bluuebunny/crossref_metadata_2025 huggingface dataset:
Obsessive-Compulsive Disorder in Children and Adolescents
Authors: Riddle Mark A.
Published: August 2016

Research in children and adolescents with obsessive-compulsive disorder (OCD) is increasing in both quantity and quality. This session will focus on new and exciting research findings regarding family genetic studies, infectious and immune etiologies, pediatric psychopharmacology, and cognitive behavioral treatment.
A Consensus Meeting on Effective Research Practice in PTSD
Authors: Charney Dennis S. , Davidson Jonathan R.T. , Friedman Matthew , Judge Rajinder , Keane Terry , McFarlane Sandy , Martenyi Ferenc , Mellman Thomas A. , Petty Frederick , Plewes John , Putnam Frank , Romano Steve , Van der Kolk Bessel A. , Yehuda Rachel , Zohar Joseph
Published: August 2016

The aim of this meeting was to obtain a consensus on what constitutes good research practice in posttraumatic stress disorder (PTSD). Objectives were to review relevant parameters of trials, such as the patients recruited, the means of assessing PTSD at baseline, and the change in symptomatology in response to treatment, and to reach a consensus on the most appropriate parameters to use in future research. The bases for the discussion were the 1995 National Institute of Mental Health (NIMH) and the National Center for PTSD consensus on the assessment of PTSD, results of drug treatment trials, and information on the assessment scales used in PTSD research.
Current Diagnostic Issues and Epidemiological Insights in PTSD
Authors: Zohar Joseph , Sasson Yehuda , Amital Daniella , Iancu Iulian , Zinger Yaffa
Published: August 2016

Posttraumatic stress disorder (PTSD) was associated in the past mainly with combatrelated events. This was reflected in the names given to the disorder, ie, “shell shock,” “soldier's heart,” “combat neurosis,” and “operational fatigue.” Only following the realization that PTSD can be related to all types of traumatic events, including noncombat associated events, were the terms “traumatic neurosis” and, later, “PTSD” coined. These new terms reflect the understanding that the condition need not necessarily be associated with war, but may also be related to events such as a severe automobile accident, violent personal assault (eg, rape, physical attack, robbery, or mugging), terrorist attack, natural or human-made disaster (such as a fire), witnessing serious injury or death due to any of the above, as well as to other situations, such as being kidnapped or being held hostage.

The tendency to interpret the symptoms of what we would consider now as PTSD, as a “normal response” to traumatic events was another factor that held up progress in the field. It is important to note that PTSD is a pathological response: The vast majority of individuals who are exposed to a traumatic event will later adapt and continue on with their lives. Only a small percent, which partially depends on the type of trauma and is partially associated with several risk factors, will develop a pathological fixation on the traumatic event, namely, PTSD.

It has been estimated that approximately one-third of the population will be exposed to a severe trauma (according to the definition of PTSD) during their lifetime.
HIV-1–Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment
Authors: Goodkin Karl , Wilkie Frances. L. , Baldewicz Teri T. , Concha Mauricio , Tyll Mary D. , LoPiccolo Charles J. , Shapshak Paul
Published: August 2016

The diagnosis of human immunodeficiency virus type 1 (HIV-1)–associated cognitive-motor disorder—either minor cognitive-motor disorder (MCMD) or HIV-1-associated dementia (HAD)—is fraught with potential pitfalls for the clinician. Before making such a diagnosis, clinicians should exclude other etiologies by using neuroimaging, lumbar puncture, and serum chemistries to screen for opportunistic and non-opportunistic infections of the brain and meninges. Clinicians should also consider psychoneurotoxicity (caused from the use of psychoactive substances and prescribed medications) and psychopathology, such as mood, anxiety, and other disorders. In addition, a thorough medical history and physical examination, including a complete neurologic and neuropsychiatric mental status examination, are necessary for an accurate diagnosis. There is also a need for standardized neuropsychological and functional status tests, since the diagnostic criteria for these disorders are partly based on these criteria. Treatment targets should include subclinical cognitive-motor impairment and neuroprotection, as well as MCMD and HAD. Currently, zidovudine remains the best proven treatment for these disorders, but other nucleoside reverse transcriptase inhibitors, as well as nonnucleoside reverse transcriptase inhibitors and protease inhibitors, show promise, and selected agents from these classes are being tested in clinical trials. Other areas that should be investigated are the modulation of inflammatory mediators (such as tumor necrosis factor α), neurotransmitter manipulation (especially of dopamine), and nutritional interventions.
Enrolling Decisionally Incapacitated Subjects in Neuropsychiatric Research
Authors: Fins Joseph J. , Miller Franklin G.
Published: August 2016

This paper discusses the National Bioethics Advisory Commissions (NBAC's) report on research involving persons with mental disorders that may affect decisionmaking capacity. After placing the NBAC recommendations into their historic context, the authors propose a strategy to enroll decisionally incapacitated subjects into neuropsychiatric research. The authors maintained that their proposed consensus model for research authorization, utilizing subject advocates, fosters valuable clinical research while protecting potentially vulnerable subjects.
Pharmacotherapeutic Options in the Treatment of Comorbid Depression and Anxiety
Authors: Pollack Mark H. , Marzol Patricia C.
Published: August 2016

Although anxiety and mood disorders are listed as separate disorders in theDiagnostic and Statistical Manual of Mental Disorders,Fourth Edition, they frequently coexist. They may be expressed phenotypically as comorbidities or as the provisional entity mixed anxiety-depressive disorder. Patients with both anxiety and depression are more symptomatic, use more health care resources, and have a worse prognosis than those with a single disorder. Recognizing and treating these patients are challenges for physicians because the symptoms of the two disorders often overlap. Administration of effective treatment, comprising both anxiolytic and antidepressant effects, can reduce patient distress and disability, as well as inappropriate utilization of medical services. Medications such as tricyclic antidepressants, selective serotonin reuptake inhibitors, nefazodone, venlafaxine XR (extended release) and mirtazapine, are highly effective in treating comorbid depression and anxiety. These newer agents now represent the pharmacotherapeutic treatments of choice for the comorbid conditions.
The Science of Antipsychotics: Mechanistic Insight
Authors: Tamminga Carol A.
Published: August 2016

With the introduction of conventional antipsychotics in the 1950s, clinicians began to expect effective treatment of positive symptoms of schizophrenia. However, these drugs do not resolve negative and cognitive symptoms of schizophrenia and are also associated with serious side effects, including extrapyramidal side effects (EPS) and tardive dyskinesia. In 1989, clozapine was introduced and labeled the first new antipsychotic owing to its improved efficacy and side-effect profile. Clozapine proved effective in alleviating many of the positive, negative, and cognitive symptoms of schizophrenia, without causing inevitable EPS or tardive dyskinesia. Over the past decade, a number of different new antipsychotics have been developed. These drugs have an affinity for multiple dopamine-receptor subtypes as well as serotonin, norepinephrine, and glutamate receptors, allowing for better treatment outcomes. The antagonism of the 5-HT2A receptor may be responsible for improvement in negative symptoms and decrease in EPS. In addition to providing enhanced efficacy, the affinity of the new drugs for multiple receptors introduces new side effects not seen with the conventional agents, including weight gain. Each new antipsychotic has a unique receptor-binding profile that corresponds to its pharmacologic and side-effect profile. Understanding the differences in mechanisms of action of new antipsychotics will allow physicians to better choose treatment that meets the needs of each individual patient.
Management of Acute Psychosis: From Emergency to Stabilization
Authors: Zimbroff Dan L.
Published: August 2016

In treating and managing acute psychosis in patients with schizophrenia, early intervention may be valuable. The need to quickly control severe symptoms, however, must be balanced with a treatment algorithm that is both safe and effective. The present management of acute psychotic agitation varies among clinicians. Key treatment goals have been to calm the agitated, assaultive, violent, or disruptive patient, minimize the danger to self and others, and achieve a smooth transition from intramuscular to oral maintenance. For many years, intramuscular treatment with benzodiazepines and/or conventional antipsychotics, such as haloperidol, has been the mainstay of treatment for acute psychosis. Unfortunately, the poor tolerability of conventional antipsychotics compromises their usefulness for both short- and long-term treatment. Although new antipsychotics have a more favorable side-effect profile, the transition from an intramuscular formulation has been problematic. Fortunately, the development of intramuscular formulations of olanzapine and ziprasidone offer new treatment options for patients experiencing acute psychotic episodes. This article will review the use of intramuscular agents, standard antipsychotics, and new antipsychotics in the emergency room setting. The strengths and limitations of each will be discussed.
The Goal of Epilepsy Therapy: No Seizures, No Side Effects, as Soon as Possible
Authors: Engel Jerome
Published: August 2016

Epilepsy is a significant health problem. Ten percent of people living a normal lifespan will experience at least one epileptic seizure and one third will develop a chronic epileptic condition. At any given time, 0.5% to 1% of the world's population has active epilepsy, amounting to over 40 million people. A World Health Organization-sponsored study determined that epilepsy accounts for 1% of the global burden of disease, measured as disability-adjusted life years equivalent to the global burden of lung cancer in men and to breast cancer in women. Disability-adjusted life years measure years of productivity lost as a result of disability or death, which is relatively high for epilepsy because this condition often begins in childhood. The cost of epilepsy in the United States has been estimated at $12.5 billion/year, and 80% of this cost is borne by the 30% of patients whose seizures are not controlled.

The cost of uncontrolled epileptic seizures to society, and to individuals with epilepsy and their families, is measured not only in economic terms, but also in terms of human suffering. In this month's first article, Michael R. Sperling, MD, who has authored seminal papers on consequences of epilepsy, provides evidence that epilepsy is not a benign disorder; that early control of epileptic seizures is important to avoid irreversible disability due to the development of psychological and social disturbances and progressive cerebral dysfunction, as well as epilepsy-related death. The burden imposed on society and on individuals by uncontrolled epileptic seizures is all the more tragic because many suffer needlessly. For a significant number of adults who have had recurrent seizures since infancy, childhood, or adolescence, more aggressive early intervention might have rescued them from a lifetime of disability. Consequently, the goal of therapy today should be no seizures and no side effects, as soon as possible.
Genetics of Posttraumatic Stress Disorder
Authors: Segman Ronnen H. , Shalev Arieh Y.
Published: August 2016

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. PTSD is disabling and commonly follows a chronic course. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. A twin study of Vietnam veterans has shown significant genetic contribution to PTSD. The fact that PTSD's underlying genotypic vulnerability is only expressed following trauma exposure limits the usefulness of family-based linkage approaches. In contrast to the other major psychiatric disorders, large studies for the search of underlying genes have not been described in PTSD to date. Complementary approaches for locating involved genes include association-based studies employing case-control or parental genotypes for transmission dysequilibrium analysis and quantitative trait loci studies in animal models. Identification of susceptibility genes will increase our understanding of traumatic stress disorders and help to elucidate their molecular basis. The current review provides an up-to-date outline of progress in the field of PTSD.
Mental Symptoms and Disorders During Pregnancy
Authors: Halbreich Uriel , Kornstein Susan G.
Published: August 2016

Pregnancy is a period of substantial neuroendocrine changes. These changes are not limited to the hypothalamic-pituitary-gonadal hormones, but also involve the placenta and its secreted hormones, especially the corticotropin releasing hormone that is a major component of the stress axis. These hormonal changes are also associated with changes in the immune/inflammatory and cardiovascular systems. The cumulative evidence that dysregulation in this multifactorial interactional field may cause deleterious effects on the fetus and its future development emphasizes the importance and clinical relevance of this line of research. When vulnerability and genetic predisposition to gestational stress and its adverse effects are added to the equation, the importance of adequate treatments and possible preventive interventions is underscored.

Pregnancy is usually perceived as a happy period. However, as demonstrated by Uriel Halbreich, MD, severe mood, behavior, and cognitive symptoms are quite prevalent during pregnancy. The magnitude of the problem is probably not reflected by the reported prevalence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or International Classification of Diseases, Ninth Edition major mental disorders. A closer evaluation and treatment of symptoms, especially when they are associated with impairment, stress, and distress, may improve the mental health of the mother and the expected baby.
Patterns of Neural Response to Emotive Stimuli Distinguish the Different Symptom Dimensions of Obsessive-Compulsive Disorder
Authors: Phillips Mary L. , Mataix-Cols David
Published: August 2016

Despite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.
Effects of Low-Dose Risperidone and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic Patients
Authors: Fagerlund Birgitte , Mackeprang Torben , Gade Anders , Hemmingsen Ralf , Glenthøj Birte Y.
Published: August 2016

Background: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogenous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal.

Objective: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogenous group of drug-naïve first-episode schizophrenic patients in a longitudinal setting.

Methods: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N-25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naïve, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time.

Results: The patients showed considerable cognitive deficits when drug-naïve. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls.

Conclusion: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naïve schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.
Management of Overactive Bladder
Authors: Romanzi Lauri J.
Published: August 2016

At least 80% of urology patients are taking several medications for any variety of other medical conditions. However, regarding treatment of overactive bladder (OAB) specifically, there are several antimuscarinic drugs available. Tolterodine and trospium chloride are, in essence, nonspecific in terms of muscarinic receptor selectivity. Solifenacin and oxybutynin show selectivity for the M1, and darifenacin is significantly M3 receptor specific (Slide 17).

The potential benefit for selective antimuscarinic agents is that they might target the bladder more specifically and avoid anticholinergic side effects in other organ systems, specifically the brain and heart. We do know that M3 receptors are also present in the intestines and in the salivary glands; thus, we might not expect organ selectivity with an M3-specific receptor because that receptor would also potentially affect the salivary gland and the intestinal tract as well.

There is a growing body of data regarding M3 activity specificity and decreased cognitive impairment in patients of various ages. This, as well as the reduction of cardiac side effects, are the major benefits of using an M3-selective anticholinergic medication rather than a nonselective agent for the treatment of OAB.
The Neurobiology of Postpartum Depression
Authors: Zonana Jessica , Gorman Jack M.
Published: August 2016

Postpartum psychiatric changes can range from maternity blues to psychosis. Causality is still undetermined, but explanations for these disturbances often focus on hormonal changes and dysregulation. Researchers have begun the process of delineating what neurobiological factors may be associated with depressive disorders in pregnancy and the postpartum. This article reviews the current literature on the roles of gonadal and pituitary hormones in the psychopathophysiology of postpartum mood disorders. Other biological factors, such as biogenic amines, neuroactive steroids, cholesterol, and fatty acids, are also discussed. The potential benefits of neuroimaging to aid in understanding neuropsychiatric changes that occur in the context of postpartum depression are also considered.
Integrating Neurobiology and Psychopathology into Evidence-Based Treatment of Social Anxiety Disorder
Authors: Liebowitz Michael R. , Ginsberg David L. , Ninan Philip T. , Schneier Franklin R. , Blanco Carlos
Published: August 2016

Social anxiety disorder (SAD) is a common, chronic psychiatric disorder characterized by a persistent fear of social or performance situations in which embarrassment can occur. This disorder typically appears during the mid-adolescent years and is unremitting throughout life if not properly treated. SAD presents as two subtypes: the more common and debilitating generalized form, and the nongeneralized form, which consists predominantly of performance anxiety. The majority of patients with SAD have comorbid mental disorders, including mood, anxiety, and substance abuse. No single development theory has been proposed to account for the origins of SAD, although current understanding of the etiology of SAD posits an interaction between psychological and biological factors. Risk factors include environmental and parenting influences and dysfunctional cognitive and conditioning events in early childhood. The neurobiology of SAD appears to involve neurochemical dysfunction, as evidenced by studies of neuroreceptor imaging, neuroendocrine function, and profiles of response to specific medications. Clinical trials have demonstrated that benzodiazepines and antidepressants are effective in the treatment of SAD. The selective serotonin reuptake inhibitors are emerging as the first-line treatment for SAD, based on their proven safety, tolerability, and efficacy. Goals for ongoing future research include development of approaches to achieve remission, to convert nonresponders and partial responders to full responders, and to prevent relapse and maintain long-term efficacy.

This monograph explores the epidemiology, clinical presentation, and differential diagnosis of SAD, with a focus on neural circuitry of social relationships and neurochemical dysfunction. The prevalence, rates of recognition and treatment, patterns of comorbidity, quality-of-life issues, and natural history of SAD are discussed as well as pharmacologic and psychosocial treatment strategies for SAD.
Posttraumatic Stress Disorder in Posttransplant Children: Creating a Clinical Program to Address Their Needs
Authors: Emre Sukru
Published: August 2016

Posttraumatic stress symptoms have been shown to occur in pediatric and adult solid-organ transplant recipients. The presence of these symptoms is associated with non-adherence to medications, increased distress, and poor outcome. Because posttraumatic stress disorder is treatable and because a transplant operation usually is an “anticipated trauma,” it is possible to address posttraumatic stress disorder symptoms in transplant recipients and attempt to prevent their development. Under my direction, the pediatric liver transplant program at Mount Sinai Medical Center in NewYork City created research and clinical programs to address posttraumatic stress symptoms and their consequences. Specifically, the focus on non-adherence to immunosuppressive medications in transplant recipients who are distressed and their parents. This article begins with a review of the data that led to the decision to start these programs. I then present the basic elements that are in place, in this particular program, to address patients' needs. I end this review with preliminary outcome data that illustrate the potential impact of such an integrated approach to patient care on medical outcomes.
Brain Reward Circuits in Alcoholism
Authors: Koob George F. , Roberts Amanda J.
Published: August 2016

This article discusses the neurocircuitry and the neurochemical systems, as well as the molecular elements within these systems, that are believed to be important in the etiology of alcoholism. Alcoholism is a complex behavioral disorder characterized by excessive consumption of alcohol; a narrowing of the behavioral repertoire toward excessive consumption; the development of tolerance and dependence; and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome.

Recent work has begun to define the neurocircuits responsible for the major sources of positive and negative reinforcement that are key to animal models of excessive alcohol intake. Alcohol appears to interact with alcohol-sensitive elements within neuronal membranes that convey the specificity of neurochemical actions. Positive reinforcement appears to be mediated by an activation γ-aminobutyric acid A receptors, release of opioid peptides and dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic alcohol administration. This is reflected by their exhibiting opposite effects during acute alcohol withdrawal, and by the recruitment of other neurotransmitter systems, such as the stress neuropeptide corticotropin-releasing factor. These neuropharmacologic actions are believed to produce allostatic changes in set-point, which set up the vulnerability to relapse that is so characteristic of alcoholism. Future challenges include a focus on understanding exactly how these neuroadaptive changes convey vulnerability to relapse in animals with a history of alcohol dependence.
Investigating Tourette Syndrome as a Neurologic Sequela of Rheumatic Fever
Authors: Kurlan Roger
Published: August 2016

Sydenham's chorea is currently recognized as the only neurologic sequela of rheumatic fever. Recent evidence suggests that there may be a spectrum of neurobehavioral disturbances, particularly including tics and obsessive-compulsive disorder, that develops following streptococcal infection by the process of molecular mimicry, whereby antibodies directed against bacterial antigens cross-react with brain targets. This proposed postinfectious, immune-mediated condition has been termed “pediatric autoimmune neuropsychiatric disorders after streptococcal infection” (PANDAS). This article reviews research evidence in favor and also against the PANDAS concept and discusses the implications of the hypothesis.
Eating Disorders and Tourette Syndrome: A Case Series of Comorbidity and Associated Obsessive-Compulsive Symptomatology
Authors: Guarda Angela S. , Treasure Janet , Robertson Mary M.
Published: August 2016

There is a well-established overlap in phenomenology between anorexia nervosa and obsessive-compulsive disorder, and between obsessive-compulsive symptoms and Tourette syndrome (TS). Five cases of eating disorders in patients with obsessive-compulsive symptoms and TS are presented. The identification of four similar cases in the literature putatively marks a subset of eating disorders with a link to TS and to obsessive-compulsive symptomatology. This association may reflect a common underlying neurobiologic imbalance.
The Genetics of Attention-Deficit/Hyperactivity Disorder
Authors: Ram Ranga , Schindler Kim M. , Bauer Amy , Pato Carlos N. , Pato Michele T.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) has an early childhood onset in the majority of cases. This has a considerable impact on the development of the affected individual, both directly (as a result of the symptoms) and indirectly (through the stresses imposed upon school, learning, socialization, and family life). Several lines of evidence point to a genetic component to ADHD. Family studies show a familial aggregation of ADHD, with a five- to sixfold increase in the incidence of ADHD among first-degree relatives. Twin studies reveal a higher concordance rate for ADHD among monozygotic twins compared with dizygotic twins. To date, molecular genetic research has focused on candidate genes in the dopaminergic system. Genes studied include the D2A1 allele of the dopamine D2 receptor gene, the dopamine transporter gene, and the dopamine D4 receptor gene. One of the major limitations to the study of the genetics of behavioral disorders in children has been the overlap among syndromes, including oppositional defiant disorder, conduct disorder, persistent (adult) ADHD, and bipolar disorder. Future research must address weaknesses in existing studies, including small samples sizes, restricted statistical power, and confounding factors such as comorbid illnesses, clinical heterogeneity with variable symptom severity, and unclear phenotypic boundaries.
The Current Course of Mood Disorders: A 3-Year Follow-Up
Authors: Lenzi Alessandro , Lazzerini Fabrizio , Marazziti Donatella
Published: August 2016

The aim of this study was to evaluate the natural course of mood disorders in 157 patients admitted consecutively to the Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie at Pisa University for an affective or schizoaffective episode and followed for 3 years.

During the follow-up, three patients committed suicide and three died of natural causes. The three suicide patients were diagnosed as suffering from a depressive episode deriving from Bipolar I disorder. Of the remaining 104 patients, 42% had no relapses, 35% had up to three relapses, and 23% had more than three relapses; there were no significant differences between these three groups.

In conclusion, recent treatments seem able to reduce the length and number of relapses in patients with mood disorders. The hyperthymic temperament seems to be a characteristic of compliant patients and a predictor of a good response to treatment. The mortality rate connected with somatic or accidental causes appears to be similar to that of the general population, while the rate of suicide is higher.
Genetics of Panic Disorder
Authors: Marazziti Donatella , Rotondo Alessandro
Published: August 2016

Systematic studies on the genetics of panic disorder as a distinct nosologic entity separate from anxiety disorders date back to the 1980s. It is, therefore, a relatively new topic for psychiatric genetic investigation. For this reason, available data are not numerous, but findings ensuing from “classical” methods, such as family and twin studies, suggest the involvement of genetic mechanisms to a broad extent, confirmed by the most recent studies. The approaches of molecular genetics, particularly linkage analyses and association studies exploring candidate genes, have led to inconclusive results but have also provided interesting findings that need to be tested in future research.
Chronic Benign Pain
Authors: Klein David A. , Greenfield Daniel P.
Published: August 2016

Chronic benign pain (CBP) can be defined as a type of unpleasant sensory experience that arises from inflammation, visceral stress or damage, or other such pathophysiologic process(es), and that is not associated with a metastatic process. A patient's complaint of pain should be taken seriously by the practitioner, both in terms of the discomfort evoked and the likelihood that the potential cause of the pain requires diagnostic evaluation. This article reviews the diagnosis and treatment of the following common conditions associated with CBP syndromes: fibromyalgia, lower back pain syndrome, sickle-cell disease, reflex sympathetic dystrophy syndrome, and peripheral neuropathies.
Consequences of Right Cerebrovascular Accident on Emotional Functioning: Diagnostic and Treatment Implications
Authors: Erhan Hulya , Ochoa Elizabeth , Borod Joan , Feinberg Todd
Published: August 2016

The relationship between lesion location and neuropsychiatric sequelae in stroke patients has been extensively studied. Emotional disorders associated with right hemisphere stroke include depression, anxiety, anger, and/or mania. Pharmacotherapy, electroconvulsive therapy, and/or psychotherapy are common treatments for these disorders. This article reviews the clinical presentations of seven right hemisphere stroke patients. The treatment rationale and course of treatment are described for two of these patients. The aims of this paper are to explore the appropriateness of various assessment tools and treatment modalities for stroke patients as well as to demonstrate the techniques of psychotherapy as applied to the two cases featured in this article. Specific factors that may significantly influence treatment outcome, such as lesion location and degree of cognitive impairment, are considered.
HIV-1 Infection, Neuroendocrine Abnormalities, and Clinical Outcomes
Authors: Kumar Mahendra , Goodkin Karl , Kumar Adarsh M. , Baldewicz Teri T. , Morgan Robert , Eisdorfer Carl
Published: August 2016

Different lines of evidence suggest that human immunodeficiency virus type 1 (HIV-1) infection is complicated by a variety of adverse effects on neuroendocrine systems. Soon after the discovery of HIV-1, reports began to appear suggesting that a number of neurotransmitter and neuroendocrine activities were negatively impacted by this infection. In 1987 it was observed that fine-needle aspiration of the lung in patients with acquired immunodeficiency syndrome resulted in syncopal reactions. Subsequently, an abnormality in the autonomic nervous system was reported in these patients. However, investigations in this area have remained limited due to the assumption that HIV-1–mediated activation of various endocrine systems was related to the major life stressor of living with a fatal disease. Evidence accumulated over the years has indicated, instead, that there are various other mechanisms in addition to life stressors that also play an important role in negatively impacting the neuroendocrine systems in this infection. This article examines various developments that have taken place in this area in order to provide avenues for future research.
Psychosis Associated with Anti-N-methyl-d-aspartate Receptor Antibodies
Authors: Nasky Kevin M. , Knittel Douglas R. , Manos Gail H.
Published: August 2016

We describe the eighth case study of a female diagnosed with anti-N-methyl-d-aspartate receptor encephalitis without an identified tumor who presented with floridly psychotic symptoms following a 2-week prodromal phase with new-onset headaches and presyncopal episodes. While hospitalized, the patient had seizures, autonomic dysfunction, involuntary movements, and a decline in mental status. A subsequent assay was positive for anti-N-methyl-d-aspartate receptor antibodies. In contrast to most reported cases, an initial trial with corticosteroids was therapeutically unsuccessful. Subsequent treatment with intravenous immunoglobulins, however, resulted in a prompt, robust clinical response and enabled the patient to be rapidly discharged from the hospital, with minimal neuropsychiatrie sequelae.
Mitochondrial Function Is Related to Alterations at Brain SPECT in Depressed Patients
Authors: Gardner Ann , Salmaso Dario , Nardo Davide , Micucci Federica , Nobili Flavio , Sanchez-Crespo Alejandro , Jacobsson Hans , Larsson Stig A. , Pagani Marco
Published: August 2016

Introduction:99mTc-d,I-hexamethylpropylene amine oxime (99mTc-HMPAO) retention in brain is proportional to cerebral blood flow and related to both the local hemodynamic state and to the cellular content of reduced glutathione. Alterations of the regional distribution of99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the99mTc-HMPAO retention at single-photon emission computed tomography in depressed patients may relate to different levels of mitochondrial function.

Methods: All patients had audiological and muscular symptoms, somatic symptoms that are common in depression. Citrate synthase (CS) activity assessed in muscle mitochondria correlated strongly with the activities of three mitochondrial respiratory chain enzymes and was used as a marker of mitochondrial function. K-means clustering performed on CS grouped eight patients with low and 11 patients with normal CS. Voxel-based analysis was performed on the two groups by statistical parametric mapping.

Results: Voxel-based analysis showed significantly higher99mTc-HMPAO retention in the patients with low CS compared with the patients with normal CS in the posterior and inferior frontal cortex, the superior and posterior temporal cortex, the somato-sensory cortex, and the associative parietal cortex.

Conclusion: Low muscle CS in depressed patients is related to higher regional99mTc-HMPAO retention that may reflect cerebrovascular adaptation to impaired intracellular metabolism and/or intracellular enzymatic changes, as previously reported in mitochondrial disorder. Mitochondrial dysfunction in varying proportions of the subjects may explain some of the discrepant results for99mTc-HMPAO retention in depression.
Unrecognized Attention-Deficit/Hyperactivity Disorder in Adults Presenting with Other Psychiatric Disorders
Authors: Barkley Russell A. , Brown Thomas E.
Published: August 2016

Many adults with a diagnosed psychiatric disorder also have attention-deficit/hyperactivity disorder (ADHD). In many cases, comorbid ADHD is unrecognized and/or undertreated. Differential diagnosis of adult ADHD can be challenging because ADHD symptoms may overlap with other psychiatric disorders and patients may lack insight into their ADHD-related symptoms. Current ADHD diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision may prevent appropriate diagnosis of many patients with significant ADHD symptoms. Adults may not be able to provide a history of onset of symptoms during childhood, and it may be difficult to confirm that ADHD symptoms are not better accounted for by other comorbid psychiatric conditions. Comorbid ADHD is most prevalent among patients with mood, anxiety, substance use, and impulse-control disorders. ADHD can negatively affect outcomes of other comorbid psychiatric disorders, and ADHD symptoms may compromise compliance with treatment regimens. Furthermore, unrecognized ADHD symptoms may be mistaken for poor treatment response in these comorbid disorders. In these individuals, ADHD pharmacotherapy seems to be as effective in reducing core ADHD symptoms, as it is in patients who have no comorbidity. Limited evidence further suggests that ADHD therapy may help to improve symptoms of certain psychiatric comorbidities, such as depression. Therefore, management of ADHD may help to stabilize daily functioning and facilitate a fuller recovery.
Pramipexole: Augmentation in the Treatment of Depressive Symptoms
Authors: Gupta Sanjay , Vincent Jennifer L. , Frank Bradford
Published: August 2016

We describe a retrospective case series of three patients, two with bipolar depression and one with unipolar depression. Pramipexole is a Food and Drug Administration-approved antiparkinsonian agent, which, when used to augment antidepressants, would be considered an off-label use and should be discussed with the patient. These patients had robust responses to pramipexole augmentation of their treatment regimen. All three patients had been taking an atypical antipsychotic. The depressive symptoms were evaluated using the Hamilton Rating Scale for Depression.
The Potentially Somatizing Effect of Clinical Consultation
Authors: Salmon Peter
Published: August 2016

Many patients who present physical symptoms that their doctors cannot explain by physical disease have persisting symptoms and impairment. An influential view has been that such symptoms are the somatization of emotional distress, but there has also been concern that medical practice contributes to shaping these presentations. Analysis of patients' accounts indicate that they approach these consultations with a sense of being the expert on the nature and reality of their symptoms and, in primary care at least, they seek convincing explanations, engagement, and support.They often describe doctors as doubting that their symptoms are real and as not taking their symptoms seriously. Observational research has demonstrated that patients presenting idiopathic symptoms in primary care generally provide cues to their need for explanation or to psychosocial difficulties. Their doctors tend to provide simple reassurance rather than detailed explanations, and often disregard psychosocial cues. Patients seem to intensify their presentation in consequence, elaborating and extending their accounts of their symptoms, perhaps in the effort to engage their doctors and demonstrate the reality of their symptoms. When doctors propose physical investigation and treatment in response to such escalating presentation, they thereby inadvertently somatize patients' psychological presentation. Consultations, therefore, have elements of contest, whereby patients seek engagement from doctors who seek to disengage. Although provision of a medical label, such as a functional diagnosis, can legitimize patients' complaints and avoid contest, this is at the risk of indicating that medicine can take responsibility for managing the symptoms. More collaborative relationships rely on doctors recognizing patients' authority in knowing about their symptoms, and providing tangible explanations that make sense to the patient and allow them to tolerate or manage the symptoms. Researchers need to study how doctors can best achieve these aims within routine consultations.
Antidepressants and Cognitive-Behavioral Therapy for Symptom Syndromes
Authors: Jackson Jeffrey L. , O'Malley Patrick G. , Kroenke Kurt
Published: August 2016

Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as adjunctive therapy. There are many possible reasons why this may work, including treating comorbid depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas that are responsible for “attention” to noxious stimuli, and the direct effects of the medications on the syndrome.There are good theoretical reasons why antidepressants with balanced norepinephrine and serotonin effects may be more effective than those that act predominantly on one pathway, though head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-behavioral therapy is most consistently demonstrated to be effective, with various antidepressants having more or less randomized controlled data supporting or refuting effectiveness.This article reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for or against treatment effectiveness is relatively robust, for many, however, the data, one way or the other is scanty.
The Dynamics of Insight in the Prodrome of Schizophrenia
Authors: Bota Robert G. , Munro J. Stuart , Ricci Walter F. , Bota Daniela A.
Published: August 2016

Introduction

Schizophrenia is characterized by diminished insight, which fluctuates with disease progression. Insight deterioration in the prodrome of schizophrenia is poorly understood. Despite pharmacologic treatment, including early interventions, there is a high risk of relapse and need of acute care in schizophrenia patients.

Objective

To study if insight deterioration occurs during the prodrome and if insight preservation early in the illness might predict a better prognosis.

Methods

Data was collected retrospectively from the records of 24 patients initially diagnosed with schizophrenia during a 2-year period. Patients' progress was then tracked over a 3-year period. Insight was determined by a physician's subjective evaluation, patient interest and participation in treatment planning, and patient accuracy in reporting behaviors and symptoms when compared with reports from collaterals.

Results

Ten patients were determined to have insight regarding the developing illness at different presentations at the hospital. Insight preservation correlated with less need for emergency visits and fewer hospitalization days (P<.005). It was also associated with more depressive and anxious mood (P<.000). Patients and family members described early, ego-dystonic perceptual disturbances followed by diminished insight. Awareness into the illness, symptoms, and attribution of symptoms to the illness fluctuated at different presentations in the insight group. In the other group, insight was nil at each presentation after the psychotic debut.

Conclusion

Most patients maintain insight during the perceptual disturbance phase. Insight diminishes as the early delusional phase sets in. Higher levels of preserved insight seem to correlate with less need for acute treatment. Further research in this area is warranted for determining if early insight oriented interventions in the prodromal phase can improve the prognosis of schizophrenia.
Efficacy and Safety of Lamotrigine for Adults with Bipolar Disorder in a Private Practice Setting
Authors: Ginsberg Lawrence D.
Published: August 2016

Introduction

Lamotrigine is approved by the Food and Drug Administration for maintenance therapy in patients with bipolar I disorder. However, several studies of acute-phase and maintenance treatment support the efficacy of lamotrigine for bipolar I and bipolar II disorders. This chart review was performed to assess the efficacy and safety of lamotrigine in the treatment of bipolar disorder in a private psychiatric practice setting and to investigate differences in response among patients with different diagnostic subtypes of bipolar disorder.

Methods

The charts of 587 adult outpatients with a primary diagnosis of bipolar disorder who received treatment with lamotrigine in a private practice setting between July 1998 and May 2004 were reviewed retrospectively. Treatment response was assessed with the Clinical Global Impression-Improvement scale and was defined as achievement of a score of ≤2.

Results

Three hundred forty-nine patients (59.5%) responded to lamotrigine. Response rates were comparable among patients wit h bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified, and among patients with bipolar I disorder who presented with depressive, manic, or mixed episodes. Nonserious rash (12.8%) and headache (2.9%) were the most frequently reported adverse events.

Conclusion

These results suggest that lamotrigine is effective and well-tolerated in the treatment of bipolar disorder across the spectrum of sub-types of the illness.