Showing papers in "Cns Spectrums in 2003"

Abuse and neglect in childhood: relationship to personality disorder diagnoses.

Abstract: Background Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples. Methods This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for ~2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution. Results Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men. Conclusion These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder.

How Well Does Cognitive-Behavioral Therapy Treat Symptoms of Complex PTSD? An Examination of Child Sexual Abuse Survivors Within A Clinical Trial

Abstract: Are brief cognitive-behavioral treatments for posttraumatic stress disorder (PTSD) also effective for the wider range of symptoms conceptualized as complex PTSD? Female rape victims, most of whom had extensive histories of trauma, were randomly assigned to cognitive-processing therapy, prolonged exposure, or a delayed-treatment waiting-list condition. After determining that both types of treatment were equally effective for treating complex PTSD symptoms, we divided the sample of 121 participants into two groups depending upon whether they had a history of child sexual abuse. Both groups improved significantly over the course of treatment with regard to PTSD, depression, and the symptoms of complex PTSD as measured by the Trauma Symptom Inventory. Improvements were maintained for at least 9 months. Although there were group main effects on the Self and Trauma factors, there were no differences between the two groups at posttreatment once pretreatment scores were covaried. These findings indicate that cognitive-behavioral therapies are effective for patients with complex trauma histories and symptoms patterns.

The neuroendocrinology of posttraumatic stress disorder: new directions.

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

Non-stimulant treatment of attention-deficit/hyperactivity disorder.

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

WCA Recommendations for the Long-Term Treatment of Obsessive-Compulsive Disorder in Adults

Abstract: What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

WCA recommendations for the long-term treatment of generalized anxiety disorder.

Abstract: What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healthcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been performed. Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Psychopharmacologic strategies for the treatment of aggression in juveniles.

Abstract: Maladaptive aggression in youth is one of the most common and troublesome reasons for referrals to child psychiatrists. It has a complex relationship with psychopathology. There are several syndromes, which are primary disturbances of clustered maladaptive aggression, most notably oppositional defiant disorder and conduct disorder. However, problems with aggression also appear in a wide range of other disturbances, such as bipolar disorder, posttraumatic stress disorder, and mood disorders. Additionally, aggression is normative, serves an adaptive purpose and can be situationally induced. These complexities need to be carefully addressed before targeting maladaptive aggression psychopharmacologically. We summarize the literature on the psychopharmacology of maladaptive aggression in youth, focusing on disorders without cognitive impairment. We delineate the subtypes of aggression which are most likely to respond to medication (reactive-affective-defensive-impulsive in their acute and chronic form) and conclude with a discussion of specific medication strategies which are supported by controlled clinical trials and clinical experience.

The link between glutamate and migraine.

Abstract: Migraine pain-relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis, and thalamus, contain glutamate-positive neurons, and glutamate activates the trigeminal nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, and central sensitization. Glutamate receptor-subtype antagonists are effective in preclinical models of migraine, and in the clinic. These preclinical and clinical observations argue for a strong link between migraine and the glutamatergic system, a link that is important to further characterize in an effort to better understand migraine mechanisms and deliver effective therapies.

Brain-imaging studies of posttraumatic stress disorder.

Abstract: Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, γ-aminobutyric acid, μ-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.

Mechanisms and the Current State of Transcranial Magnetic Stimulation

Abstract: Transcranial magnetic stimulation (TMS) is unique among the current brain stimulation techniques because it is relatively non-invasive. TMS markedly differs from vagus nerve stimulation, deep brain stimulation and magnetic seizure therapy, all of which require either an implanted prosthesis or general anesthesia, or both. Since its rebirth in its modern form in 1985, TMS has already shown potential usefulness in at least three important domains-as a basic neuroscience research instrument, as a potential clinical diagnostic tool, and as a therapy for several different neuropsychiatric conditions. The TMS scientific literature has now expanded beyond what a single summary article can adequately cover. This review highlights several new developments in combining TMS with functional brain imaging, using TMS as a psychiatric therapy, potentially using TMS to enhance performance, and finally recent advances in the core technology of TMS. TMS' ability to non-invasively and focally stimulate the brain of an awake human is proving to be a most important development for neuroscience in general, and neuropsychiatry in particular.

Obstructive Sleep Apnea and Depression

Abstract: Is there an association between obstructive sleep apnea (OSA) and depression? OSA is a common breathing-related sleep disorder. There have been reports that depressive symptoms can be associated with this sleep disorder. A number of investigations have addressed this issue. Although some have found no correlation, most studies have concluded that there is an association between OSA and depressive symptoms. Other investigations have shown that depressive symptoms improve with treatment of OSA, and that untreated OSA may contribute to treatment resistance in some cases of mood disorders. Within the framework of current psychiatric diagnostic criteria, the depressive symptoms associated with OSA can be viewed as a combination of a mood disorder secondary to a primary medical condition and an adjustment disorder with depressed mood. The question of whether OSA causes depressive symptoms can perhaps be best answered by viewing OSA and depression as having certain symptoms that are common to both disorders.

The comorbidity of migraine.

Abstract: This review addresses the methodologic issues relevant to the study of comorbidity and provides a broad overview of the medical and psychiatric conditions associated with migraine. Since the body of literature examining the comorbidity of migraine is enormous, the scope of this review will largely focus on community and case-control studies. Among the selected comorbid medical conditions, including disorders of the cardiovascular, respiratory, neurologic, gastrointestinal and immunologic systems, stroke, asthma, and allergies appear to be most strongly associated with migraine. Among the psychiatric illnesses, mood and anxiety disorders have been shown to be most strongly associated with migraine in the general population. Further research is indicated and necessary to elucidate the precise mechanism of migraine comorbidity.

Cognitive-behavioral therapy for generalized anxiety disorder with integrations from interpersonal and experiential therapies.

Abstract: After providing background information on the definition and nature of generalized anxiety disorder, this article describes cognitive-behavioral therapy (CBT) methods that have been empirically supported in the treatment of this disorder. Subsequent to this description, relevant outcome literature is briefly reviewed, along with evidence that the addition of other techniques beyond traditional CBT methods may be necessary to maximize clinical outcome. A description is then provided of an integrated interpersonal/emotional processing therapy that the authors have recently added to their CBT protocol. CBT with and without this integrated treatment is currently being evaluated in an experimental trial.

Mechanisms and the current state of deep brain stimulation in neuropsychiatry.

Abstract: Deep brain stimulation (DBS) is established as a therapy for movement disorders, and it is an investigational treatment in other neurologic conditions. DBS precisely targets neuroanatomical targets deep within the brain that are proposed to be centrally involved in the pathophysiology of some neuropsychiatric illnesses. DBS is nonablative, offering the advantages of reversibility and adjustability. This might permit therapeutic effectiveness to be enhanced or side effects to be minimized. Preclinical and clinical studies have shown effects of DBS locally, at the stimulation target, and at a distance, via actions on fibers of passage or across synapses. Although its mechanisms of action are not fully elucidated, several effects have been proposed to underlie the therapeutic effects of DBS in movement disorders, and potentially in other conditions as well. The mechanisms of action of DBS are the focus of active investigation in a number of clinical and preclinical laboratories. As in severe movement disorders, DBS may offer a degree of hope for patients with intractable neuropsychiatric illness. It is already clear that research intended to realize this potential will require a very considerable commitment of resources, energy, and time across disciplines including psychiatry, neurosurgery, neurology, neuropsychology, bioengineering, and bioethics. These investigations should proceed cautiously. CNS Spectr 2003;8(7):522-526

Depression and HIV infection: Impact on immune function and disease progression

Abstract: Can psychological factors, such as depression, affect human immunodeficiency virus progression? HIV infection is viewed as a chronic illness in which those infected often confront a number of emotional challenges and physical health and disease-related issues. Over the past 20 years, there has been increasing evidence that depression and other mood-related disturbances are commonly observed among HIV-positive individuals. There is also mounting data showing that depressive symptoms might further impact upon specific elements of immune system functioning and influence quality of life and health status. This paper will highlight studies examining the prevalence of depression during HIV infection and review some of the evidence examining the impact of depressive symptoms on immune function and HIV disease progression.

Genetics of posttraumatic stress disorder.

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

Stress management and psychoneuroimmunology in HIV infection.

Abstract: Does stress management affect psychological and immune functioning in persons with human immunodeficiency virus infections? Stress-management techniques, such as relaxation training and imagery, cognitive restructuring, coping-skills training, and interpersonal-skills training, may reduce anxiety, depression, and social isolation in HIV-infected persons by lowering physical tension and increasing a sense of control and self-efficacy. A psychoneuroimmunologic model is proposed wherein these psychological changes are hypothesized to be accompanied by an improved ability to regulate neuroendocrine functioning, which in turn may be associated with a partial normalization of immune system functions such as lymphocyte proliferation and cytotoxicity, providing more efficient surveillance of latent viruses that may contribute directly to increased HIV replication and generate opportunistic infections or cancer if left unchecked. Such a normalization of stress-associated immune system decrements are hypothesized to forestall or minimize increases in viral load and expression of clinical symptoms. This model is useful for testing the factors contributing to the health effects of stress-management interventions in HIV-infected persons. In this context, one general research strategy for testing the effects of stress-management interventions is to target them toward the more prevalent psychosocial challenges that HIV-infected people face at various points in the disease process; enroll an HIV-infected population (eg, HIV-positive homosexual and bisexual men) into a randomized trial; and monitor changes in cognitive, affective, behavioral, and social factors in parallel with hormonal, immunologic, viral, and clinical changes over the course of time. This article will review the major psychoneuroimmunologic findings that have emerged using this paradigm and suggest future research directions and clinical applications.

WCA recommendations for the long-term treatment of panic disorder.

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

Does comorbid attention-deficit/hyperactivity disorder impact the clinical expression of pediatric obsessive-compulsive disorder?

Abstract: What is the impact of attention-deficit/hyperactivity disorder (ADHD) on the phenotypic expression of pediatric obsessive-compulsive disorder (OCD). We examined phenotypic features, and functional and clinical correlates in youths with OCD, with and without comorbid ADHD, from a large sample of consecutively referred pediatric psychiatry patients. Although comorbid ADHD had no meaningful impact on the phenotypic expression or clinical correlates of OCD, it was associated with higher rates of compromised educational functioning compared with other OCD youths. Our findings suggest that the OCD phenotype runs true and is not impacted by comorbid ADHD in youths diagnosed with both OCD and ADHD. In such affected youths, both disorders contribute to morbid dysfunction and require treatment. More work is needed to determine whether OCD plus ADHD represents a developmentally and etiologically distinct form of the OCD syndrome.

Rhythmic Movement Disorder in Children

Abstract: How should sleep-related rhythmic movements in children be assessed and treated? Rhythmic movement disorder (RMD) represents an unusual variety of childhood parasomnia characterized by repetitive motion of the head, trunk, or extremities, which usually occurs during the transition from wakefulness to sleep or arises during sustained sleep. Although the condition most often affects infants and toddlers in a transient and self-limited fashion, the condition occasionally persists in a problematic fashion, which may nevertheless be amenable to treatment. Since RMD may occasionally cause injury or resemble nocturnal seizure, prompt recognition, and appropriate management on the part of the clinician is essential. This article will examine the spectrum of RMD in children, including their common clinical manifestations; data regarding their epidemiology and natural history; the role of polysomnography, electroencephalography; and other diagnostic testing. Potential causes of the condition and available methods of treatment are also examined.

Managing the risks of repetitive transcranial stimulation.

Abstract: Repetitive transcranial magnetic stimulation (rTMS), defined as the administration of a series of magnetic stimuli to the brain for the purpose of altering brain function, is an experimental medical intervention. rTMS currently is used to probe various aspects of brain function in the context of research studies approved by local ethics committees. rTMS also is under investigation as a potential treatment for various neurologic and psychiatric disorders. In light of the growing interest in using rTMS in a variety of experimental and therapeutic settings, the International Society for Transcranial Stimulation has recognized the need to formulate a consensus statement to assist the field in developing guidelines for its safe application. Whether the intended use is experimental or therapeutic, certain principles regarding the safety of rTMS apply. This statement is not aimed at guiding the therapeutic use of rTMS in any given condition or its application in any research paradigm, but rather is meant to apply broadly wherever rTMS is used. rTMS has significant risks, most importantly that of producing epileptic seizures. The degree of risk varies with the dosing parameters and individual subject factors. Therefore, rTMS should be administered only under a licensed physician's orders (ie, by prescription or through some other mechanism that makes a physician directly responsible for its administration to the individual patient or research subject). Because rTMS has potential behavior-changing effects, undesirable side effects, and therapeutic impact, careful assessment of the risk and appropriateness of rTMS in each clinical or scientific context is critical and can only be made by, or in consultation with, a physician knowledgeable and experienced in the use of rTMS and fully trained in neurology, psychiatry, or another appropriate specialty.

Topiramate in the preventive treatment of episodic migraine: a combined analysis from pilot, double-blind, placebo-controlled trials.

Abstract: The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6-8 week titration, and 8-12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.

Restless legs syndrome and drug-induced akathisia in headache patients.

Abstract: The purpose of the research presented in this article was to characterize restless leg syndrome (RLS) in a headache population and correlate treatment induced risks with dopamine blockers. Fifty patients with severe headache who were admitted to an outpatient infusion center were enrolled. The diagnosis of RLS was established using the International Restless Leg Syndrome Study Group criteria. Patients were screened for baseline akathisia using an akathisia scale and reexamined for akathisia after receiving intravenous infusion with one of four dopamine receptor blocking agents as treatment for their headaches. A change from baseline to post-infusion assessment of two points on a global assessment of akathisia was considered positive for drug-induced akathisia. Our results indicated that 41 (82%) of patients had episodic or chronic migraine. The rest had new daily persistent headache, cluster, or posttraumatic headache. Seventeen subjects (34%) met the criteria for RLS. Nineteen (38%) of the subjects developed drug-induced akathisia. Thirteen (76.5%) of the subjects with RLS developed akathisia compared with only 6 of the 33 (18.2%) without RLS (P<.0001). Finally, we concluded that headache patients with RLS are at a greatly increased risk of developing drug-induced akathisia when treated with intravenous dopamine receptor blocking agents.

New developments in electroconvulsive therapy and magnetic seizure therapy.

Abstract: New findings regarding the mechanisms of action of electro-convulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures(eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cognitive functioning. Studies designed to address the antidepressant efficacy of MST are underway. As with all attempts to improve convulsive therapy technique, the clinical value of MST will need to be established through controlled clinical trials. This article reviews the experience to date with MST, and places this work in the broader context of other means of optimizing convulsive therapy in the treatment of depression.

Beyond the treatment of epilepsy: new applications of vagus nerve stimulation in psychiatry.

Abstract: Vagus nerve stimulation (VNS) in humans generally refers to stimulation of the left vagus nerve at the cervical level VNS is an established treatment largely devoid of severe side effect for medically refractory partial onset seizures and has been used in more than 16,000 patients. Over the past 5 years, applications in other neuropsychiatric disorders have been investigated with a special emphasis on depression. Recent data from an open-label, multi-center pilot study involving 60 patients suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. The perspective of VNS as along-term treatment with the advantage of assured compliance makes it an interesting technique to potentially treat drug-resistant depression. However, definite therapeutic effects of clinical significance remain to be confirmed in large placebo-controlled trial. Results of clinical pilot studies involving patients suffering from obesity and Alzheimer's disease indicate that VNS might induce weight loss and improve cognition. Besides its clinical usefulness, VNS can be used as a research tool, allowing neurophysiologic investigations of the parasympathetic system and its interactions with other parts of the central nervous system.

Relationship of personality to dissociation and childhood trauma in borderline personality disorder.

Abstract: Background Dissociation is a prominent feature in some individuals with borderline personality disorder (BPD), yet our understanding of the meanings and implications of prominent dissociation in BPD remains limited. The purpose of this study was to investigate the relationship between dissociation and childhood trauma in BPD and to explore the relationships of dissociation and trauma to various personality features of BPD. Methods Twenty BPD subjects and 24 healthy comparison subjects of similar age and gender were administered the Dissociative Experiences Scale, the Childhood Trauma Questionnaire-short form, the Tridimensional Personality Questionnaire, the Defense Style Questionnaire, the Relationship Style Questionnaire, and the Schema Questionnaire. Results The BPD group exhibited greater dissociation and childhood trauma, as well as greater pathology in most personality variables, compared with the healthy group. Dissociation in BPD was not significantly related to total childhood trauma, but only to emotional neglect, which accounted for 23% of the variance in dissociation scores. Conclusion Within the BPD group, dissociation was associated with fearful attachment and immature defenses, while total childhood trauma and emotional neglect were associated with overconnection and disconnection schemata. This is a preliminary study with a small sample size, yet the correlates of dissociation in BPD merit further investigation.

Does diabetes protect or provoke Alzheimer's disease? Insights into the pathobiology and future treatment of Alzheimer's disease.

Abstract: Diabetes mellitus has long been considered a risk factor for the development of vascular dementia. Epidemiologic evidence has suggested that diabetes mellitus significantly increases risk for the development of Alzheimer's disease, independent of vascular risk factors. As insulin's role as a neuromodulator in the brain has been described, its significance for AD has also emerged. Insulin dysregulation may contribute to AD pathology through several mechanisms including decreased cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased oxidative stress through the formation of advanced glycation end-products; increased Tau phosphorylation and neurofibrillary tangle formation; increased b-amyloid aggregation through inhibition of insulin-degrading enzyme. Future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation.

WCA recommendations for the long-term treatment of social phobia.

Abstract: What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in longterm treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

The effects of stressful life events, coping, and cortisol on HIV infection.

Abstract: What is the role of stress and coping in changes in immunologic and clinical indicators of human immunodeficiency virus disease progression? There is substantial evidence that stressful life events and passive coping strategies, such as denial, may have a detrimental effect on HIV disease progression. Given the harmful effects of stress and passive coping, the author reviews the limited research testing the efficacy of interventions, such as cognitive-behavioral therapies for HIV-infected persons. Finally, in trying to understand psychoimmune relationships in HIV, the evidence is examined for the mediating and direct effects of cortisol, a hormone associated with stress, on HIV disease progression. Delineating the role of psychosocial factors and cortisol on HIV disease progression may aid in the development of new interventions for this devastating disease.

Long-term efficacy of exposure and ritual prevention therapy and serotonergic medications for obsessive-compulsive disorder.

Abstract: What is the long-term outcome of patients with obsessive-compulsive disorder (OCD) who are treated with exposure and response (ritual) prevention (EX/RP) alone, serotonergic medications alone, or their combination? How is the long-term outcome of these patients affected by the discontinuation? Follow-up assessments were conducted with 62 patients treated for OCD an average of 17 months posttreatment (range: 6-43 months). Patients received one of three treatments: serotonergic medications (fluvoxamine or clomipramine), intensive behavior therapy involving EX/RP, or intensive EX/RP with concurrent antidepressant medication. At follow-up, no differences in OCD symptom severity were found among the three treatment groups. However, when current medication use was taken into consideration, differences among the three treatment groups emerged. Among patients who were medication-free at the time of follow-up assessment (n=37), those in the EX/RP-alone and EX/RP-with-medication groups had lower symptom severity ratings than those in the medication-only group on 4 out of 6 measures. There were no differences in OCD severity ratings among patients taking medications at follow-up (n=25). Although these findings are interpreted with caution due to the uncontrolled nature of the study, results suggested that long-term outcome may be superior following EX/RP than following serotonergic medications, after discontinuation. For patients who remain on medications, the treatment produced benefits equivalent to EX/RP.