The complexity of obesity-related health problems after bariatric surgery: The patient perspective.

Background: Bariatric surgery aims to improve quality of life by means of weight loss. Obesity-related physical and psychological health problems should improve, but long-term data are scarce. Objectives: To evaluate preoperative physical and mental health problems perceived by the patient and the association with weight loss and quality of life, 5 years after bariatric surgery. Methods: 101 persons (response rate 67%) who had had bariatric surgery an average of 4.6 years before this study completed a written survey on obesity-related physical and psychological health problems and three psychological questionnaires collecting information on eating behavior and quality of life. Over half of the participants (55%) had had a laparoscopic adjustable gastric banding. Results: Preoperatively reported health problems improved but were not necessarily associated with weight loss. Minimal improvement in tiredness, shame and weight instability were associated with significantly less weight loss. Preoperative type 2 diabetes mellitus (T2D) improved but participants had significantly less weight loss and more dissatisfaction regarding the bariatric trajectory than participants without T2D. Eating concerns, emotional eating and external eating improved but not restrained eating. Compared to the Dutch population reference, most quality of life scores of the participants were lower. Conclusion: In this analysis, participants did report satisfaction although from a patients' perspective, improvements of weight and health did not necessarily lead to satisfaction regarding the bariatric trajectory. Participants with postoperative reported fatigue and shame as well as participants with preoperative T2D showed significant less weight loss. More long-term research is necessary to close the current knowledge gap.

No differences in olanzapine- and risperidone-related weight gain between women and men: a meta-analysis of short- and middle-term treatment.

OBJECTIVE: A plethora of data deriving from single studies as well as meta-analyses demonstrates that weight gain is associated with the exposure to the majority of antipsychotics (AP). However, potential sex differences have widely evaded the attention of AP treatment trials. It is hypothesised that female patients gain more weight compared with male patients due to their enhanced susceptibility to adverse drug reactions. METHOD: A meta-analysis was conducted using clinical trials of AP that reported weight change separately for female and male patients. Duration of AP use was stratified in four categories: <6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots were generated for men and women separately, stratified by AP as well as by duration of use. Sex differences were tested by performing meta-regression. RESULTS: Data of 26 studies were used in the present analysis because sufficient data were available only for olanzapine, risperidone and the no-medication group. Both female and male patients showed considerable weight gain after switch or initiate of olanzapine or risperidone, but meta-regression analyses did not show significant sex differences. CONCLUSION: The present meta-analysis revealed that sex differences in AP-related weight gain have been under investigated hampering the detection of sex-specific patterns. In chronic patients switching to olanzapine or risperidone receiving short-or middle-term treatment, AP were associated with weight gain in both sex subgroups and no significant differences were reported.

Psychotic experiences and risk of self-injurious behaviour in the general population: a systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that psychotic experiences (PE) in the general population are associated with an increased risk of self-injurious behaviour. Both the magnitude of this association and the level of adjustment for confounders vary among studies. A meta-analysis was performed to integrate the available evidence. The influence of possible confounders, including variably defined depression, was assessed. METHOD: A systematic review and meta-analysis was conducted including general population studies reporting on the risk of self-injurious behaviour in individuals with PE. Studies were identified by a systematic search strategy in Pubmed, PsycINFO and Embase. Reported effect sizes were extracted and meta-analytically pooled. RESULTS: The risk of self-injurious behaviour was 3.20 times higher in individuals with PE compared with those without. Subanalyses showed that PE were associated with self-harm, suicidal ideation as well as suicidal attempts. All studies had scope for considerable residual confounding; effect sizes adjusted for depression were significantly smaller than effect sizes unadjusted for depression. In the longitudinal studies, adjustment for psychopathology resulted in a 74% reduction in excess risk. CONCLUSIONS: PE are associated with self-injurious behaviour, suggesting they have potential as passive markers of suicidality. However, the association is confounded and several methodological issues remain, particularly how to separate PE from the full range of connected psychopathology in determining any specific association with self-injurious behaviour. Given evidence that PE represent an indicator of severity of non-psychotic psychopathology, the association between PE and self-injurious behaviour probably reflects a greater likelihood of self-injurious behaviour in more severe states of mental distress.

Psychotic experiences and hyper-theory-of-mind in preadolescence--a birth cohort study.

BACKGROUND: Knowledge on the risk mechanisms of psychotic experiences (PE) is still limited. The aim of this population-based study was to explore developmental markers of PE with a particular focus on the specificity of hyper-theory-of-mind (HyperToM) as correlate of PE as opposed to correlate of any mental disorder. METHOD: We assessed 1630 children from the Copenhagen Child Cohort 2000 regarding PE and HyperToM at the follow-up at 11-12 years. Mental disorders were diagnosed by clinical ratings based on standardized parent-, teacher- and self-reported psychopathology. Logistic regression analyses were performed to test the correlates of PE and HyperToM, and the specificity of correlates of PE v. correlates of any Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) mental disorder. RESULTS: Univariate analyses showed the following correlates of PE: familial psychiatric liability; parental mental illness during early child development; change in family composition; low family income; regulatory problems in infancy; onset of puberty; bullying; concurrent mental disorder; and HyperToM. When estimating the adjusted effects, only low family income, concurrent mental disorder, bullying and HyperToM remained significantly associated with PE. Further analyses of the specificity of these correlates with regard to outcome revealed that HyperToM was the only variable specifically associated with PE without concurrent mental disorder. Finally, HyperToM did not share any of the investigated precursors with PE. CONCLUSIONS: HyperToM may have a specific role in the risk trajectories of PE, being specifically associated with PE in preadolescent children, independently of other family and child risk factors associated with PE and overall psychopathology at this age.

The use of a Cumulative Needs for Care Monitor for individual treatment v. care as usual for patients diagnosed with severe mental illness, a cost-effectiveness analysis from the health care perspective.

AIMS: To study the systematic assessment of need for care and clinical parameters for use in treatment plans in patients diagnosed with severe mental illness. METHODS: The Cumulative Needs for Care Monitor (CNCM) includes various validated instruments, such as the Camberwell Assessment of Need. A Markov-type cost-effectiveness model (health care perspective, 5-year time horizon) was used to compare CNCM with care as usual (CAU). Two studies were used to determine model parameters: a before­after study (n = 2155) and a matched-control study (n = 937). RESULTS: The CNCM may lead to a gain in psychiatric functioning according to the models. CNCM patients remain in (outpatient) care, while CAU patients drop out more frequently. There is only a small difference in inpatient care. As a result, average costs per patient in the CNCM group are between €2809 (before­after model) and €5251 (matched-control model) higher. The iCER was between €45 127 and €57 839 per life year without psychiatric dysfunction gained. CONCLUSIONS: CNCM may be only cost-effective when willingness to pay for a life year without psychiatric dysfunction is higher than €45 000. However, this result is highly sensitive to the level of psychiatric dysfunctioning in patients who do not receive care.

Evidence that the wider social environment moderates the association between familial liability and psychosis spectrum outcome.

BACKGROUND: Familial liability to both severe and common mental disorder predicts psychotic disorder and psychotic symptoms, and may be used as a proxy in models examining interaction between genetic risk and the environment at individual and contextual levels. METHOD: In a representative general population sample (n=4011) in Izmir, Turkey, the full spectrum of expression of psychosis representing (0) no symptoms, (1) subclinical psychotic experiences, (2) low-impact psychotic symptoms, (3) high-impact psychotic symptoms and (4) full-blown clinical psychotic disorder was assessed in relation to mental health problems in the family (proxy for familial liability) and the wider social environment. Quality of the wider social environment was assessed in an independent sample using contextual measures of informal social control, social disorganization, unemployment and low income, aggregated to the neighbourhood level. RESULTS: The association between familial liability to severe mental illness and expression of psychosis spectrum was stronger in more deprived neighbourhoods [e.g. this association increased from ß=0.33 (p=0.01) in low-unemployment neighbourhoods to ß=0.92 (p<0.001) in high-unemployment neighbourhoods] and in neighbourhoods high in social control, while neighbourhood variables did not modify the association between familial liability to common mental disorder and the psychosis outcome. Neighbourhood variables mediated urbanicity effects. CONCLUSIONS: Contextual effects may be important in moderating the expression of psychosis liability in populations, representing a specific pathway independent of the link between common mental disorder and psychosis.

Do subthreshold psychotic experiences predict clinical outcomes in unselected non-help-seeking population-based samples? A systematic review and meta-analysis, enriched with new results.

BACKGROUND: The base rate of transition from subthreshold psychotic experiences (the exposure) to clinical psychotic disorder (the outcome) in unselected, representative and non-help-seeking population-based samples is unknown. METHOD: A systematic review and meta-analysis was conducted of representative, longitudinal population-based cohorts with baseline assessment of subthreshold psychotic experiences and follow-up assessment of psychotic and non-psychotic clinical outcomes. RESULTS: Six cohorts were identified with a 3-24-year follow-up of baseline subthreshold self-reported psychotic experiences. The yearly risk of conversion to a clinical psychotic outcome in exposed individuals (0.56%) was 3.5 times higher than for individuals without psychotic experiences (0.16%) and there was meta-analytic evidence of dose-response with severity/persistence of psychotic experiences. Individual studies also suggest a role for motivational impairment and social dysfunction. The evidence for conversion to non-psychotic outcome was weaker, although findings were similar in direction. CONCLUSIONS: Subthreshold self-reported psychotic experiences in epidemiological non-help-seeking samples index psychometric risk for psychotic disorder, with strong modifier effects of severity/persistence. These data can serve as the population reference for selected and variable samples of help-seeking individuals at ultra-high risk, for whom much higher transition rates have been indicated.

Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress.

OBJECTIVE: A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined. METHOD: A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). RESULTS: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ(2)(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ(2)(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found. CONCLUSION: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype.

Function assertive community treatment (FACT) and psychiatric service use in patients diagnosed with severe mental illness.

AIM: Previous work suggests that the Dutch variant of assertive community treatment (ACT), known as Function ACT (FACT), may be effective in increasing symptomatic remission rates when replacing a system of hospital-based care and separate community-based facilities. FACT guidelines propose a different pattern of psychiatric service consumption compared to traditional services, which should result in different costing parameters than care as usual (CAU). METHODS: South-Limburg FACT patients, identified through the local psychiatric case register, were matched with patients from a non-FACT control region in the North of the Netherlands (NN). Matching was accomplished using propensity scoring including, among others, total and outpatient care consumption. Assessment, as an important ingredient of FACT, was the point of departure of the present analysis. RESULTS: FACT patients, compared to CAU, had five more outpatient contacts after the index date. Cost-effectiveness was difficult to assess. CONCLUSION: Implementation of FACT results in measurable changes in mental health care use.

[An observational study of 'assertive outreach' with remission as outcome measure]. / Een observationele trial naar 'assertive outreach' met remissie als uitkomstmaat1.

BACKGROUND: Systems of intensive care such as the Function Assertive Community Treatment (Function-act) are advocated because they are reported to have achieved very promising results. However, comparative studies aimed at measuring the efficacy of such systems are mainly of short duration and the outcome measure is nearly always the amount of care provided. AIM: To investigate, via an observational study, changes that occurred in the number of patients going into remission and in the amount of care provided before and after the introduction of f-act. METHOD: f-act was introduced in Maastricht and the surrounding area (population 220,000) at the beginning of 2002. Cumulative routine measurements of the effect of care in the region had been performed since 1998. These measurements were used to compare the proportion of patients in remission in two non-overlapping patients cohorts, each covering a 4-year period, namely 1998-2001 and 2002-2005. results The proportion of patients who made the transition to remission increased from 19% in the period before the introduction of f-act to 31% in the period after its introduction (or = 2.21; 95% ci: 1.03-4.78), but after controlling for confounders the difference was no longer statistically significant. CONCLUSION: In routine clinical practice f-act can reduce the intensity of psychopathological symptoms, possibly because the care provided under f-act is less fragmented. However, more research is needed before the claimed beneficial effects of f-act can be proved conclusively.

Mental health care use in Parkinson's disease: a record linkage study.

BACKGROUND/AIM: Parkinson's disease (PD) is often complicated by psychiatric comorbidity, which is likely to lead to a higher use of mental health care facilities. In addition, psychiatric symptomatology and associated mental health care use may be present even before motor symptoms and PD are diagnosed, as the pathophysiology of PD and its psychiatric consequences are likely to overlap to a degree. This will be reflected in an increasing mental health care use prior to the diagnosis of PD. The aim of this study is to compare the level of mental health care use of PD patients with that of a matched control population, and to assess possible fluctuations in mental health care use in the years surrounding the diagnosis of PD. METHODS: Record linkage study comparing the number of mental health care contacts by PD patients with that of a matched control population. RESULTS: Mental health care use by PD patients already increased before the time of diagnosis of PD, and decreased again after diagnosis. The relative risk for mental health care use was increased from 3 years prior (RR 1.41; 95% CI 1.27-1.57) to 2 years after (RR 1.83; 95% CI 1.63-2.05) diagnosing PD. This increase was higher for women than for men, and higher for younger than older individuals. CONCLUSION: The early pathophysiology of PD is expressed in part as mental health problems, suggesting the possibility of early detection in particular demographic groups and a proactive approach to early intervention for comorbid psychopathology.

[Long-term service-dependent patients in mental health care: connection to urbanisation]. / Langdurig zorgafhankelijke patiënten in de ggz: samenhang met verstedelijking.

BACKGROUND: In view of the increased rate of psychiatric morbidity in urban areas there is likely to be a relation between urbanisation and the extent to which patients use the care services. It is not yet known whether this relation is particularly strong in the case of long-term service-dependent patients with mental health problems. AIM: To investigate the possible relation between the prevalence of long-term service-dependent patients and the degree of urbanisation and to find out if there are differences in the strength of this relation in the case of different types of long-term patients and between these patients and other psychiatric patients. METHOD: Data were collected from three psychiatric case registers and from the Statistics Netherlands (cbs). Distinctions were made between three types of long-term patients: 'long stay', 'residential & outpatient' and 'outpatient'. The population was divided into five categories according to the degree of urbanisation in the area of residence. Data were analysed using Poisson regression analysis, corrected for differences in age, sex, marital status and the amount of care available. RESULTS: The incidence rate ratios for the categories 'long stay', 'residential & outpatient' and 'outpatient' and for other patients were significantly higher for each category of urbanisation than for non-urbanised municipalities. There was also a significant positive linear relation. For long stay patients no significant relation was found with the degree of urbanisation. The total ratios for long-term patients were higher than the ratios for other types of patients. The ratios for residential and outpatient were higher than the ratios for outpatient. CONCLUSION: The prevalence of long-term service-dependent patients in mental health care increases with the degree of urbanisation and this increase is stronger than the increase observed for other patients. Furthermore, the relation with urbanisation for the category residential and outpatient is stronger for the category residential and outpatient than for the long-term outpatients.

[Can the "Camberwell Assessment of Need" predict changes in care consumption?]. / Voorspelt de Camberwell Assessment of Need (verandering in) psychiatrische zorgconsumptie?

BACKGROUND: Because of the shift in the Dutch psychiatric care system towards care based on actual need, we should have some kind of instrument for assessing the future need for care. The Camberwell Assessment of Need (CAN) is such an instrument. It is particularly useful when there is a clear link between the need for care and the consumption of care. AIM: To study whether the can is a predictor of (changes in) care consumption. METHOD: The Maastricht Cumulative Needs for Care Monitor (CNCM) involves an interview with all patients with psychotic disorders who are in care in the Maastricht region. The interview takes place at intake and thereafter annually. The main instrument of the CNCM is the CAN, but other instruments are also included. CNCM data are matched with care consumption data extracted from the Psychiatric Case Register South Limburg, including both care consumption in the year before and in the year after the CNCM assessment. RESULTS: Patients with intermediate or higher levels of need for care were found to use more inpatient care than patients with lower levels of need for care. In addition, the results showed that a high level of need for care was a predictor of shifts from low inpatient care consumption to high inpatient care consumption, although statistically imprecise by conventional alpha. CONCLUSION: The CAN may well be a valuable instrument for assessing future inpatient care consumption.

The combination of shared family environment and individual-specific developmental deviance as a cause for treated psychiatric morbidity in children.

OBJECTIVE: There is an incomplete understanding of why some children growing up in the same family are in need of treatment for psychiatric morbidity whilst their siblings are not. The present paper examined the possible role of individual-specific developmental risk factors. METHOD: Three case-control analyses were conducted: i) 80 children referred to the Community Mental Health Centre (cases) and 320 population controls, ii) 68 healthy siblings of cases and 272 population controls, and iii) 80 children and 68 healthy siblings. Measures of development and psychosocial circumstances were obtained from routine, longitudinal, standardized child medical records. RESULTS: Given shared family environments, additional presence of delays in speech and motor development contributed most to differential sibling mental health outcomes. In addition, cases displayed both earlier expression and more severe levels of developmental behavioural deviance than their healthy siblings, who in turn had higher levels of behavioural deviance than population controls. CONCLUSION: In siblings sharing a familial risk environment, development of psychiatric morbidity may be canalized through additional individual-specific developmental exposures.

The wider social environment and mental health service use.

OBJECTIVE: Previous studies associating neighbourhood context with mental health service use typically included limited sets of confounders. METHOD: A data set including patients registered in a Case Register and population controls was subjected to multilevel analyses, including neighbourhood exposures and individual level confounders. In addition, days of care consumption of patients was addressed. RESULTS: The association between socioeconomic deprivation and social capital on the one hand and mental health service use rates on the other could be attributed to individual level differences. However, number of days of service consumption was higher in neighbourhoods with more informal social control. In residentially stable neighbourhoods only, socioeconomic deprivation was associated with lower levels of service consumption. CONCLUSION: Higher levels of social control may induce patients to remain in contact with mental health services. Furthermore, higher levels of deprivation in neighbourhoods with little population mobility may result in reduced expectations of recovery and/or increased tolerance.

Neighbourhood socioeconomic disadvantage and behavioural problems from late childhood into early adolescence.

STUDY OBJECTIVE: This study investigates whether neighbourhood socioeconomic disadvantage may contribute to child behavioural and emotional problems, beyond the effects of parental socioeconomic status. It also examines the influence of neighbourhood disadvantage on changes in the frequency of behavioural problems from late childhood into early adolescence. DESIGN AND SETTING: The study was conducted in a large community sample in Rotterdam, the Netherlands. An index of neighbourhood socioeconomic disadvantage was calculated for each of the city's 74 neighbourhoods. Multilevel regression analysis estimated effects of neighbourhood disadvantage and individual variables (parental socioeconomic status, child's gender, and age) on behavioural problems reported by children (Youth Self-Report) and parents (Child Behavior Checklist) and on changes in these scores over a two year follow up. PARTICIPANTS: A cohort of all children born in 1978 and living in Rotterdam. Of those eligible, 73% (n=2587) participated in the first measurement (T1), at 10-12 years; 71% of the T1 respondents participated again two years later (T2), at 12-14 years. MAIN RESULTS: Neighbourhood disadvantage was associated with higher Total, Internalising, and Externalising Problems, as assessed with both the Child Behavior Checklist and the Youth Self-Report, even after controlling for parental socioeconomic status. Neighbourhood disadvantage also seemed to contribute to increases in Total Problems over the follow up. CONCLUSIONS: Living in a disadvantaged neighbourhood is associated with greater behavioural problems and may lead to an exacerbation of problems as children move from childhood into adolescence. Public health interventions to improve child mental health must take the neighbourhood environment into account.

Establishment of human embryonic stem cell-transfected clones carrying a marker for undifferentiated cells.

Human embryonic stem (ES) cells are pluripotent cell lines that have been derived from the inner cell mass (ICM) of blastocyst stage embryos [1--3]. They are characterized by their ability to be propagated indefinitely in culture as undifferentiated cells with a normal karyotype and can be induced to differentiate in vitro into various cell types [1, 2, 4-- 6]. Thus, human ES cells promise to serve as an unlimited cell source for transplantation. However, these unique cell lines tend to spontaneously differentiate in culture and therefore are difficult to maintain. Furthermore, colonies may contain several cell types and may be composed of cells other than pluripotent cells [1, 2, 6]. In order to overcome these difficulties and establish lines of cells with an undifferentiated phenotype, we have introduced a reporter gene that is regulated by a promoter of an ES cell-enriched gene into the cells. For the introduction of DNA into human ES cells, we have established a specific transfection protocol that is different from the one used for murine ES cells. Human ES cells were transfected with enhanced green fluorescence protein (EGFP), under the control of murine Rex1 promoter. The transfected cells show high levels of GFP expression when in an undifferentiated state. As the cells differentiate, this expression is dramatically reduced in monolayer cultures as well as in the primitive endoderm of early stage (simple) embryoid bodies (EBs) and in mature EBs. The undifferentiated cells expressing GFP can be analyzed and sorted by using a Fluorescence Activated Cell Sorter (FACS). Thus, we have established lines of human ES cells in which only undifferentiated cells are fluorescent, and these cells can be followed and selected for in culture. We also propose that the pluripotent nature of the culture is made evident by the ability of the homogeneous cell population to form EBs. The ability to efficiently transfect human ES cells will provide the means to study and manipulate these cells for the purpose of basic and applied research.

Involvement of branched-chain amino acid aminotransferases in the production of fusel alcohols during fermentation in yeast.

Organoleptic compounds produced by yeast during the fermentation of wort have a great impact on beer smell and taste. Among them, fusel alcohols are the major abundant volatile compounds. The availability of Saccharomyces cerevisiae mutants in which the genes coding for the two branched-chain amino acid aminotransferases have been deleted offers the possibility of further defining the role of these enzymes in the formation of higher alcohols. Comparing the production profiles of different strains, it is clear that they are not all influenced in the same way by branched-chain amino acid aminotransferase mutations. First of all, as propanol is synthesised from alpha-ketobutyrate, the first metabolic intermediate in the anabolic pathway of isoleucine, neither the eca39 nor eca40 mutations have any effect on the production of this higher alcohol. On the other hand, it can be concluded that the eca40 mutation has a drastic effect on the production of isobutanol. To a certain extent, the same conclusion can be made for the production of active amyl alcohol and isoamyl alcohol, although the results suggest that another route could lead to the formation of these two higher alcohols.