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.

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.

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.

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.

Obsessive-compulsive disorder (OCD) experienced in childhood or adolescence is often a chronic disorder with high subjective distress and impairment of family and social functioning. An early comprehensive intervention schedule can have a profound effect on outcome in later years. The clinical manifestations of OCD among children and adolescents do not seem to be inherently different from those of adult patients. In younger subjects, the clinical picture tends to be dominated by compulsions, and insight can be poor, with little recognition of the symptoms as a problem.There is often a shift in symptoms over time, with some symptoms being replaced by others, while in adults, the core obsessions and compulsions tend to be more stable. In addition to depression and anxiety disorders, the spectrum of comorbid psychopathology seen in pediatric OCD patients includes tic, disruptive behavior, and specific developmental disorders. The treatment of childhood and adolescent OCD relies on cognitive-behavioral techniques of psychotherapy and pharmacotherapeutic interventions similar to those recommended in adults. The efficacy of exposure and response prevention in pediatric OCD has been shown in numerous open studies, and four controlled trials. Pharmacotherapy relies on serotonergic medication, and all have been demonstrated to be significantly superior to placebo, as reported in a recently published meta-analysis. Current concerns with the use of SSRIs in children and adolescents were explored as regards OCD and anxiety disorders, and there is no evidence for an increase in suicide or related behaviors.

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.

This article summarizes results of all pharmacotherapy trials for obsessive-compulsive disorder (OCD) published from 2006 to 2008 as well as studies on markers for predicting response to treatment and neurobiological changes induced by pharmacotherapy. Results show that recent developments in the treatment of OCD have been modest and primarily involve evidence for the efficacy of escitalopram and other selective serotonin reuptake inhibitors (SSRIs); augmentation with antipsychotics in treatment-refractory patients and combination treatment with D-cycloserine and cognitive-behavioral therapy has also been effective. The efficacy of serotonin-norepinephrine reuptake inhibitors remains inconclusive. Studies on markers of clinical response have shown inconsistent results, however, duration and severity of OCD and the presence of comorbidities can often identify patients at risk for nonresponse. Lastly, successful treatment with an SSRI results in both serotonergic and dopaminergic changes, but more research is necessary in order to define the biological characteristics of responders and nonresponders.

The unique clinical presentation of Tourette syndrome (TS) and its symptomatic response to dopamine antagonists are widely cited as evidence for the central role of the limbic-motor interface in the pathophysiology of TS. Nonetheless, the true neuropathology of TS remains elusive, even though significant advances have been made in understanding complex interconnected circuitries within the limbic system and basal ganglia. Neuropathologic and neuroimaging studies—plagued by small samples, clinical heterogeneity, and a number of interpretative problems—are generally supportive of pathology within the orbitofrontal cortex, striatum, and their efferent projections in TS. The specific patterns of abnormalities vary widely across these studies, clouding attempts to define a unifying neuropathology for this disorder. Converging yet circumstantial evidence for frontal cortical, and basal ganglia pathology in TS comes also from studies infields ranging from neuroimmunology to neuropsychology, and from the clinical overlap between TS and disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and Sydenhams chorea. As a “model” neuropsychiatric disorder, TS has stimulated advances in several areas of neurobiology research, yet we still await a real understanding of its pathophysiology in order to move from empirically driven therapeutics to the development of targeted effective treatments.

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.

Recent research shows that single genes do not cause schizophrenia, but that multiple “susceptibility” genes each provide a genetic “bias” towards schizophrenia. Each susceptibility gene codes for a subtle molecular abnormality that hypothetically causes inefficient information processing in brain circuits that mediate the symptoms of this disorder. It is therefore not surprising that many of the susceptibility genes that have been identified for schizophrenia are known to regulate neuronal connectivity, synaptogenesis, and N-methyl-D-aspartate (NMDA) glutamate receptor functions. This includes genes for brain-derived neurotrophic factor (BDNF), dysbindin, also known as dystrobrevin-binding protein 1, neuregulin, disrupted in schizophrenia-1 (DISC-1), D-amino acid oxidase activator (DAOA), and regulator of G-protein signaling (RGS4). Hypothetically, converging molecular abnormalities expressed by defective versions of these genes could cause dysregulation of NMDA receptors and NMDA synapses, leading to vulnerability for schizophrenia due to inefficient information processing at glutamate synapses.

Migraine varies in its frequency, severity, and impact; treatment should consider these variations and the patient’s needs and goals. Migraine pharmacologic treatment may be acute (abortive) or preventive (prophylactic), and patients often require both. New medication devices are available or in development, including an intracutaneous, microneedle system of zolmitriptan and sumatriptan, and breath-powered powder sumatriptan intranasal treatment. Lasmiditan, a 5-HT1F receptor agonist, is in development for acute treatment, as are small molecule calcitonin gene-related peptide (CGRP) receptor antagonists (Gepants) for acute and preventive treatment. Antibodies to CGRP and its receptor are being developed for migraine prevention. All 4 treatments are effective and have, as of yet, no safety concerns.

Criminal conduct is not always violent, and violence does not always lead to criminal charges. Moreover, crime and violence have multifaceted etiologies. Most violence in society is not attributable to mental illness. Where there is a small relationship between violence and mental illness, the risk of violence increases for individuals with substance use histories. Underlying trauma can also play a role. Antisocial attitudes, behaviors, and peer groups further increase the risk that individuals, including those with mental illness, will find themselves at risk of criminal recidivism. Criminal histories among public mental health populations, and mental health and substance use disorders among criminal populations are each higher than general population comparisons. Care within behavioral health settings should therefore target decreased criminal recidivism and decreased violence as part of recovery for those individuals at risk, using trauma-informed approaches and peer supports. Interventions that show promise bring criminal justice and behavioral health systems together, and include police-based diversion, specialty courts, court-based alternatives to incarceration, and coordinated re-entry programs. This article reviews these options along with specific risk management strategies, such as using risk, needs, and responsivity factors as a means of improving overall outcomes for persons with mental illness, while minimizing their risk of further criminalization and victimization.