The end of 2001 is unlike any year's end in most of our memories. On September 10, my most serious worry was the chances for my beloved New York Yankees to win their fourth consecutive pennant. The next day, and ever since, that has hardly been a blip on the radar screen of concern. For those of us interested in studying the nervous system, we must remember that the most enduring fallout of the September 11 tragedy is emotional—our population is now a frightened one. Never before has the study of the neuro-science of emotion seemed more important. In subsequent issues, we will have much more to say on this topic.

For physicians and neuroscientists alike, we must also focus on the clinical and research issues that existed before September 11 and will continue to be our responsibility. This issue of CNS Spectrums offers articles on a diversity of topics: epilepsy, genetics, and the treatment of schizophrenia.

Adult attention-deficit/hyperactivity disorder (ADHD) and the spectrum of depressive disorders have high overlapping prevalence rates. Rates of depression in adults with ADHD and rates of ADHD in depressed adults provide an important epidemiologic background for clinicians treating either or both of these populations. There is a distinctive phenomenology of ADHD and depression, and distinctive diagnostic issues that present with the coexistence of these two disorders.

The study of the psychobiological bases of boredom has been limited by the vagueness of its clinical constructs and the difficulties in applying adequate experimental models. The theoretical background of previous research mainly has been based upon cognitive and behavioral psychology by using neuropsychological constructs, such as arousal, attention, motivation, sensation-seeking, and the reward system. Recently acquired data depict a complex and fragmentary picture. In this article, the author presents a review of the literature as well as some personal considerations on this intriguing topic.

Alzheimer's disease (AD) is a debilitating condition affecting millions of elderly citizens. The quality of life for AD patients significantly deteriorates in the face of worsening cognitive deficits and disabling functional declines, both contributing to manifestations of difficult behaviors. Of the estimated 4 million individuals with AD, only 60% of probable AD cases are diagnosed, with little more than half of those receiving treatment. One of the possible reasons for this problem is the large role primary care physicians (PCPs) have in diagnosing and treating AD. The barriers that PCPs confront to adequately manage these patients will be discussed. Finally, the specific challenges that geriatric psychiatrists will face in addressing these issues in an environment where there is only a limited number of trained geriatric psychiatrists will be discussed, as well as the possible role that new technology could have in finding the solution to this difficult problem.

A 48-year-old woman suffering from treatment-resistant psychogenic stiff neck and severe depression had been treated with a varied regimen of medications, including antidepressants, neuroleptics, and antiepileptics. These treatments did not result in improvement. Therefore, she was treated with a combination of sertraline and risperidone. Depressive symptoms decreased within a few weeks of treatment initiation. The psychogenic stiff neck, which had begun to improve within the first 2 weeks, had disappeared completely after 6 months of treatment with risperidone alone. This case report suggests that risperidone may be effective in some neurological motor disorders comorbid with mood disorders.

Central nervous system (CNS) vasculitis is a rare entity, especially when it occurs in isolation; it is seen more commonly as part of a multisystem vasculitis. Common presenting symptoms include persistent headache, encephalopathy, and multifocal signs. We discuss the case of a 68-year-old female who presented twice in 1 month with confusion and choreaform movements. Extensive workup was negative for a connective tissue disease or other conditions in the differential, including neurosarcoidosis, Creutzfeldt-Jakob disease, and neurosyphilis. The only significant findings were elevated erythrocyte sedimentation rate, inflammatory signs in the CNS, and diffuse slowing of the electroencephalogram. A presumptive diagnosis of isolated angiitis of the central nervous system (IACNS) was made and the patient was successfully treated with steroids. She recovered fully with no residual symptoms. The diagnosis of IACNS is often difficult given there are no definitive laboratory investigations or pathognomonic presentation. However, a series of signs, symptoms, and laboratory findings have been proposed that are helpful in making the diagnosis. To our knowledge, IACNS presenting primarily with delirium has not been previously reported in the literature. The diagnosis of IACNS is purely speculative for this case, as the gold standard for diagnosis, a leptomeningeal cortical biopsy, was not performed.

This issue of CNS Spectrums contains a unique collection of manuscripts that examine compulsivity and impulsivity from a broad range of perspectives and helps to shape our evolving understanding of compulsivity and impulsivity as orthogonal symptom dimensions arising from parallel tightly regulated brain circuits giving rise to a spectrum of overlapping diagnostic categories.

Depression and anxiety are among the top 10 health problems for which complementary and alternative therapies (CATs) are most frequently used, and medicinal herbs are among the most popular of these treatments. St. Johns wort(Hypericum perforaturn) is a perennial herb that has become a widely used depression therapy. Extracts of hypericum have shown affinity for receptors within multiple neurochemical systems. The primary active substance responsible for the antidepressant effect is not well defined, but most work has concentrated specifically on the hypericin and hyperforin components. Although hypericum has demonstrated significant antidepressant and antianxiety effects in multiple studies, there are several recent studies that do not support the previous evidence. In all reported studies, hypericum extracts have been well tolerated. In addition, new psychiatric uses for hypericum in obsessive-compulsive disorder, generalized anxiety disorder, menopausal symptoms, and alcohol dependence have been reported. Because patients are choosing to pursue CAT as a first-line therapy, psychiatrists will need to have a better understanding of phytomedicines used for treating depression and anxiety, and thus be better prepared to serve as effective allies of their patients.

Mr. F is a 60-year-old Caucasian, married, unemployed male who presented to the outpatient department of the Veterans Administration (VA) ∼10 months ago with a chief complaint of sleep difficulties. Approximately 12 years ago he had been diagnosed with posttraumatic stress disorder (PTSD) and a major depressive episode (MDE). He received very little treatment, either medication or therapy, at that time. He presented after being followed in a Veteran's Center for weekly to biweekly supportive therapy with a counselor for ∼6 months. He had gone to the Veteran's Center due to the encouragement of his wife. She had noted that he was becoming increasingly irritable and isolative at home and she had asked him to seek help for his anger and irritability. An event occurred in which he broke a chair after watching war-related news coverage and that made her insist that he present for treatment.

There has been growing evidence in recent years of the importance of gender specific issues in the addiction field. This paper explores specific problems and including specific health consequences faced by women who drink or use drugs. We describe helpful screening tools that can be used in the primary care setting and offer an understanding of some of the barriers preventing women from seeking help. This article also provides guidance on the best pharmacotherapy and psychological interventions that can be used to help women recover from their addiction.

The neurobiology of trichotillomania (TTM) has only recently received attention from the neuropsychiatrie community, and the number of studies in this area is limited. Nevertheless, there is tentative support for the hypothesis that serotonergic, dopaminergic, and opioid systems mediate hair-pulling symptoms, and that corticostriatal circuits also play a role. An understanding of the neurobiology of TTM may be of value not only for the treatment of this disorder, but also for other stereotypic behaviors.

The notion that subtle cognitive, emotional, behavioral, and functional deviations from norms are present in many individuals several years before a formal diagnosis of schizophrenia has been around for almost a century. This notion has been at the base of the developmental hypothesis of schizophrenia and has been the impetus for the use of cognition as an endophenotype for studying the illness. The recent enthusiasm for prodromal research derives from two unrelated and controversial claims: that short duration of untreated psychosis is associated with better prognosis and that novel antipsychotic drugs have a better safety profile, supposedly enabling early intervention at a relatively lower risk of side effects to the patient.

At the current level of knowledge, the risk-benefit assessment of prodromal interventions turns out to be an almost unsolvable conundrum. On one hand, the age of onset of psychosis and schizophrenia, early and mid-ado-lescence, coincides with the age at which life-long social and vocational characteristics are shaped. Any intervention that could produce even minimal delay in onset of active psychosis or ameliorate its early course might have a life-long impact. Therefore, the idea of prodromal intervention cannot be easily dismissed. On the other hand, in absence of accurate markers for imminent psychosis and strong data indicating that treatment during the prodromal phase is effective, exposing adolescents to the stigma associated with the illness and the adverse effects of antipsychotics has raised serious hesitations among many researchers and clinicians.

Two symptom clusters within the obsessive-compulsive (OC) spectrum—the impulsive cluster and the schizo-obsessive cluster—are discussed in this paper. Disorders characterized by impulsivity include disorders of impulse control (eg, intermittent explosive disorder, pyromania, kleptomania, pathologic gambling, trichotillomania); paraphilias, sexual impulsions, and sexual addictions; and impulsive aggression personality disorders (eg, borderline, antisocial, histrionic, and narcissistic personality disorders). The schizo-obsessive cluster includes comorbid symptoms of obsessive-compulsive disorder (OCD) and schizophrenia. Both clusters of disorders have a substantial impact on individuals and society. This article examines the overlap of symptoms between OCD and OC spectrum disorders, along with possible treatment options. Studies on the effectiveness of serotonin reuptake inhibitors in treating pathologic gambling, compulsive buying, and comorbid OCD and schizophrenia are presented. The need for additional large scale, adequately-controlled studies is discussed.

In this article we discuss the procedures that should be followed in order to develop diagnostic tests based on electro-physiologic parameters that would be useful to practicing psychiatrists in their efforts to diagnose mental disorders. To do this, we start by giving an overview of receiver operating characteristic (ROC) analysis, with which a candidate diagnostic test can be characterized mathematically. This methodology allows for an estimate of the overall discriminating power of the diagnostic test and thus can be used to compare the performance of one diagnostic test with that of another. However, ROC analysis cannot be used for optimizing a given diagnostic test (ie, determining the “best” cut-off) and, because it does not incorporate Bayes' theorem, it cannot be used to compare the performances of diagnostic tests when it is given to different risk groups for the target disorder. Both of these problems can be solved by using the concept of information theory. The equation for information gain automatically takes Bayes' theorem into consideration and also provides an intrinsic criterion for finding the cutoff that best discriminates between individuals who do and those who do not have the target disorder. Neither ROC analysis nor information theory are model dependent; however, if the equation for the frequency distribution of the electrophysiologic variable is known for the disease-positive and disease-negative populations, the calculations are greatly simplified. Therefore, the assumption is often made that both of these distributions (or transformations of the distributions) are Gaussian. However, studies have shown that the results of ROC analysis are quite robust to deviations from normality of the underlying distributions.

Galantamine is US-Food and Drug Administration FDA-approved for mild-to-moderate Alzheimer’s disease. However, its unique pharmacological portfolio speaks to the idea of a pluripotent agent with a broad therapeutic potential. Here, authors briefly discuss these off-label clinical indications synthesizing the extant evidence.

This supplement to CNS Spectrums focuses on the obsessive-compulsive spectrum of disorders and their relationship to anxiety. Hollander and others pioneered the concept of the obsessive-compulsive spectrum in the early 1990s, and have described its breadth and overlap with other psychiatric disorders. While its place in the psychiatric nomenclature is uncertain, the obsessive-compulsive spectrum is intertwined with the anxiety disorders in both its symptoms and biologic substrates.

Obsessive-compulsive disorder (OCD) has an important place at the center of the spectrum. While currently classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition as an anxiety disorder, OCD is distinct from these conditions in the International Classification of Diseases. There is a strong rationale for its separation from the anxiety disorders. First, OCD often begins in childhood, whereas other anxiety disorders typically have a later age of onset. OCD has a nearly equal gender distribution, unlike the other anxiety disorders, which are more common in women. Studies of psychiatric comorbidity show that, unlike the other anxiety disorders, persons with OCD generally tend not to have elevated rates of substance misuse. Family studies suggest that first-degree relatives of persons with OCD have an elevated prevalence of OCD-related disorders including body dysmorphic disorder, hypochondriasis, and grooming disorders, but not other anxiety disorders except for generalized anxiety disorder. The brain circuitry that mediates OCD appears to be different from that involved in other anxiety disorders. Lastly, OCD is unique with regard to its specific response to selective serotonin reuptake inhibitors, while noradrenergic medications, effective in the anxiety and mood disorders, are largely ineffective. On the other hand, the benzodiazepines, which have little effect on OCD, are often effective for the other anxiety disorders.