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.

We are pleased to introduce this special issue of CNS Spectrums on neuropsychiatry and human immunodeficiency virus infection. The study of psychiatric manifestations of HIV has been at the forefront of research since the early 1980s. Although information has accumulated in the past 20 years, there is still a great deal to be learned. This issue includes four comprehensive reviews of the literature in the area of HIV research. The first two papers outline the prior research examining the prevalence and effects of psychiatric symptoms in HIV-positive (HIV+) individuals. The other papers summarize the research examining the effectiveness of pharmacologic and nonpharmacologic interventions in treating these psychiatric symptoms. All four articles consider the impact of these psychiatric symptoms (or their treatments) on both the psychological and physical health of HIV+ individuals. They also help delineate some of the underlying physiologic mechanisms involved in this process that perhaps may subsequently influence the course of HIV disease.

Jane Leserman, PhD, reviews and evaluates the literature on the impact of stressors, depression, and the use of specific adverse coping strategies on alterations in immune function and disease progression among HIV+ individuals. Leserman describes a number of findings generated from the Coping in Health and Illness Project and points out that there is substantial evidence that stressful life events, depressive symptoms, and passive coping strategies can lead to immune impairments during HIV disease. She discusses some of the underlying physiological mechanisms, particularly alterations in the hypothalamic-pituitary-adrenal axis, which might mediate the relationship between psychosocial factors, immune system functioning, and disease status. The author concludes that by further understanding the impact of stress, depression, adverse coping strategies, and alterations in hormonal systems on immune function, researchers will develop a greater account of how these important factors may influence HIV progression and survival.

It has been a pleasure to assemble this month's issue of CNS Spectrums about cognitive-behavioral therapy (CBT) for anxiety disorders in which the successful treatments of five disorders are discussed. As is evident from the five papers in this issue, most patients with pathologic anxiety can be helped with available treatment, either short-term CBT or medication. Also apparent in these papers is that the work has not been completed: some patients do not benefit from the available treatments at all, and most who do respond still remain somewhat symptomatic.

Are reproductive life events in women associated with an increased risk of sexual dysfunction? Female sexual dysfunction effects up to 40% of women in the United States between 18 and 59 years of age. Sexual dysfunction may be accompanied by fluctuations in gonadal hormone secretion, making women more vulnerable to sexual symptoms, especially during times of reproductive life events. Reproductive life events, such as the use of birth control pills, various phases of the menstrual cycles, postpartum and lactation states, and perimenopause, are highly correlated with changes in sex steroids. As an understanding of the role of sex steroids on sexual functioning is elucidated, clinicians will be able to offer more specific and effective treatment options for women during various phases of reproductive life. Several case studies are presented to illustrate the unique clinical considerations that a clinician must consider when treating the biologic component of female sexual dysfunction.

The decision to devote this issue of CNS Spectrums to sleep disorders was two-fold. First, sleep disorders are of relatively high prevalence in the population with a significant impact on public health and safety. Unfortunately, their significance has been underestimated. Hence, the training of subspecialists capable to deal competently with the diagnosis and treatment of these disorders that afflict all age groups has lagged behind the training of other subspecialists. Second, the presence of psychiatric symptoms in many individuals afflicted with these disorders and the bona fide psychiatric comorbidity of many such patients have been underestimated. Psychiatric comorbidity raises some compelling issues about the need that at least selected patients presenting with a sleep problem should undergo a thorough psychiatric evaluation along with a specialized evaluation, if deemed necessary.

Although the majority of patients with sleep disorder would benefit from an initial psychiatric evaluation, such a practice may not be available at all sleep centers. A psychiatric evaluation should first assess the nature and origin of psychiatric symptoms and determine the presence of a primary or secondary psychiatric disorder. Once a reliable diagnosis has been established, the proper course of treatment can be outlined. As with most other psychiatric conditions, a combined course of pharmacotherapy and psychotherapy has the best chance of restoring functionality and preventing relapses. Thus, the role the psychiatrist can play in optimizing the care of patients with a sleep disorder cannot be overemphasized.

Brain stimulation methods in the treatment of affective disorder are electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Clinically, ECT is considered the strongest remedy in the treatment of severe depression, especially depression with psychotic features, and in the elderly. TMS, despite positive reports, is somewhat more controversial. VNS has, so far, only been used in treatment-resistant depression with limited results. DBS may be of potential use in rare cases of treatment-resistant cases of affective disorder. This article highlights the similarities and differences between the four stimulation methods. The main difference is the seizures necessary in ECT. A stronger involvement of the hippocampus following experimental seizures compared with effects in that region induced by TMS and VNS might explain the consistent findings of the superiority of ECT in the most severe cases of affective disorder.

Obesity and diabetes continue to be national health epidemics. Greater than 50% of adults in the United States are overweight, and >17 million people have diabetes—one third of whom are not diagnosed. Diabetes ranks number 1 in direct health care costs of any disease category. Patients who suffer from schizophrenia may be at twice the risk of developing diabetes compared with the general population. Some new antipsychotic agents are among several types of medications that may potentially impair glucose metabolism. For example, studies have shown that people treated with clozapine and olanzapine have developed elevated fasting serum insulin levels, suggestive of insulin resistance. Insulin resistance may be a result of irregularities in the insulin action sequence and it may occur long before overt diabetes. The further study of the effects of medications on glucose metabolism and their mechanisms, therefore, is essential to developing better treatment regimens that minimize insulin resistance and avoid associated health risks such as obesity and diabetes.

Bipolar disorder is an etiologically complex syndrome that is dearly heritable. Multiple, genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the last few decades. However, specific causal genetic mutations for bipolar disorder have not been identified. Both candidate gene studies and complete genome screens have been conducted. They have provided compelling evidence for several potential bipolar disorder susceptibility loci in several regions of the genome. The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21. Other regions of interest, including those on chromosomes 5 and 8, are also under investigation. New approaches, such as the use of genetically isolated populations and the use of endophenotypes for bipolar disorder, hold promise for continued advancement in the search to identify specific bipolar disorder genes.

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.

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.

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.

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 α-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.

About one-third of patients affected by obsessive-compulsive disorder fail to respond to serotonergic drugs and different strategies have been proposed for these resistant cases. This article reports experiences with venlafaxine in patients with obsessive-compulsive disorder who did not respond or did not tolerate serotonergic drugs.

Depression and anxiety disorders are very common in the elderly. Data accumulated over the past 2 decades have shown that most older patients can tolerate and respond to acute treatment with serotonergic antidepressants, other psychotropic agents, or manual-based psychotherapy. However, outcomes under usual-care conditions remain poor. This review proposes that clinicians may significantly improve the long-term outcomes of their older patients with depression and anxiety by focusing on four key factors: (1) identification and treatment of comorbid conditions; (2) full remission of acute symptoms; (3) education of patients, families, and professional colleagues about the need for long-term treatment; and (4) prevention and management of medication side-effects.