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Showing papers in "Cns Spectrums in 2008"


Journal ArticleDOI
TL;DR: It is demonstrated that the mean gray matter volume of this anterior cingulate cortex (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state.
Abstract: The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.

955 citations


Journal ArticleDOI
TL;DR: An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI, and directions for future research are proposed.
Abstract: Mild cognitive impairment (MCI) refers to the transitional state between the cognitive changes of normal aging and very early dementia. MCI has generated a great deal of research from both clinical and research perspectives. Several population- and community-based studies have documented an accelerated rate of progression to dementia and Alzheimer's disease in individuals diagnosed with MCI. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. Progression factors, including genetic, neuroimaging, biomarker, and clinical characteristics, are discussed. Neuropathological studies indicating an intermediate state between normal aging and early dementia in subjects with MCI are presented. The recently completed clinical trials as well as neuropsychological and nutritional interventions are discussed. Finally, the clinical utility of MCI, and directions for future research are proposed.

612 citations


Journal ArticleDOI
TL;DR: BDD prevalence decreased after 44 years of age, and a larger proportion of BDD respondents were never married, which could inform treatment by documenting rates of seeking treatment from various sources, suicide attempt rates, and the prevalence of comorbid conditions.
Abstract: Objective:In clinical samples, body dysmorphic disorder (BDD) is associated with substantial suffering and reduced quality of life. Limited surveys report widely varying prevalence estimates. To better establish the prevalence of BDD, we conducted a United States nationwide prevalence survey.Method:We conducted a random sample national household telephone survey in the spring and summer of 2004 and interviewed 2,513 adults, of whom 2,048 qualified for the BDD-module administration. The computer-assisted, structured interviews, conducted by trained lay interviewers, addressed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BDD, along with information regarding several impulse-control disorders and the respondents' financial and demographic data.Results:The rate of response was 56.3%, which compared favorably with rates in federal national health surveys. The cooperation rate was 97.6%. Respondents included a higher percentage of women and people >55 years of age than in the US adult population, and a lower percentage of Hispanics. The estimated point prevalence of DSM-IV BDD among respondents was 2.4% (49/2,048) (by gender: 2.5% for women, 2.2% for men), exceeding the prevalence of schizophrenia and bipolar disorder type I and about that of generalized anxiety disorder. BDD prevalence decreased after 44 years of age, and a larger proportion of BDD respondents were never married. Of those meeting DSM-IV criteria for BDD, 90% (45/49) met the DSM-IV distress criterion, and 51% (25/49) met the interference-with-functioning criterion.Conclusion:A study using clinically valid interviews is needed to evaluate these results. Such studies could inform treatment by documenting rates of seeking treatment from various sources, suicide attempt rates, and the prevalence of comorbid conditions.

310 citations


Journal ArticleDOI
TL;DR: An overview of how inflammation and glutamate dysfunction contribute to the pathophysiology of depression is provided and microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain.
Abstract: Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.

281 citations


Journal ArticleDOI
TL;DR: It seems reasonable to suggest that effective evaluation of, and treatment for, adult ADHD and depressive disorders is required for college students with Internet addiction.
Abstract: Objective: This study was aimed to evaluate the association between Internet addiction and depressive disorder, social phobia and adult attention-deficit/hyperactivity disorder (ADHD) in a sample of Taiwanese college students; and examine gender differences in the psychiatric comorbidity of Internet addiction in this student population. Methods: Two hundred sixteen college students (132 males, 84 females) were recruited. Internet addiction, major depressive disorder, dysthymic disorder, social phobia, and adult ADHD of all participants were diagnosed based on psychiatric diagnostic interview. Results: This study revealed that adult ADHD and depressive disorders were associated with Internet addiction among college students. However, depressive disorders were associated with Internet addiction in the males but not the females. Conclusion: With these results, it seems reasonable to suggest that effective evaluation of, and treatment for, adult ADHD and depressive disorders is required for college students with Internet addiction.

258 citations


Journal ArticleDOI
TL;DR: It is proposed that a focus on standardized testing methodologies across multiple testing modalities and their integration will be crucial for translation of research findings into clinical practice.
Abstract: Antidepressants are important in the treatment of depression, and selective serotonin reuptake inhibitors are first-line pharmacologic options. However, only 50% to 70% of patients respond to first treatment and <40% remit. Since depression is associated with substantial morbidity, mortality, and family burden, it is unfortunate and demanding on health resources that patients must remain on their prescribed medications for at least 4 weeks without knowing whether the particular antidepressant will be effective. Studies have suggested a number of predictors of treatment response, including clinical, psychophysiological, neuroimaging, and genetics, each with varying degrees of success and nearly all with poor prognostic sensitivity and specificity. Studies are yet to be conducted that use multiple measures from these different domains to determine whether sensitivity and specificity can be improved to predict individual treatment response. It is proposed that a focus on standardized testing methodologies across multiple testing modalities and their integration will be crucial for translation of research findings into clinical practice.

163 citations


Journal ArticleDOI
TL;DR: Some evidence is provided that sensory phenomena can be useful to identify more homogenous subgroups of OCD and TS patients and should be included as important phenotypic variables in future clinical, genetic, neuroimaging, and treatment-response studies.
Abstract: Introduction A variety of subjective experiences have been reported to be associated with the symptom expression of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). First described in TS patients, these subjective experiences have been defined in different ways. There is no consensus in the literature on how to best define subjective experiences. This lack of consensus may hinder the understanding of study results and prevents the possibility of including them in the search for etiological factors associated with OCD and TS. Methods The objective of this article was to review the descriptions of subjective experiences in the English-language literature from 1980-2007. This meta-analytic review was carried out using the English-language literature from 1980-2007 available on MEDLINE, PsycINFO, and the Cochrane Library databases using the following search terms: premonitory urges, sensory tics, "just-right" perceptions, sensory phenomena, sensory experiences, incompleteness, "not just-right" phenomena, obsessive-compulsive disorder and TS, including OCD and/or TS, in all combination searches. We also searched for the references cited in each article previously found that referred to the aforementioned terms. Thirty-one articles were included in the study. Results Subjective experiences, in particular, the sensory phenomena, were important phenotypic variables in the characterization of the tic-related OCD subtype and were more frequent in the early-onset OCD subtype. There is a paucity of studies using structured interviews to assess sensory phenomena, their epidemiology and the etiological mechanisms associated with sensory phenomena. Conclusion The current review provides some evidence that sensory phenomena can be useful to identify more homogenous subgroups of OCD and TS patients and should be included as important phenotypic variables in future clinical, genetic, neuroimaging, and treatment-response studies.

149 citations


Journal ArticleDOI
TL;DR: The LHb was not much discussed outside neuroanatomical circles until recently, when it was discovered that its impact on the mesotelencephalic dopamine system is probably much greater than had been assumed, and the clinical relevance of this interesting brain structure is emphasized.
Abstract: In this contribution to the CNS Spectrums neuroanatomy series, Stefanie Geisler, MD, discusses the lateral habenula (LHb). This nuclear complex is one of the areas of the brain that forms part of the cross-talk between limbic fore-brain and some important ascending modulatory pathways. Situated at the caudal end of the dorsal diencephalon and classically regarded as projecting largely to the brainstem, including the serotoninergic raphe nuclei, the LHb receives afferents from widespread forebrain areas. Therefore, the LHb is able to influence serotonin tone in the brain, and has long interested neuroanatomists as a potential limbic-motor interface. Nonetheless, the LHb was not much discussed outside neuroanatomical circles until recently, when it was discovered that its impact on the mesotelencephalic dopamine system is probably much greater than had been assumed. The LHb has become a hot topic. This article-addresses these developments and emphasizes the clinical relevance of this interesting brain structure.

144 citations


Journal ArticleDOI
TL;DR: The mechanisms of therapeutic action of MAOIs are discussed, but also the mechanisms explaining their side effects, including hypertensive interactions with dietary tyramine (so-called "cheese reactions") and drug interactions that can lead to hypertensive reactions with some drugs and serotonin toxicities with others.
Abstract: Monoamine oxidase inhibitors (MAOIs) currently have a "bad rap" and are thus infrequently used in psychopharmacology, even by experienced clinicians. Misinformation about the dietary and drug interactions of MAOIs is widespread, whereas pragmatic tips for utilizing MAOIs to minimize risks and to maximize therapeutic actions are largely lacking in the contemporary literature. While clearly not first-line treatments, MAOIs, in the hands of experienced and well-informed clinicians, can be a powerful therapeutic intervention for patients with depression, panic disorder, and other anxiety disorders who have failed first-line treatments. This article focuses on the pharmacologic mechanisms of MAOIs, since an understanding of these mechanisms may provide a rationale to empower experts to expand their use of these agents. Discussed here are not only the mechanisms of therapeutic action of MAOIs, but also the mechanisms explaining their side effects, including hypertensive interactions with dietary tyramine (so-called "cheese reactions") and drug interactions that can lead to hypertensive reactions with some drugs and serotonin toxicities with others. This article also provides practical tips on how to use MAOIs, including debunking certain myths and giving specific guidance about which foods and drugs to avoid. Those with no previous interest in MAOIs may discover in this article a new "secret weapon" to add to their therapeutic armamentarium for patients who fail to respond to the better-known agents.

136 citations


Journal ArticleDOI
TL;DR: Limited evidence further suggests that ADHD therapy may help to improve symptoms of certain psychiatric comorbidities, such as depression, which is most prevalent among patients with mood, anxiety, substance use, and impulse-control disorders.
Abstract: 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.

136 citations


Journal ArticleDOI
TL;DR: It is suggested that personality traits are better predictors than neuropsychological characteristics of whether someone has PG.
Abstract: Introduction:Pathological gambling disorder (PG) has been associated with fronto-temporal dysfunction and maladaptive personality traits, such as impulsivity and novelty seeking. The purpose of this study was to examine the predictive variance of neuropsychological and personality characteristics in PG.Methods:Persons with PG (n=25) and a comparison group (n=34) were administered a battery of neuropsychological tests, the Temperament and Character Inventory, and the Barratt Impulsiveness Scale. Subjects with PG had evidence of fronto-temporal dysfunction as assessed by the Stroop, Wisconsin Card Sorting Test-64, Wechsler Adult Intelligence Scale Letter-Number Sequencing, Controlled Oral Word Association Test, and Boston Diagnostic Aphasia Examination Animal Naming Test.Results:Subjects with PG also had impaired decision making on the Iowa Gambling Task. PG subjects had elevated levels of impulsivity, novelty seeking, and harm avoidance, and lower levels of self-directedness and cooperativeness. Logistic regression analyses indicated that neuropsychological variables did not add significant incremental variance over personality traits in predicting PG (Block χ2=5.19, P=.074), while personality variables added significant incremental variance over neuropsychological traits in predicting PG (Block χ2=25.13, P<.001).Conclusion:These results suggest that personality traits are better predictors than neuropsychological characteristics of whether someone has PG.

Journal ArticleDOI
TL;DR: Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.
Abstract: Fibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold) Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain This mechanism appears to represent a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain Importantly, after central sensitization has been established, only minimal peripheral input is required for the maintenance of the chronic pain state Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes

Journal ArticleDOI
TL;DR: There is growing evidence of the way in which the dopaminergic system is associated with cognitive-affective disturbances in depression, and provides a useful target for therapeutic interventions.
Abstract: The heterogeneity of major depression suggests that multiple neurocircuits and neurochemicals are involved in its pathogenesis. Anhedonia and psychomotor symptoms are, however, particularly characteristic features of major depression and may provide insights into its underlying psychobiology. Importantly, these symptoms appear to be mediated by dopaminergic mesolimbic and mesostriatal projections, the function of which is, in turn, influenced by key gene variants and environment stressors. Indeed, there is growing evidence of the way in which the dopaminergic system is associated with cognitive-affective disturbances in depression, and provides a useful target for therapeutic interventions. At the same time, a range of other systems are likely to contribute to the psychobiology of this condition.

Journal ArticleDOI
TL;DR: Hallucinations may involve several sensory modalities and include visual illusions, passage hallucinations, and sense of presence in Parkinson's disease patients with cognitive impairment.
Abstract: Psychosis in Parkinson's disease refers to a combination of hallucinations and delusions occurring with a clear sensorium and a chronic course. Hallucinations may involve several sensory modalities. Complex visual hallucinations are the most common type. "Minor" hallucinatory phenomena are frequently present and include visual illusions, passage hallucinations, and sense of presence. Insight may be lost in patients with cognitive impairment. Delusions of a paranoid type are more rare than hallucinations. Both hallucinations and delusions are more frequent in Parkinson's disease patients with dementia. Pathogenesis involves complex and probably multifactorial mechanisms, including pharmacologic (dopaminergic treatment and others) and disease-related factors.

Journal ArticleDOI
TL;DR: Accumulating evidence suggests a “vascular hypothesis” to be related to the pathology of Alzheimer's disease and lifestyle interventions toward an early and effective cardiovascular risk-factor management to reduce the cardiometabolic and the cognitive decline risk.
Abstract: Current evidence from epidemiological, neuroimaging, pathological, pharmacotherapeutic, and clinical studies indicate an association of Alzheimer's disease with risk factors of vascular atherosclerotic disease either in isolation or in aggregate. "Metabolic syndrome" (MetS) is the name for a clustering of risk factors for cardiovascular disease and type 2 diabetes that are of metabolic origin. These include central obesity, elevated plasma glucose, high blood pressure, atherogenic dyslipidemia, a prothrombotic state, and a proinflammatory state. In this article, we provide an overview of the relevant literature with regard to the relationship of Alzheimer's disease with MetS. Accumulating evidence suggests a "vascular hypothesis" to be related to the pathology of Alzheimer's disease. In the light of this evidence, clinician may consider lifestyle interventions toward an early and effective cardiovascular risk-factor management to reduce the cardiometabolic and the cognitive decline risk, while further research of other preventive strategies may be warranted.

Journal ArticleDOI
TL;DR: Long-term treatment with GXR was generally safe for up to 24 months of treatment, and effectiveness was maintained over this treatment period.
Abstract: Introduction:Guanfacine is a noradrenergic agonist that is believed to improve symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective actions at α2A-adrenoceptors in the prefrontal cortex. A recent double-blind, multicenter trial supports the efficacy and safety of guanfacine extended release (GXR) for pediatric ADHD. This long-term, open-label extension was conducted to study the safety profile and effectiveness of GXR for up to 2 years.Methods:Subjects were 240 children 6–17 years of age with a diagnosis of ADHD who participated in the preceding randomized trial. GXR was initiated at 2 mg/day and titrated as needed in 1-mg increments to a maximum of 4 mg/day to achieve optimal clinical response.Results:The most common adverse events were somnolence (30.4%), headache (26.3%), fatigue (14.2%), and sedation (13.3%). Somnolence, sedation, and fatigue were usually transient. Cardiovascular-related adverse events were uncommon, although small reductions in mean blood pressure and pulse rate were evident at monthly visits. ADHD Rating Scale, Version IV, total and subscale scores improved significantly from baseline to endpoint for all dose groups (P<.001 for all comparisons, intent-to-treat population).Conclusion:Long-term treatment with GXR was generally safe for up to 24 months of treatment, and effectiveness was maintained over this treatment period.

Journal ArticleDOI
TL;DR: A comprehensive test battery includes measures of baseline intellectual ability, attention, executive function, memory, language, visuospatial skills, and mood and can identify subtle deficits that may otherwise elude detection.
Abstract: Mild cognitive impairment (MCI) is a clinical diagnosis in which deficits in cognitive function are evident but not of sufficient severity to warrant a diagnosis of dementia For the majority of patients, MCI represents a transitional state between normal aging and mild dementia, usually Alzheimer's disease Multiple subtypes of MCI are now recognized In addition to presentations featuring memory impairment, symptoms in other cognitive domains (eg, executive function, language, visuospatial) have been identified Neuropsychological testing can be extremely useful in making the MCI diagnosis and tracking the evolution of cognitive symptoms over time A comprehensive test battery includes measures of baseline intellectual ability, attention, executive function, memory, language, visuospatial skills, and mood Informant-based measures of neuropsychiatric symptoms, behaviors, and competency in instrumental activity are also included Careful assessment can identify subtle deficits that may otherwise elude detection, particularly in individuals of superior baseline intellectual ability As we move closer to disease-modifying therapy for Alzheimer's disease, early identification becomes critical for identifying patients who have an opportunity to benefit from treatment

Journal ArticleDOI
TL;DR: Results from this preliminary study seem to suggest that a shorter DUI-AD may determine a better response to pharmacologic treatment in patients with GAD, and that a longer DUI (DUI-BDZ and DUI- AD) may be associated to a worse clinical course.
Abstract: Introduction:The aim of the present study was to investigate the impact of the duration of untreated illness (DUI)—defined as the time elapsing between the onset of generalized anxiety disorder (GAD) and the first adequate pharmacologic treatment—on treatment response and clinical course in a sample of subjects with GAD.Methods:One hundred patients with GAD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria, were enrolled and their main demographic and clinical features collected. Patients were then treated with selective serotonin reuptake inhibitors or venlafaxine for 8 weeks in open-label conditions. Treatment response and other clinical variables were analyzed after dividing the sample into two groups according to DUI (DUI ≤12 months and DUI >12 months).Results:When the DUI was computed with respect to the first antidepressant treatment (DUI-AD), a higher improvement (Clinical Global Impressions-Severity of Illness scale) after the pharmacologic treatment was found in the group with a shorter DUI (analysis of variance with repeated measures: time effect F=654.975, P<.001; group effect: F=4.369, P=.O39). When computed with respect to the first treatment with benzodiazepines (DUI-BDZ), the two groups did not show any significant difference in treatment response (time effect: F=652.183, P<.001; group effect: F=0.009, P=.924). In addition, patients with a longer DUI (DUI-BDZ or DUI-AD) showed an earlier age at onset, a longer duration of illness and a higher rate of comorbid psychiatric disorders with onset later than GAD.Conclusion:Results from this preliminary study seem to suggest that a shorter DUI-AD may determine a better response to pharmacologic treatment in patients with GAD, and that a longer DUI (DUI-BDZ and DUI-AD) may be associated to a worse clinical course. Further investigation on the relationship between DUI and GAD is needed.

Journal ArticleDOI
TL;DR: Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.
Abstract: Introduction Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6-12 years of age and in adults. In short-term studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD. Methods This open-label, multicenter, single-arm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for ADHD. Following 1-week screening and washout periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness. Results Of 272 subjects receiving LDX, 147 completed the study. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or electrocardiographic parameters. From baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points (P 80% of subjects at endpoint and >95% of completers at 12 months were rated "improved." Conclusion Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.

Journal ArticleDOI
TL;DR: Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics.
Abstract: Numerous "antihistamines" as well as various psychotropic medications with antihistamine properties are widely utilized to treat insomnia. Over-the-counter sleep aids usually contain an antihistamine and various antidepressants and antipsychotics with antihistamine properties have sedative-hypnotic actions. Although widely used for the treatment of insomnia, many agents that block the histamine H1 receptor are also widely considered to have therapeutic limitations, including the development of next-day carryover sedation, as well as problems with chronic use, such as the development of tolerance to sedative-hypnotic actions and weight gain. Although these clinical actions are classically attributed to blockade of the H1 receptor, recent findings with H1 selective agents and H1 selective dosing of older agents are challenging these notions and suggest that some of the clinical limitations of current H1-blocking agents at their currently utilized doses could be attributable to other properties of these drugs, especially to their simultaneous actions on muscarinic, cholinergic, and adrenergic receptors. Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics.

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

Journal ArticleDOI
TL;DR: A number of rigorous studies of mindfulness-based cognitive therapy for depression have been positive, however, much remains to be discovered about the underlying mechanisms of and clinical indications for mindfulness- based approaches.
Abstract: There is controversy about whether mindfulness-based approaches to psychotherapy represent a new wave of cognitive-behavioral therapy or a core process in all psychotherapies. One way of conceptualizing mindfulness is in terms of emotion regulation; mindfulness is a strategy aimed at opposing suppression and avoidance. Dispositional mindfulness has been associated with greater activation in prefrontal cortex and greater deactivation of amygdala during affect labeling. A number of rigorous studies of mindfulness-based cognitive therapy for depression have been positive. However, much remains to be discovered about the underlying mechanisms of and clinical indications for mindfulness-based approaches.

Journal ArticleDOI
TL;DR: Escitalopram shows good efficacy across the range of OCD symptom dimensions, andHoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin.
Abstract: Introduction: There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic intervention. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated. Methods: Data from a randomized, double-blind, placebo-controlled study of escitalopram in 466 adults with OCD were analyzed. Exploratory factor analysis of individual items of the Yale-Brown Obsessive-Compulsive Scale checklist was performed and subscale scores based on the extracted factors were determined. Analyses of covariance were undertaken to determine whether inclusion of each subscale score in these models impacted on the efficacy of escitalopram versus placebo. Results: Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoarding/symmetry, religious/sexual, and somatic/hypochondriacal). Analyses of covariance including all the subscales demonstrated that escitalopram was more effective than placebo. There was a significant interaction for the hoarding/symmetry factor, which was associated with a poor treatment response. Conclusion: Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.

Journal ArticleDOI
TL;DR: People with fibromyalgia syndrome experience unrefreshing sleep, aches, hypersensitivity, and cognitive and emotional difficulties and the generalized hypersensitivity of the body is considered to be affected by disturbances in central nervous system functions.
Abstract: People with fibromyalgia syndrome (FMS) experi-ence unrefreshing sleep, aches, hypersensitivity, and cognitive and emotional difficulties. Although no specific causative factor or biological agent is known to account for all of the features of FMS and these related diagnoses, the generalized hypersensitivity of the body is considered to be affected by disturbances in cen-tral nervous system (CNS) functions. Such CNS dis-turbances are intrinsic to the sleeping-waking brain, where the common symptom elements in all these illnesses are poor quality of sleep, nonspecific pain, fatigue, and psychological distress in the absence of known disease pathology.

Journal ArticleDOI
TL;DR: The task of prescribing, dosing, and switching antipsychotics is generally characterized by a process of trial and error, often resulting in suffering from side effects and/or lack of response while searching for the optimum treatment.
Abstract: Atypical antipsychotic treatment strategies have tended to change significantly from the time new drugs are introduced to the market. Because these drugs are associated with so many side effects, dosing strategies are largely based on the avoidance of adverse effects. A great number of issues complicate the task of effectively dosing atypical antipsychotics, including great variability and unpredictability in individual response. This often leads to extensive periods of trial and error as well as patient suffering, while physicians search for an optimum treatment. The mechanisms of action of these drugs are not entirely understood; they can be effective for both psychosis and mood disorders, possibly via actions on different systems or circuits. Furthermore, a resolution to the dilemma of dosing once or twice daily depends on issues of patient compliance and drug efficacy. This supplement puts these issues into perspective by illustrating historical discrepancies in antipsychotic use between clinical trials and practice, discussing individual response variability to antipsychotic treatment, describing current theories of antipsychotic mechanisms of action, and speculating as to the future of antipsychotic treatment strategies. The following unmet needs regarding dosing atypical antipsychotics were revealed following a vigorous assessment of activity feedback, expert faculty assessment, literature review, and through new medical knowledge: (1) although many clinicians generalize that higher doses are associated with greater efficacy and more side effects, the efficacy and tolerability profile for different doses of atypical antipsychotics are far less straightforward than that; (2) physicians continue to face huge issues of patient adherence when treating schizophrenia and bipolar disorder, which may be mitigated by addressing the most troublesome side effects caused by antipsychotics; (3) research on genetics, neurocircuitry, and new treatment methods in schizophrenia is ongoing; clinicians need to be educated on new treatment strategies as data accumulate so that they are prepared to implement these tools once they become available.

Journal ArticleDOI
TL;DR: Although the presence of NCBS is not required for a diagnosis of MCI, these symptoms are frequently present and constitute an important source of morbidity, and it is suggested that apathy may be more characteristic of amnestic MCI while nighttime behaviors may beMore characteristic of non-amnesticMCI.
Abstract: INTRODUCTION How frequent and how clinically important are mood and behavioral symptoms among older adults with mild cognitive impairment (MCI)? Although these noncognitive behavioral symptoms (NCBS) are not represented in the diagnostic criteria for MCI, their clinical significance is increasingly recognized. METHODS To address this question, the authors identified a cohort of consecutively evaluated patients from a psychiatric hospital's outpatient memory clinic. These patients' records contained both a clinical assessment and a standardized set of evaluations including the Mini-Mental State Exam, the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale. Using a standardized chart-review approach, the presence of any NPI-screened symptom was identified and the frequencies of specific NPI-screened symptoms were calculated for the Memory Clinic MCI cohort and for amnestic and non-amnestic MCI subgroups. RESULTS A total of 116 patient records were reviewed. Thirty-eight patients with MCI were identified. Twenty-two of these met criteria for amnestic MCI by Mayo Clinic criteria while 16 met criteria for non-amnestic MCI. At least one NPI-screened mood or behavioral symptom was present in 86.8% of these MCI patients. Depression/dysphoria (63.3%), apathy (60.5%), anxiety (47.4%), irritability (44.7%), and nighttime behaviors (42.1%) were the most frequent. While depression/dysphoria was distributed similarly between amnestic and non-amnestic subgroups, apathy was significantly more frequently associated with the amnestic subtype of MCI, and nighttime behaviors were more frequently associated with the non-amnestic subtype. CONCLUSION Although the presence of NCBS is not required for a diagnosis of MCI, these symptoms are frequently present and constitute an important source of morbidity. Apathy and depression may be difficult to differentiate, but targeted treatment of depression may fail to address apathy. Recognizing the limitations of this preliminary study, the authors suggest that apathy may be more characteristic of amnestic MCI while nighttime behaviors may be more characteristic of non-amnestic MCI.

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TL;DR: In the majority of larger-scale studies, once the placebo effect is accounted for, the percentage of women who respond to SSRIs or COCs is actually less than the percentageof women who do not respond at all.
Abstract: BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are almost unanimously considered to be very efficacious and the first line of pharmacologic treatment for premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). There is a need to examine if this is actually the case. More recently combined oral contraceptives (COCs) have been pursued due to their ovulation suppression effects. Their effects on PMS/PMDD should be further examined as well. METHODS: For this review of the literature from 1990 to the present MEDLINE PsychLit and Cochrane controlled trials register were searched. Randomized double-blind placebo-controlled clinical trials of SSRIs and COCs (N>20) that report the rate of responders and not just percent improvement in severity of symptoms were selected for study. The data extraction were the percentage or number of responders as reported by the original authors. RESULTS: In many studies only mean improvement in severity was reported. In all studies the main inclusion criterion was meeting criteria for PMDD; this has not however been an outcome measure. However only 16 reports that provided actual rate of responders could be included. The percentage of non-responders (100% minus active medication) to SSRIs and COCs was found to be higher than the reported percentage of women who responded to active medication (response rate to an SSRI or COC minus the response rate to placebo). CONCLUSION: In the majority of larger-scale studies once the placebo effect is accounted for the percentage of women who respond to SSRIs or COCs is actually less than the percentage of women who do not respond at all. SSRIs provide an important step forward in the treatment of PMDD and PMS. COCs provide a different option still approximately 40% of women with PMDD do not respond to SSRIs. Treatment with a currently approved COC does not substantially improve the percentage of responders. Therefore additional alternative targeted treatment modalities need to be developed.

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TL;DR: This study presents eight cases of patients with brain lesions who, for a significant period of time, were diagnosed and treated for psychiatric disorders and show that brain tumors can be neurologically silent for a sufficient period ofTime and manifest as psychiatric disorders.
Abstract: Sometimes patients with organic brain lesions in neurologically silent brain areas might present only with psychiatric symptoms, such as depression, anxiety disorders, schizophrenia, anorexia nervosa, or cognitive dysfunction. This study presents eight cases of patients with brain lesions (four cases of meningiomas, one case of intracerebral cysts, one case of anaplastic oligodendroglioma, one case of multiform glioblastoma, and one case of occlusive hydrocephalus) who, for a significant period of time, were diagnosed and treated for psychiatric disorders (three cases of Alzheimer's disease, two cases of schizoaffective disorder, one case of schizophrenia, one case of depression, and one case of organic emotional lability disorder). When neurologic symptoms developed, they underwent neuroimaging studies and organic brain lesions were diagnosed. Further treatment required neurosurgical interventions. These cases show that brain tumors can be neurologically silent for a sufficient period of time and manifest as psychiatric disorders. Therefore, neuroimaging studies are needed when atypical changes in mental status or neurologic symptoms and signs develop.

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TL;DR: Preliminary evidence is provided that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy.
Abstract: Introduction:Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent. More research examining pharmacotherapy augmentation strategies to improve outcomes is needed.Methods:In an 8-week, open-label, prospective augmentation study, we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult outpatients with generalized anxiety disorder (n=13) or panic disorder (n=10) who remained symptomatic despite treatment for at least 8 weeks with an adequate (or maximally tolerated) dose of typical pharmacotherapy.Results:Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores (paired t=4.41, df=22, P<.001) in the intent-to-treat sample of 23 individuals. Three subjects (13%) discontinued due to sedation, chest discomfort, and restlessness, respectively.Conclusion:These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy.

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TL;DR: It appears that, at least, the switch risk, and perhaps also the risk for rapid cycling and new-onset suicidality have been overinterpreted, and this raises doubt about the efficacy of anti-depressants as a primary-treatment choice in bipolar depression.
Abstract: Antidepressants constitute a central cornerstone in the treatment of depressive syndromes. In bipolar patients, however, there is an ongoing controversy about their usefulness for at least 3 decades. Early reports, mainly concerning tricyclic antidepressants, have repeatedly pointed toward unfavorable side effects on the course of the disorder, namely switching into (hypo)mania, induction of rapid cycling, and increased risk of suicide. Most evidence for both unfavorable and favorable effects has been deducted, thus far, from small studies with methodological flaws. More substantiated evidence only recently became available. From this it appears that, at least, the switch risk, and perhaps also the risk for rapid cycling and new-onset suicidality have been overinterpreted. At the same time, these new data raise doubt about the efficacy of antidepressants as a primary-treatment choice in bipolar depression.