Moving from supported to independent living: what are the barriers and facilitators for individuals with psychosis?

PURPOSE: Living independently, as opposed to in sheltered housing or with caregivers, is an important aim in the recovery of individuals with psychosis, but the transition to independence can be challenging. This study aims to investigate how individuals with psychosis move between living arrangements and to identify the barriers and facilitators of moving towards independence. METHODS: The living arrangements of 1119 individuals with non-affective psychosis from the Genetic Risk and Outcome of Psychosis study were assessed at baseline, at three- and six-year follow-ups and further categorized as either supported (sheltered housing or with parents) or independent (single or with partner/family). We estimated the probabilities of transitioning between the living statuses and investigated the influence of demographic characteristics, symptomatology, cognition, social support, and premorbid social adjustment on transition using Markov chain modelling. RESULTS: The majority of individuals living in supported housing remained there during the six-year follow-up period (~ 60%). The likelihood of moving from supported to independent living was twice as high for participants who were younger, five-to-six times higher for women, twice as high for individuals with better overall cognition, and five times higher for those with a course of low positive symptoms. CONCLUSION: This study highlights that a large group of individuals with psychosis in supported housing is unlikely to move to independent living. Older men with cognitive impairments and who show continuous severe positive symptoms are the least likely to move living independently. Tailored interventions for these at-risk individuals could increase their chances of moving to independent living.

Shaping tomorrow's support: baseline clinical characteristics predict later social functioning and quality of life in schizophrenia spectrum disorder.

PURPOSE: We aimed to explore the multidimensional nature of social inclusion (mSI) among patients diagnosed with schizophrenia spectrum disorder (SSD), and to identify the predictors of 3-year mSI and the mSI prediction using traditional and data-driven approaches. METHODS: We used the baseline and 3-year follow-up data of 1119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) cohort in the Netherlands. The outcome mSI was defined as clusters derived from combined analyses of thirteen subscales from the Social Functioning Scale and the brief version of World Health Organization Quality of Life questionnaires through K-means clustering. Prediction models were built through multinomial logistic regression (ModelMLR) and random forest (ModelRF), internally validated via bootstrapping and compared by accuracy and the discriminability of mSI subgroups. RESULTS: We identified five mSI subgroups: "very low (social functioning)/very low (quality of life)" (8.58%), "low/low" (12.87%), "high/low" (49.24%), "medium/high" (18.05%), and "high/high" (11.26%). The mSI was robustly predicted by a genetic predisposition for SSD, premorbid adjustment, positive, negative, and depressive symptoms, number of met needs, and baseline satisfaction with the environment and social life. The ModelRF (61.61% [54.90%, 68.01%]; P =0.013) was cautiously considered outperform the ModelMLR (59.16% [55.75%, 62.58%]; P =0.994). CONCLUSION: We introduced and distinguished meaningful subgroups of mSI, which were modestly predictable from baseline clinical characteristics. A possibility for early prediction of mSI at the clinical stage may unlock the potential for faster and more impactful social support that is specifically tailored to the unique characteristics of the mSI subgroup to which a given patient belongs.

Life years lost for users of specialized mental healthcare.

BACKGROUND: Mental disorders are burdensome and are associated with increased mortality. Mortality has been researched for various mental disorders, especially in countries with national registries, including the Nordic countries. Yet, knowledge gaps exist around national differences, while also relatively less studies compare mortality of those seeking help for mental disorders in specialized mental healthcare (SMH) by diagnosis. Additional insight into such mortality distributions for SMH users would be beneficial for both policy and research purposes. We aim to describe and compare the mortality in a population of SMH users with the mortality of the general population. Additionally, we aim to investigate mortality differences between sexes and major diagnosis categories: anxiety, depression, schizophrenia spectrum and other psychotic disorders, and bipolar disorder. METHODS: Mortality and basic demographics were available for a population of N = 10,914 SMH users in the north of The Netherlands from 2010 until 2017. To estimate mortality over the adult lifespan, parametric Gompertz distributions were fitted on observed mortality using interval regression. Life years lost were computed by calculating the difference between integrals of the survival functions for the general population and the study sample, thus correcting for age. Survival for the general population was obtained from Statistics Netherlands (CBS). RESULTS: SMH users were estimated to lose 9.5 life years (95% CI: 9.4-9.6). Every major diagnosis category was associated with a significant loss of life years, ranging from 7.2 (95% CI: 6.4-7.9) years for anxiety patients to 11.7 (95% CI: 11.0-12.5) years for bipolar disorder patients. Significant differences in mortality were observed between male SMH users and female SMH users, with men losing relatively more life years: 11.0 (95% CI: 10.9-11.2) versus 8.3 (95% CI: 8.2-8.4) respectively. This difference was also observed between sexes within every diagnosis, although the difference was insignificant for bipolar disorder. CONCLUSION: There were significant differences in mortality between SMH users and the general population. Substantial differences were observed between sexes and between diagnoses. Additional attention is required, and possibly specific interventions are needed to reduce the amount of life years lost by SMH users.

MicroRNAs and pro-inflammatory cytokines as candidate biomarkers for recent-onset psychosis.

BACKGROUND: Recent studies on the schizophrenia spectrum and other psychotic disorders showed that alternation of immune system components, particularly microRNAs (miRNAs) and pro-inflammatory compounds, plays a significant role in developing the illness. The study aimed to evaluate serum expression of the miRNA-26a, miRNA-106a, and miRNA-125b as genetic factors and serum levels of IL-6, IL-1ß, and TNF-α as pro-inflammatory factors in an IranianAzeri population. METHODS: Forty patients with recent-onset non-affective psychosis and 40 healthy people as a control group were involved. Expression levels of miRNAs and serum levels of the cytokines were measured using RT-qPCR and ELISA, respectively. T-test, receiver operating characteristics (ROC), and spearman correlation coefficient were carried out data analysis. RESULTS: Findings showed higher levels of IL-6, IL-1ß, TNF-α, miR-26a, and miR-106a in the plasma of the patients' group compared with the control. miRNA-26a showed a statistically significant higher level (p < .003) compared to the control group, with AUC = 0.84 (95% CI: 0.77 to 0.93, P < .001) and cut-off point = 0.17 in comparison to other miRNAs as mentioned above; in this regard, it might be a suggestive biomarker for schizophrenia in the early stage of the illness. Moreover, miRNAs' expression level was not substantially associated with the level of any measured cytokines above. CONCLUSIONS: miR-26a might be a suggestive biomarker for schizophrenia in the early stage of the illness. Given that the relationship between other miRNAs and cytokines is not yet well understood; accordingly, there are encouragement and support for continued research in this fascinating field.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis.

BACKGROUND: Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. METHODS: In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes ('normal', 'mixed' and 'impaired') in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. RESULTS: Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. CONCLUSIONS: Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Multimodal lifestyle intervention using a web-based tool to improve cardiometabolic health in patients with serious mental illness: results of a cluster randomized controlled trial (LION).

BACKGROUND: Unhealthy lifestyle behaviours contribute to alarming cardiometabolic risk in patients with serious mental illness (SMI). Evidence-based practical lifestyle tools supporting patients and staff in improving patient lifestyle are lacking. METHODS: This multi-site randomized controlled pragmatic trial determined the effectiveness of a twelve-month multimodal lifestyle approach, including a web-based tool to improve patients' cardiometabolic health, versus care-as-usual. Using the web tool, nurses (trained in motivational interviewing) assisted patients in assessing their lifestyle behaviours, creating a risk profile and constructing lifestyle goals, which were discussed during fortnightly regular care visits. Twenty-seven community-care and sheltered-living teams were randomized into intervention (N = 17) or control (N = 10) groups, including 244 patients (140 intervention/104 control, 49.2% male, 46.1 ± 10.8 years) with increased waist circumference (WC), BMI or fasting glucose. The primary outcomes concerned differences in WC after six and twelve months intervention, while BMI and metabolic syndrome Z-score were secondary outcome measures. RESULTS: General multilevel linear mixed models adjusted for antipsychotic medication showed that differences in WC change between intervention and control were - 0.15 cm (95%CI: - 2.49; 2.19) after six and - 1.03 cm (95%CI: - 3.42; 1.35) after twelve months intervention; however, the differences were not statistically significant. No intervention effects were found for secondary outcome measures. The intervention increased patients' readiness to change dietary behaviour. CONCLUSION: A multimodal web-based intervention facilitating nurses to address lifestyle changes in SMI patients did not improve patient cardiometabolic health. Web-tool use was lower than expected and nurses need more lifestyle coaching knowledge and skills. The type of intervention and delivery mode need optimization to realize effective lifestyle care for SMI patients. TRIAL REGISTRATION: Dutch Trial Registry, www.trialregister.nl , NTR3765, 21 December 2012.

Design and methods of the 'monitoring outcomes of psychiatric pharmacotherapy' (MOPHAR) monitoring program - a study protocol.

BACKGROUND: At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner. Structural support for data collection and follow-up tests seems essential for improvement of monitoring practices in psychiatric outpatients. The implementation of a structured somatic monitoring program as part of routine clinical practice, as we describe in this study protocol, may be a solution. METHODS: In order to address these issues, we developed the innovative program 'Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR)'. MOPHAR is an infrastructure for implementation of standardized routine outcome monitoring (ROM; including standardized monitoring of treatment effect), monitoring of adverse psychotropic medication effects in psychiatric outpatients, encompassing both somatic adverse effects (e.g. metabolic disturbances) and subjective adverse effects (e.g. sedation or sexual side effects) and medication reconciliation. DISCUSSION: In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program is feasible and beneficial for patients in any MHS organisation. This paper describes the objectives, target population, setting and the composition and roles of the treatment team. It also indicates what measurements are performed at which time points during outpatient treatment in the MOPHAR monitoring program, as well as the research aspects of this project. TRIAL REGISTRATION: MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014. ( NL4779 ).

Natural Medicines for Psychotic Disorders: A Systematic Review.

Patients with psychotic disorders regularly use natural medicines, although it is unclear whether these are effective and safe. The aim of this study was to provide an overview of evidence for improved outcomes by natural medicines. A systematic literature search was performed through Medline, PsycINFO, CINAHL, and Cochrane until May 2015. In 110 randomized controlled trials, evidence was found for glycine, sarcosine, N-acetylcysteine, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol, and vitamin B6 to improve psychotic symptoms when added to antipsychotics. Ginkgo biloba and vitamin B6 seemed to reduce tardive dyskinesia and akathisia. Results on other compounds were negative or inconclusive. All natural agents, except reserpine, were well tolerated. Most study samples were small, study periods were generally short, and most results need replication. However, there is some evidence for beneficial effects of certain natural medicines.

Changing the obesogenic environment to improve cardiometabolic health in residential patients with a severe mental illness: cluster randomised controlled trial.

BackgroundFor patients with severe mental illness (SMI) in residential facilities, adopting a healthy lifestyle is hampered by the obesity promoting (obesogenic) environment.AimsTo determine the effectiveness of a 12-month lifestyle intervention addressing the obesogenic environment with respect to diet and physical activity to improve waist circumference and cardiometabolic risk factors v. care as usual (Dutch Trial Registry: NTR2720).MethodIn a multisite cluster randomised controlled pragmatic trial, 29 care teams were randomised into 15 intervention (365 patients) and 14 control teams (371 patients). Intervention staff were trained to improve the obesogenic environment.ResultsWaist circumference decreased 1.51 cm (95% CI -2.99 to -0.04) in the intervention v. control group after 3 months and metabolic syndrome z-score decreased 0.22 s.d. (95% CI -0.38 to -0.06). After 12 months, the decrease in waist circumference was no longer statistically significantly different (-1.28 cm, 95% CI -2.79 to 0.23, P=0.097).ConclusionsTargeting the obesogenic environment of residential patients with SMI has the potential to facilitate reduction of abdominal adiposity and cardiometabolic risk, but maintaining initial reductions over the longer term remains challenging.

Design of the Lifestyle Interventions for severe mentally ill Outpatients in the Netherlands (LION) trial; a cluster randomised controlled study of a multidimensional web tool intervention to improve cardiometabolic health in patients with severe mental illness.

BACKGROUND: The cardiometabolic health of persons with a severe mental illness (SMI) is alarming with obesity rates of 45-55% and diabetes type 2 rates of 10-15%. Unhealthy lifestyle behaviours play a large role in this. Despite the multidisciplinary guideline for SMI patients recommending to monitor and address patients' lifestyle, most mental health care professionals have limited lifestyle-related knowledge and skills, and (lifestyle) treatment protocols are lacking. Evidence-based practical lifestyle tools may support both patients and staff in improving patients' lifestyle. This paper describes the Lifestyle Interventions for severe mentally ill Outpatients in the Netherlands (LION) trial, to investigate whether a multidimensional lifestyle intervention using a web tool can be effective in improving cardiometabolic health in SMI patients. METHODS/DESIGN: The LION study is a 12-month pragmatic single-blind multi-site cluster randomised controlled trial. 21 Flexible Assertive Community Treatment (ACT) teams and eight sheltered living teams of five mental health organizations in the Netherlands are invited to participate. Per team, nurses are trained in motivational interviewing and use of the multidimensional web tool, covering lifestyle behaviour awareness, lifestyle knowledge, motivation and goal setting. Nurses coach patients to change their lifestyle using the web tool, motivational interviewing and stages-of-change techniques during biweekly sessions in a) assessing current lifestyle behaviour using the traffic light method (healthy behaviours colour green, unhealthy behaviours colour red), b) creating a lifestyle plan with maximum three attainable lifestyle goals and c) discussing the lifestyle plan regularly. The study population is SMI patients and statistical inference is on patient level using multilevel analyses. Primary outcome is waist circumference and other cardiometabolic risk factors after six and twelve months intervention, which are measured as part of routine outcome monitoring using standard protocols. Secondary outcomes include depressive and negative symptoms, cost-effectiveness, and barriers and facilitators in intervention implementation. DISCUSSION: Adequate health care should target both mental health and lifestyle behaviours in SMI patients. This trial contributes by studying a 12-month multidimensional lifestyle intervention as a potential evidence based (nursing) tool for targeting multiple lifestyle behaviours in SMI patients. TRIAL REGISTRATION: Nederlands Trialregister NTR3765 (trialregister.nl; registered 21 December 2012).

Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype.

Polycystic ovary syndrome (PCOS), characterized by increased ovarian androgen biosynthesis, anovulation, and infertility, affects 5-7% of reproductive-age women. Genome-wide association studies identified PCOS candidate loci that were replicated in subsequent reports, including DENND1A, which encodes a protein associated with clathrin-coated pits where cell-surface receptors reside. However, these studies provided no information about functional roles for DENND1A in the pathogenesis of PCOS. DENND1A protein was located in the cytoplasm as well as nuclei of theca cells, suggesting a possible role in gene regulation. DENND1A immunostaining was more intense in the theca of PCOS ovaries. Using theca cells isolated and propagated from normal cycling and PCOS women, we found that DENND1A variant 2 (DENND1A.V2) protein and mRNA levels are increased in PCOS theca cells. Exosomal DENND1A.V2 RNA was significantly elevated in urine from PCOS women compared with normal cycling women. Forced overexpression of DENND1A.V2 in normal theca cells resulted in a PCOS phenotype of augmented CYP17A1 and CYP11A1 gene transcription, mRNA abundance, and androgen biosynthesis. Knock-down of DENND1A.V2 in PCOS theca cells reduced androgen biosynthesis and CYP17A1 and CYP11A1 gene transcription. An IgG specific to DENND1A.V2 also reduced androgen biosynthesis and CYP17 and CYP11A1 mRNA when added to the medium of cultured PCOS theca cells. We conclude that the PCOS candidate gene, DENND1A, plays a key role in the hyperandrogenemia associated with PCOS. These observations have both diagnostic and therapeutic implications for this common disorder.

Do routine outcome monitoring results translate to clinical practice? A cross-sectional study in patients with a psychotic disorder.

BACKGROUND: The use of Routine Outcome Monitoring (ROM) in mental health care has increased widely during the past decade. Little is known, however, on the implementation and applicability of ROM outcome in daily clinical practice. In the Netherlands, an extensive ROM-protocol for patients with psychotic disorders has been implemented over the last years (ROM-Phamous). The current study investigated to what extent ROM results translate to daily clinical practice. Therefore, we investigated whether clinical problems as identified with ROM were detected and used in the treatment of patients with psychotic disorders. METHODS: Out of the ROM database of 2010 (n = 1040), a random sample of 100 patients diagnosed with a psychotic disorder was drawn. ROM-data used in this study included a physical examination, laboratory tests, interviews and self-report questionnaires. Based on these data, the prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors was determined. Next, we investigated whether these problems, as identified with ROM, were reflected in the treatment plans of patients, as an indication of the use of ROM in clinical practice. RESULTS: The sample consisted of 63 males and 37 females. The mean age was 44 and the mean duration of illness was 17.7 years. The prevalence of positive and negative symptoms, psychosocial problems and cardiovascular risk factors ranged from 11 to 86 %. In the majority of cases, problems as identified with ROM were not reflected in the treatment plans of patients. CONCLUSIONS: We found a substantial discrepancy between the ROM measurements and the treatment plans, i.e. low rates of detection of symptoms, psychosocial problems and cardiovascular risk factors in the treatment plans, even though these problems were identified with ROM. The opposite occurred as well, where problems were reflected in the treatment plans but not identified with ROM. Thus, ROM and daily clinical practice appear to be two separate processes, whereas ideally they should be integrated. Strong efforts should be made to integrate ROM and consequent treatment activities. Such integration may help to provide patients with adequate and customized care and simultaneously minimize under- and over-treatment.

Disturbed Experience of Self: Psychometric Analysis of the Self-Experience Lifetime Frequency Scale (SELF).

BACKGROUND: Schizophrenia is characterized by positive and negative symptoms, but recently anomalous self-experiences, e.g. exaggerated self-consciousness (hyperreflectivity), receive more attention as an important symptom domain in schizophrenia patients. The semi-structured interview, the Examination of Anomalous Self-Experience (EASE) [Psychopathology 2005;38:236-258], examines experiences of a disturbed sense of self in a sophisticated but time-consuming manner. Therefore, we proposed the Self-Experience Lifetime Frequency scale (SELF), an instrument intended to screen for self-disturbance phenomena. Here we compared scores of patients, their siblings and healthy controls on the SELF. Methods and Sampling: The SELF is composed of a validated screener for symptoms of depersonalization complemented by questions covering several other domains of self-disturbance. A total of 426 patients with a psychotic disorder, 526 of their unaffected siblings, and 297 healthy controls completed the SELF. Patients' scores on the 12 items of the SELF were subjected to an explorative principal axis factor analysis (PAF); composite scores on factor components were compared between the three participant groups. RESULTS: The PAF revealed two components, explaining 43.9 and 9.5% of variance, respectively. The first component represents a disturbance of self-awareness; the second component reflects (milder forms of) diminished self-affection or depersonalization. The two components of the SELF revealed good internal consistency (component 1, α = 0.88; component 2, α = 0.79; x03C1; = 0.85). Patients showed significantly higher scores on both factor components in comparison with both siblings and controls. No significant differences were found between siblings and controls. CONCLUSIONS: The findings of the current study suggest that the SELF comprises two components of self-disturbance. Patients reported more (severe) symptoms of self-disturbance on both components, suggesting that it is feasible to screen for self-disturbance phenomena in patients with psychotic disorders with the SELF. Screening for symptoms of self-disturbance is important since these symptoms are associated with suffering and, moreover, these phenomena may mark the transition from intact to aberrant reality testing.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.

BACKGROUND: Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. METHODS: We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. RESULTS: We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. LIMITATIONS: The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. CONCLUSION: These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

Influence of omega-3 fatty acids on Tamoxifen-induced suppression of rat mammary carcinogenesis.

We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when ∼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA.

Changing the obesogenic environment of severe mentally ill residential patients: ELIPS, a cluster randomised study design.

BACKGROUND: Severe mentally ill (SMI) patients have a reduced life expectancy of 13-30 years compared to the general population, largely due to an increased risk of cardiovascular mortality. Unhealthy lifestyle behaviours in SMI patients contribute to this increased risk. The obesogenic living environment of patients in residential facilities may even pose an extra risk. Although several studies have shown positive effects of lifestyle interventions on SMI patients' weight status, studies including residential patients and their obesogenic environment are scarce. This paper describes the Effectiveness of Lifestyle Interventions in PSychiatry trial (ELIPS). The goal of this trial is to improve cardiometabolic health in severe mentally ill residential patients by addressing the obesogenic environment. METHODS/DESIGN: The ELIPS study is a multi-site cluster randomised controlled trial (RCT) based on the principles of a pragmatic RCT. All residential and long-term clinical care teams of two large mental health care organisations in the North of the Netherlands serving SMI patients are invited to participate. The intervention is aimed at team level. Lifestyle coaches first develop a team specific lifestyle plan that tailors the ELIPS goals and protocol and then train teams on how to create a healthy environment and stimulate healthy behaviours in patients. After three months, teams take over the intervention after they have set out goals to achieve in the following nine months. In this phase, adherence to the lifestyle plan and pre-set goals is monitored. Patients in the control arm receive care as usual. Primary outcome measure is waist circumference at three and 12 months after baseline. DISCUSSION: ELIPS is different from previously published lifestyle intervention studies in three ways. First, it follows the principles of a pragmatic design, which enables the examination of effects in everyday practice. Second, by implementing the intervention at team level, we expect lifestyle activities to be maintained when interventionists leave. Last, by targeting the obesogenic environment we create a prerequisite for any sustainable health improvement, as patients can only make healthy choices in a healthy living environment. TRIAL REGISTRATION: Nederlands Trialregister NTR2720 (Dutch Trial Register, www.trialregister.nl). Registered 27 January 2011.

Evidence for mood instability in patients with bipolar disorder: Applying multilevel hidden Markov modeling to intensive longitudinal ecological momentary assessment data.

Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized as chronic cyclical mood instability, as opposed to the traditional view of alternating discrete episodes with stable periods in-between. Recognizing this mood instability may improve care and call for high-frequency measures coupled with advanced statistical models. To uncover empirically derived mood states, a multilevel hidden Markov model (HMM) was applied to 4-month ecological momentary assessment data in 20 patients with BD, yielding ∼9,820 assessments in total. Ecological momentary assessment data comprised self-report questionnaires (5 × daily) measuring manic and depressive constructs. Manic and depressive symptoms were also assessed weekly using the Altman Self-Rating Mania Scale and the Quick Inventory for Depressive Symptomatology Self-Report. Alignment between HMM-uncovered momentary mood states and weekly questionnaires was assessed with a multilevel linear model. HMM uncovered four mood states: neutral, elevated, mixed, and lowered, which aligned with weekly symptom scores. On average, patients remained < 25 hr in one state. In almost half of the patients, mood instability was observed. Switching between mood states, three patterns were identified: patients switching predominantly between (a) neutral and lowered states, (b) neutral and elevated states, and (c) mixed, elevated, and lowered states. In all, elevated and lowered mood states were interspersed by mixed states. The results indicate that chronic mood instability is a key feature of BD, even in "relatively" euthymic periods. This should be considered in theoretical and clinical conceptualizations of the disorder. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mechanisms of oral carcinogenesis induced by dibenzo[a,l]pyrene: an environmental pollutant and a tobacco smoke constituent.

We previously reported that dibenzo[a,l]pyrene (DB[a,l]P), the most potent known environmental carcinogen among polycyclic aromatic hydrocarbons (PAH) congeners, is carcinogenic in the oral tissues of mice. We have now developed a new mouse model which employs the oral application of the fjord region diol epoxide, (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE), a metabolite of the tobacco smoke constituent DB[a,l]P, and we show its specific induction of oral squamous cell carcinoma (OSCC) in both tongue and other oral tissues. Groups of B6C3F1 mice (20/group) received 6 or 3 nmol of (±)-anti-DB[a,l]PDE administered into the oral cavity; 3 times per week for 38 weeks. Additional groups received the vehicle alone or were left untreated. Mice were sacrificed 42 weeks after the first carcinogen administration. The high dose induced 74 and 100% OSCC in the tongue and other oral tissues, respectively; the corresponding values at the lower dose were 45 and 89%. Using immunohistochemistry, we showed that DB[a,l]PDE resulted in overexpression of p53 and COX-2 proteins in malignant tissues when compared to normal oral tissues and tongues. Consistent with the carcinogenicity, we demonstrated powerful mutagenicity in cII gene in B6C3F1 (Big Blue) mouse tongue. The mutational profile in lacI reporter gene is similar to those detected in human head and neck cancer, and p53 mutations were observed in mouse oral tumor tissues. Taken together, we conclude that the formation of diol epoxides plays a major role among the mechanisms by which DB[a,l]P exerts its oral mutagenicity and tumorigenicity.