Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.

The present study investigated the effect of age of second-language acquisition (Hebrew) on verbal fluency in a random sample of 196 elderly Israelis from four distinct ethnic groups. Using conventional statistics, it was shown that phonemic fluency, particularly switching, is associated with education and the age of Hebrew acquisition, while semantic fluency, particularly clustering, is associated with age. Ethnic differences were not significant after controlling for the age of Hebrew acquisition and education. Additional analyses show that the tendency of subjects to use borrowed, non-Hebrew words on the phonemic fluency task was associated with lower total scores on this task and later age of Hebrew acquisition. In contrast, the tendency to use non-Hebrew words on the semantic fluency task was associated with age and higher total scores. These findings are discussed with regard to recent functional imaging studies of bilingual subjects. Such findings indicate that native and second languages form distinct areas of activation in the dominant anterior language area, an area often associated with phonemic processing and switching, whereas an overlap of activation of various languages has been demonstrated within the posterior language areas, those that are often associated with semantic processing.

Behçet's disease is a chronic relapsing-remitting, multi-system inflammatory disorder of unknown etiology, characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. The most common central nervous system findings are demyelization and perivascular cell infiltration; menin-goencephalitis, cerebral atrophy, and vascular thrombosis may also occur. Neuropsychiatric symptoms may include: paroxysmal dystonia, parkinsonism, delirium, hallucinations, and behavioral disturbances. We report an unusual case of explosive onset of motor and vocal tics with obsessive-compulsive symptoms in a 22-year-old male with Behçet's disease. The putative roles of infection and autoimmune mechanisms in the pathogenesis of tics and obsessive-compulsive symptoms are explored.

The raw diffusion tensor imaging data obtained after tensor calculations contain six tensor elements in each pixel. This unique data structure poses difficulties in visualizing and analyzing diffusion tensor imaging data. One of the most commonly used visualization techniques is the use of color-coded maps. This presents fiber orientation information as a mixture of three principal colors. These maps can reveal white matter substructures that may not be visible in conventional magnetic resonance imaging. By extending the fiber-orientation information into three-dimensional space, three-dimensional trajectories of white matter tracts can then be estimated. Once locations and trajectories of tracts of interest are identified, this technique allows for the utilization of tract-specific magnetic resonance analyses and/or macroscopic characterization of white matter anatomy. As an example, anatomical deformation of the white matter resultant of brain tumor is demonstrated. The potentials and limitations of the three-dimensional tract reconstruction techniques are also highlighted.

Basic and clinical studies over the past 10 years have lead to a fundamental shift in our understanding of mood disorders. These studies demonstrate that mood disorders and stress are accompanied by structural alterations in the brain; moreover, these structural alterations are reversible with antidepressant treatment. These alterations include changes in the length and number of neuronal processes, the number of neurons and glia, and even the rate of neurogenesis in the adult brain. Work is also being conducted to identify the molecular mechanisms underlying these changes and the adaptations that are critical to the therapeutic actions of antidepressant treatment. Some of the intracellular targets include second messengers, gene transcription factors, and neurotrophic factors that could oppose the actions of stress and depression. Taken together, this exciting new work describes and details structural alterations of limbic brain regions that are extremely dynamic and adaptive. Further understanding of the abnormalities in these systems that lead to mood disorders will provide more efficacious and possibly faster-acting therapeutic interventions.

This article reports on the planning, development, and implementation of a large national Internet-based panel study of how Americans are coping with the terrorist attacks of September 11, 2001. The study was designed to determine predictors and correlates of risk and resilience, both cross-sectionally and longitudinally. In order to acquire timely and meaningful data, we developed/adapted an extensive set of measures, obtained human subjects approval, and posted a research Web site just 17 days after the attacks. This article describes the major hurdles we confronted and the guidelines we recommend regarding these topics, including the methodological trade-offs inherent in Internet-based research, information technology requirements and tribulations, human subjects issues, selection of measures and securing permission for their use, and the challenges of participant recruitment. We also discuss issues that we did not anticipate, including the survey intervention. We focus not on findings, but on the concrete procedural, administrative, technical, and scientific challenges we encountered and the solutions we devised under considerable time and resource pressures.

How can functional neuroimaging be applied to clinical neurology and psychiatry? This article reviews selected contributions of functional neuroimaging to the clinical neurosciences. We review selected technical aspects of positron emission tomography, single photon emission tomography, and functional magnetic resonance imaging with a focus on the relative strengths and weaknesses of these techniques. Consumers of functional neuroimaging research are encouraged to consider the limitations of imaging techniques and theoretical pitfalls of cognitive task design when interpreting results of functional imaging studies. Then, we selectively review the contributions of functional neuroimaging to neurology and psychiatry, including the areas of epilepsy, stroke, chronic pain, schizophrenia, depression, and obsessive-compulsive disorder. Future directions of functional neuroimaging research are offered, with the emphasis that the best conclusions are informed by a convergence of research from functional neuroimaging, neurophysiological, and lesion studies.

Many factors influence the development of body image, one of which is the perception we have of our body. Perception can refer to actual visual input or the interpretation of vision; in other words, cognitive appraisal. The goal of this preliminary study is to determine if three groups (body dysmorphic disorder, obsessive-compulsive disorder, and a non-psychiatric control group) differed in the perception of their faces. Thirty individuals, 10 in each group, were asked to make changes to a computerized image of their face. In addition, affective and perceptual tests were administered. The groups did not differ on affective and perceptual organizational measures, although the obsessive-compulsive disorder group reported a higher level of anxiety than the body dysmorphic disorder group. Imaging software showed that facial features were modified by patients with body dysmorphic disorder and obsessive-compulsive disorder in about 50% of cases. No modifications were made in the control group. Future studies need to investigate the possible causes of these differences.

Psychiatric genetics, while promising to unravel the mechanisms of psychiatric disorders, has proven to be a challenging field. Psychiatric disorders, like other common genetic traits, are complex and heterogeneous. Psychiatric genetics has also suffered from a lack of quantifiable, biology-based phenotypes. However, the field is currently at an opportune moment. The work of various investigators is on the verge of paying rich dividends. Efforts at positional cloning are being greatly accelerated by the fruits of the Human Genome Project. New tools of functional genomics, such as expression profiling and proteomics, are being applied to animal models. These two methods can complement each other in an approach we have termed convergent functional genomics. Lastly, improvements in the measurement of biologically distinct endophenotypes—or phenomics—will lead to a better understanding of the mapping of genes to phenotypes in both animal and human systems.

Background: Citalopram is a racemic selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of depression. Citalopram is a racemate and its serotonin reuptake inhibitory activity resides primarily in the single S-isomer, escitalopram, which is now being evaluated for its potential usefulness in the treatment of depression and other psychiatric disorders. Results from placebo-controlled studies that also included Citalopram as an active control have shown that escitalopram is effective in treating depression and associated symptoms of anxiety. However, none of these studies was powered sufficiently to detect differences between active treatment groups. The goal of the present analysis is to evaluate the efficacy of escitalopram compared with Citalopram in the treatment of major depressive disorder.

Method: Data were pooled from three similarly designed, randomized, double-blind, placebo-controlled trials of escitalopram (10–20 mg/day) and Citalopram (20–40 mg/day). Patients were male or female, ≥18 years of age, who met criteria for a major depressive episode with a Montgomery Asberg Depression Rating Scale (MADRS) score ≥22 at baseline. Efficacy measures included change from baseline in MADRS score and the Clinical Global Impression of Improvement (CGI-I) scale. Improvement in associated symptoms of anxiety was measured using the change from baseline in the MADRS inner tension item.

Results: Both escitalopram and Citalopram significantly improved depression and anxiety symptoms compared with placebo, and there were significantly more MADRS responders (defined as ≥50% improvement in MADRS scores at end point) in the escitalopram and Citalopram treatment groups. Escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment, whereas Citalopram treatment statistically separated from placebo at the end of week 4 (CGI-I and MADRS inner tension) or week 6 (MADRS). Escitalopram treatment also was statistically significantly superior to Citalopram treatment at a number of time points.

Conclusion: These data support the effectiveness of escitalopram and Citalopram in the treatment of major depressive disorder, and suggest escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder.

The treatment of major depression remains problematic for several reasons. In particular, the therapeutic response to medications usually does not manifest itself until a week after administration has begun, and more than half the patients will not experience a full recovery with the first antidepressant drug administration. There are, however, some pharmacologic strategies that can accelerate antidepressant response. When facing a treatment-resistant depression, combination therapy offers a more time-efficient approach to achieve remission than drug substitution. These interventions have been devised on a better understanding of the basis for the therapeutic response obtained with the first- and second-generation antidepressants, and evidence derived from controlled clinical trials of their superior effectiveness is growing. The rationale for such approaches will be described in this article, as well as their advantages and potential inconveniences. Ongoing research in this field continues to fuel the development of novel, better-tolerated, and more effective pharmacotherapies for depression.

In 1992, the Food and Drug Administration (FDA) issued new guidelines governing stereoisomerism in new-drug development. The guidelines strongly encourage the development of single isomers and discourage stereoisomeric (eg, racemic) mixtures. As a result, most new chiral drugs are being developed as single enantiomers (ie, single isomers). There are three mechanisms for the identification and development of new single-isomer drugs: chiral switches (CS), chiral metashifts (CM), and new single-isomer chemical entities (NSICEs). In a CS, one of the two enantiomers of an established racemate is developed as a new drug, with the expectation that the single-isomer form has advantages over the racemic parent in terms of efficacy and/or adverse effects. Many new CS drugs are in development, eg, (S)-oxybutynin for urinary incontinence and escitalopram for depression. In a CM, a chiral metabolite of a drug is developed, in single-isomer form, as an agent with advantages over the parent. Among the current CM drugs in development are (+)-norcisapride (safer GI prokinetic agent than the racemic parent cisapride) and (S)-desmethylzopiclone (antianxiety agent, metabolite of the sedative-hypnotic zopi-clone). Many NSICEs are in development, eg, rosuvastatin as an antihypercholesterolemic, posaconazole as an antifungal, sitafloxacin as a fluoroquinolone antibacterial, pregabalin as an anticonvulsant, abarelix as an antineoplastic, etc. As in the development of any new drug, not every single-isomer candidate will reach the clinic, but there is no doubt that the move to single-isomer agents is an important step forward in the search for better and safer drugs.

This chart review examined the effects of effort on neuropsychological assessment and test performance patterns among genuine and exaggerating patients, with and without neurological findings, as aids to diagnosing symptom exaggeration. The sample consisted of 561 consecutive patients involved in compensation claims. With a flexible neuropsychological test (NPT) battery, the claims were assessed over 2 days. The sample included 303 patients evaluated for traumatic brain injury, 55 patients with neurological disease, and 203 patients assessed for other conditions (eg, depression or chronic pain). An average of 38 ability measures per patient were used to generate an overall NPT domain score. Composite scores were also computed for symptom validity tests, self-report measures of psychiatric symptoms, and memory complaint inventory. Seven NPT cognitive subdomain scores were multiply regressed onto the symptom validity test composite, accounting for 45% of its total variance. Patients were also assigned to Genuine or Exaggerator groups based on symptom validity test performance. The NPT for Exaggerating patients averaged 1.43 standard deviations below that of Genuine patients, suggesting that NPT scores for most Exaggerating patients are underestimates of their true ability. Factor analysis results differed between these groups. As a result, clinicians might avoid falsely identifying genuine patients as exaggerating by incorporating their self-reports of psychiatric symptoms and memory complaints into the diagnostic process.

We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a test of logical reasoning and “cognitive gating,” defined as the ability to discriminate between relevant and irrelevant information in confirming or disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task tests both processes under neutral and affect-laden conditions. This is done by presenting formally identical constructs using benign and emotionally arousing language. When separated by symptom profiles, we found statistically significant differences for performance and arousal response between patients with delusions, patients with formal thought disorder, and patients with neither delusions nor formal thought disorder, as well as between patients and healthy controls. When analyzed by error type, we found that nearly all errors by delusional patients were caused by overly restrictive information choice, a pattern that may be related to a delusional patient's tendency to “jump to conclusions” on Bayesian probabilistic tasks. This is in contrast to patients with formal thought disorder, whose low performance resulted also from overly extensive information choice. The tendencies towards restriction were exacerbated by arousal, which is consistent with studies on cognition and arousal in healthy individuals. After briefly examining research on emotional arousal and SZ, and the interaction between emotional arousal and restriction of perceptual cues in healthy individuals, we conclude by suggesting a model which accounts for the distinctive cognitive characteristics of delusional patients by their possessing distinct vulnerabilities to emotional arousal. Specifically, these results suggest the possibility that delusional patients process information in a manner that is essentially intact. However, delusional patients may possess an acute vulnerability to emotional arousal that might cause delusional individuals to behave cognitively as if they were healthy individuals under significantly more severe forms of stress.

Medical students from New York City were integrally involved in the response by health professionals to aid the families of victims of the September 11, 2001, attacks on the World Trade Center. The present study was performed to investigate the emotional impact of this involvement on medical students from the Mount Sinai School of Medicine in New York City. One hundred fifty-seven students responded to a mail survey that explored their personal and professional involvement in the disaster as well as their psychiatric symptoms in the week after the event and at the time of the survey (3.5 months after the event). Findings suggested a differential emotional impact on female students and on students involved in less supervised and more emotionally intense activities. However, involvement in the relief effort, per se, did not contribute to psychiatric symptomatology. It may have been associated with enhanced professional self-esteem among the students. These findings have implications for future planning of psychiatric response to disasters.

Research on effective pharmacotherapy for body dysmorphic disorder (BDD) has rapidly increased in recent years, with emerging data consistently indicating that serotonin reuptake inhibitors (SRIs) are often efficacious for this disorder. Although data are limited, it appears that higher SRI doses and longer treatment trials than those used for many other psychiatric disorders are often needed to treat BDD effectively. Approaches to treatment-resistant BDD have received little investigation, but available data indicate that switching to another SRI and several SRI-augmentation strategies may be helpful. This article reviews the empirical literature on BDD and offers a recommended approach to the pharmacotherapy of this distressing and often disabling disorder.

Neuropsychological (NP) testing is now recognized as an important method for evaluating treatment effects. However, there are limitations to how these tests are currently used in most drug treatment protocols. Changes in cognition are typically defined in statistical terms, with little knowledge as to whether the observed differences are meaningful in any other sense. Methods for assessing changes in test scores need to account for test-retest reliability, practice effects, regression to the mean, and the impact of initial performance. All of these factors may vary according to the individual characteristics of the subject. This article reviews two methods from the NP literature that have attempted to account for these sources of test-retest bias. The reliable change index provides a confidence interval for predicted change by taking into account the test-retest reliability of the measure. Standardized regression-based measures use a more sophisticated statistical approach that enables them to better account for other potential sources of confound. Use of this methodology has been limited to studies of epilepsy surgery and sports-related concussion. These methods have the potential for enhancing the interpretation of NP test data in drug treatment protocols by providing an empirically based definition of clinically meaningful change.

Do antidepressants have an equivalent risk-benefit ratio? Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is an effective antidepressant for treating major depression. The results of some clinical studies have suggested that venlafaxine may have more potent efficacy in sustaining remission in patients with major depression. Comparative clinical studies, however, lack suitable power to discern treatment differences in safety and also lack a quantitative basis for comparing risk and benefit. A global benefit-risk analysis of pooled data from eight randomized, double-blind, clinical trials of the safety and efficacy of venlafaxine and selective serotonin reuptake inhibitors (SSRIs) was performed. By using the ratio measure of risk-benefit, patients treated with venlafaxine (n=851) for 6–8 weeks experienced a relative gain of 1.57 compared with SSRI-treated patients (n=743) and a relative gain of 2.27 compared with placebo-treated patients (n=439). Subgroup analyses showed a relative gain of 1.35 for venlafaxine-treated patients (n=538) compared with fluoxetine-treated patients (n=549) and a relative gain of 2.53 compared with placebo-treated patients (n=357). A dose-response relationship was apparent between low (<75 mg/day), medium (75–150 mg/day), and high (>150 mg/day) dosages of venlafaxine; r values were 0.758, 0.822, and 1.181, respectively (P=.023, high dosage versus placebo; P=.030, medium dosage versus placebo). Important differences in risk and benefit exist between venlafaxine and SSRIs as a group compared with fluoxetine alone. A significant gain in benefit-risk in the treatment of major depression was observed with an increase in venlafaxine dosage from 75–>150 mg/day.