Alzheimer's disease is a progressive condition characterized by a loss of cognition, altered behavior, and a loss of functional ability, such as bathing, dressing, toileting, and organizing finances. Family and friends provide nearly three quarters of all care for patients with Alzheimer's disease. This informal care results in significant burden to caregivers. Caregiver burden is the set of physical, psychological or emotional, social, and financial problems that family members may experience when caring for impaired older adults. Caregivers of Alzheimer's disease patients report higher rates of physical symptoms, mortality, depression, and fatigue, as well as adverse effects on employment compared with those who are not caregivers for Alzheimer's disease patients. In many cases, the same family members are responsible for both out-of-pocket expenditures and caregiving duties. For this article, a MEDLINE search using the key words “caregiver and Alzheimer's disease” and “cost and Alzheimer's disease” was performed. The purpose of this article is to review the literature on caregiver burden, the components of caregiver burden, effects of caregiving on the health of caregivers, the cost of Alzheimer's disease on the caregiver and society, and the benefits attainable with treatment.

Recent brain-imaging studies have examined the neuroanatomy and pathophysiology of obsessive-compulsive disorder (OCD). Researchers have used computed tomography and magnetic resonance imaging to look at brain structure and single-photon emission computed tomography and positron emission tomography scanning to look at brain function in OCD subjects. In this article, we review these studies and discuss their methodology. We then present a theoretical model derived from these studies for how the brain mediates OCD symptomatology.

Functional neuroimaging studies have pointed to hyperactivity of orbitofrontal-basal ganglionic–thalamic circuitry in patients with OCD. Our model posits an imbalance between the classical “direct” and “indirect” orbitofrontal–basal ganglionic–thalamic pathways in OCD subjects. The direct circuit appears to function as a positive feedback loop and may “capture” or “lock in” symptomatic OCD subjects. The indirect circuit, which usually provides tonic inhibition to the direct circuit, may be relatively weak.

Finally, we discuss how frontal-subcortical brain circuitry may be involved in other neuropsychiatric illnesses, and we describe how monoamines, such as serotonin and dopamine, may be involved in regulating these circuits in OCD and other illnesses.

Introduction: Aripiprazole, a dopamine D2 receptor partial agonist, has also partial agonist activity at serotonin (5-HT)1A receptors and antagonist activity at 5-HT2A receptors.

Methods: In this 8-week, multicenter, randomized, parallel-group, open-label, flexible-dose study, patients diagnosed with schizophrenia or schizoaffective disorder were randomized to aripiprazole 15–30 mg/day or haloperidol 10–15 mg/day.

Results: Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total, positive, and negative scores as well as in Clinical Global Impressions scores (all P<.001). At the end of the study, the percentage of patients classified as responders—according to ≥40% reduction in the Positive and Negative Syndrome Scale negative subscale score—was significantly higher in the aripiprazole group (20%) than in the haloperidol group (0%) (P<.05). Additionally, a higher number of patients receiving haloperidol required more anticholinergic medications (P<.001) than aripiprazole-treated patients, whereas more aripiprazole (45.5%) than haloperidol-treated patients (12.9%) required benzodiazepines (P=.002). At endpoint, rates of preference of medication were higher in the aripiprazole group (63.2%) than in the haloperidol group (21.7%), as expressed by patients and caregivers (P=.001).

Conclusion: Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology. Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability (extrapyramidal symptoms) and preferred by patients and caregivers than haloperidol, significantly more aripiprazole-treated patients required benzodiazepines.

Initial investigations of the possible interaction between schizophrenia and the immune system began in the early 1900s and have proceeded in a rather halting fashion because of the methodological challenges faced by investigators. However, a confluence of recent data suggests that activation of the inflammatory response system, the cellular immune system, and the humoral immune system may be present in some patients with schizophrenia. Some of the most compelling data support the hypothesis that minor levels of immune activation may be associated with acute psychotic exacerbations. However, a second body of evidence suggests that some individuals with schizophrenia may have chronic, evolving autoimmune processes. This article is an overview of the history, rationale, and some of the recent findings on the interaction between schizophrenia and the immune system.

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterized by inattention, impulsivity, and overactivity that begins in childhood. While considerable research has focused on the neurobiological substrates of this disorder, the specific nature of the brain dysfunction in ADHD has remained elusive. However, early data from pharmacological treatment studies, as well as from basic research in animals and humans, initially led several investigators to develop neurobiological models of ADHD. These models of ADHD and more recent evidence from neuropsychological, neuroimaging, neurochemical, and genetic research are briefly reviewed. While not completely consistent, the empirical data suggest that dysfunction in prefrontal-striatal neural circuits, as well as in brain stem catecholamine systems that innervate these circuits, may underlie the executive function deficits in ADHD.

Williams syndrome is a neurodevelopmental disorder that results from the deletion of ~25-30 genes spanning about 1.5 megabases in the q11.23 region of chromosome 7. Patients with this syndrome present with a combination of a distinctive elfin-like facial appearance; growth retardation; mild mental retardation; an inconsistent cognitive profile that includes visuospatial impairments with good facial discrimination and relatively preserved expressive language skills; and cardiovascular abnormalities. In addition, a striking behavioral feature of the syndrome is the high sociability and empathy that these patients show for others. The study of patients with “partial” deletions of the chromosome band 7q11.23, mutated genes in this region and knockout mice with deletions of specific genes in the homologous G1–G2 region of mouse chromosome 5 are clarifying some genotype/phenotype relationships. Futhermore, genes located in this region that are prominently expressed have been implicated in brain development and function.The neuropsychological profile of patients with Williams syndrome is heterogeneous, highlights important dissociations between cognitive functions and suggests that the behavioral dimensions of sociability, empathy, engageability, and talkativeness may be independent of, or not easily explained by, the cognitive deficits. Williams syndrome has enormous heuristic value because its pathological feature of heightened “sociability” can be a “deficit” symptom of major complex neuropsychiatrie disorders, such as schizophrenia and autism. Data consistent with a core inability of patients with Williams syndrome to inhibit social approach suggest that this disorder may afford an opportunity to study the biological basis of the “drive” toward socialization. From a research perspective, the syndrome lends itself to neurobiological studies of sociability as a dimension that varies independently of cognition (or at least many separable cognitive processes). Importantly, from a clinical perspective, the syndrome challenges us to administer strategic psychosocial interventions that take advantage of the opportunities that “pathological” sociability provide, while avoiding its threats. An illustrative example of an effective strategically planned psychosocial intervention for a patient with Williams syndrome is briefly presented.

An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior.

The great revolution that took place in physics at the beginning of this century, which led to a total reshaping of the science and a different approach to natural phenomena, could serve as a model for future developments in other disciplines such as neuroscience. When investigated by traditional methods, the complexity of brain mechanisms remains quite elusive; the use of new strategies should, therefore, be a high priority.

Although holistic interpretations of brain functions and dysfunctions still seem futuristic, the application of chaos theories may be one way of making these interpretations more understandable. In fact, chaos mathematics can be applied to brain activity, such as that recorded, by electroencephalogram (EEG), and to the interpretation of psychopathology. Similarly, clinical phenomena could be explained in terms of nonlinear dynamics. Moreover, the application of chaos theories to psychiatry might permit the study of the relationships between genetic and environmental factors in determining syndromes and symptoms. This could encourage the development of a nonlinear dynamic psychiatry which, in turn, would allow a better understanding of research findings and, perhaps, open new horizons to psychiatric intervention.

Objective: Few studies have used a combination of objective and self-report measures to examine neuropsychological and behavioral functioning in parents of children with attention-deficit/hyperactivity disorder (ADHD). This study examined attention and inhibitory control in the parents of preschool children who were rated as “at risk” for developing ADHD as compared with parents of controls.

Methods:Preschool children (N=53) were divided into at risk for ADHD and control groups based on parent and teacher ratings of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD symptoms. One parent of each child was administered an identical pairs Continuous Performance Test (CPTIP), a Go/No-Go task, and the Brown Attention-Deficit Disorder Scale for Adults.

Results: Parents of preschoolers at risk for ADHD showed a pattern of responding on measures of vigilance characterized by slower reaction times and increased commission errors as compared with parents of controls. There were no significant group differences on self-report measures on the Brown Attention-Deficit Disorder Scale for Adults.

Conclusion: Parents of preschoolers at risk for ADHD appear to exhibit cognitive processing deficits that may not be evident using self-report measures. Further research is needed to more clearly identify the specific nature of these neuropsychological deficits and to determine whether they have a negative impact on their children.

Alzheimer's disease represents a significant challenge to the aging population. Since most estimates suggest that AD has a multifactorial etiology, the challenge to find preventative approaches is particularly great. With the aging of the population and the very high incidence from the eighth decade on, the challenge is further enhanced by the need to think of relatively safe interventions given the relative frailty of this elderly population. The need to find safe treatments, or ones with well-understood safety profiles, has led to the examination of known agents for potential dementia-preventing properties. Data supporting these interventions comes from observational studies, laboratory analyses, and clinical trials. Potential mechanisms for prevention of AD include anti-inflammatory and antioxidant approaches. Modulation of risk factors associated with cardiac disease may also reduce the risk of AD. Known agents have been examined for their potential to modify amyloid pathology. Trial designs to address prevention of AD include both primary and secondary prevention studies as well designs to assess slowing disease progression. Information can also be gathered when dementia evaluation is added to ongoing studies. As results from these studies becoming available, we will be able to refine our approach to managing this disease.

This article describes a new approach to the understanding and treatment of pathological gambling (PG). In order to foster an understanding of the pathological variations of gambling, gambling as a “normal,” widespread behavior that spans cultures and centuries is briefly reviewed, as is the current socioeconomic impact of gambling on society. PG is interpreted as an excessive exaggeration of a normal behavior (a behavioral excess disorder, or BED), similar to exaggerations of cleaning, grooming, loving, working, or shopping.

Particular developmental deficits in certain individuals and their resulting vulnerabilities make these persons prone to “getting lost” in excessive gambling activities. PG fulfills three important functions that serve to maintain these behaviors. Most frequently, it serves the intraindividual function of distraction from a cognitive, emotional, or physiologic negative state (NEST). A second, much less frequent intraindividual function is that of fast socioeconomic self-destruction in persons who develop presuicidal depression before they start gambling. In the worst disease course of this subtype, patients enter a dramatic “last game”; when they lose, “fate has decided” that they should kill themselves immediately thereafter. A third function fulfilled by PG is interactional, ie, in the “I can't be with or without you” type of relationship.

These gambling-related vulnerabilities are discussed against the background of recent studies from: (1) cognitive psychological and animal experiments regarding the prediction of future events; (2) functional brain imaging studies in obsessive-compulsive disorder; and (3) gambling experiments (prediction of future events) in patients with specific lesions in the orbitofrontal cortex. This article outlines the basics of strategic-systemic behavior therapy for these conditions, and summarizes results of the first outcome and follow-up studies.