Attention-deficit/hyperactivity disorder (ADHD) is a genetic disorder that affects both children and adults. Genetic studies have shown the heritability of ADHD to be higher than other psychiatric disorders. In addition, imaging studies have revealed various structural anomalies in the brain.

Often ADHD persists into adulthood. The presentation of ADHD into adulthood most often results from childhood onset of ADHD. Symptoms of inattention and functional behavior tend to persist. These symptoms may often be less obvious, with less overt hyperactivity and impulsiveness.

Stimulant medications remain the predominant choice for the treatment of ADHD. They are safe and offer good response. Common adverse reactions can usually be removed by changing the dose and the timing of medication administration. Of the second-line agents for treating ADHD, the tricyclic antidepressants have generated the most studies and have proved fairly efficacious.

Cervical dystonia (CD), also known as spasmodic torticollis, is the most common of the focal dystonias. Muscle hypertrophy is present in nearly all patients, and neck pain is associated with CD in about 80% of patients. Remissions can occur in about 20% of patients, though most last under a year.

Medical therapies have not generally worked well for patients with CD, and are typically associated with many side effects. Botulinum toxin (BT), which causes fewer side effects, has been considered the treatment of choice. Beyond medical therapy, various surgeries for CD have been performed for many decades. Of surgical treatments now in use, selective peripheral denervation is the most common.

In CD, botulinum toxin type A (BT-A) targets pain, dystonic posturing, limited range of motion, and tremor. BT type B (BT-B) is a serotype of BT that is ontogenetically distinct from the type A toxin. There have been three randomized, multicenter, double-blind, placebo-controlled trials of BT-B. It appears that BT-B is a safe and effective treatment for patients with CD who are responsive or resistant to BT-A.

The Fourth International Obsessive Compulsive Disorder Conference (IOCDC) was held February 10–12, 2000, on the beautiful island of St. Thomas. The IOCDC is an annual meeting which brings together the world's leading experts in obsessive-compulsive disorder (OCD) and related disorders in a small workshop setting to present recent research advances, discuss gaps in our current knowledge, and plan or international approaches that address these knowledge gaps. The IOCDC meetings have been held on islands on both sides of the Atlantic—Capri, Guadeloupe, Madeira, and now St. Thomas.

The International Organizing Committee consists of Eric Hollander, MD (USA), Joseph Zohar, MD (Israel), and Donatella Marazziti, MD (Italy). The proceedings are generously supported by an unrestricted educational grant from Solvay Pharmaceuticals Inc. and Solvay Pharmaceuticals, and we would like to acknowledge the very important contributions of Chantal Vekens and Mary Blangiardo of Solvay. Also, an mportant part of the success of these meetings stems from the very active role of the chairpersons and cochairpersons of the workshops who lead the discussions, who synthesize the future directions and prepare the manuscripts that result from these discussions that appear in this academic supplement.

The meeting led off with a state-of-the-art plenary address by Mark George, MD (USA), describing how new methods of brain stimulation are improving research and therapy in OCD and promise to revolutionize neuropsychiatric research and herapy over the next decade. He describes how transcranial magnetic stimulation (TMS) is used to test the circuits in OCD and test electrophysiologic evaluations of cortical inhibition n OCD. Newer techniques that are less invasive than ablative surgery and appear promising in OCD therapy include vagus nerve stimulation and deep brain stimulation.

This issue of CNS Spectrums explores the boundaries and relationship between anxiety and psychosis from various perspectives. Anxiety may be conceived as being secondary to psychosis, or psychosis emerging from an anxiety disorder. Anxiety might also be a symptom, or part and parcel, of a psychotic illness. Finally, pharmacologic treatment of psychosis might precipitate an anxiety disorder, or psychopharmacologic approaches to anxiety disorders might precipitate psychosis. Thus, the relationship between these two symptom clusters may be complex and multidetermined.

First, I would like to thank Stefano Pallanti, MD, of both the Institute of Neurosciences at the University of Florence Medical School and the Mount Sinai School of Medicine, for defining the challenge, assembling an international cohort of experts, and guest editing this issue.

In this issue, Rossi and colleagues present original research derived from a study of 400 inpatients that examines the pattern of comorbidity among obsessive-compulsive personality disorder (OCPD) and other personality disorders. Of interest, the highest co-occurence of OCPD is with the cluster A disorders (paranoid and schizoid)—the “odd” cluster.

Pallanti and colleagues describe the development of social phobia in 12 patients with paranoid schizophrenia during clozapine treatment. Two thirds of these patients had significant improvement of social phobic symptoms with fluoxetine augmentation of clozapine. This new observation is certainly reminiscent of the induction of obsessive-compulsive symptomatology with atypical neuroleptic treatment in schizophrenia.

The function of the immune system is to recognize foreign elements and identify them as normal or potentially harmful. The first step in this discrimination is surveillance by antigen-presenting cells (APCs), which are present throughout the body. Factors that affect the immunogenicity of a molecule include the presence of an adjuvant, the depot effect, the frequency of the antigen administration, and the quantity of the material administered.

For the various types of botulinum toxin, the issue of the effect on efficacy is particularly relevant to antibody formation. An antibody to one type of botulinum toxin may potentially bind to an antibody of a different type. Safety issues with therapeutic proteins involve allergic responses, as well as formation of immune complexes and the subsequent immune complex disease. The concerns with botulinum toxins primarily relate to the potential for inhibiting efficacy.

Protein therapeutics are important only if the antibodies have been generated against the administered therapeutic. This differs for the types of botulinum toxin. In the development of botulinum toxin type B, the factors that might increase the likelihood or magnitude of an immune response were considered and eliminated as much as possible. Only antibodies to the neurotoxin protein impact efficacy or safety.

Epilepsy is a medical disorder that presents with single or clustered seizures. There are several new drugs that effectively treat epilepsy with few side effects, and treatments of children, women, and the elderly are discussed. In the special population of children, there is a strong emphasis on the cognitive and behavioral benefits of specific therapies.

In the population of epileptic women, seizures most often occur at the start of puberty and menarche, and worsen periodically with each menstrual cycle. Relief of symptoms often occurs at menopause, but a possibility of exacerbation also exists. Women with epilepsy often battle a fear of becoming pregnant. This is a fallacy which must be widely dispelled, as the risk is less than supposed.

Among the elderly, epilepsy often presents after trauma, particularly stroke, and the incidence is three times greater for those over 60 years of age than the general population. Due to various conditions specific to the elderly, misdiagnosis is common. The greatest challenge in treating the elderly is adverse side effects.

The power of the life force is striking—in even among the most abominable conditions, like concentration camps, suicide remains relatively uncommon. Yet some human beings appear to harbor a powerful destructive force, which can under certain conditions manifest itself in violence, homicide, or suicide. Suicide has been with us since the beginning of history; it has often been romanticized, or viewed as an understandable escape from an intolerable situation. Philosophers and writers from William James to Albert Camus to Goethe have tended to view suicide as a window into the human condition, perhaps extreme but nevertheless a reflection of our shared humanity. However, highly reliable research has shown that suicide is, by and large, not a window into the human condition, but rather a manifestation of a disturbance—an abnormality of the human condition—a mental disorder.

Physicians know that the primary goal of medical treatment (after first doing no harm) is to prevent death. Death is the ultimate enemy in medical illness. In psychiatric illness, this enemy usually appears in the guise of suicide; the illness uses the hands of patients to wreak its havoc. To reduce mortality in psychiatric conditions, then, means to reduce suicide. It is indeed striking how little this matter has been analyzed. Little data are available on mortality with medications that are researched and approved for psychiatric illness. This would not be acceptable for medical illnesses outside of psychiatry today; it should not be the case in psychiatric illnesses either.

The National Institute of Mental Health (NIMH) has embarked upon a new venture—effectiveness trials, large-scale trials to test more than one treatment option for individuals affected with diverse major mental disorders. The launch follows a recent report by the NIMH National Advisory Mental Health Council, which emphasized the failure within routine clinical care to widely implement findings of randomized, controlled efficacy trials (RCTs)—perhaps, in part, because of reduced generalizability that leaves real-world application unclear.

Efficacy trials do not answer a number of key clinical questions, including: (1) Are the treatments as effective and safe in representative patient groups? (2) How does the new treatment fit within the treatment armamentarium? (3) When should the new treatment be combined with existing interventions? (4) What are the long-term benefits? (5) Do treatments differ regarding their effectiveness in patients with comorbid general medical or psychiatric disorders? (6) How do these newer treatments affect costs of routine care? Effectiveness trials can address a number of these issues and incorporate a broad range of outcomes, including symptom reduction, day-to-day function, side effect burden, and patient satisfaction.

With a major aim of effectiveness trials being increased generalizability, selection of participants is crucial. Since symptomatic volunteers, who are typically used in efficacy RCTs for major depressive disorder, may be more responsive to either the nonspecific aspects of treatment or to the treatment itself than self-declared patients with concomitant comorbidities, setting minimal exclusion criteria, recruiting large samples of patients from representative practices, and excluding symptomatic volunteers assures that patients are representative, while protecting the internal validity of the trial. In addition, treatments must be reasonably well delivered so that outcomes can be attributed to the treatment per se and not to improper implementation of an otherwise effective treatment. Frequent clinic visits, patient/family educational efforts, universal access to all protocol recommended treatments (including psychotherapy), and adequate provider compensation can ensure that treatments are reasonably well delivered.