Obsessive-compulsive disorder (OCD) is a formidable public health problem, rated by the World Health Organization as one of the top 20 most disabling diseases.The shame and secrecy associated with OCD, as well as the lack of recognition of its characteristic symptoms, particularly by primary care physicians, hinders appropriate diagnosis and treatment. Most adults with OCD report a late adolescent or early adulthood onset, yet OCD can occur throughout the life span. Pre-school children have been known to develop the disorder, as have elderly persons. OCD can cause considerable distress and disability; for example, children may fall behind in their education, and adults can become housebound. Comorbid psychiatric disorders have become an area of intense interest. Comorbid depression for example, is frequently the symptom that leads the individual to seek treatment. Patients with schizophrenia frequently develop obsessions and compulsions, and these symptoms are associated with a poorer outcome. The role of second-generation antipsychotics merits further study in the treatment of this subset of patients. An important step toward delineating specific subgroups within the OCD-schizophrenia axis may be the use of endophenotypic markers. Unfortunately, many patients with OCD will have a less than optimal treatment response. Poor treatment response is associated with serious social disability, but there are few clues to guide clinicians in predicting treatment response in patients with OCD, in terms of specific demographic variables, clinical symptoms, or the presence of comorbid psychiatric disorders.

In recent years, research-methods literature mainly addressing controlled clinical trials has arisen regarding explanatory and pragmatic treatment trials. Explanatory trials tend to examine causal mechanisms and questions of efficacy and value internal validity (creating optimal study conditions) over generalizability (using study results to understand treatment effects in real-life patient populations). In contrast, pragmatictrials value “external relevance” (generalizability) of study results over “internal elegance” so that clinicians and health policymakers can better understand how treatments might impact their patients and policies.This review draws inspiration from these contrasting explanatory and pragmatic perspectives and develops them for clinical and research pertaining to idiopathic physical symptoms and related syndromes (eg, somatization disorder, chronic fatigue syndrome, multiple chemical sensitivities, irritable bowel syndrome). Explanatory and pragmatic perspectives are used to examine these idiopathies with regard to causation, case definition, labels, and treatment. It is concluded that idiopathic symptom syndromes are fundamentally pragmatic clinical and research challenges. For epidemiologic and methodologic reasons, the complex explanations for these syndromes remain largely elusive. Even so, scientific and clinical pragmatism offers the opportunity to reduce disagreement between competing medical disciplines and between clinicians and affected patients with regard to irreconcilable etiologic questions and to remain evidence-based in the care of patients.

Introduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined.

Methods: The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0±8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks.

Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected.

Conclusion: This finding may have relevance for testing treatments of anxiety and depression.

The schizo-obsessive subtype of schizophrenia has been proposed to describe the condition of patients with chronic psychotic disorders and prominent obsessive-compulsive (OC) symptoms. These patients differ from others with schizophrenia not only in their psychopathology, but perhaps also in their prognosis and pharmacotherapeutic response. Potent serotonin reuptake blockers, such as clomipramine, fluvoxamine, andfluoxetine, in conjunction with antipsychotics, can prove helpful in improving these patients' OC symptoms. The current study to access the demographics, prevalence, and clinical features of the schizo-obsessive subtype included established outpatients with a principal diagnosis of schizophrenia or schizoaffective disorder treated at a large urban public hospital. More than 50% of the hospital's psychiatric population is Hispanic. The Modified Maudsley Obsessive Compulsive Inventory (MMOCI) was used to identify prominent compulsive symptoms. Of the 52 patients who fulfilled the specific screening criteria, 17 (33%) also had prominent OC symptoms. Surprisingly, there was a statistical trend (P=0.06) for Hispanic patients to meet our threshold for the schizo-obsessive subtype. The MMOCI proved to be an adequate and efficient self-rated screening tool. The prevalence of the schizo-obsessive subtype, especially among Hispanic patients, highlights the importance for mental health professionals working with this population to identify and appropriately treat this group of patients.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the limbs accompanied by uncomfortable sensations, leading to sleep disturbances. It is associated with psychiatric comorbidities and a decreased quality of life. RLS is common and most severe among females and the elderly. It may be primary or secondary to other conditions and may be familial. Linkage to several chromosomal loci have been demonstrated. The pathogenesis of RLS involves dopaminergic dysfunction, iron metabolism, and abnormalities in supraspinal inhibition. The mainstay of RLS therapy are dopamine agonists or levodopa.This article reviews the clinical characteristics, epidemiology, diagnosis, pathogenesis, and treatment of RLS.

Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study.

Body dysmorphic disorder (BDD) is characterized by preoccupation with a defect in appearance. Concepts of beauty play a particularly crucial role in humans' mental and social life, and may have specific psychobiologic and evolutionary underpinnings. In particular, there is a growing literature on the neurocircuitry underpinning the body schema, body image and facial expression processing, and aesthetic and symmetry judgments. Speculatively, disruptions in cognitive-affective processes relevant to judgments about physical beauty lead to BDD.

Moving from a behavioral-based to a biological-based classification of mental disorders is a crucial step toward a precision-medicine approach in psychiatry. In the last decade, a big effort has been made in order to stratify genetic, immunological, neurobiological, cognitive, and clinical profiles of patients. Making the case of obsessive–compulsive disorder (OCD), a lot have been made in this direction. Indeed, while the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of OCD aimed to delineate a homogeneous group of patients, it is now clear that OCD is instead an heterogeneous disorders both in terms of neural networks, immunological, genetic, and clinical profiles. In this view, a convergent amount of literature, in the last years, indicated that OCD patients with an early age at onset seem to have a specific clinical and biological profile, suggesting it as a neurodevelopmental disorder. Also, these patients tend to have a worse outcome respect to adult-onset patients and there is growing evidence that early-interventions could potentially improve their prognosis. Therefore, the aim of the present paper is to review the current available genetic, immunological, neurobiological, cognitive, and clinical data in favor of a more biologically precise subtype of OCD: the early-onset subtype. We also briefly resume current available recommendations for the clinical management of this specific population.

The distinction between Alzheimer's disease and vascular dementia, the two most common types of dementia, has been undermined by recent advances in epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular risk factors, traditionally regarded as distinguishing criteria between the two entities, have been shown to be associated with both AD and vascular dementia. In this article, we propose mechanisms of action of cardiovascular risk factors in AD, suggest possible explanations for the overlap with vascular dementia and discuss the implications this might have on future differential diagnosis, research, and treatment strategies.

There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment out come remain to be determined in future studies.

Reduction of core body temperature has been proposed to contribute to the increased lifespan and the anti-aging effects conferred by caloric restriction in mice and higher primates. Cooler biologically compatible core body temperatures have also been hypothesized to combat neurodegenerative disorders. Yet, validation of these hypotheses has been difficult until recently, when it demonstrated that transgenic mice engineered to have chronic low core body temperature have longer lifespan independent of alteration in diet or caloric restriction. This article reviews the literature and highlights the potential influence of core body temperature's governing role on aging and in the pathophysiology of neurodegenerative disorders in humans. What makes recent findings more significant for humans is the existence of several methods to lower and maintain low core body temperatures in human subjects. The therapeutic potential of “cooler people” may also raise the possibility that this could reverse the adverse-health consequences of elevations in core body temperature.

Clozapine is a prototype atypical antipsychotic drug and displays efficacy in 30% to 60% of schizophrenia patients who do not respond to traditional antipsychotics. There is considerable evidence supporting a concentration-response relationship for clozapine. A plasma clozapine concentration >200 to 420 ng/mL increases the probability of antipsychotic effects. Approximately 70% to 80% of variability in clozapine plasma concentration can be attributed to variability in cytochrome P450 1A2 activity. Measurement of caffeine metabolites in plasma or urine can be used as an in vivo index of cytochrome P450 1A2 activity, since caffeine is primarily eliminated by oxidative metabolism through this cytochrome P450 enzyme. Caffeine-based tests may contribute to individualization of clozapine dosages and optimization of its antipsychotic effects in schizophrenia patieents There are several lines of evidence suggesting the potential involvement of the dopamine D4 receptor in pharmacodynamic effects of clozapine. Clozapine has a 10-fold higher affinity for the dopamine D4 receptor in comparison to the D2 and the D3 receptors. Moreover, the free plasma fluid concentration of clozapine is comparable to its binding affinity for the D4 receptor in vitro. Blockade of the D4 receptor in the mesocorticolimbic region, a brain area implicated in the pathogenesis of schizophrenia, may contribute to efficacy of clozapine in negative symptoms. Moreover, the dopamine D4 receptor gene (DRD4) displays an unusual degree of genetic variation (polymorphism). In a recent preliminary study, investigated the (G)n mononucleotide repeat polymorphism within the first intron of the D4 gene in 50 schizophrenia patients refractory to traditional antipsychotics. These patients were prospectively followed for antipsychotic response during clozapine treatment. Analysis of variance found significant differences in antipsychotic response as demonstrated by mean change in Brief Psychiatric Rating Scale scores among the genotype panels for this polymorphism F[3,49]=4.1 (P=0.01). Future studies investigating the mechanistic basis of variability in response to clozapine should focus on both pharmacokinetic and pharmacodynamic factors.

Approximately 20%–30% of schizophrenia patients are resistant to current standard pharmacotherapies. Recent schizophrenia research aims to identify specific pathophysiological abnormalities and novel targets in the disease, with the goals of identifying at-risk individuals, facilitating diagnosis, prompting early and personalized interventions, and helping predict response to treatment. Metabolomics involves the systematic study of the profile of biochemical alterations early in the course of a given disorder. Major aspects of the schizophrenia metabolome have been characterized, uncovering potential selective biomarkers for the disease that may change how the disorder is diagnosed, and how patients are stratified and treated. This review focuses on the most common metabolomic fingerprints of the different pathways involved in the pathophysiology of schizophrenia, and the potential development of novel metabolomic-related pharmacotherapies for improved treatment of schizophrenia and other related idiopathic psychotic disorders.