bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Safety and Effectiveness of Mixed Amphetamine Salts Extended Release in Adults With ADHD
Authors: Biederman Joseph , Spencer Thomas J. , Wilens Timothy E. , Weisler Richard H. , Read Stephanie C. , Tulloch Simon J.
Published: August 2016

Objective: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.

Methods: A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced–dose-escalation study of MAS XR in adults (≥ 18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mgl day for 1 week, with subsequent titration up to 60 mgl day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-N). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.

Findings: ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2±13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity.

Conclusion: Treatment with MAS XR 20–60 mgl day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.
Obsessive-Compulsive Disorder and Obsessive-Compulsive Spectrum Disorders: Diagnostic and Dimensional Issues
Authors: Hollander Eric , Kim Suah , Khanna Sumant , Pallanti Stefano
Published: August 2016

Although obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the DSM-IV, recent considerations for a reclassification into an obsessive-compulsive spectrum disorders (OCSDs) cluster are gaining prominence. Similarities in symptomatology, course of illness, patient population, and neurocircuitry of OCD and OCSD are supported by comorbidity, family, and neurological studies, which also offer a critical re-evaluation of the relationship between OCD and anxiety disorders. This review examines potential classifications of OCD among the wider spectrum of affective disorders and at the interface between affective disorders and addiction. In addition, it has been suggested that the categorical diagnostic approach would be enhanced by an additional dimensional approach, including parameters such as stability of mood and ability to sustain attention. With further studies, it is ultimately the goal to define OCD and related disorders based on endophenotypes.

Despite efforts in this field, there are several fundamental unresolved issues, including the question of which disorders should be grouped together in this category and which characteristics to include as their shared common features. A reclassification of OCD among the OCSDs would allow for better scrutiny of distinct obsessive-compulsive symptoms, as currently this disorder often goes undetected in patients who complain of a broad symptom of anxiety. Advantages and disadvantages of establishing OCSDs and its implications for diagnosis, treatment, and research are discussed.
The Use of Pharmacotherapy in the Prodrome of Schizophrenia
Authors: Remington Gary , Shammi Chekkera
Published: August 2016

In treating schizophrenia there has been a shift in focus, with more attention being paid to early intervention based on the notion that effective treatment at this point can improve outcome. Most of this work has centred on pharmacotherapeutic interventions during the first psychotic break. More recently, attention has turned to the potential value of intervening even earlier, that is during the so-called “prodrome” that has been identified as predating the first psychotic break by as much as 4–5 years. We now have a limited number of published reports addressing this topic and these are reviewed here.
Achieving Remission and Favorable Outcomes in Patients with Depression/Anxiety and Substance use Disorders
Authors: Schatzberg Alan F.
Published: August 2016

Given the frequency with which patients with substance use disorders (SUDs) and those with psychiatric disorders, such as major depressive disorder (MDD) and generalized anxiety disorder (GAD), suffer relapses and recurrences, the issue of long-term treatment for SUDs warrants special attention. Faced with recommending long-term treatment, the clinician must discern the primacy of disorder, which may have been only obliquely addressed at the time of the patient's presentation and then solved by concurrent treatment. Establishing primacy relies on determining whether the psychiatric symptoms were induced by SUD or the psychiatric disorder emerged first and substance use was a means of coping with it. A third possibility exists—that the two disorders developed independently of each other, albeit becoming intermingled over time and serving to exacerbate each other. Clues to the temporal relationship of the disorders can be deduced from a meticulous history obtained from multiple sources, the effects that acute treatment has had on either condition, and the patient's willingness to remain abstinent from the addictive substance. Hasin and colleagues demonstrated the importance that a history of depression has on long-term remission and relapse outcomes in substance dependence (Slide 1).
Primary Care Management of Patients with Co-occurring Disorders
Authors: Culpepper Larry
Published: August 2016

Primary care physicians (PCPs) often provide the first line of care for the vast number of United States adults—∼30% at any given time—with either a psychiatric or a substance use disorder, or both. The widespread prevalence of this comorbidity bears reiterating: During the same 12-month period, 20% of national survey respondents with a substance use disorder (SUD) had at least one mood disorder, and 17% had at least one anxiety disorder. Conversely, at least one SUD was found among 20% of respondents with a mood disorder and 15% of those with an anxiety disorder. However, because PCPs are often not aware of or alerted to these problems, it would seem advisable that patients presenting with either a psychiatric or an alcohol use disorder should be evaluated for both conditions. Establishing the presence of co-occurring disorders may be difficult, but it is necessary for appropriate and realistic treatment planning.
The Role of L-Methylfolate in Depressive Disorders
Authors: Farah Andrew
Published: August 2016

Major depressive disorder (MDD) is a debilitating illness affecting 7% to 12% of men and 20% to 25% of women. It is usually a recurrent illness, with up to 30% of patients experiencing a depressive episode lasting over 2 years. Depression may also increase the morbidity and mortality of numerous medical conditions, such as cardiac disease, myocardial infarction, chronic pain, diabetes, cerebrovascular events, and respiratory illnesses. The goal of antidepressant therapy is to achieve full remission and functional recovery, and continuing treatment beyond the acute phase is usually necessary to maintain remission. In contrast with full remission, individuals who experience residual symptoms, however mild, have a higher chance of experiencing one or more additional episodes.
Advances in the Management of Fibromyalgia
Authors: Arnold Lesley M.
Published: August 2016

The presentation of fibromyalgia syndrome (FM) is heterogeneous. Hence, the goal of treatment is to develop an individualized approach that takes into account the severity of the patient's pain, the presence and severity of other symptoms and comorbidities or stressors, and the degree of functional impairment. This includes the identification and treatment of all pain sources that might be present in addition to FM, such as peripheral pain generators (eg, comorbid osteoarthritis or neuropathic pain) or visceral pain disorders (eg, comorbid irritable bowel syndrome). It is also important to address other symptoms or disorders that commonly occur in patients with FM, such as fatigue, sleep disturbances, and comorbid sleep disorders (eg, sleep apnea). Cognitive impairment, stiffness, mood disorders, and anxiety disorders are also commonly reported in patients with FM. Finally, the treatment should strive to improve the patient's function and global health status. In most cases, the management involves both pharmacologic and nonpharmacologic treatments (Slide 1).
Introduction
Authors: Adler Lenard A. , Newcorn Jeffrey H.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) may be the most common chronic, undiagnosed psychiatric disorder in adults. ADHD is characterized by restlessness, overactivity, disorganization, impulsivity, and inattention; and as further characterized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). For most cases, an adult ADHD diagnosis is preceded by symptoms in childhood, which is a time when the disorder is rarely inquired about and usually overlooked.

ADHD has been recognized in children for several decades, and the importance of detection and treatment is well established. Whereas it was initially believed that children outgrew the disease, researchers now know that approximately two thirds of children affected with ADHD symptoms carry the condition into adolescence and then into adulthood. Consequently, >4% of adults in the United States have ADHD. Nevertheless, the disorder is unrecognized and untreated in the vast majority of these people.
Age-Related Considerations in the Treatment of ADHD
Authors: Newcorn Jeffrey H.
Published: August 2016

Although the symptoms of attention-deficit/hyperactivity disorder (ADHD) can be found in many “normal” people, these symptoms are present to a greater extent in those affected by the disorder. In these patients, ADHD symptoms cause substantial functional impairment. Therefore, the goal of treatment is not simply to reduce core symptoms, but also to decrease the level of impairment caused by these symptoms.

Common impairments in adolescents and adults include academic and occupational problems that are particularly evident in the context of tasks requiring a high degree of organization or attentional function. These impairments result in problems related to task completion, prioritizing work and other obligations, and time management, etc. These symptoms often impact successful completion of tasks in school or at work, and can also result in a variety of problems in initiating and managing relationships (Slide 1).

Mood and anxiety disorders often co-occur with ADHD in adults. The accumulation of experiences related to impaired academic and/or occupational performance, and or persistent relationship problems, due to the symptoms of ADHD, can lead to either depressed mood or anxiety related to performance and/or social situations. Therefore, in treating adults with ADHD, reduction of those co-occurring symptom presentations is also an important goal.
Acute Nonpsychotic Mania: First Episode
Authors: Allen Michael H.
Published: August 2016

Mr. Jones, 30 years of age, presents to the office for the first time with symptoms of mania. He had gone through a period of increased spending during which he purchased thousands of dollars worth of audio and video equipment in addition to other items he could not afford. He is currently living with his parents due to his inability to meet these financial obligations. When his parents starting receiving packages at their house, they decided to have Mr. Jones evaluated. They note that he is awake much of the night talking on the phone and browsing the Internet. His bills indicate large charges for phone sex and pornography.
Mixed Episodes with Psychotic Features
Authors: Chou James C.-Y.
Published: August 2016

Mixed episode is one of the more difficult-to-treat conditions in bipolar disorder. The presence of mixed features (symptoms of both depression and mania in a single acute episode) is associated with both poorer acute treatment response and poorer longitudinal outcomes, including shorter subsequent inter-episode periods and greater suicidality. Mixed features are indicative of an overall greater severity of both acute and chronic illness (Slide 1).
The Treatment of Comorbid Insomnia
Authors: McCall W. Vaughn
Published: August 2016

There are many new findings in the area of comorbid insomnia. Almost 50% of all cases of chronic insomnia are due to a mental disorder, with depressive illness explaining the majority of cases related to mental disorder (Slide 1). Other common causes of comorbid, or secondary, insomnia include chronic respiratory disease such as asthma and chronic obstructive pulmonary disease, chronic pain, degenerative neurological disease, and some medications such as glucocorticoids and serotonin reuptake inhibitors. A general principle of management of insomnia related to mental or medical disorders is that the principal disorder must be fully treated as part of the insomnia treatment plan. If there is an offending medication, it must be discontinued if possible.
Case Report: Complex ADHD Presentation in Adolescence
Authors: Weiss Margaret
Published: August 2016

The presentation of attention-deficit/hyperactivity disorder (ADHD) in adolescence is often complex, but clinicians will attest multiple and complex comorbid conditions in adolescence are by no means unusual. Given that this is often the typical presentation, this article will describe a case to illustrate the multiple pathways to treatment of an adolescent with myriad distinct but interacting issues. Although all clinicians attempt to practice evidence-based medicine, the evidence is often limited to circumscribed disorders, and management and sequencing of treatment of adolescents with a combination of different conditions has not be adequately researched.
Obsessive-Compulsive Symptoms in Schizophrenia: Are They Manifestations of a Distinct Subclass of Schizophrenia?
Authors: Berman Ileana , Pappas Demetra , Berman Stuart M.
Published: August 2016

The association between obsessive-compulsive (OC) symptoms and schizophrenia has been discussed in the literature for many decades. Recent studies, which have been more systematic than earlier reports and benefited from more rigorous diagnostic criteria, have generated results that contradict earlier findings. The current consensus is that OC symptoms are seen in a significant number of patients with schizophrenia, and indicate a poor prognosis. These recent studies also suggest that OC symptoms are more than just expressions of persistent schizophrenic psychosis, and that they share characteristics with obsessive-compulsive disorder (OCD). This article discusses the arguments supporting the possibility that OC symptoms are either manifestations of comorbid OCD, or are characteristics of a distinct subtype of schizophrenia.
Novel Neuroleptics Improve Attentional Functioning in Schizophrenic Patients: Ziprasidone and Aripiprazole
Authors: Serper Mark R. , Chou James C.Y.
Published: August 2016

Past research has established that traditional neuroleptic treatment improves attentional functioning in schizophrenic (SZ) patients. The present investigation expands on this finding by examining attentional improvement in nine acute SZ patients treated with either the novel neuroleptic ziprasidone or aripiprazole over a 4-week inpatient period. Twelve SZ in patients receiving typical neuroleptic treatment over the same time period served as controls. The results revealed that while all patients showed marked attentional improvement from medication-free baseline to week 4 of treatment, the SZ patients who received novel antipsychotics showed significant improvement on immediate recall and reaction time measures. These results suggest that novel neuroleptic treatment, perhaps through preferential activation of the prefrontal cortical pathways, improves SZ patients' information processing speed and efficiency.
The Panic-Agoraphobic Spectrum: Rationale, Assessment, and Clinical Usefulness
Authors: Cassano Giovanni B. , Rotondo Alessandro , Maser Jack D. , Shear M. Katherine , Frank Ellen , Mauri Mauro , Dell'Osso Liliana
Published: August 2016

This paper describes a model of psychopathology termed the panic-agoraphobic spectrum. The model has been constructed by identifying different psychopathologic and clinical domains that incorporate and extend the diagnosis of panic disorder as described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).

Categorical classifications do not take into account the subthreshold, atypical, and often enduring symptoms that accompany the core manifestations of full-blown mental disorders. These often-neglected spectrums of symptoms, however, may be as distressing and debilitating as the full-blown disorders and can have unrecognized importance in selection of and response to treatment. At the Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology, Institute of Psychiatry of the University of Pisa, Italy, a spectrum approach to mental disorders (eg, bipolar, obsessive-compulsive, eating, and panic disorders) has been used extensively and has proven effective in clinical practice.

The need for systematic identification and assessment of a broad array of symptoms and behavioral features has led, as a first step, to the conceptualization of the panic-agoraphobic spectrum model. In collaboration with researchers from the University of Pittsburgh, PA, and elsewhere, the University of Pisa scientists have further refined the panic-agoraphobic spectrum model and have developed a structured interview for this spectrum called the Structured Clinical Interview for Panic-Agoraphobic Spectrum. The rationale, clinical usefulness, and heuristic significance of the panic-agoraphobic spectrum model are discussed below.
The Molecular Genetics of Pathological Gambling
Authors: Comings David E.
Published: August 2016

As gambling becomes available to more and more individuals in this country, the problem of compulsive or pathological gambling (PG) will also increase. As with other forms of addiction, both environmental and genetic factors are involved in PG. Identification of the genes that play a role in increasing a person's risk for PG will lead to a better understanding of the disorder and to more rational and effective treatment. Although studies of the molecular genetics of PG are just beginning, a number of interesting observations have been made and are reviewed in this article. As with other addictive behaviors, abnormalities in dopaminergic reward pathways a likely to be involved. Consistent with this, we have observed a significant association between PG and the D1, D2, D3, and D4 dopamine receptor genes. The fact that each these genes has an effect is consistent with a polygenic inheritance of a susceptibility to PG The involvement of multiple dopamine genes consistent with the “reward deficiency syndrome,” which suggests that addictive impulsive disorders are due, at least in part, to genetic abnormalities of the dopamine reward pathways. On the basis of this hypothesis, we describe other genes also likely to play a role in a person's susceptibility to PG.
Problem and Pathological Gambling: A Consumer Perspective
Authors: Letson Laura M.
Published: August 2016

The growth of gambling across the United States over the past decade has created significant difficulties for pathological gamblers. The rise in problem gambling, coupled with an increasing strain on social and health care services for treatment of gamblers and their families, has resulted in an urgent need for innovative interventions that target patients, health care providers, educational institutions, government, media, and the gambling industry. This article describes the impact of gambling from a consumer-protection perspective, and offers approaches to promoting public awareness of compulsive gambling as a pervasive problem that affects multiple areas of society.
Sensory-Motor Aspects of Obsessive-Compulsive Disorder
Authors: Stevens Kevin P. , Hoffman Jonathan , Hsia Curtis
Published: August 2016

This article presents an overview of sensorymotor aspects of obsessive-compulsive disorder (OCD). These phenomena have received less attention than obsessions and compulsions, but are nonetheless important in the development, maintenance, phenomenology, and treatment of the disease. In many individuals, seemingly disparate sensory-motor symptoms can be conceptualized as part and parcel of OCD. Sensory-motor aspects are discussed within the context of faulty information processing and related to neuropsychiatric systems characteristic of OCD. As the pathophysiology of OCD is highly extensive, not all sensory-motor symptoms discussed here will be observed in every individual.
The Potential Role of 5-HT1D Receptors in the Pathophysiology and Treatment of Obsessive-Compulsive Disorder
Authors: Stern Liat , Zohar Joseph , Hendler Thalma , Ianco Iulian , Sasson Yehuda
Published: August 2016

Obsessive-compulsive disorder (OCD) is a psychiatric disorder in which the patient suffers from recurrent intrusive ideas, impulses, thoughts (obsessions), and/or patterns of behavior (compulsions) that are ego-alien and produce anxiety if resisted. The ego-dystonic nature of OCD is one of the hallmarks of this disorder. OCD can be a disabling condition because the obsessions and compulsions are time-consuming and interfere with patients' everyday activities and their relationships with friends and family. In severe cases, OCD conflicts even with the simplest tasks of daily living.

Research interest in OCD has been growing steadily in the past decade. A search on MEDLINE reveals an over 300% increase in citations on OCD from 1986 to 1998. These range across the spectrum of research fields, from genetic studies, brain imaging, and neurobiological research examining the underlying pathogenesis of OCD to epidemiological studies evaluating the course of clinical symptoms, comorbidities, and outcomes. Each area represents an important piece in the complex jigsaw puzzle of OCD.
The Therapeutic Potential of 5-HT1B Autoreceptors and Heteroreceptors and 5-HT-Moduline in CNS Disorders
Authors: Sarhan Hala , Fillion Gilles
Published: August 2016

The endogenous peptide 5-HT–moduline has been characterized as a novel neuropeptide that binds to 5-HT1B receptors in the brain areas in which it is released. By inducing structural changes in these receptors, this peptide prevents 5-HT binding, thereby desensitizing the receptors and inhibiting serotonergic function. This novel mechanism may help to explain differential effects of the serotonergic system in varying areas of the brain that are innervated by the same or few neurons. In addition, dysfunction or disruption of the 5-HT–moduline system may contribute to psychiatric disorders such as depression and anxiety, and may have important implications for the development of new therapeutic agents for these disorders.
Behavioral Effects of Clomipramine on Prepubertal Boys With Autistic Disorder and Severe Mental Retardation
Authors: Brasić James Robert , Barnett Jacqueline Y. , Sheitman Brian B. , Lafargue R. Todd , Kowalik S. , Kaplan Diana , Tsaltas Margaret Owen , Ahmad Raheela , Nadrich Robert H. , de Fatima Mendonça Maria
Published: August 2016

In an open nonblind clinical trial, clomipramine was administered to five previously medicated prepubertal boys with autistic disorder and severe mental retardation unmanageable due to behavior and motor problems. Although all five boys initially displayed marked behavioral symptom reduction, they developed behavioral newotoxicity necessitating discontinuation of clomipramine for all five and immediate hospitalization for three. Serious adverse effects included increased seizure frequency and symptoms of a serotonin syndrome. Our findings indicate that clomipramine enhances adaptive behavior and produces serious adverse effects in severely retarded autistic children whose symptoms were complicated by dyskinesias.
WCA Recommendations for the Long-Term Treatment of Panic Disorder
Authors: Pollack Mark H. , Allgulander Christer , Bandelow Borwin , Cassano Giovanni B. , Greist John H. , Hollander Eric , Nutt David J. , Okasha Ahmed , Swinson Richard P.
Published: August 2016

What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzodiazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants, have also shown antipardc efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. A n integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long-term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended for at least 12–24 months, and in some cases, indefinitely.
Attenuation in the Progression of Cognitive Deterioration in Alzheimer's Disease With Rivastigmine: A Dose-Dependent Effect
Authors: Farlow Martin , Messina John , Anand Ravi , Hartman Richard , Veach Jeffrey
Published: August 2016

Objectives: Possible disease-modifying effects of rivastigmine have been suggested by analyses using a variation of the randomized start design; however, the results were somewhat confounded by differing attrition rates. We report on an alternative method investigating whether increasing doses reduce the rates of cognitive decline in patients who continue treatment.

Methods: The effect of dose on the rate of cognitive decline seen on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was explored for patients in a long-term (130-week) extension of a 26-week placebo-controlled trial using two methods: a weighted leas squares regression analysis using each individual's slope, and a weighted analysis of variance (ANOVA) comparing the slopes of patients categorized by dose (≤6 mg/d or >6 mg/d).

Results: The results from 408 patients included in the weighted least squares analysis estimated the rate of decline to attenuate by approximately 1 point/y for every 3 mg/d increase (P<.0001). The average annual rate of decline for patients whose mean dose was >6 mg/d was 4.5 points (95% Cl, 5.1–3.9), while for patients with a mean dose of≥6 mg/d a decline of 8.2 points (95% Cl, 9.1–7.3) was seen.

Conclusion: These data further support earlier results suggesting that rivastigmine reduces the rate of progression of cognitive deterioration in Alzheimer's disease.
Ziprasidone's Effect on Anxiety in a Group of Outpatients With Stable Schizophrenia
Authors: Schooler Nina R , Siu Cynthia
Published: August 2016

Objective: Nearly 50% of patients with schizophrenia hav ecomorbid anxiety disorders. Ziprasidone's unique pharmacological profile, including 5-HT1A agaonism and 5-HT and NE reuptake inhibition, may confer anxiolytic properties. And exploratory analysis was conducted to evaluate improvement in anxiety in stable schizophrenic outpatients, as standard scales assessing psychosis do not adequately address anxity. Stable outpatients were selected to reduce the influence of acute psychosis.

Methods: Patients on conventional antipsychotics (n=93), olanzapine (n=88), and risperidone (n=41) were randomized to one of three dosing schedules and received ziprasidone 40–160 mg/day in three 6-week, open-label trials. Anxiety was measured by the PANSS anxiety item (G2: 1, absent, to 7, extreme). Analysis of patients with moderate or greater anxiety (≥4), as well as analysis of those with at least minimal anxiety (≥2), was conducted. Other symptom items were analyzed to address the speccificity of potential treatment differences.

Results: In patients with moderate or greater baseline anxiety, significant improvement in the PANSS anxiety time was observed (P<0.05). Significant improvement was also seen in the group of patients with at least minimal baseline anxiety (P<0.05). There were no concomitant signigicant changes in depression or somatic concern in the moderate anxiety subsample.

Conclusions: Improvement in the PANSS anxiety item, separate from changes in depression and somatic concern, was observed. In view of the prevalence of anxiety symptoms in schizophrenia, controlled trials utilizing anxiety scales validated in this population are necessary to further evaluate ziprasidone's anxwlytk potential.
The National Institutes of Health Attention-Deficit/Hyperactivity Disorder Consensus Statement: Implications for Practitioners and Scientists
Authors: Jensen Peter S.
Published: August 2016

Although the concept of pharmacotherapyfor attention-deficit/hyperactivity disorder (ADHD) was first introduced more than 60 years ago, treatment of this disorder remains more controversial than ever. It is hoped, however, that the recent Consensus Development Conference (CDC) Statement on the diagnosis and treatment of ADHD will not only help answer some of the questions surrounding management of this disorder, but also lend needed scientific weight to debate in this area. While more research in ADHD is needed, the CDC partic ipants pointed to a solid body of evidence showing that careful medication management can result in noticeable improvement in several measures, with little risk of adverse events.
Psychopharmacology of Obsessive-Compulsive Disorder
Authors: Montgomery Stuart A.
Published: August 2016

Obsessive-compulsive disorder (OCD) was thought to be a rather rare disorder and little attention was focused on investigations of the disorder until the first placebo-controlled studies reported efficacy. In 1980 three pivotal papers were published: Montgomery reported that clomipramine was effective in OCD without concomitant depression, and Thoren et al and Marks et al reported that clomipramine was effective in OCD with varying amounts of concomitant depression. These results opened the floodgates of psychopharmacological research and encouraged a more aggressive research program aimed at providing sufficient data for OCD to be recognized as a treatable condition.
Psychosocial Function and Economic Costs of Obsessive-Compulsive Disorder
Authors: Hollander Eric , Stein Dan J. , Kwon Jee H. , Rowland Clayton , Wong Cheryl M. , Broatch James , Himelein Carol
Published: August 2016

The study presented was conducted to analyze the effects of obsessive-compulsive symptoms on patients' quality of life and the costs incurred by patients and society for the treatment of obsessive-compulsive disorder (OCD). To accomplish this, a detailed 410-item questionnaire of psychosocial function and economic cost was sent to every fourth member of the Obsessive Compulsive Foundation. Of the 2,670 members who received the survey, 701 (26.9%) returned it.

Outcome measures included symptomatology, course of illness, impact of illness on psychosocial and other functioning, effects of diagnosis and treatment, and economic consequences. The demographics of this group were similar to those in smaller treatment-seeking clinical samples, but not necessarily to OCD sufferers within the US population as a whole. More than half of the patients reported moderate to severe interference in family relationships, socializing, and ability to study or work, secondary to OCD symptoms. A 10.2-year gap was observed between the onset of symptoms and the first attempt to seek professional help, and a 17.2-year gap was observed between the onset of symptoms and receipt of effective treatment. Specific treatments, such as serotonin reuptake inhibitors and behavior therapy, showed greater symptom improvement, and significantly reduced the total annual fees incurred by OCD patients when compared with nonspecific treatments.

Our study results indicate that OCD has a profound effect on psychosocial functioning and quality of life. Large direct costs for OCD and even larger indirect costs due to lost wages and underemployment were found. Greater awareness of OCD among practitioners may result in earlier diagnosis and more appropriate and cost-effective treatments.
Third International Obsessive-Compulsive Disorder Conference: Childhood and OCD
Authors: Riddle Mark A.
Published: August 2016

Workshop 2, “Childhood and OCD,” focused on six areas of research of special relevance to children: phenomenology, age of onset, subtypes, infectious and immune etiologies, psychosocial treatments, and medication treatments. Overarching themes in this session were the relative paucity of research in children and adolescents with obsessive-compulsive disorder (OCD) in comparison to adults and the unique potential for research in children to provide answers to important questions about the etiology, subtypes, pathophysiology, and treatment of OCD.
The Continuing Evolution of Psychiatric Neurosurgery
Authors: Kopell Brian Harris , Rezai Ali R.
Published: August 2016

In this article, the authors examine the growth of the discipline of psychiatric surgery from the earliest lesioning procedures to the neuroaugmentative strategies used today. Special attention is paid to the neural circuitry that underlies psychiatric disorders and how surgical manipulation of these circuits might result in the amelioration of the disease state. Also examined is the effect that the technology curve has had on psychiatric surgery with regard to functional imaging and neurosurgical equipment. Finally, the authors use the current state of psychiatric surgery to speculate on some of the future directions that psychiatric neurosurgical procedures might take.
Is Seasonal Affective Disorder a Disorder of Circadian Rhythms?
Authors: Desan Paul H. , Oren Dan A.
Published: August 2016

Seasonal affective disorder (SAD) is a form of depression that starts in the fall and ends in the spring. This article reviews existing theories about the relationship between circadian rhythms and the disorder. Recent research indicates that as with pharmacologic antidepressants, at least 2–4 weeks are needed to demonstrate the effectiveness of bright-light therapy compared to placebo. The response to such treatment is strongest with precisely timed light exposure: treatment is optimal during the morning hours when the circadian systemt is susceptible to phase advance. Such clinical improvement is correlated with the magnitude of the phase shift induced. These observations suggest a model of circadian function in SAD and provide important guidelines for its treatment.
Subject Selection and Characterization in Clinical Trials in Children with Autism
Authors: Scahill Lawrence , Lord Catherine
Published: August 2016

The goal of psychopharmacohgic research in autism is to provide guidance to clinicians and families on the risks and benefits of specific interventions. Careful subject selection and subject characterization in clinical trials are necessary for replication, to inform clinicians about the sample, and to elucidate the type of patients who might benefit from, the treatment. At minimum, subject characterization includes demographic information, diagnosis (autism, Åsperger's syndrome, or pervasive developmental disorder-not otherwise specified), intellectual functioning, adaptive functioning, symptom severity, general behavioral profile, health status, pertinent clinical laboratory measures, height, weight, current treatments, and educational placements. Subject selection, sample size, and choice of the primary outcome measure are closely interrelated and linked to the study hypothesis. The magnitude of expected improvement on the primary outcome measure, which can be expressed by effect size, has direct implications for sample size. Large sample sizes are required to detect small effect sizes. To facilitate interpretation of study results, research reports should provide descriptive characteristics of the sample as well as the mean change and standard deviation on the primary outcome measure data to permit calculation of the effect size.
Barriers to the Management of Patients with Surgically Remediable Intractable Epilepsy
Authors: Swarztrauber Kari
Published: August 2016

It is estimated that only a small proportion of patients with surgically remediable intractable epilepsy receive surgical treatment. There are multiple reasons why this is the case. Patients with intractable epilepsy are sometimes severely disabled and disability can create barriers to getting recommended care. Patients with epilepsy are not well informed about their condition and the available treatments. The incidence of epilepsy is similar in minority populations, and surgically remediable epilepsy frequently presents in adolescence. Nevertheless, these vulnerable populations have specific barriers to receiving epilepsy care, which are often not addressed. In addition, despite scientific evidence for the benefits of the surgical treatment of epilepsy, many healthcare providers do not recommend or adequately discuss surgery with patients. Solutions to these barriers will require interventions that result in informed and capable patients who actively participate in their care and healthcare providers who practice culturally sensitive, recommended care.
A Magnetic Resonance Imaging Study of Regional Cortical Volumes Following Stereotactic Anterior Cingulotomy
Authors: Rauch Scott L. , Makris Nikos , Cosgrove G. Rees , Kim Hackjin , Cassem Edwin H. , Price Bruce H. , Baer Lee , Savage Cary R. , Caviness Verne S. , Jenike Michael A. , Kennedy David N.
Published: August 2016

The purpose of this study was to test the hypothesis that orbitofrontal cortical volume would be reduced following anterior cingulotomy for obsessive-compulsive disorder (OCD). Whole brain cortical parcellation was performed on magnetic resonance imaging (MRI) data from nine patients, before and 9(±6) months following anterior cingulotomy. No significant volumetric reductions were found in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral temporo-fusiform and posterior cingulate regions were consistent with chance differences, in the face of multiple comparisons. Therefore, though the circumscribed lesions of anterior cingulotomy have recently been associated with corresponding volumetric reductions in the caudate nucleus, no comparable volumetric reductions are evident in cortical territories. Taken together, these results are most consistent with a model of cingulo-striatal perturbation as a putative mechanism for the efficacy of this procedure. While limitations in sensitivity may have also contributed to these negative findings, the methods employed have previously proven sufficient to detect cortical volumetric abnormalities in OCD. The current results may reflect a relatively diffuse pattern of cortico-cortical connections involving the neurons at the site of cingulotomy lesions. Future functional neuroimaging studies are warranted to assess possible cortical or subcortical metabolic changes associated with anterior cingulotomy, as well as predictors of treatment response.
The Timing of Neurodevelopmental Abnormality in Schizophrenia: An Integrative Review of the Neuroimaging Literature
Authors: Lencz Todd , Bilder Robert M. , Cornblatt Barbara
Published: August 2016

In this paper we will review recent neuroimaging research in schizophrenia, with an aim to critically evaluate several recent proposals concerning the nature and the timing of the neuroanatomic abnormalities underlying the disorder. Specifically, enlargement of cerebrospinal fluid spaces, deficits in cortical gray matter, and reduced volume of mesiotemporal structures have all been reported in patients in the first episode of schizophrenia, their first-degree relatives, and individuals with schizotypal personality disorder, supporting the possibility that these abnormalities reflect a genetically mediated neurodevelopmental disorder. These findings from the empirical literature will be synthesized from the perspective of dual cytoarchitectonic trends theory of neurodevelopment, as well as in relation to current conceptions of the schizophrenia prodrome. We believe that the evidence shows that sufficient groundwork has been laid to begin longitudinal neuroimaging studies of adolescents at clinical risk for schizophrenia, in order to more definitively determine the pathophysiology of the disorder. Such information could have significant implications in terms of understanding the prediction, treatment, and ultimately the prevention of schizophrenia.
Medical Burden, Cerebrovascular Disease, and Cognitive Impairment in Geriatric Depression: Modeling the Relationships With the CART Analysis
Authors: Lavretsky Helen , Kitchen Christina , Mintz Jim , Kim Moon-Doo , Estanol Laverne , Kumar Anand
Published: August 2016

Herein, the background information reflecting roles of medical burden, cerebrovascular disease and risk factors, and cognitive impairment in geriatric depression are reviewed. The authors then propose a nonparametric statistical approach to the data analysis of multiple putative causal variables for late-life depression, the Classification and Regression Tree Analysis. This analysis presents a useful approach to modeling nonlinear relationships and interactions among variables measuring physical and mental health, as well as magnetic resonance imaging and cognitive measures in depressed elderly. This method uncovers the existing interactions among multiple predictor variables, and provide thresholds for each variable, at which its predictive power becomes statistically significant. It presents a “hierarchy” of the predictors in a form of a decision tree by finding the best combination of predictors of an outcome.

The authors present two models based on demographic variables, measures of vascular and nonvascular medical burden, neuroimaging indices, the Mini-Mental State Examination score, and neuropsychological test scores of 81 elderly depressed subjects.

Cognitive tests of verbal fluency and executive function are identified as the best predictors of depression, followed by the frontal lobe volume and Mini-Mental State Examination. The authors observed that an interaction between frontal lobe volume, total lesion volume, and medical burden was predictive of depression.
The Neuroendocrinology of Posttraumatic Stress Disorder: New Directions
Authors: Rasmusson Ann M. , Vythilingam Meena , Morgan Charles A.
Published: August 2016

Studies of the hypothalamic-pituitary-adrenal (HPA ) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at γ-arninobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.
Methylphenidate Treatment of Attention-Defit/Hyperactivity Disorder Secondary to Traumatic Brain Injury: A Critical Appraisal of Treatment Studies
Authors: Jin Charles , Schachar Russell
Published: August 2016

Objective:

Are stimulants effective in treating attention-deficit/hyperactivity disorder secondary to traumatic brain injury (ADHD/TBI)? The authors reviewed and examined the current knowledge on efficacy of stimulant treatment ADHD/TBI.

Method:

A systematic review of the literature using a quality assessment scale to assess the quality of randomized clinical trials was undertaken. We identified all studies in which stimulants had been administered to individuals with ADHD/TBI. Information was extracted on study characteristics, interventions, and outcomes. A meta-analysis was not performed because of the limited number of studies with strict research design and the heterogeneity of outcome measures. Seven studies involving 118 subjects, 41 of whom were children and adolescents, were identified.

Results:

Of the seven identified studies, one was a chart review, one used a single-blind, placebo-controlled crossover design, and five were double-blind, placebo-controlled crossovers. These studies used >50 subjective and objective tests to measure behavioral and cognitive outcomes. Methylphenidate (MPH) effects on behavior (hyperactivity, impulsivity) were evident but were not as robust as those typically observed with MPH in primary ADHD. The effect of MPH on cognition was less apparent. More favorable outcome was associated with initiation of treatment soon after head injury, although this factor was not systematically studied, and trials with relativly long durations. Studies with negative MPH response reported neither improvement in behavioral nor cognitive symptoms.

Conclusion:

There is only modest evidence to support the efficacy of MPH in the treatment of ADHD/TBI. While MPH might still be a promising treatment for ADHD/TBI, there is need for rigorous treatment outcome research among representative samples of ADHD/TBI individuals.