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.

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 γ-arninobutyric 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.

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.

What should clinicians know about sleep disorders? This article briefly introduces the reader to sleep medicine and succinctly reviews common sleep disorders. First, the authors describe the diagnostic tools unique to sleep medicine: the over-night polysomnogram and the multiple sleep latency test. Next, the authors review essential features of a subset of the sleep, described in the International Classification of Sleep Disorders-Revised, that sleep disorder specialists commonly evaluate, diagnose, and treat. The disorders reviewed include the intrinsic and circadian rhythm subsets of the dyssomnias group and the parasomnia group of sleep disorders. The authors identify the core signs and symptoms, polysomnogram findings, multiple sleep latency test findings, and treatment of these disorders.

This article reviews the impact of depressive and anxiety disorders on quality of life (QOL), disability, and economic burden in the lives of older individuals. Distinctions between the terms QOL, disability, and burden are important in understanding the extent of improvement needed in treatment for elderly patients with depression or anxiety. Treatment efforts should be extended to remediate not only signs and symptoms of psychiatric syndromes but QOL and disability as well; increased understanding toward this end is evolving, yet it is clear that these issues need to be the focus of more investigation.

Mood stabilizers have evolved considerably over the past decade. Lithium, divalproex, and olanzapine are currently Food and Drug Administration-approved for the treatment of acute mania. A number of new and traditional medications have also been tested and are commonly used in clinical practice. Several strategies for managing treatment-resistant mania have been suggested, but few have been rigorously tested. Emphases on rapid stabilization and fewer side effects have raised the bar for what is expected from mood stabilizers and the successful treatment of mania involves a delicate balance between swiftness, short-term tolerability, and long-term safety.

This article provides an overview of cognitive-behavioral therapy (CBT) for panic disorder. CBT is currently considered a first-line treatment for panic disorder. It offers benefit after short-term intervention, typically consisting of 12–15 sessions conducted in either an individual or a group format. The treatment focuses on the elimination of the patterns that underlie and perpetuate the disorder. Through CBT, patients learn about the nature of the disorder and acquire a set of strategies that counter the fears of panic attacks themselves, and break the recurring cycle of anticipatory anxiety, panic, and agoraphobic avoidance. The collaborative format of treatment, and a focus on elimination of core fears may be factors in enhancing longer-term outcome. In this article, we review the efficacy of CBT as a first-line treatment, a strategy for medication nonresponders, a replacement strategy for patients who wish to discontinue pharmacotherapy, and a potential preventive strategy for at-risk individuals. We also discuss some of the complex issues involved with combination-treatment strategies.

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.

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 β-amyloid aggregation through inhibition of insulin-degrading enzyme. Future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation.

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

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 healtcare 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 perform 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.

Sexual dysfunction related to antidepressants, particularly serotonin reuptake inhibitors is a major cause of premature treatment discontinuation. This places patients at increased risk for recurrence, relapse, chronicity, and mortality (eg, suicide). The clinical assessment requires a comprehensive evaluation of sexual function, including libido, arousal, orgasm, and resolution prior to affective disorder, disturbances associated with the emergence of depression, and changes or dysfunctions associated with antidepressant treatment. Other factors to be included for evaluating sexual dysfunction include inquiry for concurrent medical conditions, somatic treatments, lifestyle risk factors, and response to antidepressants. Current treatment approaches to antidepressant-associated sexual dysfunction have relied on open-label reports, literature reviews, and clinical wisdom. Without double-blind, placebo-controlled studies to support them, too much non-evidence-based treatment may be offered to patients. Advances into nonadrenergic-noncholinergic novel signal transduction, specifically phosphodiesterase type-5 inhibitors, offer new opportunities for developing evidence-based treatments for this side effect and improving depression disease management outcomes.

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.

What drives the human sexual response cycle? The human sexual response cycle is a highly complex phenomenon that encompasses many transmitters and transmitter systems centrally and peripherally. The endocrine system is also intricately involved in the brain and in the periphery organs. Integration of these systems is a function of the nervous system that ultimately produces a vast array of cognitive, emotional, physiological, and behavioral responses. Therefore, it is not surprising that a disturbance in even a single system will lead to dysfunction in one or more phases of the sexual response cycle. This article highlights the complex roles the aminergic system plays along with key hormones that are equally involved. The article also points out how rudimentary and fragmented our knowledge is in this field and how few controlled studies are available. The potential for development of specific agents that target selective sexual dysfunctions is exemplified in sildenafil, the first such agent ever to be brought to market.

Patient nonadherence to pharmacologic and psychosocial treatments for geriatric depression and anxiety poses a serious barrier to effective clinical care. Rates of nonadherence may be as high as 60% in older adults. Factors associated with nonadherence include lack of information and misperceptions about mental illness and its treatment, stigma, lack of family support, cognitive impairment, adverse events, side effects, cost of treatments, poor physician-patient communication or relationship, and other barriers, such as lack of transportation. Effective interventions to improve adherence are personalized and include both behavioral and educational components. Several current projects that combine pharmacotherapy and psychotherapy for geriatric depression in an integrated care model show promise as interventions to improve rates of treatment and adherence.

The clinical use of mood stabilizers and antipsychotics in children and adolescents with bipolar disorders has increased significantly over the past few years. These agents have multiple effects and interactions. This articles reviews the studies that support the use of mood stabilizers and atypical antipsychotics in children and adolescents with bipolar disorders and presents information on these agent's pharmacokinetics, dosing, and drug interactions.