Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990–2012.

Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described.

Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

Psychosis of epilepsy (POE) is a term applied to a group of psychotic disorders with a distinct phenomenology in which potential etiopathogenic mechanisms are believed to be closely related to a seizure disorder. POE can present as interictal psychotic episodes, which may often differ semiologically from primary schizophrenic disorder. They may present as ictal or postictal psychotic episodes and may be the expression of an iatrogenic process to pharmacologic and/or surgical interventions.Epilepsy and POE have a complex and bidirectional relation, as not only are patients with epilepsy at greater risk of developing a psychotic disorder, but patients with a primary psychotic disorder are also at greater risk of developing epilepsy. The prevalence of POE is more than 7 times higher than the frequency of primary schizophreniform disorders in the general population. While POE has been associated with focal epilepsy of temporal and frontal lobe origin, its etiology and pathophysiology of POE have yet to be established.The treatment of all forms of POE, with the exception of ictal psychotic episodes, requires the use of antipsychotic drugs, preferably the atypical antipsychotic agents with a very low or negligible potential to lower the seizure threshold (eg, risperidone, apiprazole), starting at a low dose with stepwise increments.

Background: Assertive community treatment (ACT) is an intensive and comprehensive treatment for clients with severe mental illness (SMI) who do not readily benefit from clinic-based services. Monitoring the implementation of such programs is critical, because better-implemented programs have been found to be effective in improving client outcomes.

Objective: We tested the hypothesis that fidelity to the ACT model would be positively correlated with improved client outcomes, as measured by reduction in psychiatric hospital use.

Methods: A scale measuring fidelity of program implementation, the Dartmouth ACT Scale, was examined in 10 newly formed ACT teams. Using the team as the unit of measure, the mean reduction in state hospital days for a 1-year period before and after program admission was calculated. Mean effect size in reduction in hospital days was used as the outcome measure in a correlational design.

Results: Pre/post comparisons showed a 43% reduction in hospital days for 317 clients (t=8.61, P<.001). The Pearson correlation between DACTS fidelity and reduction of state hospitaldays was .49, P=.08, one-tailed.

Conclusion: Several possible reasons are offered for why the study hypothesis was not confirmed. However, even if predictive validity of the Dartmouth ACT Scale is limited, it continues to be a useful tool for program monitoring and for providing corrective feedback.

Compulsive sexual behavior (CSB) is characterized by inappropriate or excessive sexual behaviors or cognitions that lead to subjective distress or impaired functioning. Both abnormal (paraphilic) and conventional (nonparaphilic) forms of sexual behavior are usually included in the definition. CSB is reported to affect 3% to 6% of the general population in the United States, occurring more frequently in men. It typically begins in the late teens or early twenties and is chronic or intermittent. The disorder has been described as a progression through four stages: preoccupation, ritualization, gratification, and despair. Men with CSB typically focus on physical sexual gratification; women focus on romantic or emotional aspects of sexuality. Psychiatric comorbidity is common, particularly substance use, mood, anxiety, and personality disorders. CSB can lead to medical complications. Risk factors are thought to include family history and childhood abuse.

Balancing efficacy with tolerability and safety of prescribed treatments is critical to optimizing antipsychotic treatment outcomes in the mentally ill. Symptom control, symptom remission, and functional recovery are only realistic goals when treatments are both effective and well tolerated. The consideration of predictable differences in antipsychotic adverse-effect profiles is central to successful illness management. Minimizing adverse effects on alertness, motivation, cognition, sexual/reproductive functioning, and physical health enhancesmental health outcomes, partly through improving treatment adherence. Neuroendocrine and metabolic side effects of antipsychotics for cardiovascular morbidity and mortality need to be addressed proactively and aggressively. In view of the widespread lack of primary care engagement and the adverse effects of psychotropic medications on cardiovascular health, psychiatric care providers should function as key facilitators of an integrated mental and physical health management approach. In addition to psychoeducation and healthy lifestyle counseling, clinicians can improve psychiatric and physical health by selecting medications carefully, routinely screening and monitoring for reversible cardiovascular risk factors, and playing an active role in the prevention and interdisciplinary management of cardiovascular risk factors and medical illness in the vulnerable mentally ill.

Catatonia and neuroleptic malignant syndrome (NMS) are uncommon disorders that can be life-threatening. Many researchers consider them as clinically divergent entities; however, they share similar and overlapping literature on causative agents, phenomenology, and treatment response. This hypothesis considers both disorders as a single entity that result from variable combinations of the following: 1) γ-aminobutyric acid (GABA) hypoactivity at the GABAA receptor; 2) dopamine hypoactivity at the D2 receptor; 3) serotonin hyperactivity at the 5-HT1A receptor and hypoactivity at the 5-HT2A receptor; and 4) glutamate hypoactivity at the N-methyl-D-aspartate (NDMA) receptor. In this paper, evidence to support this hypothesis is limited to retrospective human studies of catatonia and NMS. The four components of the hypothesis are: 1) GABAA agonists have been shown to alleviate catatonia and NMS; 2) D2 antagonism is proportional to the relative likelihood of NMS and catatonia; 3) 5-HT1A agonism with 5-HT2A antagonism is implicated in catatonia and NMS; 4) NMDA receptor antagonists, such as phencyclidine and ketamine, reduce glutamate transmission. This hypothesis proposes that it is the interaction of these systems that prediposes, initiates, and maintains the twin syndromes of catatonia and NMS.

The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. In this perspective article, we briefly review five constructs that are affected in FND: emotion processing (including salience), agency, attention, interoception, and predictive processing/inference. Examples of underlying neural circuits include salience, multimodal integration, and attention networks. The symptoms of each patient can be described as a combination of dysfunction in several of these networks and related processes. While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors. To facilitate advances in this underserved and important area, we propose a pathophysiology-focused research agenda to engage government-sponsored funding agencies and foundations.

Current evidence from epidemiological, neuroimaging, pathological, pharmacotherapeutic, and clinical studies indicate an association of Alzheimer's disease with risk factors of vascular atherosclerotic disease either in isolation or in aggregate. “Metabolic syndrome” (MetS) is the name for a clustering of risk factors for cardiovascular disease and type 2 diabetes that are of metabolic origin. These include central obesity, elevated plasma glucose, high blood pressure, atherogenic dyslipidemia, a prothrombotic state, and a proinflammatory state. In this article, we provide an overview of the relevant literature with regard to the relationship of Alzheimer's disease with MetS. Accumulating evidence suggests a “vascular hypothesis” to be related to the pathology of Alzheimer's disease. In the light of this evidence, clinician may consider lifestyle interventions toward an early and effective cardiovascular risk-factor management to reduce the cardiometabolic and the cognitive decline risk, while further research of other preventive strategies may be warranted.

The current tools used to define and diagnose mental disorders, including the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, have added specificity to the psychiatric nomenclature. However, their stereotypic rigidity in classification has resulted in the failure to identify the full range of potentially debilitating psychiatric symptoms with which patients may present. A spectrum model of psychopathology is more adept at recognizing the subclinical or threshold symptomatology that may occur concomitantly with core psychiatric disorders. The authors discuss the development of a spectrum approach to the diagnosis of mental disorders, which offers the potential to improve treatment selection and therapeutic outcomes.

Can psychological factors, such as depression, affect human immunodeficiency virus progession? HIV infection is viewed as a chronic illness in which those infected often confront a number of emotional challenges and physical health and disease-related issues. Over the past 20 years, there has been increasing evidence that depression and other mood-related disturbances are commonly observed among HIV-positive individuals. There is also mounting data showing that depressive symptoms might further impact upon specific elements of immune system functioning and influence quality of life and health status. This paper will highlight studies examining the prevalence of depression during HIV infection and review some of the evidence examining the impact of depressive symptoms on immune function and HIV disease progression.

Postpartum psychiatric changes can range from maternity blues to psychosis. Causality is still undetermined, but explanations for these disturbances often focus on hormonal changes and dysregulation. Researchers have begun the process of delineating what neurobiological factors may be associated with depressive disorders in pregnancy and the postpartum. This article reviews the current literature on the roles of gonadal and pituitary hormones in the psychopathophysiology of postpartum mood disorders. Other biological factors, such as biogenic amines, neuroactive steroids, cholesterol, and fatty acids, are also discussed. The potential benefits of neuroimaging to aid in understanding neuropsychiatric changes that occur in the context of postpartum depression are also considered.

The study of social cognition in psychiatric disorders has become increasingly popular in recent years. This is due to the its proposed link to social functioning and the inability of general neurocognitive skills to explain the spectrum of impairments observed in patients. This article reviews research into two of the processes thought to underlie social cognition (emotion perception and theory of mind) in schizophrenia and autism. This is followed by a look at neuroimaging studies and their efforts to localize the neural correlates of emotion perception and theory of mind in the two disorders. We concluded that while a specific impairment in emotion perception and theory of mind skills cannot be generalized to all individuals with autism and schizophrenia, there are subpopulations that have lingering deficits of social cognition tasks. Neuroimaging work consistently points to the involvement of the fusiform gyrus and amygdala in emotion processing, while the medial prefrontal and frontal cortex are implicated in tasks invoking theory of mind. We propose that deficits of social cognition may benefit from cognitive remediation therapy and pharmacological cognitive enhancers.

It has been proposed that certain Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders share overlapping clinical features, genetic contributions, and treatment response and fall within an “obsessive-compulsive” spectrum. Obsessive-compulsive personality disorder (OCPD) resembles obsessive-compulsive disorder (OCD) and other spectrum disorders in terms of phenomenology, comorbidity, neurocognition, and treatment response.This article critically examines the nosological profile of OCPD with special reference to OCD and related disorders. By viewing OCPD as a candidate member of the obsessive-compulsive spectrum, we gain a fresh approach to understanding its neurobiology, etiology, and potential treatments.

Binge eating disorder (BED) is the most common of eating disorders and is characterized by excessive, out-of-control, rapid food intake. This review focuses on cognitive impairments in BED, which represent an endophenotype that mediates brain function and behavior. Here we focus on reviewing impulsivity, compulsivity, attentional biases to food cues, and executive function. Behavioral regulation in BED appears to be influenced by the context of motivationally salient food cues and the degree of obesity. Deficits in delay discounting and risk taking under ambiguity are impaired in obesity irrespective of BED status. However, in BED subjects with milder obesity, greater risk seeking under explicit probabilistic risk is observed to monetary rewards, whereas this shifts to risk aversion and enhanced delay discounting in more severe obesity. Relative to non-BED obese subjects, BED is characterized by enhanced behavioral inflexibility or compulsivity across multiple domains, with subjects selecting the same choices despite change in relevance (set shifting), being no longer rewarding (habit formation), or irrespective of outcome (perseveration). The context of food cues was associated with multiple attentional and early and late inhibitory impairments and enhanced memory bias, although BED patients also have generalized cognitive interference in working memory. These findings may help explain the phenotype of binge eating. Motivationally salient food cues provoke attentional and memory biases along with impairing response inhibitory processes. Those with BED are also more susceptible to cognitive interference and have impaired decisional impulsivity, with the tendency to inflexibly stick with the same choices irrespective of changes in context. These findings suggest critical cognitive domains that may guide therapeutic interventions.

Objective: To evaluate whether posttraumatic stress disorder (PTSD) is related to outcomes in persons with severe mental illness (SMI) participating in a study of vocatinal rehabilitation programs

Background: PTSD is a common comorbid disorder in people with SMI, but it is unknown whether PTSD interferes with the ability to benefit from rehabilitation programs such as supported employment.

Methods: The relationships between PTSD and symptoms, health, quality of life, and work outcomes was examined in 176 clients with SMI participating in a 2-year randomized controlled trial of three vocational rehabilitation programs: supported employment based on the Individual Placement and Support model, a psychosocial rehabilitation program based on transitional employment, and standard services.

Results: The overall rate of current PTSD in the sample was 16%. Compared with clients without PTSD, clients with PTSD had more severe psychiatric symptoms, worse reported health, lower self-esteem, and lower subjective quality of life. Clients with PTSD who participated in the Individual Placement and Support model (the most effective vocational model of the three studied) also had worse employment outcomes over the 2-year study period than clients without PTSD, with lower rates of compeitive work, fewer hours worked, and fewer wages earned. Employment outcomes did not differ between clients with PTSD versus without PTSD in the other two vocational rehabilitation approaches.

Conclusion: The findings suggest that PTSD may contribute to worse work outcomes in clients participating in supported employment programs. Effective treatment of these clients with PTSD may improve their ability to benefit from supported employment.

ISSUE:A paradigm shift is afoot in which the “last shall be first,” namely, use of long-acting injectable (LAI) antipsychotics, rather than being reserved for use only at the last stages of schizophrenia, may be shifting to first-line treatment of early episodes of this illness.

Objective: As part of this national project, we examined barriers and strategies to implementation of two evidence-based practices (EBPs) in Indiana.

Background: Despite many advances in the knowledge base regarding mental health treatment, the implementation of EBPs in real-world setting remains poorly understood. The National EBP Project is a multi-state study of factors influencing implementation of EBPs.

Methods: Over a 15-month period we observed eight assertive community treatment (ACT) programs and six integrated dual disorders treatment (IDDT) programs and noted pertinent actions taken by the state mental health agency influencing implementation. We created a database containing summaries of monthly visits to each program and interviews with key leaders. Using this database and clinical impressions, we rated barriers and strategies at each site on seven factors: Attitudes, Mastery, Leadership, Staffing, Policies, Workflow, and Program Monitoring.

Results: At the site level, the most frequently observed barriers were in the areas of leadership, staffing and policies for ACT, and mastery and leadership for IDDT. Overall, barriers were more evident for IDDT than for ACT. Strategies were less frequently noted but generally paralleled the areas noted for barriers. However, our central finding was that ACT was generally more successfully implemented than IDDT throughout the state, and that this difference could be traced in large part to state-level factors relating to historical preparation for the practice, establishment of standards, formation of a technical assistance center, and funding.

Conclusion: In this case study, both state-level and site-specific factors influenced success of implementation of EBPs. To address these factors, the field needs systematic strategies to anticipate and overcome these barriers if full implementation is to be realized.