Glucagon-like peptide agonists for weight management in antipsychotic-induced weight gain: A systematic review and meta-analysis.

INTRODUCTION: Managing body weight in patients with antipsychotic-induced weight gain (AIWG) is challenging. Besides lifestyle interventions, pharmacological interventions may contribute to weight loss. This systematic review and meta-analysis evaluated the effect on weight loss and adverse effects of glucagon-like peptide-1 (GLP-1) agonists in patients with AIWG. MATERIALS AND METHODS: Following PRISMA guidelines, we performed a meta-analysis of blinded and open-label randomised controlled trials (RCTs), non-randomised controlled trials and cohort studies that evaluated treatment with GLP-1 in patients with AIWG, regardless of psychiatric diagnosis. PubMed, Embase, PsycINFO and Cochrane Library databases were searched. Primary outcome measures were changes in body weight and BMI. Secondary outcomes were changes in adverse effects and severity of psychopathology due to GLP-1 agonists. RESULTS: Only data for exenatide and liraglutide could be included, that is, five RCTs and one cohort study. For exenatide the mean weight loss was -2.48 kg (95% Confidence Interval (CI) -5.12 to +0.64; p = 0.07), for liraglutide the mean weight loss was -4.70 kg (95% CI -4.85 to -4.56; p < 0.001). The mean change in BMI was -0.82 (95% CI -1.56 to -0.09; p = 0.03) in the exenatide groups and -1.52 (95% CI -1.83 to -1.22; p < 0.001) in the liraglutide groups. Exenatide and liraglutide did not adversely affect psychopathology. The most common adverse events were nausea, vomiting, and diarrhoea. CONCLUSION: The GLP-1 agonists exenatide and liraglutide are promising drugs for inducing weight loss in patients with AIWG. The adverse effects are acceptable, and the addition of GLP-1 does not increase the severity of psychopathology. However, more research is needed.

A 6-year follow-up study in a community-based population: Is neighbourhood-level social capital associated with the risk of emergence and persistence of psychotic experiences and transition to psychotic disorder?

BACKGROUND: Social capital is thought to represent an environmental factor associated with the risk of psychotic disorder (PD). This study aims to investigate the association between neighbourhood-level social capital and clinical transitions within the spectrum of psychosis. METHODS: In total, 2175 participants, representative of a community-based population, were assessed twice (6 years apart) to determine their position within an extended psychosis spectrum: no symptoms, subclinical psychotic experiences (PE), clinical PE, PD. A variable representing change between baseline (T1) and follow-up (T2) assessment was constructed. Four dimensions of social capital (informal social control, social disorganisation, social cohesion and trust, cognitive social capital) were assessed at baseline in an independent sample, and the measures were aggregated to the neighbourhood level. Associations between the variable representing psychosis spectrum change from T1 to T2 and the social capital variables were investigated. RESULTS: Lower levels of neighbourhood-level social disorganisation, meaning higher levels of social capital, reduced the risk of clinical PE onset (OR 0.300; z = -2.75; p = 0.006), persistence of clinical PE (OR 0.314; z = -2.36; p = 0.018) and also the transition to PD (OR 0.136; z = -2.12; p = 0.034). The other social capital variables were not associated with changes from T1 to T2. CONCLUSIONS: Neighbourhood-level social disorganisation may be associated with the risk of psychosis expression. Whilst replication of this finding is required, it may point to level of social disorganisation as a public health target moderating population psychosis risk.

Evidence for an interrelated cluster of Hallucinatory experiences in the general population: an incidence study.

BACKGROUND: Although hallucinations have been studied in terms of prevalence and its associations with psychopathology and functional impairment, very little is known about sensory modalities other than auditory (i.e. haptic, visual and olfactory), as well the incidence of hallucinations, factors predicting incidence and subsequent course. METHODS: We examined the incidence, course and risk factors of hallucinatory experiences across different modalities in two unique prospective general population cohorts in the same country using similar methodology and with three interview waves, one over the period 1996-1999 (NEMESIS) and one over the period 2007-2015 (NEMESIS-2). RESULTS: In NEMESIS-2, the yearly incidence of self-reported visual hallucinations was highest (0.33%), followed by haptic hallucinations (0.31%), auditory hallucinations (0.26%) and olfactory hallucinations (0.23%). Rates in NEMESIS-1 were similar (respectively: 0.35%, 0.26%, 0.23%, 0.22%). The incidence of clinician-confirmed hallucinations was approximately 60% of the self-reported rate. The persistence rate of incident hallucinations was around 20-30%, increasing to 40-50% for prevalent hallucinations. Incident hallucinations in one modality were very strongly associated with occurrence in another modality (median OR = 59) and all modalities were strongly associated with delusional ideation (median OR = 21). Modalities were approximately equally strongly associated with the presence of any mental disorder (median OR = 4), functioning, indicators of help-seeking and established environmental risk factors for psychotic disorder. CONCLUSIONS: Hallucinations across different modalities are a clinically relevant feature of non-psychotic disorders and need to be studied in relation to each other and in relation to delusional ideation, as all appear to have a common underlying mechanism.

Cognitive therapy and interpersonal psychotherapy reduce suicidal ideation independent from their effect on depression.

BACKGROUND: Clinical guidelines suggest that psychological interventions specifically aimed at reducing suicidality may be beneficial. We examined the impact of two depression treatments, cognitive therapy (CT) and interpersonal psychotherapy (IPT) on suicidal ideation (SI) and explored the temporal associations between depression and SI over the course of therapy. METHODS: Ninety-one adult (18-65) depressed outpatients from a large randomized controlled trial who were treated with CT (n = 37) and IPT (n = 54) and scored at least ≥1 on the Beck Depression Inventory II (BDI-II) suicide item were included. Linear (two-level) mixed effects models were used to evaluate the impact of depression treatments on SI. Mixed-effects time-lagged models were applied to examine temporal relations between the change in depressive symptoms and the change in SI. RESULTS: SI decreased significantly during treatment and there were no differential effects between the two intervention groups (B = -0.007, p = .35). Depressive symptoms at the previous session did not predict higher levels of SI at the current session (B = 0.016, p = .16). However, SI measured at the previous session significantly predicted depressive symptoms at the current session (B = 2.06, p < .001). CONCLUSIONS: Both depression treatments seemed to have a direct association with SI. The temporal association between SI and depression was unidirectional with SI predicting future depressive symptoms during treatment. Our findings suggest that it may be most beneficial to treat SI first.

Usability of the Experience Sampling Method in Parkinson's Disease on a Group and Individual Level.

BACKGROUND: Around 50% of PD patients experience motor fluctuations, which are often accompanied by mood fluctuations. The nature of the relationship between motor and mood fluctuations remains unknown. It is suggested that the experience sampling method can reveal such associations on both a group and individual level. Revealing group patterns may enhance our understanding of symptom interactions and lead to more general treatment recommendations, whereas analyses in individual patients can be used to establish a personalized treatment plan. OBJECTIVES: To explore the usability of routinely collected experience sampling method data over a brief period of time to detect associations between motor fluctuations, affective state, and contextual factors in PD patients with motor fluctuations on a group level and on an individual level. METHODS: Eleven patients with motor fluctuations collected data at 10 semirandom moments over the day for 5 consecutive days. RESULTS: On a group level, multilevel analyses showed significant associations between all motor symptoms and positive affect. Being at home was associated with increased balance problems and rigidity. Analyses on an individual level revealed much less significant associations that mostly, but not always, were in line with the results on a group level. CONCLUSION: This exploratory study showed significant associations between affective state, motor symptoms, and contextual factors in a group of PD patients with motor fluctuations, but less so in individual patients. Given that the ultimate aim is to use the experience sampling method as an aid to personalize treatments, the sensitivity of the approach needs to be increased. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

DSM outcomes of psychotic experiences and associated risk factors: 6-year follow-up study in a community-based sample.

BACKGROUND: Psychotic experiences (PEs) may predict a range of common, non-psychotic disorders as well as psychotic disorders. In this representative, general population-based cohort study, both psychotic and non-psychotic disorder outcomes of PE were analysed, as were potential moderators. METHODS: Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011). Participants were interviewed with the Composite International Diagnostic Interview (CIDI) both at baseline and at 6-year follow-up. Participants with PE at baseline were clinically re-interviewed with the SCID-I at follow-up. The role of socio-demographics, characteristics of PE, co-occurrence of mood disorders and family history of mental disorders were tested in the association between baseline PE and follow-up diagnosis. RESULTS: In the participants with baseline PE, the psychotic disorder diagnosis rate at follow up was 7.0% - much lower than the rates of DSM-IV mood disorders without psychotic features (42.8%) and other non-psychotic disorders (24.1%). Within the group with baseline PE, female sex, lower socio-economic status, co-occurrence of mood disorders, family history of a mental disorder and persistence of PE predicted any follow-up DSM diagnosis. Furthermore, onset of psychotic v. non-psychotic disorder was predicted by younger age (15-30 years), co-presence of delusional and hallucinatory PE and family history of severe mental illness. CONCLUSION: The outcome of PE appears to be a consequence of baseline severity of multidimensional psychopathology and familial risk. It may be useful to consider PE as a risk indicator that has trans-diagnostic value.

Psychotic experiences and mood episodes predict each other bidirectionally: a 6-year follow-up study in a community-based population.

BACKGROUND: Psychotic experiences (PEs) are not exclusive to psychotic disorders and highly correlated with mood episodes. In this representative general population-based study, longitudinal bidirectional associations between the extended psychosis phenotype and mood episodes were investigated, accounting for other possible causes. METHODS: Households were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011) and at 6-year follow-up (n = 2185). Participants were interviewed with the relevant sections of the composite international diagnostic interview both at baseline and at follow-up. Sociodemographic, familial and environmental risk factors associated with the extended psychosis phenotype and mood episodes were assessed. Logistic regression and cross-lagged panel correlation models were used for the associations between the extended psychosis phenotype and mood episodes. RESULTS: PEs were associated with subsequent depressive and manic episodes. There was bidirectionality in that mood episodes were associated with subsequent PEs, and PEs were associated with subsequent mood episodes. The associations occurred in a sub-additive pattern. There were substantial synchronous and cross-lagged correlations between these psychopathology domains, with reciprocally similar cross-lagged correlations. Familial risk and adverse life events were associated with both psychopathology domains, whereas some sociodemographic risk factors and alcohol/cannabis use were associated with only one domain. CONCLUSION: The sub-additive bidirectional associations between PEs and mood episodes over time and the similarity of cross-lagged correlations are suggestive of mutually causal connections between affective and psychotic domains of psychopathology.

Evidence for interaction between genetic liability and childhood trauma in the development of psychotic symptoms.

PURPOSE: Whilst childhood trauma (CT) is a known risk factor across the spectrum of psychosis expression, little is known about possible interplay with genetic liability. METHODS: The TwinssCan Study collected data in general population twins, focussing on expression of psychosis at the level of subthreshold psychotic experiences. A multilevel mixed-effects linear regression analysis was performed including 745 subjects to assess the interaction between genetic liability and CT. The Symptom Checklist-90 (SCL-90-R) score of the co-twin was used as an indirect measure of genetic liability to psychopathology, while the Childhood Trauma Questionnaire Short-Form (CTQ-SF) was used to assess CT in the domains of physical, emotional and sexual abuse, as well as physical and emotional neglect. The Community Assessment of Psychic Experience (CAPE) questionnaire was used to phenotypically characterize psychosis expression. RESULTS: In the model using the CAPE total score, the interaction between CT and genetic liability was close to statistical significance (χ2 = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ2 = 8.8, df = 2, p = 0.012) for the CAPE-negative symptoms subscale, but not for the other two subscales (i.e. positive and depressive). CONCLUSION: The results suggest that the impact of CT on subthreshold expression of psychosis, particularly in the negative subdomain, may be larger in the co-presence of significant genetic liability for psychopathology.

Is BDNF-Val66Met polymorphism associated with psychotic experiences and psychotic disorder outcome? Evidence from a 6 years prospective population-based cohort study.

There is little research on genetic risk for the extended psychosis phenotype ranging from psychotic experiences (PEs) to psychotic disorders (PDs). In this general population-based prospective cohort study, the longitudinal associations between BDNF-Val66Met polymorphism and the different levels of the extended psychosis phenotype were investigated. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighborhoods at baseline (n = 4011). A nested case-control study (n = 366) recruited individuals with PEs and PDs as well as individuals with no psychotic symptoms. In this subgroup, blood sampling for genetic analysis and assessment of environmental exposures were carried out, followed by clinical re-appraisal at follow-up 6 years later (n = 254). The BDNF-Val66Met polymorphism was significantly associated with the extended psychosis phenotype. The pattern of the association was that the BDNF-Val66Met polymorphism impacted in a dose-response but extra-linear fashion, with stronger impact at the PD end of the extended psychosis phenotype. Associations were still significant after adjusting for sociodemographic factors and environmental exposures including life events, childhood adversity, socioeconomic status, urbanicity, and cannabis use. The BDNF-Val66Met polymorphism may index susceptibility to expression of psychosis along a spectrum.

Network analysis of symptoms in a Parkinson patient using experience sampling data: An n = 1 study.

BACKGROUND: Around 50% of Parkinson's disease patients experience motor fluctuations after long-term treatment with levodopa. These fluctuations may be accompanied by mood fluctuations. Routine cross-sectional assessments cannot capture the extent of these motor and mood fluctuations and their possible associations. Experience sampling techniques that use frequently repeated measurements of symptoms over time are able to capture such fluctuations. Based on such data, longitudinal associations between symptoms can be studied using network analysis. AIM: The purpose of this study is to identify longitudinal associations between motor symptoms and mood states in a patient with Parkinson's disease. METHODS: A 53-year-old man with Parkinson's disease and motor fluctuations collected experience sampling data during 34 consecutive days. A set of dependent variables included tremor, rigidity, balance problems, and "on/off" state, and the mood variables anxiety, cheerful, and "down." Independent variables were the same variables assessed at the preceding measurement. Regression coefficients were calculated and presented in a network graph. RESULTS: In this patient, anxiety and cheerfulness had a central position within the symptom network. Higher anxiety was prospectively associated with increased rigidity and tremor and with feeling "down." Cheerfulness was associated with less tremor. Balance problems were not influenced by cheerfulness nor anxiety, but increased balance problems were associated with reduced cheerfulness at the next assessment. Feeling "down" did not influence self-reported motor symptom severity at the next assessment. CONCLUSION: This n = 1 study shows that network analysis of experience sampling data may reveal longitudinal associations of self-reported motor symptoms and mood states that may have relevance for treatment strategies. © 2018 International Parkinson and Movement Disorder Society.

The association between psychotic experiences and traumatic life events: the role of the intention to harm.

BACKGROUND: Previous work showed traumatic life events (TLE) with intention to harm, like bullying and abuse, to be more strongly associated with psychotic experiences (PE) than other types of trauma, like accidents. However, this association is subject to reporting bias and can be confounded by demographic characteristics and by differences in dose of exposure across different trauma categories. We studied the association between TLE with and without intention to harm and PE, taking into account potential confounders and biases. METHODS: A total of 2245 children and adolescents aged 6-14 years were interviewed by psychologists. The interview included the presence of 20 PE (both self-report and psychologist evaluation). In addition, parents provided information on child exposure to trauma, mental health and PE. RESULTS: Results showed no significant association between TLE without intention to harm only and PE for the three methods of assessment of PE (self-report, parent report and psychologist rating). On the other hand, there was a positive association between PE and TLE in groups exposed to traumatic experiences with intention to harm (with intention to harm only and with and without intention to harm). Results remained significant after controlling for demographic and clinical confounders, but this positive association was no longer significant after adjusting for the number of TLE. CONCLUSIONS: TLE with intention to harm display a stronger association with PE than TLE without intention to harm, and this difference is likely reducible to a greater level of traumatic exposure associated with TLE with intention to harm.

The experience sampling method as an mHealth tool to support self-monitoring, self-insight, and personalized health care in clinical practice.

BACKGROUND: The experience sampling method (ESM) builds an intensive time series of experiences and contexts in the flow of daily life, typically consisting of around 70 reports, collected at 8-10 random time points per day over a period of up to 10 days. METHODS: With the advent of widespread smartphone use, ESM can be used in routine clinical practice. Multiple examples of ESM data collections across different patient groups and settings are shown and discussed, varying from an ESM evaluation of a 6-week randomized trial of mindfulness, to a twin study on emotion dynamics in daily life. RESULTS: Research shows that ESM-based self-monitoring and feedback can enhance resilience by strengthening the capacity to use natural rewards. Personalized trajectories of starting or stopping medication can be more easily initiated and predicted if sensitive feedback data are available in real time. In addition, personalized trajectories of symptoms, cognitive abilities, symptoms impacting on other symptoms, the capacity of the dynamic system of mental health to "bounce back" from disturbance, and patterns of environmental reactivity yield uniquely personal data to support shared decision making and prediction in clinical practice. Finally, ESM makes it possible to develop insight into previous implicit patterns of thought, experience, and behavior, particularly if rapid personalized feedback is available. CONCLUSIONS: ESM enhances clinical practice and research. It is empowering, providing co-ownership of the process of diagnosis, treatment evaluation, and routine outcome measurement. Blended care, based on a mix of face-to-face and ESM-based outside-the-office treatment, may reduce costs and improve outcomes.

Economic evaluation of an experience sampling method intervention in depression compared with treatment as usual using data from a randomized controlled trial.

BACKGROUND: Experience sampling, a method for real-time self-monitoring of affective experiences, holds opportunities for person-tailored treatment. By focussing on dynamic patterns of positive affect, experience sampling method interventions (ESM-I) accommodate strategies to enhance personalized treatment of depression-at potentially low-costs. This study aimed to investigate the cost-effectiveness of an experience sampling method intervention in patients with depression, from a societal perspective. METHODS: Participants were recruited between January 2010 and February 2012 from out-patient mental health care facilities in or near the Dutch cities of Eindhoven and Maastricht, and through local advertisements. Out-patients diagnosed with major depression (n = 101) receiving pharmacotherapy were randomized into: (i) ESM-I consisting of six weeks of ESM combined with weekly feedback regarding the individual's positive affective experiences, (ii) six weeks of ESM without feedback, or (iii) treatment as usual only. Alongside this randomised controlled trial, an economic evaluation was conducted consisting of a cost-effectiveness and a cost-utility analysis, using Hamilton Depression Rating Scale (HDRS) and quality adjusted life years (QALYs) as outcome, with willingness-to-pay threshold for a QALY set at €50,000 (based on Dutch guidelines for moderate severe to severe illnesses). RESULTS: The economic evaluation showed that ESM-I is an optimal strategy only when willingness to pay is around €3000 per unit HDRS and around €40,500 per QALY. ESM-I was the least favourable treatment when willingness to pay was lower than €30,000 per QALY. However, at the €50,000 willingness-to-pay threshold, ESM-I was, with a 46% probability, the most favourable treatment (base-case analysis). Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: We may tentatively conclude that ESM-I is a cost-effective add-on intervention to pharmacotherapy in outpatients with major depression. TRIAL REGISTRATION: Netherlands Trial register, NTR1974 .

Blink rate is associated with drug-induced parkinsonism in patients with severe mental illness, but does not meet requirements to serve as a clinical test: the Curacao extrapyramidal syndromes study XIII.

BACKGROUND: Drug-induced parkinsonism (DIP) has a high prevalence and is associated with poorer quality of life. To find a practical clinical tool to assess DIP in patients with severe mental illness (SMI), the association between blink rate and drug-induced parkinsonism (DIP) was assessed. METHODS: In a cohort of 204 SMI patients receiving care from the only mental health service of the previous Dutch Antilles, blink rate per minute during conversation was assessed by an additional trained movement disorder specialist. DIP was rated on the Unified Parkinson's Disease Rating Scale (UPDRS) in 878 assessments over a period of 18 years. Diagnostic values of blink rate were calculated. RESULTS: DIP prevalence was 36%, average blink rate was 14 (standard deviation (SD) 11) for patients with DIP, and 19 (SD 14) for patients without. There was a significant association between blink rate and DIP (p < 0.001). With a blink rate cut-off of 20 blinks per minute, sensitivity was 77% and specificity was 38%. A 10% percentile cut-off model resulted in an area under the ROC curve of 0.61. A logistic prediction model between dichotomous DIP and continuous blink rate per minute an area under the ROC curve of 0.70. CONCLUSIONS: There is a significant association between blink rate and DIP as diagnosed on the UPDRS. However, blink rate sensitivity and specificity with regard to DIP are too low to replace clinical rating scales in routine psychiatric practice. TRIAL REGISTRATION: The study was started over 20 years ago in 1992, at the time registering a trial was not common practice, therefore the study was never registered.

The interplay of psychosis and victimisation across the life course: a prospective study in the general population.

PURPOSE: Psychosis has been associated with adult victimisation. However, it remains unclear whether psychosis predicts incident adult victimisation, or whether adult victimisation predicts incident psychosis. Furthermore, a moderating effect of childhood victimisation on the association between psychosis and adult victimisation has not been investigated. METHODS: The longitudinal association between baseline psychotic experiences and six-year incidence of adult victimisation was assessed in a prospective general population cohort of 6646 adults using logistic regression analysis. The association between baseline adult victimisation and six-year incidence of psychotic experiences was examined as well. Furthermore, the moderating effect of childhood victimisation on these bidirectional associations was analysed. RESULTS: Psychotic experiences and childhood victimisation were both associated with an increased risk of incident adult victimisation. However, this was through competing pathways, as suggested by a negative interaction between psychotic experiences and childhood victimisation. Baseline adult victimisation and childhood victimisation both independently increased the risk of incident psychotic experiences, but there was no interaction between adult victimisation and childhood victimisation. CONCLUSIONS: Psychosis and victimisation are interconnected throughout the life course. Childhood victimisation is connected to psychosis through two pathways: one direct and one indirect through adult victimisation. In individuals without childhood victimisation, psychosis and adult victimisation bidirectionally impact on each other.

The impact of electroconvulsive therapy on the tryptophan-kynurenine metabolic pathway.

BACKGROUND: There is still limited knowledge about the mechanism of action of electroconvulsive therapy (ECT) in the treatment of depression. Substantial evidence suggests a role for the immune-moderated tryptophan (TRP)-kynurenine (KYN) pathway in depression; i.e. a depression-associated disturbance in the balance between the TRP-KYN metabolites towards a neurotoxic process. We, therefore, aimed to investigate the impact of ECT treatment on the TRP-KYN pathway, in association with ECT-related alterations in depressive symptoms. METHOD: Twenty-three patients with unipolar or bipolar depression, treated with bilateral ECT twice a week were recruited. Blood serum samples, and depression scores using the Hamilton Depression Rating Scale-17 items (HDRS) as well as the Beck Depression Inventory (BDI) were collected repeatedly during the period of ECT and until 6 weeks after the last ECT session. TRP and KYN metabolites were analyzed in serum using the High Performance Liquid Chromatography. Four patients could not complete the study; thereby yielding data of 19 patients. Analyses were performed using multilevel linear regression analysis. RESULTS: There was an increase in kynurenic acid (KYNA) (B=0.04, p=0.001), KYN/TRP ratio (B=0.14, p=0.001), KYNA/KYN ratio (B=0.07, p<0.0001), and KYNA/3-hydroxykynurenine ratio (B=0.01, p=0.008) over time during the study period. KYN (B=-0.02, p=0.003) and KYN/TRP (B=-0.19, p=0.003) were negatively associated with total HDRS over time. Baseline TRP metabolite concentrations did not predict time to ECT response. CONCLUSION: Our findings show that ECT influences the TRP-KYN pathway, with a shift in TRP-KYN metabolites balance towards molecules with neuroprotective properties correlating with antidepressant effects of ECT; thereby providing a first line of evidence that the mechanism of action of ECT is (co)mediated by the TRP-KYN pathway.

Psychotic disorder and educational achievement: a family-based analysis.

BACKGROUND: Early social and cognitive alterations in psychotic disorder, associated with familial liability and environmental exposures, may contribute to lower than expected educational achievement. The aims of the present study were to investigate (1) how differences in educational level between parents and their children vary across patients, their healthy siblings, and healthy controls (effect familial liability), and across two environmental risk factors for psychotic disorder: childhood trauma and childhood urban exposure (effect environment) and (2) to what degree the association between familial liability and educational differential was moderated by the environmental exposures. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 629), 552 non-psychotic siblings and 326 healthy controls from the Netherlands and Belgium were studied. Participants reported their highest level of education and that of their parents. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire-Short Form. Urban exposure, expressed as population density, was rated across five levels. RESULTS: Overall, participants had a higher level of education than their parents. This difference was significantly reduced in the patient group, and the healthy siblings displayed intergenerational differences that were in between those of controls and patients. Higher levels of childhood urban exposure were also associated with a smaller intergenerational educational differential. There was no evidence for differential sensitivity to childhood trauma and childhood urbanicity across the three groups. CONCLUSION: Intergenerational difference in educational achievements is decreased in patients with psychotic disorder and to a lesser extent in siblings of patients with psychotic disorder, and across higher levels of childhood urban exposure. More research is required to better understand the dynamics between early social and cognitive alterations in those at risk in relation to progress through the educational system and to understand the interaction between urban environment and educational outcomes.

Childhood trauma and childhood urbanicity in relation to psychotic disorder.

BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim of this study was twofold: (1) to investigate whether childhood urbanicity moderates the effect of childhood trauma, in a model predicting psychotic disorder; (2) to investigate whether there is an association between the urban environment and childhood trauma and whether this is moderated by genetic liability for psychotic disorder. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 1119) and 589 healthy controls from the Netherlands and Belgium were studied. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire Short Form. Urban exposure was defined at four levels, considering the population density, using data from Statistics Netherlands and the equivalent database in Belgium. RESULTS: There was a significant interaction between childhood urbanicity on the one hand and childhood trauma on the other, indicating that trauma was significantly associated with psychotic disorder, with increasing odds ratios for higher levels of childhood urbanicity. In addition, there was weak evidence that childhood urbanicity was associated with childhood trauma in the patient group: higher levels of childhood urbanicity were associated with higher trauma scores. CONCLUSION: The urban environment may moderate the risk-increasing effect of childhood trauma for psychotic disorder and childhood urbanicity may be a risk factor for childhood trauma in individuals who later develop psychotic disorder.

Serotonergic, noradrenergic and dopaminergic markers are related to cognitive function in adults with 22q11 deletion syndrome.

Patients with 22q11 deletion syndrome (22q11DS) have a high prevalence of psychiatric disorders and intellectual disability. At present the neurobiology underlying psychopathology in 22q11DS is still not understood. In the present study, we analyzed urinary serotonergic, dopaminergic and noradrenergic markers in 67 adults with 22q11DS. Levels of serotonin and the catecholamine metabolite homovanillic acid were significantly lower in the 22q11DS subjects compared to healthy controls. Within the 22q11DS group, levels of dopamine, homovanillic acid, norepinephrine, vanillyl mandelic acid and serotonin positively correlated with Full Scale Intelligence Quotient scores. Our results suggest that cognitive deficits in 22q11DS are associated with abnormal function of several neurotransmitters.

Evidence that childhood urban environment is associated with blunted stress reactivity across groups of patients with psychosis, relatives of patients and controls.

PURPOSE: Psychosis is associated with urban upbringing, and increased emotional reactivity is associated with psychosis. The aim of this study was to examine to what degree urban upbringing impacts emotional reactivity, and how this may be relevant for psychotic disorder and familial risk of psychotic disorder. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 57), 59 first degree relatives of patients and 75 healthy comparison subjects were studied with the experience sampling method (a random time sampling technique to assess affective experience in relation to fluctuating stressors in the flow of daily life), to measure a change in negative affect in relation to subjective stress. Urban exposure was defined at 5 levels, considering the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. RESULTS: Multilevel random regression analyses showed that urban upbringing was consistently and strongly associated with a reduced increase in negative affect in relation to SS in adulthood in a dose-response fashion in all three groups. Regression coefficients in the patient group decreased from 0.148 (p < 0.001) in the lowest urbanicity level to 0.094 (p < 0.001) in the highest urbanicity level. CONCLUSION: The findings suggest that urban upbringing may occasion "habituation" rather than "sensitization" across groups, which may or may not be relevant for the onset of psychotic disorder.