We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a test of logical reasoning and “cognitive gating,” defined as the ability to discriminate between relevant and irrelevant information in confirming or disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task tests both processes under neutral and affect-laden conditions. This is done by presenting formally identical constructs using benign and emotionally arousing language. When separated by symptom profiles, we found statistically significant differences for performance and arousal response between patients with delusions, patients with formal thought disorder, and patients with neither delusions nor formal thought disorder, as well as between patients and healthy controls. When analyzed by error type, we found that nearly all errors by delusional patients were caused by overly restrictive information choice, a pattern that may be related to a delusional patient's tendency to “jump to conclusions” on Bayesian probabilistic tasks. This is in contrast to patients with formal thought disorder, whose low performance resulted also from overly extensive information choice. The tendencies towards restriction were exacerbated by arousal, which is consistent with studies on cognition and arousal in healthy individuals. After briefly examining research on emotional arousal and SZ, and the interaction between emotional arousal and restriction of perceptual cues in healthy individuals, we conclude by suggesting a model which accounts for the distinctive cognitive characteristics of delusional patients by their possessing distinct vulnerabilities to emotional arousal. Specifically, these results suggest the possibility that delusional patients process information in a manner that is essentially intact. However, delusional patients may possess an acute vulnerability to emotional arousal that might cause delusional individuals to behave cognitively as if they were healthy individuals under significantly more severe forms of stress.

ISSUE:The low incidence of extrapyramidal side effects associated with the atypical antipsychotic iloperidone may be linked to its unique binding profile of high affinity antagonism of both α1 adrenergic receptors and serotonin 2A receptors.

Depression is a common psychiatric condition characterized by affective, cognitive, psychomotor, and neurovegetative symptoms that interfere with a person's ability to work, study, deal with interpersonal relationships, and enjoy once-pleasurable activities. After the serendipitous discovery of the first antidepressants, for years the only pharmacodynamic mechanisms explored in the search of novel antidepressants were those related to the 3 main monoamines: serotonin, norepinephrine, and dopamine. New-generation monoaminergic antidepressants, such as selective-serotonin and dual-acting serotonin/norepinephrine reuptake inhibitors, improved treatment and quality of life of depressed patients. Nevertheless, there are still important clinical limitations: the long latency of onset of the antidepressant action; side effects, which can lead to early discontinuation; low rate of response; and high rate of relapse/recurrence. Therefore, in the last several years, the focus of research has moved from monoamines toward other molecular mechanisms, including glutamatergic (Glu) neurotransmission. This review provides a comprehensive overview of the current knowledge on the Glu system and on its relationships with mood disorders. Up to now, N-methyl-D-aspartate (NMDA) receptor antagonists, in particular ketamine, provided the most promising results in preclinical studies and produced a consistent and rapid, although transient, antidepressant effect with a good tolerability profile in humans. Although data are encouraging, more double-blind, randomized, placebo-controlled trials are needed to clarify the real potentiality of ketamine, and of the other Glu modulators, in the treatment of unipolar and bipolar depression.

Despite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.

Somnambulism, a previously unreported side effect of quetiapine, is described in two cases. Both cases involved individuals who had no prior or family history of somnambulism and had attention-deficit/hyperactivity disorder. The possible significance of this will also be discussed. Somnambulism is a common parasomnia that reflects an impairment in the normal mechanisms of arousal from sleep in which motor behaviors are activated without full consciousness. Motor behaviors are initiated during deep non-rapid eye movement or slow-wave sleep (stages 3-4), and may be limited to relatively simple manifestations, such as sitting up, fumbling with objects or bedclothes, or mumbling.

Long-acting injectable (LAI) antipsychotics can have considerable advantages over oral medications for the management of patients with schizophrenia. Despite the high prevalence of treatment nonadherence with oral pharmacotherapy, LAI antipsychotics are significantly underutilized in this patient population. The availability of newer LAI antipsychotic preparations combined with a resurgent interest in the use of typical antipsychotics has rekindled awareness of the value of LAI medications. This article is intended to provide a visual understanding of the various kinetic profiles of LAI antipsychotics to facilitate initiation and greater use of these agents.

This systematic review aimed to examine whether neurobiological methods, or other methods independent of clinical judgment, have been investigated to assist decision making in forensic mental health services and, if so, whether this may be a useful strategy for predicting outcomes. OVID-Medline, Embase, and PsychInfo (inception–January 2015) were searched, limiting to English and human studies, using terms relating to “predict,” “outcome,” “psychiatry,” and “forensic” to identify primary research articles reporting on predictors of outcome in forensic mental health services not reliant on clinical judgment/self-report. Fifty studies investigating demographic, neuropsychological/neurophysiological, and biological predictors were identified, reporting on 3 broad outcomes: (i) inpatient violence, (ii) length of stay, (iii) reoffending. Factors associated positively, negatively, and showing no relationship with each outcome were extracted and compiled across studies. Of various demographic predictors examined, the most consistent associations were between previous psychiatric admissions and inpatient violence; a more “severe” offense and a longer length of stay; and young age and reoffending. Poor performance on tests of cognitive control and social cognition predicted inpatient violence while a neurophysiological measure of impulsivity showed utility predicting reoffending. Serum cholesterol and creatine kinase emerged as biological factors with potential to predict future inpatient violence. Research in this field is in its infancy, but investigations conducted to date indicate that using objective markers is a promising strategy to predict clinically significant outcomes.

Multiple medication use is a common phenomenon, especially in patients with comorbid conditions and those treated with psychiatric drugs such as antidepressants. Combination treatment may result in potentially harmful drug-drug interactions (DDIs). Results of DDIs range from nuisance side effects to serious adverse consequences. DDIs may also result in improved efficacy. Augmentation strategies, for example, are intentional therapeutic DDIs. Pharmacokinetic DDIs occur when a second drug alters the absorption, distribution, metabolism, or clearance of the first drug. Research has concentrated on the relative effects of antidepressants on cytochrome P450 enzymes and, more recently, on drug transporters as potential mediators of clinically important pharmacokinetic DDIs. The most common, clinically relevant pharmacokinetic DDIs involve alteration in oxidative drug metabolism. Pharmacodynamic DDIs occur when the effects of a second drug quantitatively or qualitatively alters those of the first drug. Pharmacodynamic DDIs are not typically studied in vivo because of the potential for a serious adverse effect. All antidepressants can interact pharmacodynamically with certain other drugs. The risk of harmful DDIs can be reduced by recognizing variables that affect dose-concentration-effect relationships. It is important for physicians to weigh the risks and benefits of potential DDIs against the risks that accompany timid or ineffective disease treatment.

Epidemiologic studies have consistently demonstrated a greater incidence of depressive disorders and anxiety among women. Many women experience these conditions during the reproductive years. The dramatic expanse of literature focusing on the use of medications often has failed to pay homage to the potential impact of the disorders. When considering the extant human and laboratory data on mental illness and stress during pregnancy and the postpartum period, it is evident that some degree of exposure (be it treatment or illness) always occurs. The primary goal of the risk-benefit assessment for the treatment of mental illness during these periods is to assist patients and their families in choosing the path of potential exposure that possesses the least risk for them. Once this decision is made, the goal is to limit the number of exposures for the fetus/neonate.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

Brain imaging techniques, especially those based on magnetic resonance imaging (MRI) and magnetoencephalography (MEG), have been increasingly applied to study multiple large-scale distributed brain networks in healthy people and neurological patients. With regard to neurodegenerative disorders, amyotrophic lateral sclerosis (ALS), clinically characterized by the predominant loss of motor neurons and progressive weakness of voluntary muscles, and frontotemporal lobar degeneration (FTLD), the second most common early-onset dementia, have been proven to share several clinical, neuropathological, genetic, and neuroimaging features. Specifically, overlapping or mildly diverging brain structural and functional connectivity patterns, mostly evaluated by advanced MRI techniques—such as diffusion tensor and resting-state functional MRI (DT–MRI, RS–fMRI)—have been described comparing several ALS and FTLD populations. Moreover, though only pioneering, promising clues on connectivity patterns in the ALS–FTLD continuum may derive from MEG investigations. We will herein overview the current state of knowledge concerning the most advanced neuroimaging findings associated with clinical and genetic patterns of neurodegeneration across the ALS–FTLD continuum, underlying the possibility that network-based approaches may be useful to develop novel biomarkers of disease for adequately designing and monitoring more appropriate treatment strategies.

For the first time in 20 years, the American Psychiatric Association (APA) updated the psychiatric diagnostic system for mood disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Perhaps one of the most notable changes in the DSM-5 was the recognition of the possibility of mixed symptoms in major depression and related disorders (MDD). While MDD and bipolar and related disorders are now represented by 2 distinct chapters, the addition of a mixed features specifier to MDD represents a structural bridge between bipolar and major depression disorders, and formally recognizes the possibility of a mix of hypomania and depressive symptoms in someone who has never experienced discrete episodes of hypomania or mania. This article reviews historical perspectives on “mixed states” and the recent literature, which proposes a range of approaches to understanding “mixity.” We discuss which symptoms were considered for inclusion in the mixed features specifier and which symptoms were excluded. The assumption that mixed symptoms in MDD necessarily predict a future bipolar course in patients with MDD is reviewed. Treatment for patients in a MDD episode with mixed features is critically considered, as are suggestions for future study. Finally, the premise that mood disorders are necessarily a spectrum or a gradient of severity progressing in a linear manner is argued.

Oxytocin and vasopressin are highly conserved neuropeptides that play a key role in social attachment and affiliation, including parental care and pair-bonding. Oxytocin attenuates neural responses to aversive pictures and has been associated with reduced coupling of amygdala to brainstem regions involved in the fear response. Differential activation of the amygdala has been found to be associated with different genetic variants of the vasopressin receptor. There is growing evidence that oxytocin and vasopressin receptor variants are associated with individual differences in prosocial behavior. It is humbling that differences in complex human behaviors may be partially explicable on the basis of relatively simple neuropeptide systems. Nevertheless, such findings potentially allow for targeted interventions for a range of psychiatric disorders in which such systems play a role.

In this article, we present rationales for using complex combination therapy in treatment-refractory bipolar patients and discuss the agents available for use in this therapeutic approach. We review a case example of successful remission that was achievable only with complex combination therapy, and examine its theoretical implications. Practical approaches to devising the optimal complex combination treatment for individual patients are explained, and we look to the development of new methodologies and a more systematic database for decision making in the future.

Background: Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations.

Methods: Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli.

Results: In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group.

Conclusions: Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.

Computer-based measures to evaluate cognition have been used with growing frequency in recent years. These batteries are shown to be useful for identifying mild cognitive impairment (MCI) and dementia. There are few requirements to administer these tests. All that is typically needed is a computer, a response pad for patients to input their answers, and an examiner. In many cases, the examiner does not need to be a trained neuropsychologist. These computer-based assessments should yield a score report detailing the patient’s cognitive profile.

An important advantage of computerized assessments over standard paper-and-pencil testing is that they can provide precise measurement at the millisecond level. This can be a more sensitive measure of cognitive impairment, especially in high-functioning older adults and in patients with milder levels of cognitive deficit. Computer tests also have a shorter assessment time. Many batteries take <1 hour to administer, whereas many standard neuropsychological batteries require >4 hours to complete. The presentation of items in some batteries can be adapted to patients’ performance levels to avoid floor effects (the test restricts how low a patients’ scores can be) and ceiling effects (the test restricts how high scores can be). Computer tests have increased standardization; they are administered the same way every time. Scoring is automatic, meaning the results are available immediately and human scoring error is reduced. Examiner effects are reduced, which is an important advantage because clinicians may differ in how they administer standard tests, which may impact patients’ responses. In addition, the batteries are easily transported, and multiple tasks can be made available on a single computer.