bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-National Epidemiology of Obsessive-Compulsive Disorder
Authors: Weissman Myrna M.
Published: August 2016

Our knowledge of the prevalence and demographic and clinical characteristics of obsessive-compulsive disorder (OCD) has, until recently, been based almost exclusively on patient samples. The epidemiology of OCD was first described in a large United States household sample from the Epidemiologic Catchment Area (ECA) study. Since these original observations, the rates of OCD in household populations determined from diagnostic procedures similar to those used in the United States have been published from different parts of the world. Detailed comparisons of rates, sex ratios, age at onset, and demographic and clinical characteristics of OCD in these samples are now available.

This article reports on the cross-national epidemiology of OCD from seven international epidemiologic surveys, including the United States ECA study. Each survey used the Diagnostic Interview Schedule (DIS), a highly structured interview, developed for use in epidemiologic surveys, that yields Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) psychiatric diagnoses. All investigators provided the data from their study to be pooled at Columbia University, and the prevalence rates were standardized to the age and sex distribution of the five-site ECA household population so that more precise estimates and comparisons could be made.
Comorbidity of Posttraumatic Stress Disorder and Depression in Israeli Veterans
Authors: Solomon Zahava , Bleich Avi
Published: August 2016

This article reviews a series of studies conducted on Israeli war veterans that assessed the interrelationship of posttraumatic stress disorder (PTSD) and comorbid disorder, focusing on five issues in particular: (1) the frequency of comorbidity among veterans diagnosed with PTSD; (2) how this comorbidity can be accounted for; (3) whether PTSDs with and without comorbidity are different; (4) the validity of PTSD as a distinct diagnosis; and (5) the clinical implications of comorbidity of PTSD.
Summary of the Genetics of Obsessive-Compulsive Disorder Proceedings of the Third IOCDC
Authors: Pato Michele T. , Pato Carlos N. , Kennedy James L. , Pauls David L.
Published: August 2016

The “Genetics of Obsessive-Compulsive Disorder” session at the Third International Obsessive-Compulsive Disorder Conference focused on the strong evidence of familial transmission of obsessive-compulsive disorder (OCD) and the new strategies available for molecular genetic research in this area. The opportunity to create a truly collaborative approach to the genetic study of OCD with standard methodology and large-scale cooperation among groups was emphasized. The importance of phenotype definition, including systematic subtyping, was discussed in the context of reducing heterogeneity and false-positive results.
Psychobiology of Boredom
Authors: Maggini Carlo
Published: August 2016

The study of the psychobiological bases of boredom has been limited by the vagueness of its clinical constructs and the difficulties in applying adequate experimental models. The theoretical background of previous research mainly has been based upon cognitive and behavioral psychology by using neuropsychological constructs, such as arousal, attention, motivation, sensation-seeking, and the reward system. Recently acquired data depict a complex and fragmentary picture. In this article, the author presents a review of the literature as well as some personal considerations on this intriguing topic.
Factors in Antipsychotic Drug Selection: Tolerability Considerations
Authors: Nasrallah Henry A.
Published: August 2016

With the widespread use of atypical antipsychotics over the past several years, adverse metabolic effects have emerged as the most serious medical consequences of pharmacotherapy with some of these agents. Initially, weight gain and obesity were observed (especially with clozapine and olanzapine), but subsequently, type 2 diabetes and dyslipidemia became apparent as well. Further, many reports suggest that sudden and severe (occasionally fatal) diabetes ketoacidosis (DKA) can emerge during treatment with some atypical antipsychotics, even in the absence of adiposity. A marked increase of serum lipids (especially triglycerides) has also been reported, to varying degrees, with different atypicals. This article reviews the data regarding metabolic dysfunction in patients with psychosis (schizophrenia and bipolar disorder). Populations with psychosis have a 2–3-fold higher prevalence of diabetes even before treatment with any antipsychotics, suggesting a possible genetic linkage or comorbidity; this was confirmed with glucose regulation studies in schizophrenia and mania. The induction of type 2 diabetes with atypicals has further increased the prevalence of noninsulin-dependent diabetes from about 6%–8% to 11%–15% according to recent studies, and even higher rates of subclinical hyperglycemia. Serious weight gain (eg, 26–29 lbs after 1 year of clozapine or olanzapine treatment) is an important risk factor, but sudden DKA has now been reported in patients with minimal weight gain, suggesting alternative mechanisms, such as insulin resistance, as a direct effect of some atypicals. Psychiatrists can reduce the risk of metabolic disorders in schizophrenia and bipolar disorder by avoiding the use of certain atypicals as first-line treatment in patients with a personal or family history of diabetes, obesity, and hyperlipidemias. Regulatory agencies in some countries have already taken action in this regard.
Quality of Life in Geriatric Patients with Mood and Anxiety Disorders
Authors: Maddux Rachel E. , Delrahim Katia K. , Rapaport Mark H.
Published: August 2016

This article reviews the impact of depressive and anxiety disorders on quality of life (QOL), disability, and economic burden in the lives of older individuals. Distinctions between the terms QOL, disability, and burden are important in understanding the extent of improvement needed in treatment for elderly patients with depression or anxiety. Treatment efforts should be extended to remediate not only signs and symptoms of psychiatric syndromes but QOL and disability as well; increased understanding toward this end is evolving, yet it is clear that these issues need to be the focus of more investigation.
Impact of Recent Findings on Study Design of Future Autism Clinical Trials
Authors: Hollander Eric , Phillips Ann , King Bryan H. , Guthrie Donald , Aman Michael G. , Law Paul , Owley Thomas , Robinson Ricki
Published: August 2016

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.
Autism Clinical Trials: Biological and Medical Issues in Patient Selection and Treatment Response
Authors: Anderson George M. , Zimmerman Andrew W. , Akshoomoff Natacha , Chugani Diane C.
Published: August 2016

Biomedical measures are critical in the initial patient-screening and -selection phases of a clinical trial in autism and related disorders. These measures can also play an important role in the assessment and characterization of response and can provide an opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical measures, including clinical laboratory analyses, metabolic screening, and chromosomal analysis, are used to screen for potential safety-related problems, to decrease biological and genetic heterogeneity, and to define subgroups. Neurobiological measures can be examined as possible predictors, modifiers or surrogates of therapeutic response, and adverse effects. Neurobiological research measures can also be used to study mechanisms and extent of drug action and to perform baseline and longitudinal investigations of possible pathophysiologic alterations. The potential utility and desirability of specific measures are considered and the general approach to choosing measures for incorporation is discussed.
The Cerebrovascular Model of Depression in Late Life
Authors: Lyness Jeffrey M.
Published: August 2016

Depression in older people, especially depression with an older age of onset, may be a manifestation of acquired brain disease. The cerebrovascular model of depression, often referred to as “vascular depression,” hypothesizes that otherwise clinically occult small vessel brain disease contribute to the pathogeneses of some late-life depressive conditions. This paper reviews several lines of evidence supporting the cerebrovascular model and addresses the limitations of the existing literature. Several directions for future research are noted, including empirical testing of the notion that cerebrovascular disease might underlie the pathogeneses of depression with prominent executive dysfunction or other cognitive impairments. At this time, there are no specific therapeutic options for patients with suspected vascular depression beyond standard approaches to depression treatments, although education about the possibly greater risks of chronicity should be included in treatment planning. Therapy of cerebrovascular risk factors and stroke-risk reduction are important as consistent with general practice guidelines, although it is not known whether this will reduce the incidence or improve the outcome of late-life depression.
Acute Stress Reactions: Can Biological Responses Predict Posttraumatic Stress Disorder?
Authors: Bryant Richard A.
Published: August 2016

What biological responses characterize those acute trauma reactions that develop into chronic psychiatric disorder? The need to understand the genesis of posttraumatic psychological disorders has resulted in much attention on biological reactions in the initial aftermath of trauma exposure. This review outlines the prevailing biological models of acute stress reaction and critiques the available evidence concerning biological responses to trauma that are associated with subsequent psychological disorder. The roles of peritraumatic dissociation and vulnerability factors for acute stress reaction are also reviewed. The major challenges for research on psychobiological responses to trauma are highlighted.
Contemporary Longitudinal Methods for the Study of Trauma and Posttraumatic Stress Disorder
Authors: King Lynda A. , King Daniel W. , Salgado Dawn M. , Shalev Arieh Y.
Published: August 2016

Traditional methods for analyzing trends in longitudinal data have typically emphasized average group change over time. In this article, we propose multilevel, regression-based methods for examining inter-individual differences in intra-individual change and apply these methods to research in trauma and posttraumatic stress disorder (PTSD). The outcome or dependent variable of interest is reconceptualized as an index of dynamic change reflecting the trend or trajectory of an individual's PTSD symptom severity scores across time. A basic statistical model is presented, and analyses and findings are demonstrated with an existing database used in previously published studies. The methods offer promise for future study of the natural course of PTSD chronicity or recovery, risk and resilience factors that influence individual growth or decline, and critical timepoints for intervention.
Women's Mental Health During Pregnancy Influences Fetal and Infant Developmental and Health Outcomes
Authors: Federenko Ilona S. , Wadhwa Pathik D.
Published: August 2016

Women's mental health during pregnancy has important implications not only for the well-being of the mother, but also for the development, health, and well-being of her unborn child. A growing body of empirical evidence from population-based studies suggests that two indicators of women's mental health during pregnancy—psychosocial stress and social support—may exert a significant influence on fetal development and infant birth outcomes, such as birth weight and length of gestation, even after controlling for the effects of established sociodemographic, obstetric, and behavioral risk factors. This paper describes the role of three major biological systems involved in the physiology of pregnancy and stress physiology: neuroendocrine, immune/inflammatory, and cardiovascular systems. These systems have been hypothesized to mediate the effects of maternal mental health on fetal developmental and health outcomes, and a central role has been proposed for placental corticotropin-releasing hormone in this process. However, not all women reporting high prenatal stress and/or low social support proceed to develop adverse birth outcomes, raising the question of the determinants of susceptibility/vulnerability in the context of high stress and/or low social support. In this context, the role of race/ethnicity and genetic predisposition are. discussed as two promising avenues of further investigation.
Improvement in Prosocial Functioning After a Switch to Ziprasidone Treatment
Authors: Loebel Antony , Siu Cynthia , Romano Steven
Published: August 2016

Background: Cognitive, social, and affective impairments are major features of schizophrenia, despite not being represented in the formal diagnostic criteria. These impairments are associated with major reductions in quality of life for patients with schizophrenia. Treatment with newer antipsychotic medications has been reported to improve all of these areas of functioning, but most studies have not examined the direct association between changes in cognitive functioning and other aspects of the illness.

Objectives: The goal of this analysis was to examine relationships between cognitive and affective symptoms and their impact on social impairments in patients switched to ziprasidone treatment.

Methods: In this study, which is a re-analysis of previously published data, 270 patients were switched from previous treatment with conventional antipsychotics, risperidone, or olanzapine to treatment with ziprasidone. Patients were tested with a cognitive assessment battery, rated with the Positive and Negative Syndrome Scale (PANSS), and received other assessments of safety and tolerability. PANSS scores were divided into factors based on previously published factor analyses, with a focus on the cognitive, prosocial, and anxiety-depression factors.

Results: Statistically significant improvements for global cognitive functioning and the three PANSS subscales were found across the studies. When the data were pooled for a path analysis, changes in cognitive functioning indexed by the PANSS cognitive subscales was the primary predictor of improvements in PANSS prosocial functions, with changes in anxiety-depression accounting for much less variance.

Conclusion: These results suggest a direct relationship between improvements in cognitive and prosocial functioning in patients with schizophrenia and indicate that treatments that enhance cognitive functioning, such novel antipsychotics, have the potential to improve aspects of outcome in schizophrenia even in short-term treatment studies. This issue should be addressed in future double-blind studies of the effects of atypical medications in schizophrenia.
The Clinical Efficacy and Safety of Galantamine in the Treatment of Alzheimer's Disease
Authors: Dengiz Alan N. , Kershaw Paul
Published: August 2016

Alzheimer's disease is a progressive, neurodegenerative condition characterized by deficits in cognition, inability to perform activities of daily living, and alterations in behavior. Galantamine hydrobromide is the newest acetylcholin esterase inhibitor (AChEI) approved in the United State for the treatment of mild-to-moderate AD. The safety and efficacy of galantamine has been demonstrated in multiple randomized, Phase III trials of > 2,600 patients with mild-to-moderate AD. Studies have found that galantamine improved or maintained performance in all domains of AD (cognition, function, behavior, and caregiver burden in the short term and slowed the decline in performance or maintained baseline performance through 12 months. The dual mechanism of action may make galantamine a reasonable treatment option for both newly diagnosed patients and patients who have not benefitted from or have poorly tolerated current therapy.
Leptin Functioning in Eating Disorders
Authors: Monteleone Palmiero , DiLieto Antonio , Castaldo Eloisa , Maj Mario
Published: August 2016

Leptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.
Unmasking Anticholinergic Load: When 1 + 1= 3
Authors: Kay Gary , Ginsberg David L. , Pollock Bruce G. , Romanzi Lauri J.
Published: August 2016

The cholinergic system is a major neuromodulatory neurotransmitter system, interacting with core regions of the brain and affecting learning and memory function. Cholinergic function is severely reduced in patients with pathologic conditions, such as Alzheimer's disease. Muscarinic receptors M1–M5 are located at the postsynaptic level of the central cholinergic synapse. Blockage of certain muscarinic receptors has been shown to affect cognitive functioning. The roles of the individual receptor subtypes has implications for pharmacotherapy; eg, nonselective antimuscarinic/anticholinergic medications may block muscarinic neurotransmission, causing deficits in recall and new learning, while M1-receptor agonists and M2-receptor antagonists may not interfere with cognitive functioning. Studies investigating central nervous system (CNS) depressant effects of drugs have shown that antimuscarinic agents have the potential to cause impairment of CNS functioning. CNS dysfunction may be manifested as changes in memory, disruption of sleep, hallucinations, confusion, and delirium.

Anticholinergic load refers to the cumulative effect of taking multiple drugs with anticholinergic activity. The extent to which a particular drug affects the cholinergic system can be determined by its ability to cross the blood-brain barrier, the integrity of which decreases with age. Elderly individuals are also at high risk for increased anticholinergic load due to reductions in metabolism and elimination as well as pharmacokinetic drug interactions. In addition, elderly people are often prescribed several medications that have direct anticholinergic properties and take over-the-counter medications which may also carry substantial anticholinergic burden. The cumulative effect of these medications in vulnerable elderly patients may precipitate early cognitive declines or further exacerbate cognitive deficits in those already suffering from dementia. Risk of cognitive impairment in patients with overactive bladder can thus be reduced through use of M3-selective antagonists, such as darifenacin, and via alternatives to pharmacotherapy, such as behavioral modification, pelvic floor strengthening, and bladder-retraining exercises.
Contributions of GABAA Receptor Subtype Selectivity to Abuse Liability and Dependence Potential of Pharmacological Treatments for Anxiety and Sleep Disorders
Authors: Ator Nancy A.
Published: August 2016

When benzodiazepines (BZs) supplanted barbiturates as a favored, safer treatment for anxiety and sleep disorders in the 1960s, the abuse liability and dependence potential of these drugs were little understood. Widespread recognition of the difficulty of stopping use of chronically taken BZs emerged through the popular press in the late 1970s, which resulted in reluctance to prescribe these otherwise clinically useful compounds. Evolution of the understanding of the biochemical basis for BZ effects in the 1980s and 1990s, coupled with regulatory emphasis on collection of data used in legal scheduling decisions, made possible a targeted search for drugs that would provide effective treatment for anxiety disorders in the absence of abuse liability or dependence potential. Compounds that have selective efficacy at subtypes of the γ-aminobutyric acid type A receptor, are active in preclinical anxiolytic screens, but negative in preclinical studies of behavior relevant to evaluation of abuse liability appear to be one promising means for achieving this end.
Psychostimulant-Induced Behavior as an Animal Model of Obsessive-Compulsive Disorder: An Ethological Approach to the Form of Compulsive Rituals
Authors: Eilam David , Szechtman Henry
Published: August 2016

Rats treated chronically with the D2/D3, dopamine receptor agonist quinpirole show a pattern of behavior that meets a set of ethologically derived criteria of compulsive behavior in obsessive-compulsive disorder (OCD). Moreover, in both quinpirole-treated rats and OCD patients, the structure of compulsive rituals appear similar in being composed of relatively few motor acts that are organized in a flexible yet recurrent manner. In addition, the development of compulsive behavior in quinpirole-treated rats is attenuated by the OCD pharmacotherapeutic drug clomipramine. These similarities support the validity of quinpirole-treated rats as a psychostimulant-induced animal model of OCD. Considering that the induction of compulsive behavior in the rat model involves chronic hyperstimulation of dopamine receptors, this raises the possibility that dopaminergic mechanisms may play a role in OCD, at least in some subtypes of this disorder.
The Role of Glutamate in Anxiety and Related Disorders
Authors: Cortese Bernadette M. , Phan K. Luan
Published: August 2016

Anxiety, stress, and trauma-related disorders are a major public health concern in the United States. Drugs that target the γ-aminobutyric acid or serotonergic system, such as benzodiazepines and selective serotonin reuptake inhibitors, respectively, are the most widely prescribed treatments for these disorders. However, the role of glutamate in anxiety disorders is becoming more recognized with the belief that drugs that modulate glutamatergic function through either ionotropic or metabotropic glutamate receptors have the potential to improve the current treatment of these severe and disabling illnesses. Animal models of fear and anxiety have provided a method to study the role of glutamate in anxiety. This research has demonstrated that drugs that alter glutamate transmission have potential anxiolytic action for many different paradigms including fear-potentiated startle, punished responding, and the elevated plus maze. Human clinical drug trials have demonstrated the efficacy of glutamatergic drugs for the treatment of obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social phobia. Recent data from magnetic resonance imaging studies provide an additional link between the glutamate system and anxiety. Collectively, the data suggest that future studies on the mechanism of and clinical efficacy of glutamatergic agents in anxiety disorders are appropriately warranted.
Emotional Learning and Glutamate: Translational Perspectives
Authors: Gillespie Charles F. , Ressler Kerry J.
Published: August 2016

Anxiety disorders are a common focus of clinical concern and certain forms of anxiety may be conceptualized as disorders of emotional learning. Behavior therapies effective in the treatment of anxiety are modeled on extinction training as a means of reducing pathological anxiety. The present understanding of human anxiety has been informed by preclinical research using rodent models to study the acquisition and extinction of fear. Glutamate appears to have a central role in both of these processes. The authors review this literature and discuss novel applications of D-cycloserine, a partial N-methyl-D-aspartate agonist, for the treatment of anxiety.
Magnetic Resonance Imaging Changes in a Patient with Migraine Attack and Transient Global Amnesia After Cardiac Catheterization
Authors: Fernandez Andres , Rincon Fred , Mazer Sean P. , Elkind Mitchell S.V.
Published: August 2016

The presence of magnetic resonance imaging (MRI) abnormalities in patients with transient global amnesia has been an interesting phenomenologic finding. Several theories surround the occurrence of this syndrome, but little is known about its true physiopathology. We present a case of transient global amnesia after cardiac catheterization associated with migraine headache and MRI changes compatible with an ischemic insult. A discussion on potential explanations for this finding is made, as well as a review of the pertinent literature.
Forgiveness and Psychopathology:Psychobiological and Evolutionary Underpinnings
Authors: Stein Dan J. , Kaminer Debra
Published: August 2016

We present a case of psychotherapy where a process of forgiveness occurs. Then we review the relevant cognitive-affective neuroscience and clinical implications. Resentment and forgiveness emerge within particular kinds of social interactions and can now increasingly also be conceptualized as embodied in particular neurocircuitry. There may be an association between increased psychopathology and decreased forgiveness, and the implications of this for assessment and treatment deserve further study. There may be gender differences in forgiveness; a highly speculative hypothesis suggests that these would reflect sexual divergence in the evolutionary origins of reconciliatory behavior.
Diagnostic Testing in Epilepsy
Authors: Blum David
Published: August 2016

On the surface, epilepsy seems like an easy diagnosis to make—how could anyone miss a major event like a seizure? However, epilepsy can be deceiving. There are many types of seizures that are more subtle than the obvious tonic-clonic seizure, and many seizure types that look bizarre are misdiagnosed as nonepileptic. As a result, a large number of people with epilepsy experience lengthy delays before appropriate diagnosis and therapy provide relief. Conversely, there are many nonepileptic events that are easily mistaken for seizures, which lead to numerous misdiagnoses of epilepsy in nonepileptic patients. These patients are subjected to unnecessary treatment with toxic medications. In this article, I examine the range of diagnostic tests that can be used to establish a diagnosis of epilepsy, to help select the most appropriate form of therapy, to monitor and adjust therapy, to select appropriate surgical candidates, and to decide when therapy can be discontinued.
Social Issues and Epilepsy
Authors: Drazkowski Joseph F.
Published: August 2016

People with epilepsy live and struggle every day with social issues that are relatively minor for people without epilepsy. Apprehension about securing and maintaining one's job or getting a driver's license is significantly greater for the person with epilepsy. Misconceptions held by the general public about epilepsy contribute to and often compound the difficulties and fears experienced by people with epilepsy. Because different people in society react to seizures in different ways, it is important to foster a supportive environment for people with epilepsy. This can be achieved by health care providers and families of people with epilepsy, who can help minimize the negative and inaccurate perceptions that are prevalent regarding people with epilepsy, and maximize their opportunities to integrate successfully into society.
Psychiatric Comorbidity in Children with Epilepsy
Authors: Leonard Elizabeth L. , Kerrigan John F. , Onufrak Elizabeth
Published: August 2016

Epilepsy in children and adolescents is associated with a higher rate of comorbid psychiatric disorders than other chronic childhood illnesses. This article describes various psychiatric disorders that occur in children and their effects on brain development, neurologic and intellectual function, and psychological adaptation for children and their families.
Nonepileptic Seizures: Issues in Differential Diagnosis and Treatment
Authors: Bortz Jennifer J.
Published: August 2016

Nonepileptic seizures (NES) are clinical events that can resemble almost any seizure phenotype, but are behavioral and emotional manifestations of psychological distress, conflict, or trauma. Intractable NES is a disabling disorder that drastically affects patients' emotional well-being. Differential diagnosis, assessment, and treatment of NES is complex, with differentials scattered across an array of neurological and psychiatric disorders. This paper provides an overview of issues related to the diagnosis and treatment of NES. It highlights characteristics and risk factors of the disorder, issues in differential diagnosis, and treatment considerations.
Neurocognitive Deficits and Recovery in Chronic Alcohol Abuse
Authors: Nixon Sara Jo , Phillips Julia A.
Published: August 2016

The excessive and chronic use of alcohol is associated with a variety of neurocognitive changes in a substantial number of detoxified alcoholics. These deficits extend across a wide variety of neuropsychological domains and can be observed over a period of months following detoxification. Furthermore, they are seen in both male and female alcoholics, despite the fact that female alcoholics often have shorter drinking histories. Although these deficits are widely observed, there is considerable heterogeneity both within and across studies. Currently, the sources of this variability are only poorly understood. In this article, we review these neurocognitive and neurophysiological deficits, their pattern of recovery, potential contributing or confounding factors, and some of the clinical implications of these findings.
Apathy in Neuropsychiatric Disorders
Authors: Silva Susan G. , Marin Robert S.
Published: August 2016

Apathy is a common neurobehavioral feature in a variety of neuropsychiatric disorders. Apathy is often interpreted as a sign of depression or as a nonspecific symptom of other medical conditions. However, recent research indicates that the essential meaning of apathy is lack of motivation. This article presents a framework for the classification and differential diagnosis of apathy and addresses issues related to the assessment and treatment of apathy in neuropsychiatric patients.
Genetics of Schizophrenia: Current Findings and Issues
Authors: Kennedy James L. , Pato Michele T. , Bauer Amy , Carvalho Celia , Pato Carlos N.
Published: August 2016

The genetics of schizophrenia are characterized by a set of complex questions, with few answers forthcoming. However, molecular genetic approaches remain the most promising avenue to the understanding of etiologic mechanisms. Powerful discoveries may arise in the near future from candidate gene studies that are benefiting from the extensive neurobiology research in schizophrenia over the past decades. Furthermore, there are promising new divisions of the phenotype into more manageable subtypes that may make both candidate gene and genome scan studies more revealing. The following review discusses selected highlights of the epidemiology, molecular genetic strategies, candidate genes, and genome scan investigations in schizophrenia.
Variability in Response to Clozapine: Potential Role of Cytochrome P450 1A2 and the Dopamine D4Receptor Gene
Authors: Özdemir Vura , Masellis Mario , Basile Vincenzo S. , Kalow Werner , Meltzer Herbert Y. , Lieberman Jeffrey A. , Kennedy James L.
Published: August 2016

Clozapine is a prototype atypical antipsychotic drug and displays efficacy in 30% to 60% of schizophrenia patients who do not respond to traditional antipsychotics. There is considerable evidence supporting a concentration-response relationship for clozapine. A plasma clozapine concentration >200 to 420 ng/mL increases the probability of antipsychotic effects. Approximately 70% to 80% of variability in clozapine plasma concentration can be attributed to variability in cytochrome P450 1A2 activity. Measurement of caffeine metabolites in plasma or urine can be used as an in vivo index of cytochrome P450 1A2 activity, since caffeine is primarily eliminated by oxidative metabolism through this cytochrome P450 enzyme. Caffeine-based tests may contribute to individualization of clozapine dosages and optimization of its antipsychotic effects in schizophrenia patieents There are several lines of evidence suggesting the potential involvement of the dopamine D4 receptor in pharmacodynamic effects of clozapine. Clozapine has a 10-fold higher affinity for the dopamine D4 receptor in comparison to the D2and the D3receptors. Moreover, the free plasma fluid concentration of clozapine is comparable to its binding affinity for the D4receptor in vitro. Blockade of the D4receptor in the mesocorticolimbic region, a brain area implicated in the pathogenesis of schizophrenia, may contribute to efficacy of clozapine in negative symptoms. Moreover, the dopamine D4receptor gene(DRD4)displays an unusual degree of genetic variation (polymorphism). In a recent preliminary study, investigated the (G)nmononucleotide repeat polymorphism within the first intron of the D4gene in 50 schizophrenia patients refractory to traditional antipsychotics. These patients were prospectively followed for antipsychotic response during clozapine treatment. Analysis of variance found significant differences in antipsychotic response as demonstrated by mean change in Brief Psychiatric Rating Scale scores among the genotype panels for this polymorphism F[3,49]=4.1(P=0.01).Future studies investigating the mechanistic basis of variability in response to clozapine should focus on both pharmacokinetic and pharmacodynamic factors.
Chronic Malignant Pain in Cancer Patients
Authors: Landolfi Joseph C.
Published: August 2016

Although the incidence of cancer and cancer-related deaths has declined in recent years, undertreatment of cancer-related pain continues to be a significant problem. By thoroughly assessing chronic malignant pain (CMP) as it relates to cancer and achieving a more complete understanding of the CMP syndromes experienced by cancer patients, psychiatrists and neurologists can formulate accurate diagnoses of patients' clinical pain syndromes and construct well-defined, individual management plans for each patient.
Frontal Lobe Epilepsy Presenting as a Psychotic Disorder With Delusions and Hallucinations: A Case Study
Authors: Ramsey Bonnie J.
Published: August 2016

Although psychotic symptoms are a recognized manifestation of epilepsy, these are more often associated with seizures of the temporal lobe type. While 10% of children with temporal lobe epilepsy develop a psychotic disorder by adulthood, the literature does not report any cases of psychotic disorders associated with frontal lobe seizures in children. This article presents a unique case of a girl whose frontal lobe seizures were associated with delusional psychotic symptoms. Once her seizure disorder was identified through electroencephalography (EEG) and appropriate anticonvulsant therapy was initiated, her associated psychotic symptoms resolved.
Opioid Antagonists and Alcoholism Treatment
Authors: Swift Robert M.
Published: August 2016

The increasing evidence for a neurobiologic basis for alcoholism has spurred the search for pharmacologic agents to treat alcohol abuse. The complex set of symptoms and behaviors that characterizes alcoholism has been linked to dopaminergic and opioid neurotransmitter systems, suggesting that opioid antagonists, such as naltrexone, may alter the positive reinforcement effects and craving involved in alcoholism. Laboratory and clinical investigations of naltrexone have demonstrated the potential for this agent to reduce craving, increase the aversive effects of alcohol, decrease drinking days, and increase abstinence. While naltrexone and other opioid antagonists, such as nalmefene, may be effective components of an alcohol-treatment program, they should only be used in combination with psychosocial interventions, such as support groups and psychotherapy.
Central Nervous System Opportunistic Infections in HIV-1 Infection
Authors: Concha Mauricio , Rabinstein Alejandro
Published: August 2016

Neurologic disease is commonly encountered in the population infected with human immunodeficiency virus type 1 (HIV-1). Although HIV-1 is responsible for many of these neurologic complications, other organisms will affect the nervous system as the immune deficiency state progresses. With the wide use of potent antiretroviral therapy, the mortality from and incidence of opportunistic infections (OIs) among persons with advanced HIV-1 infection has decreased. Nevertheless, these diseases are still seen frequently, especially among those with limited access to new antiretroviral therapies. Therefore, it remains important to recognize the most common OIs of the central nervous system (CNS) as well as primary CNS lymphoma, which will be the focus of this review.
Cognitive Effects of HIV-1 Infection
Authors: Wilkie Frances L. , Goodkin Karl , van Zuilen M. H. , Tyll Mary D. , Lecusay Robert , Edwin Tony
Published: August 2016

The major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.
Lessons Learned in Deep Brain Stimulation for Movement and Neuropsychiatric Disorders
Authors: Skidmore Frank M. , Rodriguez Ramon L. , Fernandez Hubert H. , Goodman Wayne K. , Foote Kelly D. , Okun Michael S.
Published: August 2016

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that “chronically” implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.
Non-Motor Aspects of Parkinson's Disease
Authors: Borek Leora L. , Amick Melissa M. , Friedman Joseph H.
Published: August 2016

Parkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.
Impulse-Control Disorders in Parkinson's Disease
Authors: Ferrara Joseph M. , Stacy Mark
Published: August 2016

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.
Behavioral and Psychological Symptoms of Dementia and Bipolar Spectrum Disorders: Review of the Evidence of a Relationship and Treatment Implications
Authors: Dorey Jean-Michel , Beauchet Olivier , Anterion Catherine Thomas , Rouch Isabelle , Krolak-Salmon Pierre , Gaucher Jacques , Gonthier Régis , Akiskal Hagop S.
Published: August 2016

Dementia is a neuropsychiatric disorder characterized by cognitive impairment and behavioral disturbances. The behavioral and psychological symptoms of dementia (BPSD) are common, contributing to caregiver burden and premature institutionalization. Management of BPSD is complex and often needs recourse to psychotropic drugs. Though widely prescribed, there is a lack of consensus concerning their use, and serious side effects are frequent. This is particularly the case with antidepressant treatment based on the assumption that BPSD is depressive in nature. A better understanding of BPSD etiology could lead to better management strategies. We submit that some BPSD could be the consequence of both dementia and an undiagnosed comorbid bipolar spectrum disorder, or a pre-existing bipolar diathesis pathoplastically altering the clinical expression of dementia. The existence of such a relationship is based on clinical observation, as far as the high frequency of bipolar spectrum disorders in the general population, with a prevalence estimated to be between 5.4% and 8.3%, and the psychopathological similarities between BPSD and mood disorder episodes in bipolar illness. We will review the concept of the bipolar spectrum and explain BPSD before proposing clinical pointers of a possible bipolar spectrum contaminating the phenomenology of dementia, which could lead to the targeted prescription of mood-stabilizing agents in lieu of antidepressant monotherapy. These considerations are of heuristic interest in reconceptualizing the origin of the behavioral manifestations of dementia, with important implications for geriatric practice.
Muscarinic Agonists for the Treatment of Cognition in Schizophrenia
Authors: Sellin Angela K. , Shad Mujeeb , Tamminga Carol
Published: August 2016

It is widely accepted that cholinergic activity at muscarinic receptors is required to maintain cognitive functions, including learning and memory. Memory domains are especially impaired in schizophrenia, which may explain difficulties in psychosocial rehabilitation of individuals with this illness. However, little is known about the mechanism of this impairment. To understand our current knowledge, we reviewed the literature since 1990 via a PubMed search for the terms “muscarinic”, “schizophrenia” “cognition,” “memory,” “learning,” and “agonist” in combination. We found 89 basic science/laboratory studies, case reports/series, case-control studies, cross-sectional studies, standardized controlled animal trials, standardized controlled human trials, and reviews. Although further research is required to fully understand the neuropharmacology of the cholinergic system in cognitive function in schizophrenia, we have examined the data currently available. In general, these data suggest that agonist activity at acetylcholine muscarinic type 1 (M1) receptors would enhance memory and learning in schizophrenia. We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1muscarinic agonists.
Rationalizing Therapeutic Approaches in Alzheimer's Disease
Authors: Grossberg George T.
Published: August 2016

Deficits in cholinergic and glutamatergic neurotransmission have been linked to the symptomatology of Alzheimer's disease, and current therapies for Alzheimer's, including cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine, have been developed to compensate for these deficits. This article reviews the results of clinical trials involving agents approved by the United States Food and Drug Administration for use in the treatment of Alzheimer's disease (namely, ChEIs for mild to moderate Alzheimer's and memantine for moderate to severe Alzheimer's). In particular, the efficacy of current monotherapy strategies in the treatment of cognitive and functional symptoms of Alzheimer's disease will be addressed. In addition, data from a clinical trial examining the use of a ChEI in combination with memantine will also be discussed, as it has been hypothesized that ChEIs and memantine may offer synergistic benefits due to their distinct mechanisms of action.