Effectiveness of a mindfulness-based intervention for persons with early psychosis: A multi-site randomized controlled trial.

BACKGROUND: The Mindfulness Ambassador Program (MAP) is a group-based, facilitated mindfulness-based intervention (MBI). We sought to determine the effectiveness of MAP on reducing negative psychotic symptoms and enhancing mindfulness skills among persons experiencing early psychosis. METHODS: We conducted a pragmatic randomized controlled trial (RCT) at three early psychosis intervention (EPI) programs in Ontario, Canada. Participants (N = 59) were randomly assigned to receive MAP (n = 29) for 1-hour weekly sessions over 3 months, or to treatment as usual (TAU, n = 30). Assessments were conducted at baseline, 3 months, and 6 months using the Self-Evaluation of Negative Symptoms (SNS) and Kentucky Inventory of Mindfulness Skills (KIMS). Linear mixed methods were used to assess the joint effects of group and time. RESULTS: At 3 months, participants who received MAP (n = 17) demonstrated greater reductions on the SNS relative to TAU (n = 15), which were clinically and statistically significant (-4.1; 95%CI -7.5, -0.7; p = 0.019). At 6 months, the difference between MAP (n = 10) and TAU (n = 13) was no longer statistically significant (-1.2; 95%CI -5.2,2.7; p = 0.54). On the KIMS, no significant effects were found at 3 months (+0.3; 95%CI -2.0,2.5; p = 0.82) or 6 months (+0.4; 95%CI -2.2,2.9; p = 0.79). CONCLUSIONS: We conducted one of the first multi-site RCTs of a MBI for early psychosis. Our findings indicated that MAP was more effective in reducing negative symptoms compared to TAU in the short term. Earlier reductions in negative psychotic symptoms may help facilitate recovery in the long term.

A pilot study of participatory video in early psychosis: Qualitative findings.

For people with psychotic disorders, developing a personal narrative about one's experiences with psychosis can help promote recovery. This pilot study examined participants' reactions to and experiences of participatory video as an intervention to help facilitate recovery-oriented narrative development in early psychosis. Outpatients of an early psychosis intervention program were recruited to participate in workshops producing short documentary-style videos of their collective and individual experiences. Six male participants completed the program and took part in a focus group upon completion and in an individual semistructured interview three months later. Themes were identified from the focus group and interviews and then summarized for descriptive purposes. Prominent themes included impacts of the videos on the participants and perceived impacts on others, fulfilment from sharing experiences and expressing oneself, value of collaboration and cohesion in a group, acquiring interpersonal and technological skills, and recommendations for future implementation. Findings of this study suggest that participatory video is an engaging means of self-definition and self-expression among young people in recovery from early psychosis.

Meaning-Centered Men's Groups: Initial Findings of an Intervention to Enhance Resiliency and Reduce Suicide Risk in Men Facing Retirement.

Objectives: To assess the preliminary effectiveness of Meaning-Centered Men's Groups (MCMG), a 12-session existentially-oriented, community-based, psychological group intervention designed to enhance psychological resiliency and prevent the onset or exacerbation of suicide ideation among men who are concerned about or struggling with the transition to retirement.Methods: We recruited 30 men (n= 10 per group), 55 years and older (M= 63.7, SD= 4.1) from community settings to participate in a course of MCMG to be delivered in a community center. Participants completed eligibility, pre-, mid-, and post-group assessments of suicide ideation and psychological risk and resiliency factors.Results: Participants experienced significant increases in attitudinal sources of meaning in life, psychological well-being, life satisfaction, retirement satisfaction, and general health, and decreases in depression, hopelessness, loneliness, and suicide ideation.Conclusions: Preliminary findings suggest that MCMG is a novel men's mental health intervention that may help to enhance psychological well-being and potentially reduce the severity or prevent the onset of symptoms of depression, hopelessness, and suicide ideation.Clinical Implications: Upstream psychological interventions may serve an important role in mental health promotion and suicide prevention with potentially vulnerable individuals facing challenging life transitions.

Intrauterine Growth Restriction Modifies the Accumbal Dopaminergic Response to Palatable Food Intake.

Intrauterine growth restriction (IUGR) associates with increased preference for palatable foods and altered insulin sensitivity. Insulin modulates the central dopaminergic response and changes behavioral responses to reward. We measured the release of dopamine in the accumbens during palatable food intake in IUGR rats both at baseline and in response to insulin. From pregnancy day 10 until birth, gestating Sprague-Dawley rats received either an ad libitum (Control), or a 50% food restricted (FR) diet. In adulthood, palatable food consumption and feeding behavior entropy was assessed using an electronic food intake monitor (BioDAQ®), and dopamine response to palatable food was measured by chronoamperometry recordings in the nucleus accumbens (NAcc). FR rats eat more palatable foods during the dark phase, and their eating pattern has a higher entropy compared to control rats. There was a delayed dopamine release in the FR group in response to palatable food and insulin administration reverted this delayed effect. Western blot showed a decrease in suppressor of cytokine signaling 3 protein (SOCS3) in the ventral tegmental area (VTA) and an increase in the ratio of phospho-tyrosine hydroxylase to tyrosine hydroxylase (pTH/TH) in the NAcc of FR rats. Administration of insulin also abolished this latter effect in FR rats. FR rats showed metabolic alterations and a delay in the dopaminergic response to palatable foods. This could explain the increased palatable food intake and behavioral entropy found in FR rats. IUGR may lead to binge eating, obesity and its metabolic consequences by modifying the central dopaminergic response to sweet food.

Youth-focused group mindfulness-based intervention in individuals with early psychosis: A randomized pilot feasibility study.

AIM: To assess the feasibility of a randomized pilot trial that evaluated the acceptability and potential clinical utility of the Mindfulness Ambassador Program (MAP), a unique, standardized 12-session facilitated group mindfulness-based intervention (MBI) for youth experiencing early psychosis. METHODS: Twenty-one patients of an early psychosis intervention program were randomized to receive MAP (n = 11) or treatment as usual (n = 10). Acceptability was measured by group attendance rate and client satisfaction; feasibility of the study design was measured by the recruitment and retention rate. The means, standard deviations, and 95% confidence intervals were described for outcomes of interest. RESULTS: MAP is associated with a high degree of acceptability and has beneficial effects for depression and fatigue. The randomized trial design is feasible. CONCLUSIONS: This study provides important pilot data supporting a larger randomized trial of effectiveness for MAP as a group MBI for early psychosis. Details of MAP and study limitations are discussed.

Understanding the role of the family physician in early psychosis intervention.

BACKGROUND: The family physician is key to facilitating access to psychiatric treatment for young people with first-episode psychosis, and this involvement can reduce aversive events in pathways to care. Those who seek help from primary care tend to have longer intervals to psychiatric care, and some people receive ongoing psychiatric treatment from the family physician. AIMS: Our objective is to understand the role of the family physician in help-seeking, recognition and ongoing management of first-episode psychosis. METHOD: We will use a mixed-methods approach, incorporating health administrative data, electronic medical records (EMRs) and qualitative methodologies to study the role of the family physician at three points on the pathway to care. First, help-seeking: we will use health administrative data to examine access to a family physician and patterns of primary care use preceding the first diagnosis of psychosis; second, recognition: we will identify first-onset cases of psychosis in health administrative data, and look back at linked EMRs from primary care to define a risk profile for undetected cases; and third, management: we will examine service provision to identified patients through EMR data, including patterns of contacts, prescriptions and referrals to specialised care. We will then conduct qualitative interviews and focus groups with key stakeholders to better understand the trends observed in the quantitative data. DISCUSSION: These findings will provide an in-depth description of first-episode psychosis in primary care, informing strategies to build linkages between family physicians and psychiatric services to improve transitions of care during the crucial early stages of psychosis. DECLARATION OF INTEREST: None.

In vivo and in vitro bisphenol A exposure effects on adiposity.

In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.

Sex-specific effects of maternal and postweaning high-fat diet on skeletal muscle mitochondrial respiration.

Exposure to maternal over-nutrition in utero is linked with developmental programming of obesity, metabolic syndrome and cardiovascular disease in offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal muscle mitochondrial function contributes to substrate metabolism and is impaired in metabolic disease. We examined muscle mitochondrial respiration in male and female mice exposed to maternal HF diet in utero, followed by postweaning HF diet until middle age. After in utero exposure to maternal control (Con) or HF diet (45% kcal fat; 39.4% lard, 5.5% soybean oil), offspring were weaned to Con or HF, creating four groups: Con/Con (male/female (m/f), n=8/8), Con/HF (m/f, n=7/4), HF/Con (m/f, n=9/6) and HF/HF (m/f, n=4/4). Oxidative phosphorylation (OXPHOS) and electron transfer system (ETS) capacity were measured in permeabilized gastrocnemius bundles. Maternal HF diet increased fasting glucose and lean body mass in males and body fat percentage in both sexes (P⩽0.05). Maximal adenosine diphosphate-stimulated respiration (complex I OXPHOS) was decreased by maternal HF diet in female offspring (-21%, P=0.053), but not in male (-0%, P>0.05). Sexually divergent responses were exacerbated in offspring weaned to HF diet. In females, OXPHOS capacity was lower (-28%, P=0.041) when weaned to high-fat (HF/HF) v. control diet (HF/Con). In males, OXPHOS (+33%, P=0.009) and ETS (+42%, P=0.016) capacity increased. Our data suggest that maternal lard-based HF diet, rich in saturated fat, affects offspring skeletal muscle respiration in a sex-dependent manner, and these differences are exacerbated by HF diet in adulthood.

An examination of components of recovery after five years of treatment in an early intervention program for psychosis.

Recovery from psychotic disorders includes both symptomatic and functional components. Progress in understanding recovery requires careful replication and extension of findings using comparable measures. In the current paper, we present a study of five year recovery rates in an early intervention program in London, Canada with the same operational criteria as those used in a previous report from the OPUS cohort in Denmark. Our analysis extends the OPUS reports by including additional potential predictors of overall recovery, such as cognitive functioning, adherence to medication and early social support, and examining rates and predictors of individual components of recovery at five year follow-up. Consistent with reports from OPUS, we found younger age of onset and lower initial severity of negative symptoms to predict greater likelihood of overall recovery. Different patterns of predictors emerge when we examine individual components of recovery. Adherence to medication during the first year was the sole independent predictor of remission of positive symptoms, while early social adjustment and social support were more likely to predict negative symptom and functional aspects of recovery at five years. Cognitive functioning, as represented by IQ, did not predict any aspects of recovery. Our findings suggest the importance of examining the predictors of individual components in the quest to improve overall recovery.

Untreated illness and recovery in clients of an early psychosis intervention program: a 10-year prospective cohort study.

PURPOSE: To investigate whether duration of untreated psychosis (DUP) and duration of untreated illness (DUI) are associated with measures of both subjective and objective recovery 10 years after a first episode of psychosis. METHODS: A cohort of 65 clients from an early psychosis intervention program completed a battery of outcome measures 10 years following initial treatment for first-episode psychosis (FEP). The outcomes of interest were self-perceived recovery scores (Maryland Assessment of Recovery in People with Serious Mental Illness Scale) and occupational activity, defined as engagement in work and/or school on a full/part-time basis. Multiple linear and logistic regression analyses were used to estimate the associations between DUP and DUI with each measure of recovery, adjusting for potential confounding factors. RESULTS: We did not find a statistically significant association between DUP and either occupational activity (OR = 1.26, 95% CI 0.81-1.95) or self-perceived recovery score (ß = - 0.73, 95% CI - 2.42 to 0.97). However, we found a significant negative association between DUI and self-perceived recovery score (ß = - 0.52, 95% CI - 0.87 to - 0.16). CONCLUSIONS: Our findings suggest that DUI may have a stronger influence than DUP on recovery from FEP at 10-year follow-up. This suggests the potential value in targeted interventions for people with a long DUI to increase the likelihood of achieving recovery after the first episode of psychosis.

Stability of outcomes after 5 years of treatment in an early intervention programme.

AIM: It has been hypothesized that the first 5 years are critical in determining long-term recovery from psychotic disorders. We examine stability in recovery indices after 5 years for 56 patients treated in an early intervention programme for psychosis. METHODS: Assessments of symptom remission and functional recovery were carried out 5 and 10 years after initiation of treatment. RESULTS: Although overall rates of recovery were comparable at both times, there were significant changes for individuals reflecting both improvement and deterioration. CONCLUSIONS: Evidence concerning the critical period hypothesis should examine stability in individuals rather than relying on cumulative indices.

The differential effects of a focus on symptoms versus recovery in reducing stigma of schizophrenia.

PURPOSE: We extend investigations of the impact of the content of video contact with an individual with schizophrenia on stigma reduction. We examine whether differential impacts persist over a 2-week period and the extent to which they are mediated by perceived similarity and feelings of empathy and/or sympathy. METHOD: We used a randomized control trial wherein participants were exposed to a video in which an individual described his recovery from schizophrenia, or the same person described acute symptoms of schizophrenia, or a no-video control condition. Outcomes included impressions of and preferred social distance to the person in the video and people in general with schizophrenia and well as perceptions of similarity and feelings of sympathy and empathy. We also measured an overt behaviour, seating distance, at 2-week follow-up. RESULTS: The recovery-focused material was generally more effective in improving impressions and reducing preferred level of social distance. Although the symptom-focused video resulted in great sympathy for the person, this did not translate into positive impressions or reduced social distance. Mediational analyses yielded findings consistent with the benefits of the recovery video being mediated by increased perceptions of similarity and lower feelings of sympathy. Exposure to the recovery-focused video resulted in less anxiety in anticipation of meeting the person in the video relative to the control condition. CONCLUSIONS: Video contact emphasizing potential for recovery from schizophrenia was more effective in reducing stigmatizing responses than contact highlighting acute symptoms. Increased sympathy does not necessarily translate into reductions in stigma.

Determinants of self-esteem in early psychosis: The role of perceived social dominance.

Self-esteem plays a role in the formation and maintenance of symptoms and in the recovery from psychotic illness. This study examines the relative contribution of perceived social dominance and other known predictors in determining self-esteem in 102 individuals in an early intervention program for psychosis. Regression analysis demonstrated that scores on the Perceived Relational Evaluation Scale (PRES), depressed mood, social dominance, gender and positive symptoms significantly contributed to the prediction of scores on the Rosenberg Self-esteem Scale (RSES), whereas self-stigma and negative symptoms did not. Our study suggests that low self-esteem in early psychosis can be understood in part as a reflection of low levels of perceived social value and status.

Intrauterine growth restriction modifies the hedonic response to sweet taste in newborn pups - Role of the accumbal µ-opioid receptors.

Intrauterine growth restriction (IUGR) is associated with increased preference for palatable foods. The hedonic response to sweet taste, modulated by the nucleus accumbens µ-opioid-receptors, may be involved. We investigated hedonic responses and receptor levels in IUGR and Control animals. From pregnancy day 10, Sprague-Dawley dams received either an ad libitum (Control), or a 50% food restricted (FR) diet. At birth, pups were cross-fostered, and nursed by Adlib fed dams. The hedonic response was evaluated at 1 day after birth and at 90 days of life, by giving sucrose solution or water and analyzing the hedonic facial responses (within 60s). Control pups exposed either to water or sucrose resolved their hedonic responses after 16 and 18s, respectively, while FR hedonic responses to sucrose persisted over 20s. FR pups had deceased phospho-µ-opioid-receptor (p=0.009) and reduced phosphor:total mu opioid receptor ratio compared to controls pups (p=0.003). In adults, there was an interaction between group and solution at the end of the evaluation (p=0.044): Control decreased the response after sucrose solution, FR did not change over time. There were no differences in phosphorylation of µ-opioid-receptor in adults. These results demonstrate IUGR newborn rats exhibit alterations in hedonic response accompanied by a decrease in µ-opioid-receptor phosphorylation, though these alterations do not persist at 3 months of age. Opioid system alterations in early life may contribute to the development of preference for highly palatable foods and contribute to rapid weight gain and obesity in IUGR offspring.

Prevention and Early Intervention Program for Psychoses (PEPP).

The Prevention and Early Intervention Program for Psychoses (PEPP) was established in 1997 for individuals with first-episode non-affective psychotic disorder. The objectives of PEPP are to improve outcomes for clients by providing a prompt, comprehensive, coordinated and effective treatment program as well as to advance research concerning early intervention for psychotic disorders. This article describes the clinical and research program and the lessons learned.

The course of negative symptoms over the first five years of treatment: Data from an early intervention program for psychosis.

BACKGROUND: Cross-sectional studies suggest that negative symptoms are constituted by separable domains of reduced expressiveness and reduced motivation, but there is little data on the longitudinal course of these symptoms. We examined evidence for differences in the course and correlates of these two domains in a prospective study of patients presenting with a first episode of psychosis. METHODS: Of 132 patients who were followed up for five years, it was possible to monitor reduced expressiveness and motivation on a weekly basis for 127. Information on treatment delay, premorbid adjustment, intellectual functioning, anxiety, depression and psychosocial functioning were also collected. RESULTS: Over the five year follow-up, symptoms of reduced motivation occurred in 95.3% of patients and reduced expressiveness in 68.5%; and deficits in motivation were more likely to be unremitting (15.7%) than expressive deficits (5.5%). There were differences in the correlates of the proportion of time each patient experienced symptoms of each domain. Depression, weeks of full time occupation and weeks on a disability pension were associated with both domains. Anxiety was associated only with diminished motivation. Lower performance IQ; extrapyramidal symptoms (EPS) and dysrhythmic EEG were associated only with proportion of time showing reduced expressiveness. CONCLUSIONS: The prospective data support previous cross-sectional findings that, while these domains of negative symptoms are correlated, they do show differences in prevalence over time and in their correlates.

Programmed regulation of rat offspring adipogenic transcription factor (PPARγ) by maternal nutrition.

We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPARγ with variable changes in co-repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPARγ with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPARγ expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPARγ co-regulators are necessary to establish their role in PPARγ-mediated programmed obesity.

Negative future self as a mediator in the relationship between insight and depression in psychotic disorders.

Awareness of illness in psychotic disorders is associated with better clinical outcomes, but also poorer psychological well-being. This is known as "The Insight Paradox". Understanding of the paradox has focused on the role of self-stigma. This study examines possible future self as a mediator in the relationship between insight and depression in 102 individuals in an early intervention program for psychosis. Mediation analysis demonstrated that negative possible self was the sole significant independent mediator in a model which included self-stigma. Our study shows that awareness of mental illness and perception that it will negatively impact future self increases likelihood of depression.

Epigenomics, gestational programming and risk of metabolic syndrome.

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.

Cognition and the prediction of functioning in patients with a first treated episode of psychosis: a prospective study.

Past research on the role of cognitive performance in predicting later psychosocial functioning for individuals with first treated episode of a psychotic disorder has yielded inconsistent results. Several factors have been suggested as determining the strength of any such relationship including the type of functioning measured, time of the cognitive assessment, covariates included and the use of global versus specific measures of cognitive functioning. In the current study, we examined the importance of these factors in a five year prospective study of individuals with first episode psychotic disorders. Just over 80% of the sample had a schizophrenia spectrum disorder. Cognitive assessments were carried out after initiation of treatment on 113 patients, and at one year for 79 patients. There was evidence that cognition predicted occupational functioning and use of a disability pension, but not a summary index of functioning or use of supervised housing, at follow-up. Overall I.Q. was a more consistent predictor than measures of specific cognitive functions, and there was evidence that cognition assessed after presentation for treatment, particularly after a year of treatment, was more predictive of later functioning than premorbid I.Q. Cognitive functioning, however, did not add to the prediction of outcomes beyond the level possible using past educational achievement or academic premorbid adjustment.