Context and Expectations Matter: Social, Recreational, and Independent Functioning among Youth with Psychosis in Chennai, India and Montreal, Canada.

OBJECTIVES: Most cross-cultural psychosis research has focused on a limited number of outcomes (generally symptom-related) and perspectives (often clinician-/observer-rated). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to patient-reported measures of social, recreational, and independent functioning. Addressing this gap, this study aimed to compare these outcomes in first-episode psychosis at a high-income site and a lower middle-income site. METHODS: Patients receiving similarly designed early intervention for psychosis in Chennai, India (N = 164) and Montreal, Canada (N = 140) completed the self-reported Social Functioning Scale-Early Intervention, which measures prosocial, recreation, and independence-performance functioning. Their case managers rated expected independence-performance functioning. Both sets of assessments were done at entry and Months 6, 18, and 24. Linear mixed model analyses of differences between sites and over time were conducted, accounting for other pertinent variables, especially negative symptoms. RESULTS: Linear mixed models showed that prosocial, recreation, and independence-performance functioning scores were significantly higher in Montreal than Chennai and did not change over time. Expected independence-performance was also higher in Montreal and increased over time. Negative symptoms and education independently predicted prosocial, recreation, and expected independence-performance functioning. When added to the model, expected independence-performance predicted actual independence-performance and site was no longer significant. At both sites, prosocial and recreation scores were consistently lower (<40%) than independence-performance (40-65%). CONCLUSION: This is the first cross-cultural investigation of prosocial, recreation, and independent functioning in early psychosis. It demonstrates that these outcomes differ by socio-cultural context. Differing levels of expectations about patients, themselves shaped by cultural, illness, and social determinants, may contribute to cross-cultural variations in functional outcomes. At both sites, social, recreational, and independent functioning were in the low-to-moderate range and there was no improvement over time, underscoring the need for effective interventions specifically designed to impact these outcomes.

Trust of patients and families in mental healthcare providers and institutions: a cross-cultural study in Chennai, India, and Montreal, Canada.

PURPOSE: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada, and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. METHODS: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Nonparametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. RESULTS: The study included 333 patients (Montreal = 165, Chennai = 168) and 324 family members (Montreal = 128, Chennai = 168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. CONCLUSION: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes.

Unfinished business: Functional outcomes in a randomized controlled trial of a three-year extension of early intervention versus regular care following two years of early intervention for psychosis.

OBJECTIVE: To investigate whether first-episode psychosis patients receiving extended early intervention had better functional outcomes than those in regular care and to examine the predictors of functional outcomes. METHODS: This is a randomized controlled single-blind trial of 220 patients randomized after 2 years of early intervention to receive early intervention or regular care for the subsequent 3 years. Outcomes included cumulative time in functional recovery during the 3-year trial assessed using the Social and Occupational Functioning Assessment Scale (SOFAS); and employment/education at last assessment which were, respectively, analyzed using multiple linear regression and logistic regression, accounting for well-known predictors. Linear mixed and generalized linear models were also used to examine the course of SOFAS and employment/education over the 3-year period. RESULTS: The extended early intervention and regular care groups did not differ on time in functional recovery (mean = 50.17 weeks, SD = 46.62 vs. mean = 46.18 weeks, SD = 51.54); percent employed/in school (60.4% vs. 68.8%) or change in SOFAS or employment/education status over time. SOFAS scores were stable between years 2 and 5. Individuals with longer periods of total symptom remission experienced significantly longer periods of functional recovery and were likelier to be employed/in school. Those who had completed high school were nine times likelier to be employed/studying. CONCLUSION: Most individuals maintained functional gains accrued from 2 years of early intervention with no further improvement whether in extended early intervention or regular care. There was a gap between symptomatic and functional recovery, and one-third were unemployed/not in school at year 5. The lack of additional progress even in extended early intervention suggests that specific interventions addressing functional roles need to be provided beyond the first 2 years of early intervention. Sustaining symptom remission and high-school completion may be additional avenues for targeting functional recovery.

Suicidality Over the First 5 Years of Psychosis: Does Extending Early Intervention Have Benefits?

OBJECTIVE: We aimed to investigate whether individuals with first-episode psychosis (FEP) receiving extended early intervention (EI) were less likely to experience suicidal ideation and behaviors than those transferred to regular care after 2 years of EI. Another objective was to examine the 5-year course of suicidality in FEP. METHODS: We conducted a secondary analysis of a randomized controlled trial where 220 patients were randomized after 2 years of EI to receive extended EI or regular care for the subsequent 3 years. Suicidality was rated using the Brief Psychiatric Rating Scale. Linear mixed model analysis was used to study time and group effects on suicidality. RESULTS: Extended EI and regular care groups did not differ on suicidality. There was a small decrease in suicidality over time, F(7, 1038) = 1.84, P = 0.077, with an immediate sharp decline within a month of treatment, followed by stability over the remaining 5 years. Patients who endorsed suicidality at entry (46.6%) had higher baseline positive, negative, and depressive symptoms. The 5-year course fell in 3 groups: never endorsed suicidality (33.9%), endorsed suicidality at low-risk levels (43.1%), and endorsed high-risk levels (23.0%). The high-risk group had a higher proportion of affective versus nonaffective psychosis diagnosis; higher baseline positive and depressive symptoms; higher 5-year mean depression scores, and fewer weeks of positive symptom remission over the 5-year course. CONCLUSIONS: The first month of treatment is a critical period for suicide risk in FEP. Although early reductions in suicidality are often maintained, our findings make the case for sustained monitoring for suicide risk management.

Progress of negative symptoms over the initial 5 years of a first episode of psychosis.

BACKGROUND: Specialized early intervention (EI) following a first episode of psychosis (FEP) are effective at reducing negative symptoms, although its trajectory warrants systematic assessment. However, findings are equivocal as to whether extended gains are made post 2 years of EI and whether there is additional benefit of extending EI for an additional 3 years. METHODS: Data on 178 FEP patients, from a randomized controlled trial of a 3-year extension of EI service v. transfer to regular care following 2 years of EI service, were used for this report. Repeated measures analysis of variance were conducted separately for the initial 2 years of treatment in an EI service, and for the 3-year post-randomization to examine trajectories of negative symptoms over the two periods in the two arms of the study. RESULTS: There were significant improvements in total negative symptoms over the first 2 years of EI F(4.612, 797.905) = 25.263, p < 0.001 and in domains of 'expressivity' and 'motivation'. In the following 3 years, there were further significant improvements in negative symptoms F(4.318, 759.908) = 4.182, p = 0.002 with no difference between groups F(4.318, 759.908) = 1.073, p = 0.371. Changes in negative symptoms over the extension period were driven by expressivity F(4.01, 674.73) = 7.19, p < 0.01, but not motivation F(6.58, 1112.18) = 0.95, p = 0.46. CONCLUSION: Negative symptoms improve significantly over the first 2 years of EI. Subsequent amelioration was largely the result of expressivity. Motivation deficits remained stable. Extended EI offered no advantage over regular care post-randomization.

Real-life assessment of aripiprazole monthly (Abilify Maintena) in schizophrenia: a Canadian naturalistic non-interventional prospective cohort study.

BACKGROUND: With previously established efficacy of aripiprazole once-monthly injectable formulation (AOM) in pre-registration randomized controlled trials, the current study was designed to evaluate its effectiveness in patients treated for schizophrenia in regular clinical settings in Canada. METHODS: Following their clinicians' decision to prescribe AOM, 193 patients with a diagnosis of schizophrenia, were recruited from 17 Canadian community or hospital-based settings. The primary outcome of global functioning was assessed with the Global Assessment of Functioning Scale (GAF) at 3-month intervals for 1 year. Secondary outcomes (social and occupational functioning and illness severity) and adverse drug reactions (ADR) were also assessed. RESULTS: A majority of the 169 evaluable patients were within the first 5 years of diagnosis (early phase). A linear mixed model analysis showed a significant main effect of time (Type III test p < 0.001) after adjusting for baseline GAF score, with a change in mean GAF scores from 49 at baseline to 61 at 12 months. No differences between early vs late phase were observed. Results on secondary outcome measures of function (Social and Occupational Functioning Scale) and illness severity (Clinical Global Impression-Severity Scale and Brief Psychiatric Rating Scale) were similar. Serious ADRs were observed in 29 (14.6%) patients and akathisia in 18 (9.1%) patients. At month-12, significant (≥7%) weight gain was observed in 25.7% (n = 27/105) of patients. CONCLUSIONS: Treatment with AOM is effective in improving symptoms and functioning in schizophrenia patients treated in regular clinical settings. Akathisia was infrequent while one quarter of patients gained clinically significant weight. TRIAL REGISTRATION: Unique identifier: NCT02131415 . First posted: 06 May 2014.

Effectiveness of Community Treatment Order in Patients with a First Episode of Psychosis: A Mirror-Image Study.

OBJECTIVE: Poor adherence to antipsychotic medications is strongly associated with psychotic relapses and hospitalizations. This may hinder patients' ability to function, particularly in a first episode of psychosis (FEP). Poor adherence to treatment may be due to poor insight that can alter the capacity to consent to care, including pharmacotherapy. When patients are judged legally lacking the capacity to consent to care, treatment can be mandated through community treatment orders (CTOs). This naturalistic study examines the effects of CTOs in FEP patients. METHOD: This study examines 38 FEP patients legally deemed unable to consent to care during their follow-up. Using a naturalistic mirror-image approach, we compare clinical (Scale for the Assessment of Positive Symptoms [SAPS], Scale for the Assessment of Negative Symptoms [SANS]), functional (Global Assessment of Functioning Scale [GAF], Social and Occupational Functioning Assessment Scale [SOFAS]), and service use (number of emergency room visits, length of hospitalizations) indicators before and after CTO. RESULTS: After the CTO, 37 of 38 patients complied with treatment. Statistically significant improvements in clinical (▵SAPS = -6.3; 95% CI, 4.5 to 8.1 and ▵SANS = -2.2; 95% CI, 0.9 to 3.4, P < 0.01) and functional (▵GAF = +15.0; 95% CI, 8.4 to 21.6, ▵SOFAS = +18.6; 95% CI, 12.8 to 24.4, P < 0.01) outcomes were observed. Significant reduction in emergency room visits ( P = 0.016) and days of hospitalization per month in acute care units ( P < 0.05) were identified with no difference in hospital days per month in short-stay units. Moreover, encounters with case managers ( P = 0.008) and attendance of cognitive therapy sessions ( P = 0.031) were significantly higher. However, patients' weight significantly increased after CTO (▵weight = +8.0 kg, P < 0.01). CONCLUSIONS: In FEP patients, CTOs improve compliance to treatment, which contributes to reducing positive and negative symptoms, shortening hospital stays, and improving functioning.

A NEET distinction: youths not in employment, education or training follow different pathways to illness and care in psychosis.

PURPOSE: The early phases of psychosis, including the prodrome, often feature educational/occupational difficulties and various symptoms and signs, that can render or keep youths "Not in Employment, Education or Training" (NEET). Conversely, NEET status itself may increase risk for illness progression and impaired functioning, and impede access to appropriate services for psychosis. As these issues have not been investigated, we aimed to examine differences in the illness and care pathways and characteristics of youths with psychosis who are NEET and non-NEET. METHODS: Youths entering a catchment-based Canadian early intervention service for psychosis (N = 416) were assessed as being NEET or non-NEET and compared on symptomatology, premorbid adjustment, prodrome and duration of untreated psychosis (DUP). RESULTS: Thirty-nine percent of the sample was NEET. Compared to non-NEET youths, NEET youths had 34% higher negative symptoms scores, longer prodromes (median of 52 weeks vs. 24 weeks), and were more often continuously ill after their first psychiatric change until the onset of psychosis (62% vs. 45%). Both groups had similar premorbid adjustment scores until late adolescence when scores were significantly worse for NEET youths. Accounting for other predictors, NEET youths had 23% longer DUPs on average, despite having made more help-seeking attempts. CONCLUSIONS: Despite being more narrowly defined, NEET status was thrice as prevalent in our sample as in the Canadian population. The NEET group followed a distinct trajectory of persistent symptoms and functional decline before presenting with a psychotic disorder. The systemic delays that NEET youths encountered indicate a need for better-targeted early identification efforts.

Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats.

Diabetes is an increasingly prevalent disease state with a global impact. It is important that effective and cost-efficient methods be developed to treat this disease state. Zucker diabetic fatty rats, an animal model of type 2 diabetes, were treated with montbretin A (MbA), a selective human pancreatic α-amylase inhibitor, isolated from the corms of the Crocosmia crocosmiiflora plant that may have potential as a glucose-lowering agent. The study purpose was to determine if MbA was an orally effective treatment for diabetes. The effect of MbA was compared to a current clinical treatment modality, acarbose that is associated with gastrointestinal side effects known to affect patient compliance. MbA and acarbose were administered daily in the drinking water. Body weight and fluid intake were measured daily to calculate dose consumption. Plasma glucose levels were determined twice weekly in both the fed and fasted state. At termination samples were collected to assess increased risk of secondary complications related to diabetes and oxidative stress. There was no effect of either MbA or acarbose treatment on insulin levels. Plasma glucose levels were significantly lower following MbA treatment in the ZT group which persisted throughout the study period (day 49: 12.1 ± 1.2 mM). However, while there was an initial decrease in plasma glucose levels in the acarbose-treated fatty group, this effect was not sustained (day 49: 20.6 ± 1.3 mM) through to termination. MbA improved the oxidative status of the fatty diabetic animals as well as attenuated markers for increased risk of cardiovascular complications associated with diabetes. This study demonstrated that, at a lower dose as compared to acarbose (10 mg/kg/day), chronic oral administration of MbA (7.5 mg/kg/day) was an effective glucose-lowering agent in the treatment of type 2 diabetes.

Caregiving appraisal and disease activity in early inflammatory arthritis.

OBJECTIVE: The caregiving process accompanying inflammatory arthritis can be stressful to both caregivers and care recipients. In this study, we examined how caregiving involvement and caregiving appraisal as perceived by both patients and their caregiving spouses relate to disease activity and mental health of patients in early inflammatory arthritis. METHODS: Patients in the early phase (> 6 weeks, <18 months duration) of inflammatory arthritis were recruited from a larger early inflammatory arthritis registry, which recorded sociodemographic data and disease characteristics. Disease activity was measured with the Disease Activity Score in 28 joints (DAS28). Current depressive symptoms were measured using the Center for Epidemiologic Studies - Depression Mood Scale. Patient and spouse perceived caregiving involvement and caregiving appraisal were assessed using the Caregiving Involvement Questionnaire and Caregiving Appraisal Scale, respectively. RESULTS: The study sample consisted of 73 patients living with spouse. Mean age was 54 years, 64.4% were women and mean illness duration was 7.48 months. Patients' positive caregiving appraisal was associated with less disease activity (DAS28) (p = 0.003) and less total depressive mood (p < 0.001). In multivariate analysis, patients' appraisal of the caregiving context was negatively associated with disease activity (DAS28) after controlling for caregiving involvement and depression (p = 0.035). CONCLUSION: This study indicates that, in early inflammatory arthritis, patients' caregiving appraisal might be important to consider when assessing disease activity. Clinicians are encouraged to include both patients and their spouse caregivers in interventions.

Trust of patients and families in mental healthcare providers and institutions: A cross-cultural study in Chennai, India and Montreal, Canada.

Purpose: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. Methods: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Non-parametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. Results: The study included 333 patients (Montreal=165, Chennai=168) and 324 family members (Montreal=128, Chennai=168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. Conclusion: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes.

Subjective quality of life among first-episode psychosis patients in Chennai, India and Montreal, Canada.

Differences in subjective quality of life among persons receiving early intervention for psychosis in varying geo-sociocultural contexts have rarely been examined. Our prospective longitudinal study compared the quality of life of persons with first-episode psychosis receiving two years of similar early intervention in Chennai, India and Montreal, Canada. We hypothesized that general life satisfaction would be higher in Chennai compared to Montreal, and that social relations (a specific quality of life component) would also be higher in Chennai and positively contribute to general life satisfaction. Participants completed the general satisfaction and social relations domains of the Wisconsin Quality of Life Index at baseline, months 12 and 24. Baseline weighted mean general satisfaction and social relations scores were in the low to moderate range. Generalized estimating equation analyses showed that general satisfaction scores increased with time [Wald χ2 (1) = 125.28, p < 0.001] and were higher in Chennai than in Montreal [Wald χ2 (1) = 7.50, p = 0.006]. Social relations scores showed the highest association with general satisfaction scores (B = 0.52), followed by positive symptom remission (B = 0.24) and gender (B = 0.18) with Chennai males having the highest general satisfaction scores. Social relations weighted mean scores increased with time [Wald χ2 (1) = 87.30, p < 0.001] and were positively associated with years of education [Wald χ2 (1) = 4.76, p = 0.029] and early negative symptom remission [Wald χ2 (1) = 7.38, p = 0.007]. Our results suggest that subjective quality of life may improve following early intervention for psychosis across contexts. Our findings advance knowledge about the role of sociocultural (e.g., gender) and clinical factors in influencing subjective outcomes in psychosis, and point to social support networks and symptom remission as avenues to boost quality of life.

Whose responsibility? Part 2 of 2: views of patients, families, and clinicians about responsibilities for addressing the needs of persons with mental health problems in Chennai, India and Montreal, Canada.

BACKGROUND: Individuals with mental health problems have many insufficiently met support needs. Across sociocultural contexts, various parties (e.g., governments, families, persons with mental health problems) assume responsibility for meeting these needs. However, key stakeholders' opinions of the relative responsibilities of these parties for meeting support needs remain largely unexplored. This is a critical knowledge gap, as these perceptions may influence policy and caregiving decisions. METHODS: Patients with first-episode psychosis (n = 250), their family members (n = 228), and clinicians (n = 50) at two early intervention services in Chennai, India and Montreal, Canada were asked how much responsibility they thought the government versus persons with mental health problems; the government versus families; and families versus persons with mental health problems should bear for meeting seven support needs of persons with mental health problems (e.g., housing; help covering costs of substance use treatment; etc.). Two-way analyses of variance were conducted to examine differences in ratings of responsibility between sites (Chennai, Montreal); raters (patients, families, clinicians); and support needs. RESULTS: Across sites and raters, governments were held most responsible for meeting each support need and all needs together. Montreal raters assigned more responsibility to the government than did Chennai raters. Compared to those in Montreal, Chennai raters assigned more responsibility to families versus persons with mental health problems, except for the costs of substance use treatment. Family raters across sites assigned more responsibility to governments than did patient raters, and more responsibility to families versus persons with mental health problems than did patient and clinician raters. At both sites, governments were assigned less responsibility for addressing housing- and school/work reintegration-related needs compared to other needs. In Chennai, the government was seen as most responsible for stigma reduction and least for covering substance use services. CONCLUSIONS: All stakeholders thought that governments should have substantial responsibility for meeting the needs of individuals with mental health problems, reinforcing calls for greater government investment in mental healthcare across contexts. The greater perceived responsibility of the government in Montreal and of families in Chennai may both reflect and influence differences in cultural norms and healthcare systems in India and Canada.

Patient satisfaction with random assignment to extended early intervention for psychosis vs regular care: Relationship with service engagement.

AIM: We investigated whether individuals varied in their satisfaction with being randomized to an extension of early intervention (EI) for psychosis or regular care after 2 years of EI, and whether satisfaction was associated with service engagement 3 years later. METHODS: Following randomization, patients (N = 220) indicated if they were happy with, unhappy or indifferent to their group assignment. Follow-up with service providers was recorded monthly. RESULTS: Patients randomized to extended EI were more likely to express satisfaction with their group assignment than those in the regular care group (88.2% vs 31.5%, χ2 = 49.96, P < .001). In the extended EI group, those happy with their assigned group were likelier to continue seeing their case manager for the entire five-year period than those who were unhappy/indifferent (χ2 = 5.61, P = .030). CONCLUSIONS: Perceptions about EI, indicated by satisfaction with being assigned to extended EI, may have lasting effects on service engagement.

Renal expression of arachidonic acid metabolizing enzymes and RhoA/Rho kinases in fructose insulin resistant hypertensive rats.

Fructose feeding has been shown to induce insulin resistance and hypertension. Renal protein expression for the cytochrome P (CYP) 450 arachidonic acid metabolizing enzymes has been shown to be altered in other models of diet-induced hypertension. Of special interest is CYP4A, which produces the potent vasoconstrictor, 20-hydroxyeicosatetraenoic acid and CYP2C, which catalyzes the formation of the potent dilators epoxyeicosatrienoic acids as well as soluble epoxide hydrolase (sEH) which metabolizes the latter to dihydroxyeicosatrienoic acids. The RhoA/Rho kinase (ROCK) signaling pathway is downstream of arachidonic acid and is reported to mediate metabolic-cardio-renal dysfunctions in some experimental models of insulin resistance and diabetes. The aim of the present study was to determine the expression of CYP4A, CYP2C23, CYP2C11, sEH, RhoA, ROCK-1, ROCK-2, and phospho-Lin-11/Isl-1/Mec-3 kinase (LIMK) in kidneys of fructose-fed (F) rats. Male Wistar rats were fed a high fructose diet for 8 weeks. Body weight, systolic blood pressure, insulin sensitivity, and renal expression of the aforementioned proteins were assessed. No change was observed in the body weight of F rats; however, euglycemia and hyperinsulinemia implicating impaired glucose tolerance and significant elevation in systolic blood pressure were observed. Renal expression of CYP4A and CYP2C23 was significantly increased while that of CYP2C11 and sEH was not changed in F rats. Equal expression for RhoA in both control and F rats and an enhanced level of ROCK-1 and ROCK-2 constitutively activate 130 kDa cleavage fragments as well as phospho-LIMK. These data suggest that the kidneys could be actively participating in the pathogenesis of insulin resistance-induced hypertension through the arachidonic acid CYP 450-RhoA/Rho kinase pathway(s).

Insulin resistance and endothelial dysfunction: Are epoxyeicosatrienoic acids the link?

Epoxyeicosatrienoic acids (EETs), the cytochrome P450 epoxygenase metabolites of arachidonic acid, are potent vasodilators and are believed to be the endothelium-derived hyperpolarizing factor in a number of vascular beds. In addition, EETs may play a role in the secretion and action of insulin and the metabolism of carbohydrates and lipids. Pharmacological manipulation of EETs may be a useful therapeutic approach for disease states such as hypertension, diabetes mellitus and the metabolic syndrome. EET mimetics and antagonists and drugs that increase EET synthesis or decrease their degradation are currently under investigation. The cellular mechanism of action of EETs appears to be complex and is being intensively studied by a number of investigators. In the present article, EET production, metabolism, isomerism and vasodilatory effects will be reviewed and potential mechanisms of action discussed. The role of EETs in insulin secretion and sensitivity and their implication in diabetes mellitus and the metabolic syndrome will also be reviewed. Drugs affecting EET bioavailability and action may be promising agents to use to treat hypertension/insulin resistance. The effects of these agents in experimental vascular disorders will also be discussed.

Early Stabilization of Weight Changes Following Treatment With Olanzapine, Risperidone, and Aripiprazole: A 12-Month Naturalistic Study of First Episode Psychosis.

OBJECTIVE: The study objective was to examine whether and when antipsychotic-induced weight gain in first episode psychosis (FEP) stabilizes over a 12-month exposure to the same antipsychotic in a sample of previously untreated FEP patients. METHODS: In this prospective naturalistic outcome study, 109 patients diagnosed with non-affective or affective psychosis (DSM-IV) were treated with the same antipsychotic medication (olanzapine n = 45, risperidone n = 39, or aripiprazole n = 25) throughout the first year of treatment. Body weight was measured and body mass index calculated at baseline and 1, 2, 3, 6, 9, and 12 months. Additional weight data over the second year were available, making extending the comparison for a second year possible. RESULTS: Linear mixed model analysis showed a significant main effect of time (Type III test P < .001) after adjusting for baseline weight values. Post hoc pairwise comparisons showed that incremental weight changes subsequent to month 6 were insignificant, suggesting weight stabilization by month 9. No significant difference (P = .243) between groups or time × group interaction (P = .111) was observed. Similar findings were obtained with BMI. A follow-up analysis, of a subsample who continued treatment with the same antipsychotic for an additional 12 months (n = 57), confirmed weight stabilization in the second year. There was no significant main effect of time (P = .641), group (P = .539), or time × group interaction (P = .250). CONCLUSIONS: Antipsychotic-induced weight gain occurs mostly in the first few months of treatment. Preventive interventions concurrent to second-generation antipsychotic treatment initiation in medication-naive FEP patients might be warranted.

Caught in the "NEET Trap": The Intersection Between Vocational Inactivity and Disengagement From an Early Intervention Service for Psychosis.

OBJECTIVE: Given the benefits of early intervention for psychosis and the social disengagement of youths not in education, employment, or training (NEET), this study sought to examine how being vocationally inactive (NEET) affects engagement in early intervention services. Both baseline vocational status and vocational trajectory in the first year of treatment were analyzed. METHODS: Data from 394 patients of a Canadian early intervention service were analyzed using time-to-event and Cox proportional hazards regression analyses. Two-year disengagement rates were compared between patients who were vocationally inactive and active at baseline and between those who remained vocationally inactive until month 12 and those who were vocationally inactive only at baseline. Pertinent sociodemographic (age, sex, visible minority status, social and material deprivation indices, and family involvement), and clinical (duration of untreated psychosis, substance use disorder, medication nonadherence, and baseline positive and negative symptoms) factors were considered. RESULTS: There was no statistically significant difference between the disengagement rates of those who were vocationally inactive (N=154) and those who were vocationally active (N=240) at baseline. Those who remained vocationally inactive at month 12 (N=77) were likelier to disengage in the second year than those who were vocationally inactive only at baseline (N=48) (χ2=5.44, df=1, p<0.05). This comparison remained significant in the regression analysis (hazard ratio [HR]=8.52, 95% confidence interval [95% CI]=1.54-47.1). The association of disengagement from services with lack of family contact with the treatment team (HR=3.91, 95% CI=0.98-15.6) and with greater material deprivation (HR=1.03, 95% CI=1.00-1.07) trended toward significance. CONCLUSIONS: The functional recovery of youths who are vocationally inactive when they enter services can affect their long-term service engagement and merits targeting by evidence-based interventions.