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The aim of this study was to develop self-report and clinician-rated versions of an insight scale that would be easy to administer, sensitive to small changes, and inclusive of the core dimensions of clinical insight into psychosis. Ten-item self-report (VAGUS-SR) and five-item clinician-rated (VAGUS-CR) scales were designed to measure the dimensions of insight into psychosis and evaluated in 215 and 140 participants, respectively (www.vagusonline.com). Tests of reliability and validity were performed. Both the VAGUS-SR and VAGUS-CR showed good internal consistency and reliability. They demonstrated good convergent and discriminant validity. Both versions were strongly correlated with one another and with the Schedule for the Assessment of Insight and Birchwood Insight Scale. Exploratory factor analyses identified three possible latent components of insight. The VAGUS-CR and VAGUS-SR are valid, reliable and easy to administer. They are build on previous insight scales with separate clinician-rated and self-report versions. The VAGUS-SR exhibited a multidimensional factor structure. Using a 10-point Likert scale for each item, the VAGUS has the capacity to detect small, temporally sensitive changes in insight, which is essential for intervention studies with neurostimulation or rapidly acting medications.

Patients with schizophrenia experience higher rates of obesity as well as related morbidity and mortality than the general population does. Women with schizophrenia are at particular risk for antipsychotic-associated weight gain, obesity, and related medical disorders such as diabetes and cardiovascular disease. Given preclinical studies revealing the role of the endogenous opioid systems in human appetite and the potential of antipsychotic medications to interfere with this system, we hypothesized that opioid antagonists may be beneficial in arresting antipsychotic-associated weight gain and promoting further weight loss in women with schizophrenia. In the present study, 24 overweight women with a diagnosis of schizophrenia or schizoaffective disorder were randomized to placebo or naltrexone (NTX) 25 mg/d for 8 weeks. The primary outcome measure was a change in body weight from baseline. The patients in the NTX group had significant weight loss (-3.40 kg) compared with weight gain (+1.37 kg) in the patients in the placebo group. Mainly, nondiabetic subjects lost weight in the NTX arm. These data support the need to further investigate the role of D2 blockade in reducing food reward-based overeating. A larger study addressing the weaknesses of this pilot study is currently underway.

SummaryGenes disrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise healthy families. Furthermore, during normal brain development, genes are expressed in patterns specific to developmental stage and neuroanatomical structure. We identified de novo mutations in persons with schizophrenia and then mapped the responsible genes onto transcriptome profiles of normal human brain tissues from age 13 weeks gestation to adulthood. In the dorsolateral and ventrolateral prefrontal cortex during fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network significantly enriched for transcriptional coexpression and protein interaction. The 50 genes in the network function in neuronal migration, synaptic transmission, signaling, transcriptional regulation, and transport. These results suggest that disruptions of fetal prefrontal cortical neurogenesis are critical to the pathophysiology of schizophrenia. These results also support the feasibility of integrating genomic and transcriptome analyses to map critical neurodevelopmental processes in time and space in the brain.

Individuals with schizophrenia are not physically active and experience high rates of obesity, diabetes, and heart disease. Research shows that the Internet is a valuable and convenient source of health information for individuals with schizophrenia. Despite its importance, online physical activity, exercise, and sport information for this population has not been assessed. The purpose of this review was to evaluate the accuracy, quality, and readability of online physical activity, exercise, and sport information for people with schizophrenia. This review followed an adapted methodology proposed by Jetha, Faulkner, Gorczynski, Arbour, and Martin Ginis (2011). Websites were obtained from mental health organizations and following a standardized search protocol. Websites were included in the review if they discussed physical activity, exercise, or sport information and individuals with schizophrenia. Overall, 17 websites were included in the review. Two researchers independently evaluated each website for descriptive characteristics, information accuracy, technical quality, theoretical behavioral quality, targeting strategies, and readability. Information on physical activity, exercise, or sport was mostly provided on websites designed by community organizations (41%) and news agencies (41%). Most websites (59%) did not provide information that was supported by any physical activity guidelines for aerobic or resistance exercises. Nearly all websites (94%) mentioned the benefits and barriers to active living, but few (29%) discussed other cognitive or behavioral aspects that could promote physical activity participation. The majority of websites (88%) required a reading grade level of 10 or higher. More research is necessary to help tailor online physical activity, exercise, and sport information for this population.

Consumers of mental health services die an average of 25 years earlier than the general public. Many of the health conditions that are associated with death in the United States and premature death in mental health consumers can be prevented and managed with positive health habits. The six most common causes of death are heart disease, cancer, stroke, lung conditions, accidents, and diabetes. We assert that many of the known risk factors for early death can be addressed with positive health habits. We discuss barriers to ideal health care, describe what is known about effective interventions for common risk factors, and, where information is available, what kinds of special interventions have been found to be effective for mental health consumers. We close with a set of recommendations based on three levels of interventions: those that can be readily implemented with little additional resource; those that require local leadership and some resources; and those that require national leadership to transform ...

Gerard E. Hogarty was a scholar and clinician whose career was dedicated to improving the lives of persons with schizophrenia through the rigorous development and testing of novel psychosocial treatment approaches. During the course of his career, he is credited with the development of many of the psychosocial treatments that have become the pillars of evidence-based practices for schizophrenia today. This review outlines the evolution of Hogarty's contributions to the development of psychosocial approaches for schizophrenia by presenting a chronological history of the 4 distinct treatments he developed during the course of his career. These include major role therapy, an early precursor to clinical case management; family psychoeducation, an approach to ally with and educate family members to reduce intrafamilial distress; personal therapy, a flexible, individual psychotherapy, aimed at teaching patients stress management and affective regulation techniques; and finally, cognitive enhancement therapy, a comprehensive, developmental approach to the remediation of social- and nonsocial-cognitive deficits. Each of these treatments built upon the findings of the previous one, and as a consequence, each significantly improved the lives of persons with schizophrenia and expanded the treatment possibilities available to such individuals. These efforts represent a lifelong dedication to advancing the treatment of schizophrenia through rigorous scientific inquiry and exemplify a unique combination of science and humanism that has left a lasting impact on the field and the lives of many individuals suffering from this disease.

The prevalence of obesity in the United States population is increasing, and similar trends can be observed among schizophrenia patients. No thorough examination of the actual nutritional composition of the diet of schizophrenia patients in the United States has been carried out. We therefore employed a 24-hour diet recall in 146 schizophrenia outpatients to gather information on different nutritional variables, such as total caloric intake and total fat, protein, carbohydrate, cholesterol, and fiber content. Data were subsequently compared to data for the general population collected in the Third National Health and Nutrition Examination Survey (NHANES III). Schizophrenia patients as a group ate more food when compared to NHANES III subjects, but the relative percentages of calories derived from fat, protein, and carbohydrates were not found to be different. Therefore, it is unlikely that schizophrenia patients make dietary choices different from those of people in the general population. Instead, schizophrenia patients seem to eat more of the same food.

Reasons for switching patients to different antipsychotic drugs and strategies for doing so are reviewed. Atypical antipsychotics have better adverse-effect profiles than conventional agents and may have subtle advantages in terms of efficacy. Patients who do not respond satisfactorily to one atypical antipsychotic agent may do so to another. Thus, many patients taking antipsychotic agents may benefit from a switch to another drug. However, the transition from one agent to another is itself associated with risks and uncertainties. Several switching strategies have been proposed that involve the abrupt or gradual cessation of the old drug combined with the abrupt or gradual initiation of the new drug. There are few data to suggest that one strategy is superior to another. A clinical appraisal of the conditions under which switching of drugs should occur and a careful evaluation of the appropriate strategy can help minimize the risks of switching. Planning and follow-up should include the patient, the patient's family, and social-support personnel. Guidelines for switching drugs and managing patients during the transition are being developed. When switching patients from one antipsychotic to another, good clinical judgment and a conservative approach can be used to balance the risk of clinical exacerbation with that of increased adverse effects.

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.

Over a 5-year period, 77 patients in their first episode of psychosis were recruited into a study of autoimmune factors in the pathogenesis of schizophrenia. In this article their demographic and clinical characteristics are compared to those of chronic patients recruited into the same study as well as to the entire outpatient population of a schizophrenia clinic in a Pittsburgh community mental health center. There were no significant demographic differences between the first-episode patients and either of the other groups of schizophrenic patients. There was a significantly higher proportion of black subjects in the clinic population compared to the catchment area from which they were drawn. Clinically, first-episode patients differed from chronic patients in having fewer negative symptoms and more of certain positive symptoms. Age of onset was not significantly different in male and female first-episode cases, although there was a trend of females to be slightly older. We conclude that if diagnosis includes followup and reassessment, findings from research cohorts such as ours can be generalized to populations of outpatient schizophrenic subjects volunteering for treatment.

Objective: Aripiprazole is a second-generation antipsychotic that is increasingly prescribed in a variety of psychiatric disorders. The goal of this study was to investigate patient and treatment factors associated with aripiprazole treatment continuation on hospital discharge in psychiatric inpatients. Method: This was a retrospective cohort analysis of patients admitted to a psychiatric hospital between January 1, 2003, and June 30, 2006, and treated with aripiprazole. The goal was to determine factors associated with continuation of aripiprazole throughout the hospital stay and on discharge from the hospital. Covariates assessed included patient demographics, prior psychiatric hospitalizations, diagnoses, prior antipsychotic use, and concomitant psychotropic medications. Aripiprazole-specific covariates were starting and maximum dose and dose titration pattern. Diagnoses were identified using ICD-9-CM codes. Results: There were 1957 aripiprazole-treated patients included in this study, and 1573 (80%) continued aripiprazole treatment at the time of hospital discharge. Median starting doses were lower (5 mg/day) for younger and older patients, and patients with psychotic disorders received higher doses than other patients. Approximately 58% of patients had at least 1 aripiprazole dose titration while hospitalized, and most (73%) of those patients had a dose titration within 3 days of admission. Predictors of treatment continuation in this broad patient population were younger age, a diagnosis of bipolar or major depressive disorder, higher maximum aripiprazole doses, and upward dose titration within 3 days of admission. Patients receiving concomitant anticholinergics or antipsychotics were less likely to continue treatment as were those receiving aripiprazole at the time of hospitalization. Conclusion: In this acute inpatient psychiatric setting, continuation of aripiprazole treatment on discharge was achieved in most patients. Demographic, diagnostic, and treatment factors predicting aripiprazole treatment effectiveness were identified. (J Clin Psychiatry 2008;69:1393‐1397)

Compared with the general population, individuals with schizophrenia demonstrate an increased prevalence of obesity. While most antipsychotics are associated with weight gain, certain second-generation antipsychotics (SGAs) appear to be especially problematic. Weight gain and obesity are highly distressing to these patients, can reduce treatment adherence, and may increase the relative risk of serious medical conditions and all-cause premature mortality. The selection of an antipsychotic on the basis of its effectiveness and relative side effect profile is recognized as an important initial consideration in the treatment of schizophrenia. However, less is known regarding the efficacy of dietary, pharmacologic, and behavioral therapy in reducing antipsychotic-related weight gain and obesity. Behavioral therapy, in particular, is understudied, and there are relatively few controlled trials of its effectiveness in reducing SGA-induced weight gain. Although weight loss resulting from behavioral therapy has been observed mostly as a result of effective short-term interventions, controlled behavioral studies do exist to suggest that weight can be controlled long term. In addition, a small pilot study in patients with schizophrenia or schizoaffective disorder recently demonstrated that behavioral therapy that utilizes stepped interventions, involving body weight self-monitoring, diet, and exercise, can prevent weight gain in patients initiating treatment with SGAs. Additional studies of behavioral therapy for long-term weight control in patients with schizophrenia and other forms of severe mental illness are warranted.

A case-control association study was conducted among patients with schizophrenia (DSM-III-R, n = 141) and unaffected controls (n = 177) of Caucasain and African-American ethnicity. No significant differences in the distribution of a dinucleotide repeat polymorphism in the neurotrophin-3 (NT-3) gene were noted between the two groups. This study does not support an association between schizophrenia and the NT-3 gene locus in a United States cohort.

The autoimmune basis for schizophrenia has been investigated for the last 60 years. Although numerous immune abnormalities have been reported, the current literature is viewed with much skepticism because most of the studies have failed to control for extraneous factors that may have influenced the findings. Principally, antipsychotic medication, duration of illness, and current clinical state (acutely psychotic or remitted) may considerably alter immune response, as may other factors such as nutritional status, substance abuse, and concurrent medical illness. We review recent studies that employed current diagnostic criteria and modern immunologic techniques. (These studies were located by use of a Medline search on the terms schizophrenia and psychosis, cross-referenced with immune abnormalities, lymphokines, antibodies, lymphocytes, HLA, and medication, and by perusing the reference lists in the articles found through this search.) Immune abnormalities that have been replicated in studies of schizophrenic patients include increased prevalence of antinuclear antibodies, decreased production of interleukin-2, and increased serum concentrations of interleukin-2 receptor and interleukin-6. Given the current importance of autoimmunity as an etiologic mechanism in several branches of medicine, further studies are needed, especially those having a longitudinal design and including drug-naive patients.

Lack of association between schizophrenia and a CAG repeat polymorphism of the hSKCa3 gene in a North Eastern US sample

Background In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone. Methods In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued. Results The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (± standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 ± 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61–0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; p < 0.0001) and in PANSS positive (-3.0; p < 0.0001), negative (-0.9; p = 0.171) and anxiety/depression (-1.4; p = 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal. Conclusion When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated. Trial registration ClinicalTrials.gov NCT00378183