Introduction Neuroticism has societal, mental and physical health relevance, with an etiology involving genetic predisposition, psychological influence, and their interaction. Objectives To understand whether the association between polygenic risk score for neuroticism (PRS-N) and neuroticism is moderated by affective well-being. Methods Data were derived from TwinssCan, a general population twin cohort (age range=15-35 years, 478 monozygotic twins). Self-report questionnaires were used to measure well-being and neuroticism. PRS-N was trained from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB). Multilevel mixed-effects models were used to test baseline and changes in well-being and neuroticism. Results Baseline wellbeing and neuroticism were associated (β=-1.35, p<0.001). PRSs-N were associated with baseline neuroticism (lowest p-value: 0.008 in GPC, 0.01 in UKB). In interaction models (PRS x wellbeing), GPC PRS-N (β=0.38, p=0.04) and UKB PRS-N (β=0.81, p<0.001) had significant interactions. PRSs-N were associated with changes in neuroticism (lowest p-value: 0.03 in GPC, 0.3 in UKB). Furthermore, changes in wellbeing and neuroticism were associated (β =-0.66, p<0.001). In interaction models (PRS x change in wellbeing), only UKB PRS-N had a significant interaction (β=0.80, p<0.001). Conclusions Interaction between polygenic risk, wellbeing and neuroticism, were observed regarding baselines measures and change over time. Depending on the analysis step, the direction of the effect changed. Disclosure of Interest None Declared

Introduction Prior evidence suggests that men and women might be differentially susceptible to distinct types of childhood adversity (CA), but research on gender-specific associations between CA subtypes and psychiatric symptoms is limited. Objectives To test the gender-specific associations of CA subtypes and psychiatric symptoms in the general population. Methods Data from 791 twins and siblings from the TwinssCan project were used. Psychopathology and CA exposure were assessed using the Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire (CTQ), respectively. The associations between the total CTQ scores and SCL-90 scores (i.e. total SCL-90, psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety) were tested in men and women separately. The associations between the five CA subtypes (i.e. physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect) and total SCL-90 were tested in a mutually adjusted model. As exploratory analyses, the associations between all CA subtypes and the nine SCL-90 subdomain scores were similarly tested. The regression coefficients between men and women were compared using Chow’s test. All models were adjusted for age and family structure. Results Total CTQ was significantly associated with total SCL-90 in men (B = 0.013, SE = 0.003, P < .001) and women (B = 0.011, SE = 0.002, P < .001). The associations with the nine symptom domains were also significant in both genders (P < .001). No significant gender differences in the regression coefficients of total CTQ were detected. The analyses of CA subtypes showed a significant association between emotional abuse and total SCL-90 in women (B = 0.173, SE = 0.030, P < .001) and men (B = 0.080, SE = 0.035, P = .023), but the association was significantly stronger in women (ꭓ2(1) = 4.10, P = .043). The association of sexual abuse and total SCL-90 was only significant in women (B = 0.217, SE = 0.053, P < .001). The associations of emotional neglect (B = 0.061, SE = 0.027, P = .026) and physical neglect (B = 0.167, SE = 0.043, P < .001) with total SCL-90 were only significant in men. The explorative analyses of SCL-90 subdomains revealed significant associations of emotional abuse with all nine symptom domains and of sexual abuse with seven symptom domains in women. Significant associations of physical neglect with six symptom domains and of emotional neglect with depression were also detected in men. No other significant associations between CT subtypes and total SCL-90 or symptom domain scores were observed in men and women. Conclusions CA exposure was associated with diverse psychopathology similarly in both genders. However, women are more sensitive to abuse, but men are more sensitive to neglect. Gender-specific influences of CA subtypes on psychopathology should be considered in future studies. Disclosure of InterestNone Declared

OPS 29: Green space and neurological effects, Room 411, Floor 4, August 28, 2019, 1:30 PM - 3:00 PM Background: Exposure to greenness has been associated with beneficial effect on cognitive and behaviour development. However, so far no studies addressed intelligence as outcome. We studied if the level of urbanicity can modify the association between residential greenness and intelligence and behaviour in children. Methods: Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) in 614 children (307 twin pairs) between 7 and 15 years old. From a subset of 436 twins neurobehaviour was determined based on the Achenbach Child Behaviour Checklist (CBCL). Prenatal and adulthood residential addresses were geocoded and used to assign greenness indicators. Mixed modelling was performed to investigate greenness in association with intelligence and problem behaviour while adjusting for potential confounding factors. Results: We found that the association between residential greenness and both IQ and behaviour in children was modified by the degree of urbanicity (p for interaction = <0.0001). In children living in an urban environment, multivariable adjusted mixed modelling analysis revealed that an IQR increment of residential greenness (3000 m radius) was associated with a 2.7 points (95% CI: 1.4 to 4.0; p=0.0008) higher total IQ and 2.3 points (95% CI: -4.4 to -0.3; p=0.03) lower child behaviour total score. In children residing in a rural or suburban environment no association between residential greenness indicators and IQ or behaviour was found. Conclusions: Our results indicate that children living in urban regions might benefit more from residential greenness than children living in rural areas. These findings are relevant for policy makers and urban planners designing urban environments to create an optimal environment for children to develop their full neuro-cognitive potential.

Citation for published version (APA): Hasmi, L., Drukker, M., Guloksuz, S., Menne-Lothmann, C., Decoster, J., van Winkel, R., ... van Os, J. (2017). Network Approach to Understanding Emotion Dynamics in Relation to Childhood Trauma and Genetic Liability to Psychopathology: Replication of a Prospective Experience Sampling Analysis. Frontiers in Psychology, 8, [1908]. https://doi.org/10.3389/fpsyg.2017.01908

Purpose: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology.Methods: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model.Results: Linear analyses showed that emotional stress reactivity was not associated with onset (beta = .02; P =.56) or persistence (beta = -01; P = .78) of symptoms. There was a significant effect of baseline symptom score (beta = .53; P < .001) and average negative affect (NA: beta = .19; P < .001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (beta =.25; P < .001), but not moderate (beta = -03; P = .65) or severe (beta = -.06; P = .42), stressors was associated with symptom persistence one year later.Discussion: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology. (C) 2017 Published by Elsevier Masson SAS.

OBJECTIVE:Altered social reward functioning is associated with psychosis irrespective of stage and severity. Examining the role of social reward functioning prospectively in relation to psychotic experiences before these become persistent and potentially disabling can aid in elucidating social mechanisms that induce shifts toward more severe psychotic states, without the confounding effects of clinical disorder.METHOD:In a longitudinal general population sample (N = 566), the experience sampling method (repetitive random sampling of momentary emotions and social context) was used to assess daily life social functioning at baseline. Persistence of subclinical psychotic experiences was based on the Community Assessment of Psychic Experiences assessed three times over 14 months. Analyses examined to what degree i) social context and ii) appreciation thereof differentiated between those who did and did not develop persistent psychotic experiences.RESULTS:Although individuals with persistent psychotic experiences did not differ in overall level of positive effect, the amount of time spent alone or the level of social satisfaction compared to individuals without persistent psychotic experiences, they were more sensitive to the rewarding effects of social company.CONCLUSION:Alterations in social reward experience may form one of the mechanisms that precede the development of the extended psychosis phenotype over time.

Intrauterine factors important for cognitive development, such as birth weight, chorionicity and umbilical cord characteristics were investigated. A total of 663 twin pairs completed the Wechsler Intelligence Scale for Children-Revised and scores were available for Performance, Verbal and Total Intelligence Quotient (IQ). The intrauterine factors examined were birth weight, placental weight and morphology, cord knots, cord length and cord insertion. IQ scores for the varying levels of the intrauterine markers adjusting for gender and gestational age were calculated. The heritability of IQ and the association between IQ and intrauterine environment were examined. Twins with lower birth weight and cord knots had lower IQ scores. The aetiology of IQ is largely distinct from that of birth weight and cord knots, and non-shared environment may influence the observed relationships.

Psychotic disorders are thought to represent altered neural function. However, research has failed to map diagnostic categories to alterations in neural networks. It is proposed that the basic unit of psychotic psychopathology is the moment-to-moment expression of subtle anomalous experiences of subclinical psychosis, and particularly its tendency to persist from moment-to-moment in daily life, under the influence of familial, environmental, emotional and cognitive factors. In a general population twin sample (n= 579) and in a study of patients with psychotic disorder (n=57), their non-psychotic siblings (n=59) and unrelated controls (n=75), the experience sampling paradigm (ESM; repetitive, random sampling of momentary mental states and context) was applied. We analysed, in a within-person prospective design, (i) transfer of momentary anomalous experience at time point ( t–1 ) to time point ( t ) in daily life, and (ii) moderating effects of negative affect, positive affect, daily stressors, IQ and childhood trauma. Additionally, (iii) familial associations between persistence of momentary anomalous experience and psychotic symptomatology were investigated. Higher level of schizotypy in the twins (but not higher level of psychotic symptoms in patients) predicted more persistence of momentary anomalous experience in daily life, both within subjects and across relatives. Persistence of momentary anomalous experience was highest in patients, intermediate in their siblings and lowest in controls. In both studies, persistence of momentary anomalous experience was moderated by higher levels of negative affect, daily stressors and childhood trauma (only in twins), and by lower levels of positive affect. The study of alterations in the moment-to-moment transfer of subtle anomalous experience of psychosis, resulting in their persistence, helps to explain why psychotic and emotional dysregulation tend to cluster in a single phenotype such as schizophrenia, and how familial and environmental risks increase the risk of expression of psychosis from, first, subtle momentary anomalous experience to, second, observable clinical symptoms.

Researchers have long called for greater recognition and use of longitudinal, individual-level research in the study of psychopathology and psychotherapy. Much of our current research attempts to indirectly investigate individual-level, or idiographic, psychological processes via group-based, or nomothetic, designs. However, results from nomothetic research do not necessarily translate to the individual-level. In this review, we discuss how idiographic analyses can be integrated into psychotherapy and psychotherapy research. We examine and review key statistical methods for conducting idiographic analyses. These methods include factor-based and vector autoregressive approaches using longitudinal data. The theoretical framework behind each approach is reviewed and critically evaluated. Empirical examples of each approach are discussed, with the aim of helping interested readers consider how they may use idiographic methods to analyze longitudinal data and psychological processes. Finally, we conclude by citing key limitations of the idiographic approach, calling for greater development of these analyses to ease their successful integration into clinical settings.

Background Genes for depression may act by making individuals more sensitive to childhood trauma. Given that childhood adversity is a risk factor for adult psychosis and symptoms of depression and psychosis tend to cluster within individuals and families, the aim was to examine whether the association between childhood adversity and psychotic-like symptoms is moderated by genetic liability for depression. A secondary aim was to determine to what degree a depression-related increase in stress sensitivity or depressive symptoms themselves occasioned the moderating effect. Method Female twins (n=508) completed both prospective and retrospective questionnaires regarding childhood adversity [the Symptom Checklist-90 – Revised (SCL-90-R) and SCID-I (psychotic symptoms)] and psychotic trait liability [the Community Assessment of Psychic Experiences (CAPE)]. Stress sensitivity was indexed by appraisals of event-related stress and negative affect (NA) in the flow of daily life, assessed with momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of childhood adversity by genetic liability for depression in the prediction of follow-up psychotic experiences. Results The effect of childhood adversity was significantly moderated by genetic vulnerability for depression in the model of both follow-up psychotic experiences (SCL-90-R) and follow-up psychotic trait liability (CAPE). The moderation by genetic liability was mediated by depressive experience but not by stress sensitivity. Conclusions Genetic liability for depression may potentiate the pathway from childhood adversity to psychotic-like symptoms through dysfunctional emotional processing of anomalous experiences associated with childhood trauma.

OBJECTIVE:The daily life, affective phenotypes of momentary negative affect (NA), positive affect (PA) variability and NA variability are associated with future depressive symptomatology. This study investigates the extent to which genetic and environmental factors contribute to the inter-individual differences in these daily life, affective phenotypes.METHOD:Two hundred and seventy-nine female twins from the Flemish (Belgium) general population participated in an experience sampling study measuring affect in daily life. Structural equation modelling was used to fit univariate and bivariate models.RESULTS:Genetic factors explained, respectively, 18%, 18% and 35% of the inter-individual differences in momentary NA, PA variability and NA variability. Non-shared environmental factors were found to explain the remaining inter-individual variation. In addition, 41% of the association between positive and NA variability was attributed to shared genetic factors.CONCLUSION:Results of this study show that daily life patterns of affective expression are subject to substantial environmental influence. Prospective assessments of the effect of interventions on these expressions may therefore represent a powerful tool to prevent transition from subclinical depressive symptomatology to a clinical outcome or to reduce symptomatology in those with clinical depression.

Background Negative life events are strongly associated with the development of depression. However, the etiologic relationship between life events and depression is complex. Evidence suggests that life events can cause depression, and depression increases the risk for life events. Additionally, third factors influencing both phenotypes may be involved. In this work we sought to disentangle these relationships using a genetically informative longitudinal design. Method Adult female twins ( n =536, including 281 twin pairs) were followed up for measurements of negative life event exposure and depressive symptoms. Four follow-ups were completed, each approximately 3 months apart. Model fitting was carried out using the Mx program. Results The best-fitting model included causal paths from life events to depressive symptoms for genetic and shared environmental risk factors, whereas paths from depressive symptoms to life events were apparent for shared environmental factors. Shared latent influence on both phenotypes was found for individual-specific effects. Conclusions Life events and depressive symptoms have complex inter-relationships that differ across sources of variance. The results of the model, if replicated, indicate that reducing life event exposure would reduce depressive symptoms and that lowering depressive symptoms would decrease the occurrence of negative life events.

The aim of this study was to examine the effects of amygdalohippocampal deep brain stimulation (AH-DBS) on cognitive functioning in patients with refractory temporal lobe epilepsy. The population consisted of 10 patients (7 men) who underwent ipsilateral (n=8) or bilateral (n=2) AH-DBS. Intellectual and neuropsychological evaluation was performed before and 6 months after initiation of AH-DBS. Group analyses revealed no overall pattern of change in cognitive measures, but improvement was seen in emotional well-being. Individual results varied over a broad spectrum ranging from no cognitive effects to negative effects on intelligence capacities, divided attention, and concept formation, to positive effects on speed of information processing and speed of finger movements. AH-DBS is a valuable treatment alternative for patients with refractory epilepsy that appears to have no major adverse neuropsychological consequences and enhances emotional well-being on the group level. Individual results are too diverse at this moment to allow viable interpretation. Additional studies are needed to confirm these preliminary results.

Solving the problem of therapy resistance in epilepsy: a challenge for basic and clinical research. Clinical added value of MEG in patients with refractory partial epilepsy and non-localizing conventional presurgical evaluation. Angiotensin II type 2 receptor stimulation decreases tyrosine hydroxylase activity in the rat striatum. The pharmacodynamic profile of aripiprazole is not altered in a model of striatal dopaminergic hypersensitivity. Lithium chloride induces macrophage apoptosis in rabbit atherosclerotic plaques. Hypoxia enhances the relaxing influence of perivascular adiopose tissue. Activity of sunitinib in advanced malignant melanoma and its correlation with potential predictive biomarkers. No evidence for increased activity of the L-arginine/NO pathway in migraine patients. Increased cerebral type 1 cannabinoid receptor availability in migraine patients. Combined experimental and computational approaches to study the action of blockers of small conductance calcium-activated potassium (SK) channels. Connexin channels contribute to endothelial Ca 2+ dynamics and alter blood-brain barrier function. Mild hypothermia after a transient focal cerebral ischemia in rats: influence on cytokines. A reduction of glucose-induced bursting frequency in pancreatic islets correlates with decreased insulin release an impaired glucose tolerance in Trpm5 /-mice.

Objective: Daily life affective responses are closely linked to vulnerability and resilience in depression. Prediction of future clinical course may be improved if information on daily life emotional response patterns is taken into account.Method: Female subjects with a history of major depression (n = 83), recruited from a population twin register, participated in a longitudinal study using momentary assessment technology with 4 follow-up measurements. The effect of baseline daily life emotional response patterns (affect variability, stress-sensitivity and reward experience) on follow-up depressive symptomatology was examined.Results: Both reward experience (B = -0.30, p = 0.001) and negative affect variability (B = 0.46, p = 0.001) predicted future negative affective symptoms independent of all other dynamic emotional patterns and conventional predictors.Conclusion: Daily life information on dynamic emotional patterns adds to the prediction of future clinical course, independent of severity of symptoms and neuroticism score. Better prediction of course may improve decision-making regarding quantitative and qualitative aspects of treatment. (C) 2009 Elsevier B.V. All rights reserved.

OBJECTIVE:To examine prospectively whether high reward experience (the ability to generate positive affect boosts from pleasurable daily events) protects against affective symptoms and whether environmental or genetic risk factors moderate protective effects.METHOD:At baseline, 498 female twins participated in an experience sampling study measuring reward experience in daily life. They also completed questionnaires on childhood adversity and recent stressful life events (SLE). Affective symptoms were measured at baseline and at four follow-ups using SCL-90 anxiety and depression subscales. Co-twin affective symptoms were used as indicators of genetic risk.RESULTS:Baseline reward experience did not predict follow-up affective symptoms, regardless of level of genetic risk. However, high reward experience was associated with reduced future affective symptoms after previous exposure to childhood adversity or recent SLE.CONCLUSION:High daily life reward experience increases resilience after environmental adversity; modification of reward experience may constitute a novel area of therapeutic intervention.