This narrative review provides an overview of the three new oral second-generation antipsychotics that have become available in the US: iloperidone, asenapine and lurasidone. Although they are associated with less weight gain and fewer metabolic abnormalities than some of the older second-generation antipsychotics, iloperidone, asenapine and lurasidone have differences that make them unique from each other. Examples of these differences include dosing frequency, specific instructions on dosing with food, titration requirements, and potential association with sedation, extrapyramidal side effects, akathisia, and prolongation of the ECG QT interval. Additional information is provided regarding agents in late stage clinical development for the treatment of schizophrenia: cariprazine and brexpiprazole (both are dopamine D2 receptor partial agonists) and bitopertin (a glycine transport inhibitor that may have antipsychotic effects).

Pharmacoepidemiology, the study of the effects of drugs in large numbers of people, is a relatively new discipline that applies the methods of epidemiology to clinical pharmacology. Premarketing clinical trials remain the only way to scientifically determine whether a drug is causally effective, yet these trials do not provide information that allows for estimates about rare, late, or off-label toxicities associated with the drug in question. Increasing concern about common and debilitating adverse effects of medications has highlighted the need for enhanced postmarketing surveillance to follow up on clinical trials. There is a further concern regarding the broader issue of the risk-benefit ratio of certain medications. Computerized databases are a good source of information on which to lay the foundations of postmarketing research. A system of cross-linked computerized medical records may better enable researchers and physicians to realistically monitor postmarketing safety and incorporate monitoring benefits. The same research could also elucidate the net public health effect of regulatory decisions. The Veterans Affairs database in the United States and PHARMO in the Netherlands may represent good models on which to base future postmarketing surveillance studies.

In this expert roundtable supplement, Brian L. Strom, MD, provides an overview of the appropriate use of large computer databases in pharmacoepidemiology studies. Philip Wang, MD, DrPH, discusses the advantages of pharmacoepidemiologic studies over clinical trials in correctly detecting drug safety issues. Francesca Cunningham, PharmD, reviews a large computer database that is currently in use within the VA healthcare system, and Ron M.C. Herings, PharmD, PhD, discusses the development of the PHARMO system in the Netherlands.

An overview is provided regarding neuroimaging in obsessive-compulsive disorder (OCD). The author emphasizes convergent research results across various experimental paradigms and their implications for neurobiological models of OCD. The article concludes with an outline of future considerations that highlights emerging concepts and techniques. This work was intended to serve as a concise summary of the field, and thus to provide a springboard for discussion about this topic at the upcoming International Obsessive Compulsive Disorder Conference.

The emergence of repetitive transcranial magnetic stimulation (rTMS) as a relatively noninvasive probe of cortical function provides an opportunity to explore the relationships between regional brain activity and symptomatology across neuropsychiatric illnesses. In this article, we briefly review evidence from functional neuroimaging studies (principally those using positron emission tomography [PET] or single-photon emission computed tomography [SPECT]) and other studies suggesting regional brain involvement in anxiety disorders, specifically obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). We also review an initial controlled study conducted by our group using rTMS as a probe of prefrontal mechanisms in OCD. This discussion is not intended to be comprehensive, but rather to provide examples of disorders that, based on current knowledge, might be good candidates for the use of rTMS as a probe. In addition, we present case reports from pilot studies of rTMS in three patients with different primary anxiety disorder diagnoses, which illustrate some of the issues involved in such studies, as well as the effects observed. The possibility that rTMS may have therapeutic potential in anxiety disorders is also discussed.

Visual anosognosia (Anton syndrome) is a rare complication of cortical blindness that results from injury to the visual association cortex, in which patients who are unable to see deny that they are blind. They sometimes confabulate explanations for their visual problems (“there is not enough light to see”), or endanger themselves in efforts to “prove” that they can see (eg, tripping or walking into walls). Without functioning visual-association centers, these patients lack the concept of sight and are unable to acknowledge their impairment. Usually, Anton syndrome is encountered in patients with bilateral occipital infarcts but no other cause for impaired vision. We present an atypical case of Anton syndrome in which the patient's underlying visual deficit was due to advanced glaucoma.

Several of this month's articles and interviews touch on themes that relate to spectrum phenomena as well as the Diagnostic and Statistical Manual of Mental Disorders developmental process.

First, Darrel A. Regier, MD, MPH, director of the Division of Research at American Psychiatric Association, discusses, in an interview with CNS Spectrums, the developmental process for DSM-V. He emphasizes the use of dimensional measures to determine both thresholds for disorders, and to assess response to treatments. He also highlights a focus on spectra of disorders that cut across traditional diagnostic boundaries as one way to deal with issues of comorbidity. Finally, he discusses new approaches to the five DSM axes, and the need to link together the DSM and International Classification of Diseases processes. Three other articles in this issue also clearly relate to these obsessive-compulsive spectra issues.

For example, Leonardo F. Fontenelle, MD, PhD, describes how, although much attention has been paid to patients who lack insight into their obsessional beliefs, less importance has been given to individuals with obsessive-compulsive disorder (OCD) who display perceptual disturbances typically found in psychotic disorders, including schizophrenia, schizoaffective disorders, or mood disorders with psychotic features. The authors call attention to a phenomenon that has been neglected in the psychiatric literature (ie, the occurrence of hallucinations and related phenomena in patients with OCD). They describe five patients with OCD with hallucinations in several different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and the cenesthetic modalities, and suggest that further psychopathological research should clarify the clinical significance of hallucinations among patients with OCD.

The comorbidity of schizophrenia and obsessive-compulsive disorder (OCD) might be approached from two different directions. One is the OCD with psychotic features, and the other is the schizophrenic patient with OCD.

In this review, the history of the concept of the body image in neuropsychiatry is presented. Links between the parietal cortex and the body image are discussed and the possible role of the parietal lobe in psychiatric disorders noted. The link between parietal lobe function and some neurophilosophical concepts are introduced.

Epidemiologic studies have shown a significantly greater likelihood of substance misuse in persons with psychiatric disorders. One of the largest studies showed that 60.7% of people with bipolar I disorder had a lifetime diagnosis of a substance use disorder (SUD). Moreover, 32% of individuals with any mood disorder, including depression, were found to suffer from substance abuse or dependence. In general population surveys, it has been found that the presence of a mood disorder at least doubles the odds of having SUD.

Patients with schizophrenia have a 20% shorter lifespan than people without the disorder. An increased risk of cardiovascular morbidity and mortality is also associated with schizophrenia. Atypical antipsychotics may contribute to the prevalence of cardiovascular disease by causing weight gain and increased adiposity, risk of insulin resistance, hyperglycemia, diabetes, and hyperlipidemia. Atypical antipsychotics that produce the greatest degree of weight gain also appear to impose the greatest risk of diabetes and hyperlipidemia. Recent evidence suggests that atypical antipsychotics may even affect glucose and lipid metabolism independent of weight gain. Among the currently marketed antipsychotics, clozapine and olanzapine appear to produce the greatest degree of weight gain. Moderate increases in weight are also observed with quetiapine and risperidone. Only ziprasidone and aripiprazole appear to be weight neutral. Atypical antipsychotics that produce the greatest degree of weight gain also appear to carry the greatest risk of diabetes and hyperlipidemia. Because of the potential for atypical antipsychotics to cause weight gain and adversely affect glucose and lipid metabolism, clinical monitoring of these parameters is critical. Dietary modification and exercise may be critical to addressing antipsychotic-induced weight gain and its consequences. In patients with persistent weight gain, evaluation of the risks and benefits of ongoing medications and consideration of switching to an antipsychotic with lower weight-gain liability may improve health outcomes.

Deficits in cholinergic and glutamatergic neurotransmission have been linked to the symptomatology of Alzheimer's disease, and current therapies for Alzheimer's, including cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine, have been developed to compensate for these deficits. This article reviews the results of clinical trials involving agents approved by the United States Food and Drug Administration for use in the treatment of Alzheimer's disease (namely, ChEIs for mild to moderate Alzheimer's and memantine for moderate to severe Alzheimer's). In particular, the efficacy of current monotherapy strategies in the treatment of cognitive and functional symptoms of Alzheimer's disease will be addressed. In addition, data from a clinical trial examining the use of a ChEI in combination with memantine will also be discussed, as it has been hypothesized that ChEIs and memantine may offer synergistic benefits due to their distinct mechanisms of action.

Alzheimer's disease (AD) is a progressive disorder in which neurodegeneration begins decades before clinical symptoms appear. Detecting AD during this preclinical phase presents both the enormous challenge of identifying at-risk patients prior to symptom onset and the potential reward of treating patients early enough to prevent or slow disease progression. Given that a 5-year delay in the onset of the clinical manifestations of AD could result in almost a 50% reduction in disease prevalence, early detection of AD is a major focus of clinical research. Several objective, measurable indicators of preclinical and clinical characteristics of AD are currently available or in development. These biomarkers are promising because they promote identification of individuals at risk for AD onset and disease progression; diagnostic accuracy and treatment during the early stages of AD; and the development of disease-modifying therapies that may potentially slow or prevent disease progression during the preclinical phase of AD.