Over 30 years of STEP: The Pittsburgh experience with first-episode psychosis.

AIMS: For over 30 years, combined research and treatment settings in the US have been critical to conceptualizing care for first-episode psychosis (FEP). Here we describe an early example of such a context, the Services for the Treatment of Early Psychosis (STEP) clinic, which is affiliated with the University of Pittsburgh. METHODS: We describe STEP's historical roots and establishment in the early 1990s; STEP's research and treatment contributions, alongside its growth and ongoing leadership. RESULTS: Research-based clinics, like STEP, preceded and helped pave the way for the Recovery After an Initial Schizophrenia Episode project in the US and the ensuing Coordinated Specialty Care (CSC) approach, now widely adopted in the US. Early clinic-based research at STEP helped establish protocols for psychopharmacology, the relevance of effective early treatment, including psychosocial approaches, and highlighted disparities in treatment outcomes across race/ethnicity. Multidisciplinary collaboration and dialogue with consumers contributed to early treatment, combining psychosocial and pharmacological approaches. STEP adopted CSC and is situated within a bi-state Learning Health System. STEP has retained a relatively unique 5-year treatment model and exists within continuum of care ideally suited to studying psychotic illness and treatment outcomes. CONCLUSIONS: STEP remains the largest academic FEP clinic in Pennsylvania. Academic FEP clinics like STEP will have a critical role within Learning Health Systems nationally to model participatory approaches, sustain early intervention treatment quality and ongoing treatment developments.

Body composition, pre-diabetes and cardiovascular disease risk in early schizophrenia.

AIM: This preliminary study examines the relationship between body composition, insulin resistance and NCEP-III-defined cardiovascular disease risk factors in persons early in the course of schizophrenia exposed to commonly prescribed atypical antipsychotic medications. METHODS: Subjects underwent modified oral glucose tolerance tests (OGTTs) and DEXA (dual X-ray absorptiometry) scans corrected for relevant sociodemographic data, including activity levels. We used linear multiple regression models to evaluate relationships between body composition and metabolic variables. RESULTS: Thirty-six individuals diagnosed with schizophrenia, receiving atypical antipsychotic monotherapy, and within 5 years of illness onset, participated. Average age was 25.1 ± 3.6 years (range, 19-34) and duration of illness was 2.5 years (30 ± 18 months). Mean body mass index (BMI) was 28.3 ± 4.9, with a mean total body fat mass of 28.6 ± 8.4%, suggesting an increase in fat relative to BMI. Ten participants (28%) had pre-diabetes (fasting glucose 100-126 mg dL-1 or 2-h OGTT 140-200 mg dL-1 ), but no participant had diabetes. Insulin resistance (HOMA-IR) was predicted by total body mass (BMI) more so than by body fat mass, with an incremental contribution derived from antipsychotics. Insulin secretion in response to glucose challenge was predicted by BMI, body fat mass and antipsychotic medication. CONCLUSIONS: Fat mass relative to BMI was increased in early schizophrenia patients receiving atypical antipsychotics. Body composition accounted for most of the variance in risk for abnormalities in glucose metabolism. Incremental contributions were derived from atypical antipsychotics, in line with their known adipogenicity. If direct fat mass measures are unavailable, frequent BMI measures may be practical proxy markers for metabolic risk.

Adherence to Diabetes Medication in Individuals with Schizophrenia: A Systematic Review of Rates and Determinants of Adherence.

INTRODUCTION: Despite the importance of medication adherence for the effective treatment of type II diabetes mellitus (T2DM), little research has examined adherence with diabetes medication treatment in schizophrenia. The purpose of this systematic review was to: 1) evaluate rates of adherence and determinants of adherence with medication for T2DM in individuals with schizophrenia; and, where possible, 2) examine the relationship between medication adherence and glycemic control. METHODS: Studies were included if they presented information on dosing regimens and adherence or compliance rates for T2DM and included samples where at least 50% of the participants were individuals with schizophrenia. RESULTS: Six studies were included in this review that predominantly examined men over the age of 50 years. Studies confirmed that many individuals with schizophrenia were not adhering to their diabetes medication as adherence rates ranged from 51-85%. Two studies that compared medication adherence in individuals with and without schizophrenia found those with the mental illness had higher rates of adherence. One study reported that blood glucose control levels were not statistically different between those who did and did not adhere to their medication, indicating more research is necessary in this area. Factors that improved adherence included disease and medical service and medication-related factors. CONCLUSIONS: Interventions to increase diabetes medication adherence in schizophrenia need to address disease and medical service and medication-related factors. Further research needs to examine diabetes medication adherence in women, younger individuals, and those recently diagnosed with diabetes as these individuals have been underrepresented in the literature.

Physical activity and sedentary behavior measured objectively and subjectively in overweight and obese adults with schizophrenia or schizoaffective disorders.

OBJECTIVE: Describe objective and subjective physical activity levels and time spent being sedentary in adults with schizophrenia or schizoaffective disorders (SZO/SA). METHOD: Baseline physical activity and sedentary behaviors were assessed among 46 overweight and obese community-dwelling adults (aged 18-70 years; BMI > 27 kg/m(2)) diagnosed with SZO/SA by DSM-IV-TR, with mild symptom severity (Positive and Negative Syndrome Scale score < 90) who were interested in losing weight and participated in the Weight Assessment and Intervention in Schizophrenia Treatment (WAIST) study from 2004 to 2008. Objective physical activity levels, measured using actigraphs, in WAIST were compared to a nationally representative sample of users (n = 46) and nonusers (n = 46) of mental health service (MHS) from the National Health and Nutrition Examination Survey (NHANES 2003-2004) matched by sex, BMI, and age. RESULTS: On average, adults with SZO/SA wore actigraphs more than 15 h/d for 7 days averaging 151,000 counts/d. The majority of monitoring time (81%) was classified as sedentary (approximately 13 h/d). Moderate/vigorous and light physical activity accounted for only 2% (19 min/d) and 17% (157 min/d) of monitoring time/d, respectively. Primary source of activity was household activities (409 ± 438 min/wk). Fifty-three percent reported walking for transportation or leisure. Adults with SZO/SA were significantly less active (176 min/d) and more sedentary (756 min/d) than NHANES users of MHS (293 and 640 min/d, respectively) and nonusers of MHS (338 and 552 min/d, respectively) (P < .01). CONCLUSIONS: Overweight and obese adults with SZO/SA were extremely sedentary; engaged in unstructured, intermittent, low-intensity physical activity; and significantly less active than NHANES users and nonusers of MHS. This sedentary lifestyle is significantly lower than those of other inactive US populations, is costly for the individual and community, and highlights the need for physical activity promotion and interventions in this high risk population.

Perfectionistic self-presentation and suicide in a young woman with major depression and psychotic features.

A woman in her midtwenties with a history of major depressive disorder and a recent major depressive episode with mood-congruent psychotic features died by suicide. Two weeks before her death, she demonstrated exceptional elevations on the nondisplay of imperfection factor of Hewitt and Flett's Perfectionistic Self-Presentation Scale. Perfectionism and especially perfectionistic self-presentation have been strongly associated with suicide across several populations, accounting for unique variance in suicidality beyond depression and hopelessness. Yet interpersonal facets of perfectionism are not recognized as clinical risk factors for suicide. There is also a paucity of research on perfectionism in relation to psychotic symptoms. This case account illustrates the role of perfectionistic self-presentation in suicides that occur seemingly without warning and, to our knowledge, this is the first examination of perfectionistic self-presentation and suicide in a case where psychotic features occurred. This study, though single case-based, draws attention to perfectionism and perfectionistic self-presentation and their potential roles in suicide, especially when accompanied by other risk factors. Future research in this area may elucidate the role of perfectionism in suicide, singularly and in the context of a comprehensive clinical risk assessment, demonstrating whether perfectionism confers information about suicide risk beyond known clinical risk factors.

The VAGUS insight into psychosis scale--self-report and clinician-rated versions.

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.

A randomized, double-blind, placebo-controlled pilot study of naltrexone to counteract antipsychotic-associated weight gain: proof of concept.

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.

Testing a modification of cognitive adaptation training: streamlining the model for broader implementation.

Cognitive adaptation training (CAT) is a home-based, manualized treatment that utilizes environmental supports to improve target behaviors and functional outcomes in persons with schizophrenia. Although clinical trials have shown CAT to be effective across functional, clinical, and treatment adherence domains, when the intervention is withdrawn clients experience significant declines. The aim of the current study was to test a modified version of CAT, which decreases the duration of intensive CAT intervention while utilizing ongoing case management-supported CAT to maintain the fundamental components of the treatment. Twenty-three people participated in an outcome study of the modified version of CAT, evaluating improvements after 4months of CAT specialist intervention and after an additional 5months of case manager support. Analysis revealed significant improvements in adaptive functioning, psychiatric symptomatology, and goal attainment, which were maintained throughout case management follow-up. This suggests that an intervention that has previously demonstrated good functional outcomes in randomized trials might sustain its impacts in an abbreviated format with support from existing case managers.

Sedentary behavior and psychiatric symptoms in overweight and obese adults with schizophrenia and schizoaffective disorders (WAIST Study).

OBJECTIVE: Examine the association between sedentary behavior and psychiatric symptoms among overweight and obese adults with schizophrenia or schizoaffective disorders (SZO/SA). DESIGN: Randomized clinical trial; Weight Assessment and Intervention in Schizophrenia Treatment (WAIST) Study: baseline data collected 2005-2008. SETTING: University of Pittsburgh Medical Center, Pittsburgh, PA, USA. PARTICIPANTS: Community-dwelling adults diagnosed with SZO/SA, with mild symptom severity [Positive and Negative Syndrome Scale (PANSS)<90], who were interested in losing weight, age 18-70years, BMI>27kg/m(2). MEASUREMENTS: Objectively measured sedentary behavior by accelerometry, and psychopathology assessed by PANSS. Participants wore the actigraphs for 7 consecutive days during their waking hours. Sedentary behavior was defined as ≤100 counts per minute during wear-time and excluded sleep and non-wear time. RESULTS: On average, 81% of the participant's monitoring time or 756min/day was classified as sedentary behavior using accelerometry. No association was observed between sedentary behaviors and PANSS psychiatric symptoms [total (p≥0.75), positive (p≥0.81), negative (p≥0.59) and general psychopathology (p≥0.65) subscales]. No association was observed between sedentary behaviors and age, race, gender and BMI. CONCLUSION: From a clinical and public health perspective, the amount of time (approximately 13h) and percentage of time (81% excluding non-wear time associated with sleeping) engaged in sedentary behavior among overweight and obese adults in this population is alarming, and points to an urgent need for interventions to decrease sedentary behaviors. The lack of associations between sedentary behavior and psychiatric symptoms may be due to a ceiling effect for sedentary behavior.

Health-related quality of life, adiposity, and sedentary behavior in patients with early schizophrenia: preliminary study.

OBJECTIVE: To examine adiposity and sedentary behavior in relation to health-related quality of life (QoL) in patients with early schizophrenia. METHODS: A cross-sectional study was used to assess adiposity by dual-energy X-ray absorptiometry scans, habitual physical activity and idle sitting time by the Short Form International Physical Activity Questionnaire, and health-related QoL by the RAND Medical Outcomes Study SF-36. QoL scores were compared with age-adjusted Canadian normative population data. RESULTS: There were 36 participants with early schizophrenia, average age 25.1 (±3.6). Twenty-nine (72.5%) were males. Mean illness duration was 30 (±18) months, and mean body mass index was 28.3 (±5). Females had higher body fat content than males (30.8 ±6.9 vs 24.7 ± 10.6; t = -2.6, df = 34; P = 0.015). Total body fat (F = 14; P = 0.001), lean body mass (F = 10.2; P = 0.001), and sedentary behavior (F = 5; P = 0.013) significantly increased across body mass index categories. Total body fat was correlated with sedentary behavior (r = 0.62; P = 0.001), and total lean body mass was negatively correlated with sedentary behavior (r = 0.39; P = 0.03). Based on SF-36 scores, participants had significantly lower physical functioning (P = 0.0034), role physical (P = 0.0003), general health (P < 0.0001), vitality (P = 0.03), and physical component scores (P = 0.003) than Canadian population comparisons. Habitual sedentary behavior, more than activity or adiposity levels, was associated with health-related QoL in early schizophrenia. CONCLUSION: Health-related QoL is lower in early schizophrenia and is predominantly experienced in the physical domain. QoL in early schizophrenia relates to sedentary behavior more than to activity and adiposity levels.

Cognitive remediation for individuals with psychosis in a supported education setting: a pilot study.

Cognitive remediation (CR) is a treatment approach that is being increasingly examined as a means through which the cognitive impacts of schizophrenia might be ameliorated. While CR has demonstrated good outcomes when paired with supported employment, little is known regarding how it might be integrated within supported education contexts. In this study CR was examined in a supported education context with 16 individuals with psychosis. The findings indicated that CR aligned well with the academic curriculum with very low attrition, was found useful by students, and showed similar pre-post differences on cognitive measures as those found in previous work.

Changes in weight and other metabolic indicators in persons with schizophrenia following a switch to aripiprazole.

For patients who gain a troublesome amount of weight on antipsychotics, switching to a less obesogenic agent is an option. Aripiprazole appears to cause less weight gain than many other antipsychotics. We report on changes in weight, and other risk factors for heart disease, in thirty-three schizophrenia patients who agreed to switch from other antipsychotics to aripiprazole in an open, flexible-dose, eight-week trial. All patients were successfully switched. There were no significant changes in PANSS symptom scores or in CGI. Weight (Wt), waist circumference (WC), and low-density lipoprotein (LDL) decreased significantly in the group as a whole. In patients switched from olanzapine to aripiprazole, Wt, WC, LDL, fasting glucose, and triglycerides were significantly decreased as compared to baseline. Substantial decreases in several risk factors were also seen in patients switched from quetiapine, but these changes did not reach statistical significance.

Prevention of metabolic syndrome in serious mental illness.

The interaction of lifestyle, socioeconomic status, genetic factors, and treatment with antipsychotic medications likely accounts for the high risk of metabolic syndrome, diabetes, heart disease, and premature mortality in people with serious mental illness. Given the high risk of developing diabetes and cardiovascular disease in persons with serious mental illness, psychiatrists who treat these individuals need to ensure they are familiar with these risks, monitor metabolic parameters in their patients, and educate their patients (and caregivers) about the risks and how to prevent them.

Low cardiorespiratory fitness and physical functional capacity in obese patients with schizophrenia.

BACKGROUND: Low cardiorespiratory fitness is a prominent behavioral risk factor for cardiovascular disease (CVD) morbidity and mortality, as cardiorespiratory fitness is strongly associated with CVD outcomes. High rates of CVD have been observed in the schizophrenia population, translating into a markedly reduced life expectancy as compared to healthy controls. Surprisingly however, while cardiorespiratory fitness is an eminent indicator for overall cardiovascular health as well as eminently modifiable risk factor for CVD, no studies have systematically assessed cardiorespiratory fitness in schizophrenia. METHODS: Community-dwelling schizophrenia patients underwent graded-exercise tests, to ascertain maximal oxygen uptake (Max Vo2), considered to be the gold standard for the evaluation of cardiorespiratory fitness and physical functional capacity. The modified Bruce protocol was used to ascertain cardiorespiratory fitness and physical functional capacity; data was normalized and compared to population standards derived from the ACLS (Aerobics Center Longitudinal Study) and the National Health and Nutrition Examination Surveys (NHANES), Cycles III and IV. RESULTS: Data for n=117 participants (41% male, 46% white) was analyzed. Mean age (y) was 43.2±9.9, and mean BMI was 37.2±7.3. Peak HR attained during exercise was 145.6±19.6, after 8.05±3.6 min, achieving 111.2±44.2W. Max Vo2 was 1.72±6.6l/min, MaxVCo2 1.85±7.2l/min, and minute ventilation (VE) was 55.6±21.9 ml/s. PANSS Positive subscores (13.3±4.4; r=-0.21, p=0.024) were inversely correlated with Max Vo2 ml(-1)min(-1) kg(-1). Neither PANSS Total (56.3±12.3; r=-0.105, p=0.72), PANSS Negative (14±5.1; r=-0.52, p=0.57) nor PANSS General Psychopathology (28.4±7.4; r=-0.28, p=0.76) scores were correlated with Max Vo2 ml(-1) min(-1) kg(-1). Peak heart rate and duration of exercise were not correlated with PANSS scores. Compared to healthy controls derived from the ACLS and NHANES, respectively, 115 participants achieved 'low levels' of fitness only, as well as highly significantly reduced Max Vo2, across all age groups. CONCLUSION: The test was generally well received and tolerated by those who elected to participate; and adherence to the protocol was good. Among participants with schizophrenia, most of whom were obese, and across all age groups, cardiorespiratory fitness was exceedingly poor. Only two participants in our entire sample fit the categorization of 'moderate fitness level'; that is, a fitness level at or above the 20th percentile of ACLS-derived population comparisons. Conversely, this left 98.3% of participants with schizophrenia below population standards. Low cardiorespiratory fitness emerges as an eminent modifiable risk factor for CVD mortality and morbidity in schizophrenia complicated by obesity.

Web-based psychoeducational intervention for persons with schizophrenia and their supporters: one-year outcomes.

OBJECTIVE: This study examined the use of a uniquely designed Web site and home computers to deliver online multifamily psychoeducational therapy to persons with schizophrenia and their informal supports (family and friends). Web site usage and outcome benefits are reported. METHODS: Thirty-one persons with schizophrenia or schizoaffective disorder and 24 support persons were randomly assigned to the online intervention (telehealth) or treatment as usual (usual care) condition. At three, six, and 12 months, interviewer-administered assessments were conducted with participants. Intention-to-treat analyses compared persons with schizophrenia in the two study conditions on severity of positive symptoms and knowledge of schizophrenia. Support persons in the two study conditions were compared on knowledge of schizophrenia. Each participant's usage of the Web site was logged. RESULTS: Persons with schizophrenia in the telehealth condition had a large and significant reduction in positive symptoms (p=.042, d=-.88) and a large and significant increase in knowledge of schizophrenia compared with their counterparts in the usual care condition. Support persons in the telehealth condition showed a large and significant increase in knowledge about prognosis compared with those in the usual care condition (p=.036, d=1.94). Persons with schizophrenia used the Web site to a much greater extent (pages viewed and time spent) than support persons. CONCLUSIONS: These findings suggest that online delivery of psychotherapeutic treatment and educational resources to consumers' homes has considerable potential to improve consumer well-being and offers several advantages over standard clinic-based delivery models.

Predictors of aripiprazole treatment continuation in hospitalized patients.

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.

Addressing cardiometabolic risk during treatment with antipsychotic medications.

PURPOSE OF REVIEW: To raise awareness of and inform evidence-based practice regarding medical and behavioral interventions for antipsychotic medication-induced metabolic abnormalities. RECENT FINDINGS: The current literature indicates that individuals with severe and persistent mental illness have significantly worse health outcomes and premature mortality than the general population, owing to a combination of under-recognition and treatment of medical risk factors, reduced access to care, sedentary lifestyle and poor diet, and the potential contribution of adverse metabolic side effects of antipsychotic medications such as weight gain, hyperglycemia and dyslipidemia. A combination of administrative, behavioral and medical approaches to addressing these medical risks may be more effective than any one of these approaches alone. SUMMARY: Treatment with antipsychotic medications can induce significant weight gain and abnormalities in lipid and glucose metabolism that increase risk for cardiovascular disease and diabetes in a population already at risk from multiple other sources. Managing the side effects of antipsychotics and lowering risk in general is an important aspect of the management of chronic mental illness. There are a variety of effective medical and behavioral interventions that can be employed to achieve primary and secondary prevention aims.