Interaction of Cannabis Use Disorder and Striatal Connectivity in Antipsychotic Treatment Response

Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD

Cost-Effectiveness of Comprehensive, Integrated Care for First Episode Psychosis in the NIMH RAISE Early Treatment Program

This study compares the cost-effectiveness of Navigate (NAV), a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis (FEP) and usual Community Care (CC) in a cluster randomization trial. Patients at 34 community treatment clinics were randomly assigned to either NAV (N = 223) or CC (N = 181) for 2 years. Effectiveness was measured as a one standard deviation change on the Quality of Life Scale (QLS-SD). Incremental cost effectiveness ratios were evaluated with bootstrap distributions. The Net Health Benefits Approach was used to evaluate the probability that the value of NAV benefits exceeded its costs relative to CC from the perspective of the health care system. The NAV group improved significantly more on the QLS and had higher outpatient mental health and antipsychotic medication costs. The incremental cost-effectiveness ratio was $12 081/QLS-SD, with a .94 probability that NAV was more cost-effective than CC at$40 000/QLS-SD. When converted to monetized Quality Adjusted Life Years, NAV benefits exceeded costs, especially at future generic drug prices

A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes

Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30mg/d) or risperidone (1-6mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications

Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders: Baseline Results From the RAISE-ETP Study

IMPORTANCE: The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear. OBJECTIVE: To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS: Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment. EXPOSURE: Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision. MAIN OUTCOMES AND MEASURES: Body composition and fasting lipid, glucose, and insulin parameters. RESULTS: In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P≤.01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P≤.02). CONCLUSIONS AND RELEVANCE: In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program

The primary aim was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis designed for implementation in the U.S. healthcare system, to Community Care on quality of life

Prescription Practices in the Treatment of First-Episode Schizophrenia Spectrum Disorders: Data From the National RAISE-ETP Study

Treatment guidelines suggest distinctive medication strategies for first episode and multi-episode patients with schizophrenia. How much community clinicians adjust their usual treatment regimens for first episode patients is unknown. We examined prescription patterns and factors associated with prescription choice within a national cohort of early phase patients

The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and Description of Psychosocial Components

Comprehensive coordinated specialty care programs for first episode psychosis have been widely implemented in other countries, but not in the U.S. The National Institute of Mental Health’s (NIMH) Recovery After Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first episode treatment programs designed for the U.S. healthcare system. This paper describes the background, rationale, and nature of the intervention developed by the Early Treatment Program project, the NAVIGATE program, with a particular focus on its psychosocial components. NAVIGATE is a team-based, multi-component treatment program designed to be implemented in routine mental health treatment settings and aimed at guiding people with a first episode of psychosis (and their families) towards psychological and functional health. The core services provided in the NAVIGATE program include the Family Education Program, Individual Resiliency Training, Supported Employment and Education, and Individualized Medication Treatment. NAVIGATE embraces a shared decision-making approach with a focus on strengths and resiliency, and collaboration with clients and family members in treatment planning and reviews. The NAVIGATE program has the potential to fill an important gap in the U.S. healthcare system by providing a comprehensive intervention specially designed to meet the unique treatment needs of persons recovering from a first episode of psychosis. The program is currently being evaluated in cluster randomized controlled trial comparing NAVIGATE to usual community care

Climate drives the geography of marine consumption by changing predator communities

Este artículo contiene 7 páginas, 3 figuras, 1 tabla.The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth’s ecosystems.We acknowledge funding from the Smithsonian Institution and the Tula Foundation.Peer reviewe