbaum Bradley R. , Grady Cheryl L. , Alain Claude
Published: August 2016

Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions.
Observed vulnerability of Filchner-Ronne Ice Shelf to wind-driven inflow of warm deep water
Authors: Darelius E. , Fer I. , Nicholls K. W.
Published: August 2016

The average rate of melting at the base of the large Filchner-Ronne Ice Shelf in the southern Weddell Sea is currently low, but projected to increase dramatically within the next century. In a model study, melt rates increase as changing ice conditions cause a redirection of a coastal current, bringing warm water of open ocean origin through the Filchner Depression and into the Filchner Ice Shelf cavity. Here we present observations from near Filchner Ice Shelf and from the Filchner Depression, which show that pulses of warm water already arrive as far south as the ice front. This southward heat transport follows the eastern flank of the Filchner Depression and is found to be directly linked to the strength of a wind-driven coastal current. Our observations emphasize the potential sensitivity of Filchner-Ronne Ice Shelf melt rates to changes in wind forcing.