bluuebunny/crossref_metadata_2025 huggingface dataset:
Restless Legs Syndrome: A Review
Authors: Chahine Lama M. , Chemali Zeina N.
Published: August 2016

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the limbs accompanied by uncomfortable sensations, leading to sleep disturbances. It is associated with psychiatric comorbidities and a decreased quality of life. RLS is common and most severe among females and the elderly. It may be primary or secondary to other conditions and may be familial. Linkage to several chromosomal loci have been demonstrated. The pathogenesis of RLS involves dopaminergic dysfunction, iron metabolism, and abnormalities in supraspinal inhibition. The mainstay of RLS therapy are dopamine agonists or levodopa.This article reviews the clinical characteristics, epidemiology, diagnosis, pathogenesis, and treatment of RLS.
Longitudinal Studies of PTSD:Overview of Findings and Methods
Authors: Peleg Tamar , Shalev Arieh Y.
Published: August 2016

Posttraumatic stress disorder (PTSD) has a discernible starting point and typical course, hence the particular appropriateness of longitudinal research in this disorder. This review outlines the salient findings of longitudinal studies published between 1988 and 2004. Studies have evaluated risk factors and risk indicators of PTSD, the disorder's trajectory, comorbid disorders and the predictive role of acute stress disorder. More recent studies used advanced data analytic methods to explore the sequence of causation that leads to chronic PTSD. Advantages and limitations of longitudinal methods are discussed.
Memory of the Traumatic Event as a Risk Factor for the Development of PTSD:Lessons from the Study of Traumatic Brain Injury
Authors: Gil Sharon , Caspi Yael , Ben-Ari Irit , Klein Ehud
Published: August 2016

Traumatic memories, and the mechanisms by which they operate, continue to occupy a central role in the scientific investigation of risk factors for the development of posttraumatic stress disorder (PTSD). However, empirically based studies are constrained by practical and ethical considerations and are limited to naturalistic models. Consequently, the paradigms most appropriate for the exploration of the relationship between traumatic memories and PTSD have been identified in conditions involving traumatic events where memories may be compromised. Indeed, traumatic brain injury, a condition that is commonly associated with memory impairment, has often been utilized as a naturally occurring model for the study of traumatic memory and its contribution to the development of PTSD. This article presents a critical review of these research efforts and discusses their theoretical and clinical implications.
Sleep Disturbances in the Aftermath of Trauma and Posttraumatic Stress Disorder
Authors: Mellman Thomas A. , Hipolito Maria Mananita S.
Published: August 2016

Sleep disturbances, including nightmares and insomnia, are prominent following trauma and with posttraumatic stress disorder (PTSD) and likely contribute to the pathogenesis of the disorder. Findings from laboratory studies of PTSD have been inconsistent in terms of documenting objective impaired sleep maintenance but have been somewhat more consistent in indicating alterations of rapid eye movement (REM) sleep. Studies of the early aftermath of trauma can reduce the complexity associated with chronicity and comorbidity, and may have implications for early diagnosis and prevention. Multiple studies indicate that dream content is affected by recent threatening experiences. The development of PTSD is associated with a more replicative type of nightmare content. Sleep is reported to be generally disrupted following trauma especially among those developing PTSD. The limited number of studies that provide objective recorded indices during the early aftermath of trauma also provide a mixed picture regarding overall sleep maintenance. Recent data suggest that a more specific disruption of REM sleep may be associated with the development of PTSD and that this disruption is associated with an increased signal of sympathetic nervous system activation during REM sleep. Disrupted REM sleep and increased sympathetic/noradrenergic activity may have implications for understanding recent promising interventions for PTSD sleep disturbance that can be applied to early intervention.
Participation in Clinical Trials May Improve Care of Acute Schizophrenia Inpatients in a General Hospital
Authors: Halbreich Uriel , Smail Nancy , Tu Xin , Halbreich Judith
Published: August 2016

Introduction: This report demonstrates parameters of quality of care and treatment outcome of acute schizophrenia patients who were involved as subjects in a clinical trial of two marketed widely used antipsychotics compared with their fellow patients who received routine clinical hospital care.

Methods: Patients were newly admitted severely agitated schizophrenia patients who agreed to participate in a double-blind randomized trial of short-term (5 days) rate of improvement in response to two second-generation oral antipsychotics. Treatment outcomes as measured by the Clinical Global Impression and parameters of quality of care were compared with the general population of inpatients in the same county hospital.

Results: Of 145 patients screened, 109 patients did not meet study inclusion and exclusion criteria. It is of note that systematic diagnostic interview did not confirm the clinical diagnosis of schizophrenia in 17 patients (11.7%). Study patients had shorter length of stay (6.75 days vs 15.3 days of total psychiatric patients at the hospital during the study period), no physical restraints (vs 21.9%), no use of antipsychotics as chemical restraints (vs 19.8%), and less recidivism following the trial (28.1%) compared with prior to the trial (64.3%).

Conclusion: Patients who participate in structured clinical research with well-delineated procedures, clinical outcome measures, and clear expectations, faired better than their fellow patients in the same non-research hospital wards. Application of some characteristics of clinical research to the diagnosis and treatment of clinical non-research patients may be considered.
The Contemporary Face of Bipolar Illness:Complex Diagnostic and Therapeutic Challenges
Authors: Fountoulakis Konstantinos N.
Published: August 2016

Manic depression, or bipolar disorder, is a multifaceted illness with an inevitably complex treatment. The current article summarizes the current status of our knowledge and practice concerning its diagnosis and treatment. While the prototypic clinical picture concerns the “classic” bipolar disorder, today mixed episodes with incomplete recovery and significant psychosocial impairment are more frequent. The clinical picture of these mixed episodes is variable, eludes contemporary classification systems, and possibly includes a constellation of mental syndromes currently classified elsewhere. Treatment includes the careful combination of lithium, antiepileptics, atypical antipsychotics, and antidepressants, but not all of the agents in these broad categories are effective for the treatment of bipolar disorder.
Making a Diagnosis When One is Not Apparent: Bridging the Gap Between Somatic Patient and Frustrated Physician
Authors: Gorman Jack M.
Published: August 2016

From medical school, we all know the secret code words: “functional”, “supertentorial”, “idiopathic”, and so forth. These, of course, are some of the ways that physicians may refer to patients for whom they cannot make a definitive diagnosis. Such patients, often labeled “somatisizers”, frequent primary care and specialty care physicians' offices as well as emergency rooms.They present with complaints of a variety of aches and pains, fatigue, insomnia, poor concentration, diarrhea, constipation, etc. Any one of these could be the initial signal of a serious medical problem but for this group of patients nothing can be found on physical examination or laboratory and blood tests.

Depending on the specialty of the physician, somatisizers receive a variety of diagnoses. Neurologists cite tension headache, rheumatologists cite fibromyalgia, internists cite chronic fatigue syndrome, gastroenterologists cite irritable bowel syndrome, and psychiatrists cite depression or an anxiety disorder. With the exception of the latter, no treatment has proven particularly successful, and many of these patients, regardless of the diagnosis, wind up being prescribed antidepressants. Does that mean that all somatisizers are suffering from underlying depression or anxiety? Some insist that is the case, but advocacy groups and many patients themselves resist that classification. Physicians are often afraid to suggest to patients that what they are complaining about is really due to a psychiatric problem, fearful of insulting the person. Some doctors, fearing they might overlook something, send the patient for increasingly sophisticated tests, running up healthcare costs and exposing patients to some risk. Inevitably, a test result comes back on the border of abnormality, thus, creating a reason to push forward with even more tests.
Explanatory and Pragmatic Perspectives Regarding Idiopathic Physical Symptoms and Related Syndromes
Authors: Engel Charles C.
Published: August 2016

In recent years, research-methods literature mainly addressing controlled clinical trials has arisen regarding explanatory and pragmatic treatment trials. Explanatory trials tend to examine causal mechanisms and questions of efficacy and value internal validity (creating optimal study conditions) over generalizability (using study results to understand treatment effects in real-life patient populations). In contrast, pragmatictrials value “external relevance” (generalizability) of study results over “internal elegance” so that clinicians and health policymakers can better understand how treatments might impact their patients and policies.This review draws inspiration from these contrasting explanatory and pragmatic perspectives and develops them for clinical and research pertaining to idiopathic physical symptoms and related syndromes (eg, somatization disorder, chronic fatigue syndrome, multiple chemical sensitivities, irritable bowel syndrome). Explanatory and pragmatic perspectives are used to examine these idiopathies with regard to causation, case definition, labels, and treatment. It is concluded that idiopathic symptom syndromes are fundamentally pragmatic clinical and research challenges. For epidemiologic and methodologic reasons, the complex explanations for these syndromes remain largely elusive. Even so, scientific and clinical pragmatism offers the opportunity to reduce disagreement between competing medical disciplines and between clinicians and affected patients with regard to irreconcilable etiologic questions and to remain evidence-based in the care of patients.
Multisomatoform Disorder: Agreement Between Patient and Physician Report of Criterion Symptom Explanation
Authors: Rost Kathryn M. , Dickinson W. Perry , Dickinson L. Miriam , Smith Robert C.
Published: August 2016

Objective

To determine the level of agreement between patients and expert physicians in whether criterion multisomatoform (MSD) symptoms are explained.

Methods

We systematically collected reports from 280 primary care patients about whether they had suffered from any of 15 criterion MSD symptoms in the past month and whether they had received a medical explanation from a physician for positive criterion symptoms. The research team compared MSD symptom diagnoses derived from patient report with MSD symptom diagnoses derived from an expert physician report.

Results

MSD symptom diagnoses derived from patient report had 98.7% sensitivity, 97.9% specificity, 89.3% positive predictive value, and 99.7% negative predictive value compared with MSD symptom diagnoses derived from an expert physician report. Analysis demonstrated that 15.0% of patients met symptom criteria for MSD, according to patient and physician report; 83.0% failed to meet symptom criteria for MSD, according to patient and physician report; 1.8% of patients met symptom criteria for MSD, according to patient report but not physician report, while 0.2% met symptom criteria for MSD according to physician report but not by patient report.

Conclusion

Patients demonstrated high agreement with a physician expert in somatization about whether criterion MSD symptoms are explained, suggesting revised screeners may accurately identify somatizing patients.
Suicide in Bipolar Disorder: Risks and Management
Authors: Baldessarini Ross J. , Pompili Maurizio , Tondo Leonardo
Published: August 2016

Bipolar disorders are prevalent, often severe, and disabling illnesses with elevated lethality largely due to suicide. Suicide rates average ∼1% annually, or perhaps 60 times higher than the international population rate of 0.015% annually. Suicidal acts typically occur early in bipolar disorders and in association with severe depressive or mixed states. The high lethality of suicidal acts in bipolar disorders is suggested by a much lower ratio of attempts:suicide (∼3:1) than in the general population (∼30:1). Risk factors can help to identify patients at increased suicidal risk, but ongoing clinical assessment is essential to limit risk. Empirical short-term interventions to manage acute suicidal risk include close clinical supervision, rapid hospitalization, and electroconvulsive therapy. Remarkably, however, evidence of the long-term effectiveness of most treatments against suicidal behavior is rare. A notable exception is lithium prophylaxis, which is associated with consistent evidence of major (∼80%), sustained relative reductions of risk of suicides and attempts, and lower lethality (increased attempts:suicide ratio). Such benefits are unproved for other treatments commonly used to treat bipolar disorder patients, including anticonvulsants, antipsychotics, antidepressants, and psychosocial interventions. Applying available knowledge systematically, with close and sustained clinical supervision, can enhance management of suicidal risk in bipolar disorders patients.
Romantic Attachment in Patients with Mood and Anxiety Disorders
Authors: Marazziti Donatella , Dell'Osso Bernardo , Dell'Osso Mario Catena , Consoli Giorgio , Debbio Alessandro Del , Mungai Francesco , Vivarelli Laura , Albanese Francesco , Piccinni Armando , Rucci Paola , Dell'Osso Liliana
Published: August 2016

Introduction

Romantic attachment is the establishment of a relationship with a partner and is strongly influenced by the individual's attachment style. While several studies have shown that attachment style may contribute to the development of psychopathology, less information is available for romantic attachment.The aim of the present study was to compare romantic attachment styles among patients with different mood and anxiety disorders and control subjects.

Method

The study sample included a total of 126 outpatients, 62 of whom were affected by bipolar disorders, 22 by major depressive disorder (MDD), 27 by panic disorder, 15 by obsessive-compulsive disorder, and 126 healthy control subjects. Romantic attachment was assessed by means of the Italian version of the “Experiences in Close Relationships” (ECR) questionnaire.

Results

The results showed that the secure attachment style was more frequent in the control group, while the preoccupied style prevailed among the patients, with no difference among the diagnostic categories.The scores of the ECR anxiety and avoidance scales were significantly higher in the patients than in the control subjects. A trend toward higher ECR anxiety scale scores in women with panic disorder was detected, with the opposite being true for MDD.

Conclusion

Our findings indicate that patients with different psychiatric disorders would be characterized by higher scores on both the ECR anxiety and the avoidance scales, as well as by the preoccupied style of attachment. In addition, women with panic disorder and MDD seem to be characterized by, respectively, higher and lower scores of the ECR anxiety scale than men.
Development of Tics in a Thirteen-Year-Old Male Following Atomoxetine Use
Authors: Sears Jessica , Patel Nitin C.
Published: August 2016

Tics and Tourette syndrome are common comorbidities of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD). One of the mainstay pharmacologic therapies for ADHD has been stimulants. However, this class of drugs has been associated with tic exacerbations, thus limiting their utility in this patients subgroup. Atomoxetine has been explored as an alternative treatment as one of the few non-stimulants available to treat ADHD. Early data identifies atomoxetine's influence on Tourette symptomatology to be not merely equivocal but potentially suppressive in the manifestation of tics. There are, however, case studies describing patients experiencing recurrences of tics following treatment with atomoxetine. We present a unique case of a patient, without any prior history of a movement disorder, who developed tics following a single dose of atomoxetine that did not improve until interventional therapy was initiated.
Taking the Next Steps in the Diagnosis of Alzheimer's Disease: The Use of Biomarkers
Authors: DeKosky Steven T.
Published: August 2016

Alzheimer's disease (AD) is a progressive disorder in which neurodegeneration begins decades before clinical symptoms appear. Detecting AD during this preclinical phase presents both the enormous challenge of identifying at-risk patients prior to symptom onset and the potential reward of treating patients early enough to prevent or slow disease progression. Given that a 5-year delay in the onset of the clinical manifestations of AD could result in almost a 50% reduction in disease prevalence, early detection of AD is a major focus of clinical research. Several objective, measurable indicators of preclinical and clinical characteristics of AD are currently available or in development. These biomarkers are promising because they promote identification of individuals at risk for AD onset and disease progression; diagnostic accuracy and treatment during the early stages of AD; and the development of disease-modifying therapies that may potentially slow or prevent disease progression during the preclinical phase of AD.
Structural Changes in the Brain in Depression and Relationship to Symptom Recurrence
Authors: Bremner J. Douglas
Published: August 2016

Depression is an important public health problem affecting about 15% of the general population; however, little is known about possible changes in the brain that might underlie the disorder. Neuroimaging has been a powerful tool to map actual changes in the brain structure of depressed patients that might be directly related to their symptoms of depression. Some imaging studies of brain structure have shown smaller hippocampal volume with the chronicity of depression correlating to a reduction in volume. Although the meaning of these findings is unclear, other studies have shown increased amygdala volume. Studies have found reductions in volume of the frontal cortex, with some studies showing specific reductions in subregions of the frontal cortex, including the orbitofrontal cortex. Findings of an increase in white matter lesions in elderly patients with depression have been replicated and correlated with late-onset depression, as well as impairments in social and cognitive function. These findings point to alterations in a circuit of brain regions hypothesized to include the frontal cortex, hippocampus, amygdala, striatum, and thalamus, that underlie symptoms of depression.
The “Good Enough” Mood Stabilizer: A Review of the Clinical Evidence
Authors: Kahn David , Chaplan Rebecca
Published: August 2016

A growing family of medications is used for mood stabilization in bipolar disorder. These medications fall into two broad categories according to likely mechanisms of action. Within the categories, specific drugs may vary in their efficacy for different phases of the disorder. The first category, including lithium, anticonvulsants, and some novel treatments, appears to have mechanisms related to intracellular second messengers. These medications have more pronounced antimanic than antidepressant effects, except for lamotrigine, which has antidepressant effects without precipitating mania. The second group of mood stabilizers is the atypical antipsychotics, which act through dopamine and other monoamines. Olanzapine and in all likelihood other drugs in the class possess marked, acute antimanic properties and possible antidepressant properties, but require further study before they can be used as routine options in long-term care. It is clear that the advent of multiple mood stabilizer candidates has not yet led to a single ideal therapy for bipolar disorder, but rather to options that can be flexibly tailored to the lifetime needs of individual patients, in sequences or combinations, and perhaps in conjunction with other classes of psychotropics.
Neuropsychological Testing: Evolution and Emerging Trends
Authors: Randolph Christopher
Published: August 2016

Neuropsychological (NP) test batteries have evolved as an amalgam of intelligence tests, various individual measures of “biological” cognition, and sensory and motor testing. The early emphasis of NP testing was to identify “organicity” and central nervous system lesion localization. More recent approaches have emphasized the profiling of performance across individual neurocognitive domains (eg, attention, memory, and language) to facilitate diagnosis and treatment planning. However, the field is still hampered by the use of many tests that are antiquated, excessively long, or of dubious psychometric quality. Some of these problems may have contributed to the current under-utilization of NP testing in diagnostic workups of neuropsychiatric disorders. This paper reviews some of the recent changes in the field that hold promise for substantially shortening assessments, improving diagnostic reliability, and making NP testing more cost-effective and practical.
A Review of Cognitive and Behavioral Treatment for Body Dysmorphic Disorder
Authors: Neziroglu Fugen , Khemlani-Patel Sony
Published: August 2016

Until recently, body dysmorphic disorder (BDD) had been vastly ignored in the scientific literature. Despite a recent surge in interest, treatment studies are still surprisingly neglected. Reports from the 1970s–1990s discuss few case descriptions and suggest anecdotal treatment strategies. Since the 1990s, information about the treatment of BDD has increased slightly. The intent of this paper is to review the current state of knowledge regarding cognitive and behavior therapy, which so far has been found to be effective. The current literature suggests that there is no difference between the efficacy of one treatment strategy over another nor the combination of cognitive and behavior therapy over behavior therapy. However, more research is needed in this area before definitive conclusions can be made.
The Medical Student Experience With Disasters and Disaster Response
Authors: Katz Craig L. , Gluck Natalie , Maurizio Andrea , DeLisi Lynn E.
Published: August 2016

Medical students from New York City were integrally involved in the response by health professionals to aid the families of victims of the September 11, 2001, attacks on the World Trade Center. The present study was performed to investigate the emotional impact of this involvement on medical students from the Mount Sinai School of Medicine in New York City. One hundred fifty-seven students responded to a mail survey that explored their personal and professional involvement in the disaster as well as their psychiatric symptoms in the week after the event and at the time of the survey (3.5 months after the event). Findings suggested a differential emotional impact on female students and on students involved in less supervised and more emotionally intense activities. However, involvement in the relief effort, per se, did not contribute to psychiatric symptomatology. It may have been associated with enhanced professional self-esteem among the students. These findings have implications for future planning of psychiatric response to disasters.
Non-Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder
Authors: Pliszka Steven R.
Published: August 2016

Stimulants are a highly efficacious and safe treatment for attention-deficit/hyperactivity disorder (ADHD), with 75% to 90% of patients responding well if two different stimulants (amphetamine and methylphenidate) are used. Nonetheless, a subset of ADHD patients will either fail to respond to stimulants or have side effects that preclude their use (tics, severe loss of appetite, marked insomnia). For such patients, there are a number of non-stimulant agents that serve as second-line treatments. Tricyclic antidepressants (TCAs) are the most studied of these drugs. They are superior to placebo in the treatment of ADHD and may reduce abnormal movements in patients with ADHD/tic disorder. TCAs often produce side effects of sedation, dry mouth, and constipation. Bupropion is superior to placebo in the treatment of ADHD and has a more favorable side-effect profile than the TCAs. A new selective norepinephrine reuptake inhibitor, atomoxetine, has been shown to be efficacious in the treatment of ADHD and has recently received an approvable letter from the Food and Drug Administration. The α-agonists clonidine and guanfacine have also been used as alternative agents in ADHD, though the controlled data are more limited. A recent controlled clinical trial suggests a combination of methylphenidate and clonidine has advantages in the treatment of comorbid ADHD and tics over either medication alone. Clinical guidelines for each of these agents, as well as their use in combination with stimulants in comorbid conditions, will be discussed.
The Role of Cardiovascular Risk Factors in Alzheimer's Disease
Authors: Ravona-Springer Ramit , Davidson Michael , Noy Shlomo
Published: August 2016

The distinction between Alzheimer's disease and vascular dementia, the two most common types of dementia, has been undermined by recent advances in epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular risk factors, traditionally regarded as distinguishing criteria between the two entities, have been shown to be associated with both AD and vascular dementia. In this article, we propose mechanisms of action of cardiovascular risk factors in AD, suggest possible explanations for the overlap with vascular dementia and discuss the implications this might have on future differential diagnosis, research, and treatment strategies.
Posttraumatic Stress Disorder in the General Population After Mass Terrorist Incidents: Considerations About the Nature of Exposure
Authors: Galea Sandro , Resnick Heidi
Published: August 2016

Epidemiologically, disasters represent multiple forms of possible exposures, including exposure type (eg, natural versus human-made), intensity, and duration. It has been suggested that the consequences of human-made disasters (eg, terrorist incidents) may be more severe than those of natural disasters; recent evidence suggests that there may be a high prevalence of posttraumatic stress disorder (PTSD) among both direct survivors of such attacks and in the general population. Several studies after the September 11, 2001, terrorist attacks found that the prevalence of PTSD was higher in New York City than it was in the rest of the US and that there was a substantial burden of PTSD among persons who were not directly affected by the attacks. This raises important questions about the meaning of “exposure” to a disaster. Using data from an assessment of PTSD in the first 6 months after September 11th we considered the nature of the PTSD experienced by persons who were not directly affected by the September 11th attacks. These data suggest that persons in the general population may have clinically important posttraumatic stress symptomatology after a mass terrorist incident. Future research should consider mechanisms through which persons in the general population may be at risk for PTSD after such incidents.
Mental Health Care for Ethnic Minority Individuals and Communities in the Aftermath of Disasters and Mass Violence
Authors: Norris Fran H. , Alegria Margarita
Published: August 2016

Findings from research on psychiatric epidemiology, disaster effects, discrepancies in service use, and cross-cultural psychology are reviewed to generate guidelines for culturally responsive postdisaster interventions. Ethnicity and culture influence mental health care at various points: on need for help; on availability and accessibility of help; on help-seeking comfort (stigma, mistrust), and on the probability that help is provided appropriately. There are aspects of disaster mental health practice that may ameliorate many of barriers that contribute to ethnic disparities in service use. It is proposed that interventions should give greater attention to socially engaged emotions and functioning. To promote disaster recovery, practitioners are advised to: assess community needs early and often; provide easily accessible services; work collaboratively and proactively to reduce stigma and mistrust and engage minorities in care; validate and normalize distress and help-seeking; value interdependence as well as independence as an appropriate developmental goal; promote community action; and advocate for, facilitate, or conduct treatment and evaluation research. Notwithstanding the pain and stress they cause, disasters create opportunities to de-stigmatize mental health needs and build trust between providers and minority communities.
Pharmacotherapy of Seasonal Affective Disorder
Authors: Pjrek Edda , Winkler Dietmar , Kasper Siegfried
Published: August 2016

Seasonal affective disorder is a common variant of recurrent major depressive disorder or bipolar disorder. Treatment with bright artificial light has been found to be effective in this condition. However, for patients who do not respond to light therapy or those who lack compliance, conventional drug treatment with antidepressants also has been proposed. Substances with selective serotonergic or noradrenergic mechanisms should be preferred over older antidepressants. Although there are a number of open and controlled studies evaluating different compounds, these studies were often limited by relatively small sample sizes. Furthermore, there are no studies specifically addressing bipolar seasonal depression. This article will review the published literature on pharmacotherapy of seasonal affective disorder.
The Treatment of Neuropathic Pain
Authors: Freeman Roy
Published: August 2016

Neuropathic pain is responsible for a significant amount of the morbidity associated with generalized and focal peripheral neuropathies. It is a consequence of alterations in neuronal function, chemistry, and structure that occur secondary to nerve injury. These manifestations of neuronal plasticity occur in the peripheral nerve, spinal cord, and brain. A variety of agents from diverse pharmacologic classes, the so-called adjuvant analgesics, have been used to treat neuropathic pain. These include antidepressants, first- and second-generation anticonvulsants, antiarrhythmic agents, topical agents, N-methyl-D-aspartate receptor antagonists, and opioid analgesics. The use of these adjuvant analgesics, either alone or in combination, should result in the alleviation of neuropathic pain in most patients. Recent advances in the understanding of pain mechanisms at multiple central nervous system levels should pave the way toward more effective treatment modalities.
Characteristics of Aggression in Clinically Referred Children
Authors: Bambauer Kara Zivin , Connor Daniel F.
Published: August 2016

Objective

We investigated the phenomenology of aggression in a group of psychiatrically referred children and in a comparison group of children.

Introduction

Children (N=275) were evaluated at a pediatric psychopharmacology clinic in an academic medical center and compared with 100 non-referred children from the community. To assess the influence of several predictors on the child's level of clinical impairment we conducted stepwise regression analyses.

Results

Aggression occurred across many different psychiatric diagnoses in psychiatrically referred children. Aggression in referred children was more frequent, physical, intense, lasted for a longer duration per episode, was more resistant to intervention, and occurred at an earlier age of onset in contrast with comparison children. Controlling for psychiatric diagnosis and demographic variables, family income and number of aggressive episodes in the last 6 months were the only significant predictors of child impairment.

Discussion

Phenomenologically, aggression may be more maladaptive in children with a psychiatric disorder compared with non-referred youths. These phenomenological differences in characteristics of aggression support the concept of an aggressive syndrome in psychiatrically referred children.

Conclusion

Results support the need for development of specific treatment interventions for excessive maladaptive aggression independent of psychiatric diagnosis in referred children and adolescents.
DNA Microarray Technology in the Clinical Environment:The AmpliChip CYP450 Test for CYP2D6 and CYP2C19 Genotyping
Authors: de Leon Jose , Susce Margaret T. , Johnson Maria , Hardin Mike , Maw Lorraine , Shao Alison , Allen Antonette C.P. , Chiafari Francis A. , Hillman Grantland , Nikoloff D. Michele
Published: August 2016

Introduction:An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology.

Methods:A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype.

Results:In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.1%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%).

Conclusion:We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.
An Integrated Analysis of the Safety and Tolerability of Desvenlafaxine Compared with Placebo in the Treatment of Major Depressive Disorder
Authors: Clayton Anita H. , Kornstein Susan G. , Rosas Gregory , Guico-Pabia Christine , Tourian Karen A.
Published: August 2016

Introduction: The safety and tolerability profiles of antidepressants can often influence the treatment choices of clinicians treating major depressive disorder. The purpose of this investigation was to characterize the safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in treating depression.

Methods: An integrated analysis of all short-term, randomized, double-blind, placebo-controlled registration studies for major depressive disorder (four flexible-dose and five fixed-dose studies) was performed. Adult outpatients with major depressive disorder received desvenla-faxine doses ranging from 50–400 mg/day or placebo for 8 weeks. Treatment-emergent adverse events, laboratory values, vital signs, and discontinuation symptoms were evaluated. In the subset of fixed-dose studies, dose-related effects were analyzed.

Results: In the overall population (placebo: n=1,116; desvenlafaxine: n=1,834), adverse events resulted in discontinuations in 3% of placebo-treated patients and 12% of desvenla-faxine-treated patients; in the subset of fixed-dose studies, the rates were 4% with placebo and increased with desvenlafaxine dose (50 mg/ day: 4%; 400 mg/day: 18%). The most common treatment-emergent adverse event was transient nausea that was generally mild to moderate. The most common sexual dysfunction associated with desvenlafaxine treatment was erectile dysfunction in men (7% vs 1% with placebo) and anorgasmia in women (1% and 0%). One desvenlafaxine-treated patient died of a completed suicide; there were four suicide attempts (three desvenlafaxine, one placebo) and eight cases of suicidal ideation (five desvenlafaxine, three placebo) during the on-therapy period. Small but statistically significant changes in mean blood pressure occurred at all desvenlafaxine doses; clinically meaningful changes were observed in 1% of placebo-treated patients and 2% of desvenlafaxine-treated patients. Desvenlafaxine was associated with small but statistically significant mean changes in laboratory assessments, particularly lipid and liver enzyme elevations, and electrocardiograms; few cases of these changes were clinically relevant.

Conclusion: Desvenlafaxine in the treatment of major depressive disorder exhibited a safety and tolerability profile generally consistent with the serotonin-norepinephrine reuptake inhibitor class. The most common adverse event was transient nausea. At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo.
Theta Burst Stimulation in the Treatment of Incapacitating Tinnitus Accompanied by Severe Depression
Authors: Soekadar Surjo R. , Arfeller Carola , Rilk Albrecht , Plontke Stefan K. , Plewnia Christian
Published: August 2016

This case report describes the use of transcranial magnetic theta burst stimulation (TBS) in the treatment of incapacitating tinnitus accompanied by symptoms of severe depression. Tinnitus is known to be associated with hyperactivity and maladaptive cortical reorganization of the central auditory system. Combined with anxiety and depression, it can occasionally constitute a psychiatric emergency. Recently, it has been demonstrated that tinnitus can be temporarily suppressed by non-invasive transcranial magnetic stimulation. TBS is a newly developed technique for rapid and lasting modulation of cortical excitability. Herein, we present a case of a 54-year-old woman with incapacitating tinnitus that has significantly decreased after three cycles of 1-week treatment with continuous TBS to the temporo-parietal auditory association cortex. According to the Tinnitus Questionnaire, tinnitus intensity decreased from 84 points before to 59 points after treatment. Hamilton Rating Scale for Depression score dropped from 44 to 23 points. TBS showed to be efficient, well-tolerated, and practical in the management of distressing tinnitus accompanied by symptoms of severe depression.
Applying the Principles of Adult Learning to the Teaching of Psychopharmacology: Audience Response Systems
Authors: Stahl Stephen M. , Davis Richard L.
Published: August 2016

Medical presentations can be enhanced by systematically collecting audience feedback. This is readily accomplished with polling systems, called audience response systems. Several systems are now available that are small, inexpensive, and can be readily integrated into standard powerpoint presentations without the need for a technician. Use of audience response systems has several advantages. These include improving attentiveness, increasing learning, polling anonymously, tracking individual and group responses, gauging audience understanding, adding interactivity and fun, and evaluating both participant learning and instructor teaching. Tips for how to write questions for audience response systems are also included.
Cytokine Polymorphisms in the Pathophysiology of Mood Disorders
Authors: Clerici Mario , Arosio Beatrice , Mundo Emanuela , Cattaneo Elisabetta , Pozzoli Sara , Dell'Osso Bernardo , Vergani Carlo , Trabattoni Daria , Altamura A. Carlo
Published: August 2016

Introduction:An increasing amount of data suggests that dysregulation of the immune system, including the cytokine network, is associated with the etiology and pathophysiology of mood disorders. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. The aim of this study was to define the genetic immunologic scenario associated with major depressive disorder (MDD) and bipolar disorder.

Methods:Eighty-four Italian outpatients affected by bipolar disorder type I, bipolar disorder type II, or MDD, and 363 healthy controls were enrolled into the study. We analyzed allele and genotype distribution of −308 (G/A) tumor necrosis factor-α (TNF-α), +874 (T/A) interferon-γ (IFN-γ), -174 (G/C) interleukin (IL)-6, and −1082 (G/A) IL-10 promoter polymorphisms by Polymerase Chain Reaction Sequence Specific Primers technique.

Results:We observed different genotype and allele distributions of TNF-α, IFN-γ, and IL-10 polymorphisms in the three groups of patients analyzed. In particular, bipolar II patients were characterized by an absence of adenine (A) high producer allele of TNF-α (P<.001) and a lower percentage of TT high producer genotype of IFN-γ (P<.001); bipolar I individuals showed reduced percentage of AA low producer genotype of IL-10 (P<.001). Both bipolar I and bipolar II patients not carrying guanine (G) high producer IL-6 allele showed a lower mean age at onset (P=.048).

Conclusion:These data support the existence of a genetic profile related to pro-inflammatory cytokines in patients affected by mood disorders. The differences observed across the three clinical phenotypes suggest the presence of different pathogenetic mechanisms involved in the susceptibility of phenotypically different mood disorders.
Clinical Perspectives on the Combination of D-Cycloserine and Cognitive-Behavioral Therapy for the Treatment of Anxiety Disorders
Authors: Otto Michael W. , Basden Shawnee L. , Leyro Teresa M. , McHugh R. Kathryn , Hofmann Stefan G.
Published: August 2016

In a particular success for translational research agendas, characterization of the neuronal circuits underlying fear extinction, and basic research in animal extinction paradigms, has led to intervention studies examining the use of D-cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive-behavioral therapy (CBT). In this article, we review these intervention studies, and discuss DCS augmentation of CBT relative to more traditional combination-treatment strategies in the treatment of anxiety disorders. We offer an accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and discuss the advantages of isolated-dosing strategies with DCS relative to these limitations. This strategy is contrasted with the chronic-dosing applications of DCS for schizophrenia and Alzheimer's disease, and future directions for isolated-dosing strategies are discussed.
An Association of Intrusive, Repetitive Phrases with Lamotrigine Treatment in Bipolar II Disorder
Authors: Kemp David E. , Gilmer William S. , Fleck Jenelle , Dago Pedro L.
Published: August 2016

Introduction:

Bipolar disorder is frequently associated with obsessional symptoms. However, no reports have identified a pattern of obsessionality that is associated with a specific mood stabilizer treatment.

Methods:

A chart review was conducted on five patients with bipolar II disorder who spontaneously reported a form of obsessionality characterized by intrusive, recurrent phrases after taking lamotrigine.

Results:

Development of the phrases occurred from 7–42 years after mood disorder onset and occurred only after initiation of lamotrigine treatment. The phrases improved with lamotrigine discontinuation or dose reduction and recurred with lamotrigine re-challenge or upon dose escalation.

Conclusion:

A possible mechanism for the development of the intrusive phrases involves the influence of lamotrigine on glutamatergic regulation in a bipolar II disorder population vulnerable to the expression of obsessionality. Limitations of this report include its observational nature, small number of cases reported, and confound of concomitant medication use.
Factors in the Assessment of Suicidality in Youth
Authors: Posner Kelly , Melvin Glenn A. , Stanley Barbara , Oquendo Maria A. , Gould Madelyn
Published: August 2016

Suicide remains a leading cause of death among youth, and suicide ideation and behavior are relatively common in both normal and clinical populations. Clinicians working with young people must assess for the presence of suicidal ideation, suicidal behavior, and other risk factors, in order to determine the level of risk. This paper provides the clinician with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior.
Recalling Safety: Cooperative Functions of the Ventromedial Prefrontal Cortex and the Hippocampus in Extinction
Authors: Corcoran Kevin A. , Quirk Gregory J.
Published: August 2016

Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.
Body Image and the Parietal Lobes
Authors: Trimble Michael
Published: August 2016

In this review, the history of the concept of the body image in neuropsychiatry is presented. Links between the parietal cortex and the body image are discussed and the possible role of the parietal lobe in psychiatric disorders noted. The link between parietal lobe function and some neurophilosophical concepts are introduced.
Opioids:From Physical Pain to the Pain of Social Isolation
Authors: Stein Dan J. , van Honk Jack , Ipser Jonathan , Solms Mark , Panksepp Jaak
Published: August 2016

The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.