Is human immunodeficiency virus still a terminal condition? Recent advances in treatment have significantly reduced both mortality and morbidity associated with HIV, but these treatments have not been successful in eradicating the virus itself. As such, HIV has evolved into a chronic condition that is complicated by neurocognitive factors. Cognitive difficulties associated with HIV are characterized by a subcortical pattern with primary deficits in information processing speed and psychomotor speed. These deficits interfere with the ability of patients to complete important instrumental activities of daily living even in the absence of dementia. Treatment of HIV improves neurocognitive functioning, but the regimens are complex and patient adherence is critical. Cognitive factors can negatively impact treatment adherence, which in turn results in poorer immunological, cognitive, and psychiatric outcome. This cycle emphasizes the important interrelationships between symptom expression and treatment outcome in patients with HIV. The nature of these relationships will change with further developments in treatment regimens such as once-daily dosing. Less complex treatment approaches should improve health outcome as well as provide additional opportunities to further understand the impact of HIV on brain function.

How did the 1995 Oklahoma City bombing differ from prior disasters and what implications did it have for disaster mental health services and service delivery? The federal disaster mental health approach in this country developed largely out of experiences with natural disasters. The 1995 Oklahoma City bombing differed in several important ways, including the large number of human casualties, higher rates of psychopathology, and an extended period of concern due to the criminal investigation and trials, which suggested the need to consider modifications in the program. Outreach was extensive, but psychiatric morbidity of direct victims was greater than that of victims of natural disasters, emphasizing the need for attention to the triage and referral process. Other concerns that warrant consideration include practices related to record keeping and program evaluation.

Neuropsychiatric practice provides for the interested practitioner a bewildering yet exciting array of symptoms and syndromes. Some are quite common, such as a psychosis is in epilepsy, but many are rare, and sometimes the rarer they are, the more startling and challenging they seem. Take the Moebius syndrome. This is an unusual condition in which there is a congenital palsy of some cranial nerves—most notably the 6th and 7th—usually with hypoplasia or agenesis of the respective nerve nuclei. For example, the patient I was asked to see, because of unremitting seizures, was a girl in her late teens, who had never had any facial expression. She could not smile or express laughter, she could not look angry, she could not contort her face to tears or grief. But did she feel emotions? Of course. She got angry like the rest of us, teared when sad, and was able laugh. The vocalizations of her affects were all present, she simply could not show emotions.

Not surprisingly, this had affected her social development, and inhibited her interactions with her peers. She was frustrated by this inhibition and, in the course of her adolescence, had developed depression and panic attacks, which had been mistakenly diagnosed as epilepsy. This is one variant of the pseudoseizure spectrum.

The purpose of this article is to review aspects of the neuropsychology of temporal lobe epilepsy. Evidence will be presented to demonstrate that the cognitive consequences of this focal seizure disorder can be more generalized in nature than expected. Consistent with the extratemporal neurocognitive findings, careful quantitative magnetic resonance imaging volumetrics have shown that structural brain changes may be detected outside the temporal lobes. Many factors can potentially affect cognition and brain structure. We focus on the potential neurodevelopmental impact of early-onset temporal lobe epilepsy on brain structure and cognition positing that this disorder can have both immediate and lifespan implications for cognition and psychosocial status.

How schizophrenia (SZ) is maintained at roughly 1% of the population despite diminished reproduction is one puzzle currently facing researchers. De novo mutations were first proposed over half a century ago as a source for new SZ genes. Current evidence linking advancing paternal age to SZ risk makes revisiting this hypothesis important. Advancing paternal age is the major source of new mutations in the human population. This article will examine potential mechanisms whereby parental age may impact new mutations, as well as review recent data supporting such a hypothesis.

This article will briefly review the history of diffusion physics and diffusion imaging beginning with Brown's initial observations of the diffusion phenomenon in the early part of the 19th century, through the development of diffusion-weighted imaging, and diffusion tensor imaging. The basic principles and limitations of diffusion tensor imaging are discussed. We conclude by reflecting on some of the open interpretative questions in diffusion imaging.

What is the best way to provide early interventions for psychiatric disorders after trauma? The terrorist attacks of September 11, 2001, have raised urgent concerns about the evidence for early treatments after trauma that can prevent psychiatric disorders. This review outlines the expected course of posttraumatic stress reactions and discusses the current means of identifying people who are at risk of developing disorders. A critique of psychological debriefing and an analysis of evidence for cognitive-behavioral therapy as an early intervention is provided. The major challenges for early intervention are discussed, including increasing treatment effectiveness, delivering therapy when it is required by thousands of people, and developing early interventions for a wide array of psychiatric disorders in addition to posttraumatic stress disorder that can develop following trauma.

Underdiagnosis and undertreatment of late-life depression is common, especially in primary care settings. To help assess whether physicians' attitude and confidence in diagnosing and managing depression serve as barriers to care, a total of 176 physicians employed in 18 primary care groups were administered surveys to assess attitudes towards diagnosis, treatment, and management of depression in elderly patients, (individuals over 65 years of age). Logistic regression was performed to assess the association of physician characteristics on attitudes. Nearly all of the physicians surveyed felt that depression in the elderly was a primary care problem, and 41% reported late-life depression as the most common problem seen in older patients. Physicians were confident in their ability to diagnose and manage depression, yet 45% had no medical education on depression in the previous three years. Physicians' confidence in their ability to diagnose, treat, and manage depression, and their reported adequacy of training, do not appear to correspond to the amount of continuing medical education in depression, suggesting that physician overconfidence may potentially be serving as a barrier to care.

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

Many commonly prescribed drugs exist as a mixture of two distinct chiral isomer forms (enantiomers), each with its own unique chemistry, receptor affinity, and pharmacokinetic profile. Much is unknown concerning the clinical utility of these single enantiomers. This review of the stereoisomers of two commonly used drugs—albuterol for asthma and omeprazole for gastroesophageal reflux disease (GERD) and peptic ulcers—examines the improved efficacy, pharmacokinetics, decreased adverse effects, and fewer drug-drug interactions associated with single enantiomers.

Herein, the background information reflecting roles of medical burden, cerebrovascular disease and risk factors, and cognitive impairment in geriatric depression are reviewed. The authors then propose a nonparametric statistical approach to the data analysis of multiple putative causal variables for late-life depression, the Classification and Regression Tree Analysis. This analysis presents a useful approach to modeling nonlinear relationships and interactions among variables measuring physical and mental health, as well as magnetic resonance imaging and cognitive measures in depressed elderly. This method uncovers the existing interactions among multiple predictor variables, and provide thresholds for each variable, at which its predictive power becomes statistically significant. It presents a “hierarchy” of the predictors in a form of a decision tree by finding the best combination of predictors of an outcome.

The authors present two models based on demographic variables, measures of vascular and nonvascular medical burden, neuroimaging indices, the Mini-Mental State Examination score, and neuropsychological test scores of 81 elderly depressed subjects.

Cognitive tests of verbal fluency and executive function are identified as the best predictors of depression, followed by the frontal lobe volume and Mini-Mental State Examination. The authors observed that an interaction between frontal lobe volume, total lesion volume, and medical burden was predictive of depression.

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.

It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder which effects an estimated 3% to 5% of children. Despite estimates that ADHD persists in 30% to 70% of adults having had the disorder in childhood, ADHD in adulthood remains controversial. This report summarizes current thinking in the diagnosis and etiology of adult ADHD. Most theories posit that ADHD is related to anomalies in frontal lobe function and dopaminergic transmission. However, there is debate as to whether ADHD is a unitary disorder with different manifestations, a syndrome, or multiple disorders. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classifies ADHD into inattention, hyperactivity-impulsivity, and combined subtypes. Although problems with cognition are core ADHD symptoms, self reporting has not been a reliable predictor of neuropsychological test performance. Nevertheless, we suggest that a performance-based diagnosis, including empirically derived, age-sensitive neuropsychological tests, provides the best hope of dissociating ADHD from psychiatric disorders with similar symptoms. We also describe the promise of new neuroimaging technologies, such as functional magnetic resonance imaging, in elucidating the pathophysiology of ADHD and similar psychiatric disorders.

Depression is one of the most prevalent disorders in the general population, causing personal and social disability and impairment. Major studies assessing the diagnosis and management of depression have shown that it is often underdiagnosed and undertreated. A pan-European study aimed at assessing the extent and consequences of depression in six different countries is reported in this article. Different types of depressive profiles are analyzed and their respective management has been compared. The importance of improving diagnosis and treatment of depression is underlined. Appropriate management of depression depends on the recognition of depressive symptoms by patients, their possibility of seeking care, and the ability of the primary care physician to recognize the disorder and prescribe the appropriate medicines. Improvement in all of these fields is necessary.

Provision of care to an older adult with dementia is an important societal resource. This resource may also come at a high cost to informal caregivers, most of whom are family members. In this paper we provide an overview of recent research on dementia caregiving and caregiver interventions. First, we provide background information on the prevalence and costs of Alzheimer's disease and related disorders. Second, we describe the specific stressors and broader mental and physical health outcomes of dementia caregiving. Third, recent evidence of the efficacy of caregiver interventions for both caregiver and patient outcomes is reviewed. Throughout the paper, we describe promising new directions for future research in this area, including assessment and intervention with family caregivers of older patients with comorbid dementia and depression, and the focus on sleep disturbance as a critical health consequence of dementia caregiving.

There is limited systematic data assessing alternate pharmacotherapy of social anxiety disorder in patients failing to tolerate or fully respond to initial treatment; no data specifically address the efficacy of citalopram in this scenario. We present a prospective open-label trial of citalopram in 10 patients with generalized social anxiety disorder, 6 of 10 of whom had not responded to or not tolerated a prior treatment intervention for the disorder. Citalopram, at a mean dose of 55 mg (SD+12.7 mg) was well tolerated, and patients improved significantly on all outcome measures. Results of this study suggest that citalopram may be a safe and effective treatment for generalized social anxiety disorder, including patients who have failed to tolerate or respond to a prior treatment trial.