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Contains fulltext : 290737.pdf (Publisher’s version ) (Open Access) DNA methylation (DNAm) is one of the most frequently studied epigenetic mechanisms facilitating the interplay of genomic and environmental factors, which can contribute to externalizing behaviours and related psychiatric disorders. Previous epigenome-wide association studies (EWAS) for externalizing behaviours have been limited in sample size, and, therefore, candidate genes and biomarkers with robust evidence are still lacking. We 1) performed a systematic literature review of EWAS of attention-deficit/hyperactivity disorder (ADHD)- and aggression-related behaviours conducted in peripheral tissue and cord blood and 2) combined the most strongly associated DNAm sites observed in individual studies (p

Contains fulltext : 219574.pdf (Publisher’s version ) (Open Access) This study examined whether teachers' perceptions of students' behavior (referring to halo effects) and the behavior of teacher-perceived friends (referring to association effects) influenced teachers' ability to recognize students identified as bullies, victims, and prosocial by their peers. Data came from 1,458 children (M age = 10.5, 47.5% girls) and 56 teachers (M age = 41.4, 63.5% females). Perceived likeability was associated with decreased odds and teachers' perceptions of popularity and externalizing behavior were associated with increased odds for teacher attunement to bullying. Perceived likeability and affiliation were associated with decreased odds for teacher attunement to victimized students. Teachers' perceptions of externalizing behavior were associated with decreased odds, whereas teachers' perceptions of affiliation and academic competence were associated with increased odds for attunement to prosociality. Finally, a positive association was found between teacher attunement and the average behavior of teacher-perceived friends for bullying, victimization, and prosociality. 18 p.

Impulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional-defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD-specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.

Purpose This pilot study was carried out to determine the effect of acupressure on agitation in the elderly with dementia who receive institutional care. Methods The study sample consisted of 38 elderly individuals (acupressure group [AG] = 19, usual-care group = 19). Acupressure application was performed on four points. The results were measured at the beginning (T-0), the week after acupressure was completed (T-1), and 2 weeks after acupressure was completed (T-2). Findings The change in the total Cohen-Mansfield Agitation Inventory score across the groups at T-1, T-2, and T(3)was statistically significant in favor of AG. Practical Implications The acupressure used in this study can be used for managing agitation in the elderly with dementia. WOS:000579772000001 2-s2.0-85092335574 PubMed: 33044041

Background Non-pharmacological interventions are recommended for the treatment of challenging behaviours in individuals with intellectual disabilities by clinical guidelines. However, evidence for their effectiveness is ambiguous. The aim of the current meta-analysis is to update the existing evidence, to investigate long-term outcome, and to examine whether intervention type, delivery mode, and study design were associated with differences in effectiveness. Method An electronic search was conducted using the databases Medline, Eric, PsychINFO and Cinahl. Studies with experimental or quasi-experimental designs were included. We performed an overall random-effect meta-analysis and subgroup analyses. Results We found a significant moderate overall effect of non-pharmacological interventions on challenging behaviours (d = 0.573, 95% CI [0.352-0.795]), and this effect appears to be longlasting. Interventions combining mindfulness and behavioural techniques showed to be more effective than other interventions. However, this result should be interpreted with care due to possible overestimation of the subgroup analysis. No differences in effectiveness were found across assessment times, delivery modes or study designs. Conclusions Non-pharmacological interventions appear to be moderately effective on the short and long term in reducing challenging behaviours in adults with intellectual disabilities.

Background Non‐pharmacological interventions are recommended for the treatment of challenging behaviours in individuals with intellectual disabilities by clinical guidelines. However, evidence for their effectiveness is ambiguous. The aim of the current meta‐analysis is to update the existing evidence, to investigate long‐term outcome, and to examine whether intervention type, delivery mode, and study design were associated with differences in effectiveness. Method An electronic search was conducted using the databases Medline, Eric, PsychINFO and Cinahl. Studies with experimental or quasi‐experimental designs were included. We performed an overall random‐effect meta‐analysis and subgroup analyses. Results We found a significant moderate overall effect of non‐pharmacological interventions on challenging behaviours (d = 0.573, 95% CI [0.352–0.795]), and this effect appears to be longlasting. Interventions combining mindfulness and behavioural techniques showed to be more effective than other interventions. However, this result should be interpreted with care due to possible overestimation of the subgroup analysis. No differences in effectiveness were found across assessment times, delivery modes or study designs. Conclusions Non‐pharmacological interventions appear to be moderately effective on the short and long term in reducing challenging behaviours in adults with intellectual disabilities.

Male house mice excrete large amounts of protein in their urinary scent marks, mainly composed of Major Urinary Proteins (MUPs), and these lipocalins function as pheromones and pheromone carriers. Here, we review studies on sexually dimorphic MUP expression in house mice, including the proximate mechanisms controlling MUP gene expression and their adaptive functions. Males excrete 2 to 8 times more urinary protein than females, though there is enormous variation in gene expression across loci in both sexes. MUP expression is dynamically regulated depending upon a variety of factors. Males regulate MUP expression according to social status, whereas females do not, and males regulate expression depending upon health and condition. Male-biased MUP expression is regulated by pituitary secretion of growth hormone (GH), which binds receptors in the liver, activating the JAK2-STAT5 signaling pathway, chromatin accessibility, and MUP gene transcription. Pulsatile male GH secretion is feminized by several factors, including caloric restriction, microbiota depletion, and aging, which helps explain condition-dependent MUP expression. If MUP production has sex-specific fitness optima, then this should generate sexual antagonism over allelic expression (intra-locus sexual conflict) selectively favoring sexually dimorphic expression. MUPs influence the sexual attractiveness of male urinary odor and increased urinary protein excretion is correlated with the reproductive success of males but not females. This finding could explain the selective maintenance of sexually dimorphic MUP expression. Producing MUPs entails energetic costs, but increased excretion may reduce the net energetic costs and predation risks from male scent marking as well as prolong the release of chemical signals. MUPs may also provide physiological benefits, including regulating metabolic rate and toxin removal, which may have sex-specific effects on survival. A phylogenetic analysis on the origins of male-biased MUP gene expression inMus musculussuggests that this sexual dimorphism evolved by increasing male MUP expression rather than reducing female expression.

Contains fulltext : 248360.pdf (Publisher’s version ) (Open Access) Monoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Among these, Monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene have been associated with Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function, specifically in dopaminergic (DA) neurons. Here we generated human induced pluripotent stem cell (hiPSC)-derived DA neurons from three individuals with Brunner syndrome carrying different mutations and characterized neuronal properties at the single cell and neuronal network level in vitro. DA neurons of Brunner syndrome patients showed reduced synaptic density but exhibited hyperactive network activity. Intrinsic functional properties and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected in DA neurons of individuals with Brunner syndrome. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of the GRIN2A and GRIN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), resulting in increased NMDAR-mediated currents. By correcting a MAOA missense mutation with CRISPR/Cas9 genome editing we normalized GRIN2A and GRIN2B expression, NMDAR function and neuronal population activity to control levels. Our data suggest that MAOA mutations in Brunner syndrome increase the activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to the etiology of Brunner syndrome associated phenotypes.

The aim of this study was to evaluate the effect of 16L:8D photoperiod with green (GREEN) or white (WHITE) lights during incuba-tion on hatching performance, blood melatonin, corti-costerone, and serotonin levels, hypothalamic expressions of genes related to photoreception, seroto-nin, and stress systems in layers in relation with feather pecking behavior. Dark incubation (DARK) was the control. Eggs (n = 1,176) from Brown Nick breeders in 2 batches (n = 588/batch) were incubated in the exper-iment. A total of 396 female chicks and 261 hens were used at rearing and laying periods until 40 wk. Incuba-tion lighting did not affect hatchability, day-old chick weight, and length, but resulted in a more synchronized hatch as compared with the DARK. The effect of incu-bation lighting on blood hormones was not significant except for reduced serotonin in the GREEN group at the end of the experiment. There was no effect of incu-bation lighting on gentle, severe, and aggressive peck-ing of birds during the early rearing period. From 16 wk, GREEN hens showed increased gentle pecking with increasing age. WHITE hens had the highest gen-tle pecking frequency at 16 wk while they performed less gentle but higher severe and aggressive pecks at 24 and 32 wk. At hatching, the hypothalamic expression of CRH, 5-HTR1A, and 5-HTR1B was higher for the WHITE group compared with both GREEN and DARK, however, 5-HTT expression was higher in GREEN than WHITE which was similar to DARK. Except for the highest VA opsin expression obtained for WHITE hens at 40 wk of age, there was no change in hypothalamic expression levels of rhodopsin, VA opsin, red, and green opsins at any age. Although blood hormone levels were not consistent, results provide pre-liminary evidence that incubation lighting modulates the pecking tendencies of laying hens, probably through the observed changes in hypothalamic expres-sion of genes related to the serotonin system and stress. Significant correlations among the hypothalamic gene expression levels supplied further evidence for the asso-ciations among photoreception, serotonin, and stress systems., Ege University [16-ZRF-071, 18-ZRF-026], ACKNOWLEDGMENTS Rudie Koopmanschap from Wageningen University is acknowledged for the analysis of whole-blood serotonin levels. This study was funded by Ege University (grant numbers: 16-ZRF-071, and 18-ZRF-026) .

Anxiety, aggression/agitation, apathy and disinhibition are common neuropsychiatric consequences of acquired brain injury (ABI); these consequences can cause functional impairment and lead to reduced social integration. This systematic review aims to provide an examination of the current evidence on psychological interventions for treating these consequences. Two reviewers selected potential relevant articles, retrieved from five literature databases; methodological quality was assessed and appraised. A total of 5207 studies were found, of which 43 were included: 21 studies for anxiety, 18 for aggression, two studies for apathy, and six for disinhibition. Three studies addressed multiple consequences. Four high-quality (i.e., Class I and II) studies showed significant decreases in anxiety after cognitive behavioural therapy (CBT). In total, 14 studies consistently showed significant decreases in aggression/agitation after behavioural management techniques or anger management sessions. Substantial variability existed in the examined interventions and in their effects on apathy and disinhibition. Unfortunately, firm conclusions and recommendations for clinical practice are considered premature, due to concerns about the methodology used. However, this review yielded new evidence on the effectiveness of CBT for anxiety symptoms post-ABI and there has been some response to the ongoing call for studies with high methodological quality.

Contains fulltext : 217705.pdf (Publisher’s version ) (Open Access) Background: Attributions are cognitive variables that influence a person's behaviour. Although a large volume of research has been conducted on the attributions of support staff with regard to challenging behaviour (CB) exhibited by people with intellectual disabilities (ID), studies on patterns of attributional dimensions (i.e. attributional styles) are scarce. Method: Using semi-structured interviews, 19 support staff members were asked to describe incidents of aggressive, self-injurious and sexualized challenging behaviour. Data on attributions were analysed using the Leeds Attributional Coding System. Results: Four attributional styles differed significantly for aggressive, self-injurious and sexualized challenging behaviour. In addition, support staff members largely attributed these three types of CB to characteristics and behaviour of clients with ID. Conclusions: The results indicate that it is important to train support staff to recognize and understand the ways in which their attributions and behaviour influence the existence and maintenance of CB. 10 p.

Objectives: To systematically review literature on efficacy of amantadine on behavior (irritability/aggression/agitation, emotional lability, apathy, impairment of executive functioning), participation, quality-of-life (QoL), and safety, in patients with acquired brain injury (ABI). Amantadine is widely used clinically, so comprehensive information on efficacy, participation, QoL and safety is relevant. Methods: We used PRISMA Guidelines. We searched PubMed/EMBASE/CINAHL (last search 28-8-2018) Two independent reviewers performed selection and data-extraction. Quality of studies was assessed, using CONSORT and Quality Assessment Tool for Quantitative Studies (QATFQS). Results: Eleven out of 500 studies were included. Of five RCTs, two reported significant effects on irritability/aggression, and one no effect. One RCT on cognition no effect. One prospective cohort study showed a significant effect on executive functioning. One retrospective study was inconclusive. One single-case experimental design (SCED) study reported significant effect on apathy and three case-reports indicated effects on behavior. QoL and societal participation were not measured. No safety issues emerged. Conclusion: Amantadine may be efficacious on irritability and aggression after ABI. Amantadine is a safe drug in the presence of adequate creatinine clearance. Future studies should use designs, suitable for the heterogeneous ABI population, like randomized SCEDs, and should include the effect on societal participation and QoL.

The ABC method is a behaviour management technique for use by nurses. ABC refers to the identification of Antecedent events, target Behaviours, and Consequent events. In this longitudinal intervention study with double baseline measurements we evaluated the effectiveness of the ABC method in patients with behavioural problems after acquired brain injury. Fifty-six patients participated in this study. Outcome was measured in terms of overall neuropsychiatric problem behaviour, aggression, apathy and emotional burden experienced by nurses. A process evaluation was performed to investigate usability and acceptability of the method and identify factors that influenced effectiveness. Friedman's ANOVA showed a small significant reduction over time in overall neuropsychiatric problem behaviour and aggression. The reduction was most prominent between the first baseline measurement and the post-implementation and follow-up measurements, not between the second baseline measurement and the post-implementation or follow-up measurements. This first group study on the effects of the ABC method could not prove this technique is effective for patients with behavioural problems after acquired brain injury. Nurses indicated that the ABC method was not fully implemented in their daily routines. This may have influenced results and makes it yet premature to draw firm conclusions on the effects of the ABC method.

Introduction: Experimental models of neuropsychiatric disorders, for example, ADHD, are used to mimic specific phenotypic traits of a complex human disorder. However, it remains unresolved to what extent the animal phenotype reflects the specific human trait. The null mutant mouse of the serotonin-synthesizing tryptophan hydroxylase-2 (Tph2(-/-)) gene has been proposed as experimental model for ADHD with high face validity for impulsive, aggressive, and anxious behaviors. To validate this ADHD-like model, we examined the Tph2(-/-) phenotype in humans when considering allelic variation of TPH2 function ("reverse phenotyping").Methods: 58 participants (6 females, 8-18 years) were examined, of whom 32 were diagnosed with ADHD. All participants were phenotyped for impulsivity, aggression, and anxiety using questionnaires, behavioral tests, and MRI scanning while performing the 4-choice serial reaction time task. Additionally, participants were genotyped for the TPH2 G-703T (rs4570625) polymorphism. To analyze the relation between TPH2 G-703T variants and the impulsive/aggressive/anxious phenotype, mediation analyses were performed using behavioral and MRI data as potential mediators.Results: We found that the relation between TPH2 G-703T and aggression as part of the reverse Tph2(-)/(-) phenotype was mediated by structure and function of the right middle and inferior frontal gyrus.Conclusion: At the example of trait aggression, our results support the assumption that the Tph2 null mutant mouse reflects the TPH2 G-703T-dependent phenotype in humans. Additionally, we conclude that "reverse phenotyping" is a promising method to validate experimental models and human findings for refined analysis of disease mechanisms.

Introduction Experimental models of neuropsychiatric disorders, for example, ADHD, are used to mimic specific phenotypic traits of a complex human disorder. However, it remains unresolved to what extent the animal phenotype reflects the specific human trait. The null mutant mouse of the serotonin‐synthesizing tryptophan hydroxylase‐2 (Tph2 ‐/‐) gene has been proposed as experimental model for ADHD with high face validity for impulsive, aggressive, and anxious behaviors. To validate this ADHD‐like model, we examined the Tph2‐/‐ phenotype in humans when considering allelic variation of TPH2 function (“reverse phenotyping”). Methods 58 participants (6 females, 8–18 years) were examined, of whom 32 were diagnosed with ADHD. All participants were phenotyped for impulsivity, aggression, and anxiety using questionnaires, behavioral tests, and MRI scanning while performing the 4‐choice serial reaction time task. Additionally, participants were genotyped for the TPH2 G‐703T (rs4570625) polymorphism. To analyze the relation between TPH2 G‐703T variants and the impulsive/aggressive/anxious phenotype, mediation analyses were performed using behavioral and MRI data as potential mediators. Results We found that the relation between TPH2 G‐703T and aggression as part of the reverse Tph2‐/‐ phenotype was mediated by structure and function of the right middle and inferior frontal gyrus. Conclusion At the example of trait aggression, our results support the assumption that the Tph2 null mutant mouse reflects the TPH2 G‐703T‐dependent phenotype in humans. Additionally, we conclude that “reverse phenotyping” is a promising method to validate experimental models and human findings for refined analysis of disease mechanisms., The Tph2‐/‐ mouse has been proposed as an experimental model for ADHD. Translation of an animal phenotype into humans to examine its face validity (reverse phenotyping). Phenotyping included impulsivity, aggression, and anxiety, reflecting comorbid conditions of ADHD. Use of the RDoC approach to address phenotype dimensions in an isolated manner.

Background: Little is known about how the workforce influences quality in long term care facilities for older people. Staff numbers are important but do not fully explain this relationship.Objectives: To develop theoretical explanations for the relationship between long-term care facility staffing and quality of care as experienced by residents. Design: A realist evidence synthesis to understand staff behaviours that promote quality of care for older people living in long-term care facilities. Setting: Long-term residential care facilitiesParticipants: Long-term care facility staff, residents, and relatives Methods: The realist review, (i) was co-developed with stakeholders to determine initial programme the-ories, (ii) systematically searched the evidence to test and develop theoretical propositions, and (iii) vali-dated and refined emergent theory with stakeholder groups.Results: 66 research papers were included in the review. Three key findings explain the relationship be-tween staffing and quality: (i) quality is influenced by staff behaviours; (ii) behaviours are contingent on relationships nurtured by long-term care facility environment and culture; and (iii) leadership has an im-portant influence on how organisational resources (sufficient staff effectively deployed, with the knowl-edge, expertise and skills required to meet residents' needs) are used to generate and sustain quality-promoting relationships. Six theoretical propositions explain these findings.Conclusion: Leaders (at all levels) through their role-modelling behaviours can use organisational re-sources to endorse and encourage relationships (at all levels) between staff, residents, co-workers and family (relationship centred care) that constitute learning opportunities for staff, and encourage quality as experienced by residents and families.Crown Copyright (c) 2021 Published by Elsevier Ltd. All rights reserved.

Background Previous systematic reviews showed no significant association between epilepsy and challenging behaviours in adults with intellectual disabilities. Aims To identify whether there is an association between epilepsy and challenging behaviour in adults with intellectual disabilities by carrying out a systematic review of published data. PROSPERO registration number: CRD42020178092. Method We searched five databases and hand-searched six journals. Two authors independently screened titles, abstracts and full articles using a standardised eligibility checklist. Several meta-analyses were carried out. Results The narrative analysis of data from 34 included articles (14 168 adults with intellectual disabilities, 4781 of whom also had epilepsy) showed no significant association between epilepsy and challenging behaviour. Meta-analysis was possible on data from 16 controlled studies. This showed no significant intergroup difference but after sensitivity analysis meta-analysis of 10 studies showed a significantly higher rate of overall challenging behaviour in the epilepsy group (effect size: 0.16) compared with the non-epilepsy group. Aggression and self-injurious behaviour both showed a statistically significant higher rate in the epilepsy group, with very small effect sizes (0.16 and 0.28 respectively). No significant intergroup difference was observed in the rate of stereotypy. Conclusions The findings are contradictory and must be interpreted with caution because of the difficulty in pooling data from varied studies, which is likely to introduce confounding. Where significant differences were found, effect sizes are small and may not be clinically significant, and there are major methodological flaws in the included studies, which should be addressed in future large-scale properly controlled studies.

Children’s atypical processing of social behavior of teachers may explain poor teacher-child relationships. To test this assumption, we developed the Social Information Processing in Teacher-child Interactions Test (SIP-TIT) and evaluated its psychometric properties. The SIP-TIT examines children’s SIP in ambiguous situations with teachers asking children to respond to 4 audio-taped hypothetical vignettes. The sample consisted of 302 primary school children (Mage=10.75, SD=0.95) and 12 teachers. Children and teachers completed questionnaires on teacher-child relationships quality (closeness, conflict, and dependency) and teachers also rated child aggression. Scale reliability and construct validity were examined. Children’s SIP and in particular hostile intent attribution was associated with child perceptions of poor teacher-child relationships. Hostile intent attribution and Rejection of prosocial response were associated with more aggression. https://www.tandfonline.com/eprint/VQEIAHSTPACQGANDQXBK/full?target=10.1080/17405629.2019.1699402 ispartof: European Journal Of Developmental Psychology vol:17 issue:4 pages:1-13 status: Published online

This study investigates three important aspects of the classroom context in shaping adolescents' classroom engagement trajectories: (a) teacher support, (b) peer norms (i.e., descriptive and popularity norms), and (c) ethnic classroom composition (i.e., ethnic heterogeneity and proportion of majorities). An ethnically diverse sample of 730 adolescents from Grades 9 to 11 was followed annually. Longitudinal multilevel models revealed that more teacher support and higher classroom-levels of engagement (i.e., descriptive norms) promote adolescents' behavioral and emotional engagement. Moreover, more ethnic heterogeneity in the classroom related to less steep decreases in behavioral engagement over time, whereas higher proportions of majorities in the classroom were associated with steeper decreases in emotional engagement over time. Associations were the same for ethnic minorities and majorities. Furthermore, teacher support and descriptive norms jointly buffered against declining behavioral engagement trajectories. In general, this study underscored the importance of the classroom context in adolescents' behavioral and emotional engagement. ispartof: Journal Of Applied Developmental Psychology vol:69 pages:1-14 status: published

Gene-environment interaction (GxE) determines the vulnerability of an individual to a spectrum of stress-related neuropsychiatric disorders. Increased impulsivity, excessive aggression, and other behavioural characteristics are associated with variants within the tryptophan hydroxylase-2 (Tph2) gene, a key enzyme in brain serotonin synthesis. This phenotype is recapitulated in naïve mice with complete, but not with partial Tph2 inactivation. Tph2 haploinsufficiency in animals reflects allelic variation of Tph2 facilitating the elucidation of respective GxE mechanisms. Recently, we showed excessive aggression and altered serotonin brain metabolism in heterozygous Tph2-deficient male mice (Tph2+/−) after predator stress exposure. Here, we sought to extend these studies by investigating aggressive and anxiety-like behaviours, sociability, and the brain metabolism of dopamine and noradrenaline. Separately, Tph2+/− mice were examined for exploration activity in a novel environment and for the potentiation of helplessness in the modified swim test (ModFST). Predation stress procedure increased measures of aggression, dominancy, and suppressed sociability in Tph2+/− mice, which was the opposite of that observed in control mice. Anxiety-like behaviour was unaltered in the mutants and elevated in controls. Tph2+/− mice exposed to environmental novelty or to the ModFST exhibited increased novelty exploration and no increase in floating behaviour compared to controls, which is suggestive of resilience to stress and despair. High-performance liquid chromatography (HPLC) revealed significant genotype-dependent differences in the metabolism of dopamine, and norepinephrine within the brain tissue. In conclusion, environmentally challenged Tph2+/− mice exhibit behaviours that resemble the behaviour of non-stressed null mutants, which reveals how GxE interaction studies can unmask latent genetically determined predispositions. © 2020 The Authors. The authors' work reported here was supported by Deutsche Forschungsgemeinschaft (DFG:CRC TRR58A1/A5), DAAD (to ES), the European Union's Seventh Framework Programme (FP7/2007–2013) under Grant No.602805 (Aggressotype) and the Horizon 2020 Research and Innovation Programme under Grant No.728018 (Eat2beNICE) (to KPL and TS) and the President's program of PhD Exchange of RF-2017 (to TS and DA). We appreciate the valuable technical help of Natalia Bazhenova, Drs. Alexander Trofimov and Natalia Markova with this project.

Objective: APOE status has been associated to affective symptoms in cognitively impaired subjects, with conflicting results.Methods: Databases CINAHL, Embase, PsychINFO and PubMed were searched for studies evaluating APOE genotype with affective symptoms in MCI and AD dementia. Symptoms were meta-analyzed separately and possible sources of heterogeneity were examined.Results: Fifty-three abstracts fulfilled the eligibility criteria. No association was found between the individual symptoms and APOE epsilon 4 carriership or zygosity. For depression and anxiety, only pooled unadjusted estimates showed positive associations with between-study heterogeneity, which could be explained by variation in study design, setting and way of symptom assessment.Conclusions: There is no evidence that APOE epsilon 4 carriership or zygosity is associated with the presence of depression, anxiety, apathy, agitation, irritability or sleep disturbances in cognitively impaired subjects. Future research should shift its focus from this single polymorphism to a more integrated view of other biological factors.

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of dopaminergic neurons in vitro and in vivo. For this reason, GDNF is currently in clinical trials for the treatment of Parkinson’s disease (PD). However, how endogenous GDNF influences dopamine system function and animal behavior is not fully understood. We recently generated GDNF hypermorphic mice that express increased levels of endogenous GDNF from the native locus, resulting in augmented function of the nigrostriatal dopamine system. Specifically, Gdnf wt/hyper mice have a mild increase in striatal and midbrain dopamine levels, increased dopamine transporter activity, and 15% increased numbers of midbrain dopamine neurons and striatal dopaminergic varicosities. Since changes in the dopamine system are implicated in several neuropsychiatric diseases, including schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, and ectopic GDNF delivery associates with side-effects in PD models and clinical trials, we further investigated Gdnf wt/hyper mice using 20 behavioral tests. Despite increased dopamine levels, dopamine release and dopamine transporter activity, there were no differences in psychiatric disease related phenotypes. However, compared to controls, male Gdnf wt/hyper mice performed better in tests measuring motor function. Therefore, a modest elevation of endogenous GDNF levels improves motor function but does not induce adverse behavioral outcomes.

Background: Cross-sectional studies report relations between externalizing behavior and structural abnormalities in cortical thickness of prefrontal regions and volume reductions in subcortical regions. To understand how these associations emerge and develop, longitudinal designs are pivotal. Method: In the current longitudinal study, a community sample of children, adolescents and young adults (N = 271) underwent magnetic resonance imaging (MRI) in three biennial waves (680 scans). At each wave, aspects of externalizing behavior were assessed with parent-reported aggression and rule-breaking scores (Child Behavior Checklist), and self-reported aggression scores (Buss-Perry Aggression Questionnaire). Regions of interest (ROIs) were selected based on prior research: dorsolateral prefrontal (dlPFC), orbitofrontal (OFC), anterior cingulate cortex (ACC), insula, and parahippocampal cortex, as well as subcortical regions. Linear mixed models were used to assess the longitudinal relation between externalizing behavior and structural brain development. Structural covariance analyses were employed to identify whether longitudinal relations between ROIs (maturational coupling) were associated with externalizing behavior. Results: Linear mixed model analyses showed a negative relation between parent-reported aggression and right hippocampal volume. Moreover, this longitudinal relation was driven by change in hippocampal volume and not initial volume of hippocampus at time point 1. Exploratory analyses showed that stronger maturational coupling between prefrontal regions, the limbic system, and striatum was associated with both low and high externalizing behavior. Conclusions: Together, these findings reinforce the hypothesis that altered structural brain development coincides with development of more externalizing behavior. These findings may guide future research on normative and deviant development of externalizing behavior.

Research suggests that restrictive measures are widely used on adolescents with mild intellectual disabilities. In the Netherlands, restrictive measures are defined as all measures that limit the freedom of a person. In most countries, legislation and policies that seek to reduce the use of restrictive measures focus on seclusion and mechanical and physical restraints. The study aimed to investigate the extent to which restrictive practices are used in the care of adolescents with mild intellectual disabilities while also exploring the attitudes of support staff toward these interventions. A survey study was done among a nationally representative Dutch research sample consisting of support staff. A structured questionnaire was completed by 195 staff members (response of 68.7%) working in settings providing care for people with intellectual disabilities. The measures generally used by staff members who work with adolescents with mild intellectual disabilities involved restricting the freedom of movement and so‐called social restrictions (such as limiting the use of mobile phones). Nearly all respondents considered restrictive measures to be justified in the case of danger, physical aggression, or sexually abusive behavior (87.8–96.8%). Frequently mentioned reasons for using restrictive measures were averting or avoiding danger (90.4 and 83.0%, respectively) and calming the adolescent (63.8%). Although seclusion and mechanical and physical restraints were generally considered most intrusive, staff members were aware that social restrictions could also be instrusive. The fact that current policies do not address these measures makes support staff question the lawfulness of their actions. As well as staff training to reduce the use of restrictive measures, rules, and legislation are also needed to clarify the options and limits to using such measures in the professional care of adolescents with mild intellectual disabilities.

Australoheros facetus is a neotropical cichlid and an exotic species in the Guadiana and Odelouca basins (Southern Portugal). In this research, we aimed to characterize the main behavioural patterns and circulating hormones, 17 beta-estradiol (E-2) for females, and testosterone, 11-ketotestosterone (11KT) and cortisol for both sexes, during the formation of social groups, a crucial step in the life-history of A. facetus. A pair-breeding strategy with territorial behaviour and aggressive interactions was found, with a positive correlation between dominance and size for both sexes. There were no significant differences between non-territorial and territorial individuals in the baseline levels of hormones, but 11KT was higher in males when they became territorial, as E-2 for territorial females, while there was no clear pattern for testosterone. In contrast, cortisol was higher in non-territorial males and correlated negatively with social dominance. These results suggest that size is the main driver for social dominance and that formation of stable hierarchies result in higher circulating 11KT and lowers stress in territorial males. Related to A. facetus' behaviour, aggressiveness and biparental care may be an advantage during the invasion process of A. facetus, facilitating colonization of new habitats. National Council for Technological and Scientific Development of Brazil (CNPq), Program Science without Borders [245971/20122] FCT-Foundation for Science and Technology [UID/Multi/04326/2013, SFRH/BPD/67008/2009] info:eu-repo/semantics/publishedVersion

This study summarizes the literature about alcohol- and drug-related public violence in Europe. The proportion of all public violent incidents linked to alcohol was about 50 percent in the UK and ranged from 26 percent to 43 percent in Germany, Austria and the Netherlands. Public violence related to drugs is much lower (1.5–18.0 percent). Relatively many public violent incidents occur in relation to nightlife (80 percent of alcohol-related incidents). Though a considerable proportion of public violence was alcohol or drug related, the actual use of such substances was rarely ascertained in perpetrators’ specimens. Such analysis is a prerequisite to heavier penalize alcohol- or drug-intoxicated perpetrators of public violence. More capacity should be deployed to measure alcohol and drugs in the specimens of violent perpetrators by analytical-chemical tests. As a result, more accurate estimates of substance-related public violence are obtained, which will serve policy makers and police enforcement officials to take measures for securing a safer public environment and sustainable nightlife industry in the future.

According to Blatt’s theory on personality development, adolescents with high levels of self-criticism and dependency are more vulnerable to diverse types of psychopathology. However, relatively little is known about intervening processes involved in this personality-based vulnerability. The goal of this study is to examine, on the basis of Self-Determination Theory, the explanatory role of the psychological needs for autonomy, competence, and relatedness in associations between self-criticism and dependency on the one hand and adolescents’ internalizing and externalizing problems on the other hand. In this cross-sectional and multi-informant study, 284 adolescents (58,5% female; mean age = 14.15; SD = .93) and their parents reported about the adolescent’s internalizing and externalizing problems. Adolescents also completed measures assessing self-criticism, dependency, and psychological needs experiences. Data were analyzed using structural equation modeling. Self-criticism and dependency were significantly related to higher levels of both internalizing and externalizing problems, with psychological need frustration fully mediating these associations. This study suggests that psychological need frustration is an important explanatory mechanism in personality-related vulnerability for adolescent psychopathology. More generally, it provides further evidence for the integration between two major theoretical approaches in the domain of adolescent development and psychopathology.

Objectives: To systematically review literature on efficacy of amantadine on behavior (irritability/aggression/agitation, emotional lability, apathy, impairment of executive functioning), participation, quality-of-life (QoL), and safety, in patients with acquired brain injury (ABI). Amantadine is widely used clinically, so comprehensive information on efficacy, participation, QoL and safety is relevant. Methods: We used PRISMA Guidelines. We searched PubMed/EMBASE/CINAHL (last search 28-8-2018) Two independent reviewers performed selection and data-extraction. Quality of studies was assessed, using CONSORT and Quality Assessment Tool for Quantitative Studies (QATFQS). Results: Eleven out of 500 studies were included. Of five RCTs, two reported significant effects on irritability/aggression, and one no effect. One RCT on cognition no effect. One prospective cohort study showed a significant effect on executive functioning. One retrospective study was inconclusive. One single-case experimental design (SCED) study reported significant effect on apathy and three case-reports indicated effects on behavior. QoL and societal participation were not measured. No safety issues emerged. Conclusion: Amantadine may be efficacious on irritability and aggression after ABI. Amantadine is a safe drug in the presence of adequate creatinine clearance. Future studies should use designs, suitable for the heterogeneous ABI population, like randomized SCEDs, and should include the effect on societal participation and QoL.

Converging evidence suggests a role of serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of 5-HT synthesis in the brain, in modulating long-term, neurobiological effects of early-life adversity. Here, we aimed at further elucidating the molecular mechanisms underlying this interaction, and its consequences for socio-emotional behaviors, with a focus on anxiety and social interaction. In this study, adult, male Tph2 null mutant (Tph2(-/-)) and heterozygous (Tph2(+/-)) mice, and their wildtype littermates (Tph2(+/+)) were exposed to neonatal, maternal separation (MS) and screened for behavioral changes, followed by genome-wide RNA expression and DNA methylation profiling. In Tph2(-/-) mice, brain 5-HT deficiency profoundly affected socio-emotional behaviors, i.e., decreased avoidance of the aversive open arms in the elevated plus-maze (EPM) as well as decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Tph2(+/-) mice showed an ambiguous profile with context-dependent, behavioral responses. In the EPM they showed similar avoidance of the open arm but decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Notably, MS effects on behavior were subtle and depended on the Tph2 genotype, in particular increasing the observed avoidance of EPM open arms in wildtype and Tph2(+/-) mice when compared to their Tph2(-/-) littermates. On the genomic level, the interaction of Tph2 genotype with MS differentially affected the expression of numerous genes, of which a subset showed an overlap with DNA methylation profiles at corresponding loci. Remarkably, changes in methylation nearby and expression of the gene encoding cholecystokinin, which were inversely correlated to each other, were associated with variations in anxiety-related phenotypes. In conclusion, next to various behavioral alterations, we identified gene expression and DNA methylation profiles to be associated with TPH2 inactivation and its interaction with MS, suggesting a gene-by-environment interaction-dependent, modulatory function of brain 5-HT availability.

Converging evidence suggests a role of serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of 5-HT synthesis in the brain, in modulating long-term, neurobiological effects of early-life adversity. Here, we aimed at further elucidating the molecular mechanisms underlying this interaction, and its consequences for socio-emotional behaviors, with a focus on anxiety and social interaction. In this study, adult, male Tph2 null mutant (Tph2\(^{-/-}\)) and heterozygous (Tph2\(^{+/-}\)) mice, and their wildtype littermates (Tph2\(^{+/+}\)) were exposed to neonatal, maternal separation (MS) and screened for behavioral changes, followed by genome-wide RNA expression and DNA methylation profiling. In Tph2\(^{-/-}\) mice, brain 5-HT deficiency profoundly affected socio-emotional behaviors, i.e., decreased avoidance of the aversive open arms in the elevated plus-maze (EPM) as well as decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Tph2\(^{+/-}\) mice showed an ambiguous profile with context-dependent, behavioral responses. In the EPM they showed similar avoidance of the open arm but decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Notably, MS effects on behavior were subtle and depended on the Tph2 genotype, in particular increasing the observed avoidance of EPM open arms in wildtype and Tph2\(^{+/-}\) mice when compared to their Tph2\(^{-/-}\) littermates. On the genomic level, the interaction of Tph2 genotype with MS differentially affected the expression of numerous genes, of which a subset showed an overlap with DNA methylation profiles at corresponding loci. Remarkably, changes in methylation nearby and expression of the gene encoding cholecystokinin, which were inversely correlated to each other, were associated with variations in anxiety-related phenotypes. In conclusion, next to various behavioral alterations, we identified gene expression and DNA methylation profiles to be associated with TPH2 inactivation and its interaction with MS, suggesting a gene-by-environment interaction-dependent, modulatory function of brain 5-HT availability.

Place: Oxford Publisher: Pergamon-Elsevier Science Ltd WOS:000514255000004; International audience; Individual stress coping style (reactive, intermediate and proactive) was determined in 3 groups of 120 pit tagged European seabass using the hypoxia avoidance test. The same three groups (no change in social composition) were then reared according to the standards recommended for this species. Then, 127 days later, individuals initially characterized as reactive, intermediate or proactive were submitted to an acute confinement stress for 30 min. Blood samples were taken to measure plasma cortisol levels 30 min (Stress30) or 150 min (Stress150) after the end of the confinement stress. Individuals were then sacrificed to sample the telencephalon in order to measure the main monoamines and their catabolites (at Stress30 only). Individuals from Stress150 were sampled for whole brain for a transcriptomic analysis. The main results showed that reactive individuals had a lower body mass than intermediate individuals which did not differ from proactive individuals. The physiological cortisol response did not differ between coping style at Stress30 but at Stress150 when intermediate and proactive individuals had recovered pre stress levels, reactive individuals showed a significant higher level illustrating a modulation of stress recovery by coping style. Serotonin turnover ratio was higher in proactive and reactive individuals compared to intermediate individuals and a significant positive correlation was observed with cortisol levels whatever the coping style. Further, the confinement stress led to a general increase in the serotonin turnover comparable between coping styles. Stress150 had a significant effect on target mRNA copy number (Gapdh mRNA copy number decreased while ifrd1 mRNA copy number increased) and such changes tended to depend upon coping style.

Two studies investigated whether parent–child discussion of peer provocations reduces young children's hostile attributional bias. Study 1 (N = 109, age 4–7)—an observational study—showed that parent–child discussion of nonhostile attributions (when reading a picture book) predicted reductions in children's hostile attributional bias from pre‐ to postdiscussion. Study 2 (N = 160, age 4–6)—an experimental study—showed that stimulating parents to discuss either nonhostile attributions or normative beliefs (vs. a control condition) reduced children's hostile attributional bias in response to hypothetical vignettes, but not in response to a staged peer provocation. These findings suggest that by framing social situations, parents may help their children perceive less hostility in their social worlds.

Contains fulltext : 200490.pdf (Publisher’s version ) (Open Access) Burnout in nursing staff is a major cause for turnover and absenteeism. Identifying risk and protective factors may be helpful in decreasing burnout symptoms. Moreover, research indicates that ambulatory assessments of the autonomic nervous system might be helpful in detecting long-term stress and burnout symptoms. One hundred and ten forensic nursing staff members completed questionnaires measuring experiences with aggressive behaviour, emotional intelligence, personality, and job stress during four waves of data collection across a 2-year period. Multilevel analyses were used to test the predicted associations and moderation effects with (the development of) burnout symptoms. Burnout was predicted by a combination of emotional intelligence, job stress, aggression, personality factors, and skin conductance, but no moderation effects over time were found. Over a period of 2 years, the model approximately predicts a change in one burnout category on the Maslach Burnout Inventory. The amount of burnout symptoms in nurses might be used as an indicator to predict turnover and absenteeism considering the increase in symptoms over time. Nursing staff who experience severe aggression and who have relatively low levels of emotional intelligence and altruism and high levels of neuroticism and job stress should be monitored and supported to decrease the risk of burnout. Staff members can be trained to increase their emotional intelligence and relieve stress to decrease their burnout symptoms and turnover and absenteeism on the long term. Ambulatory assessment might be helpful as a nonintrusive way to detect increasing levels of burnout. 12 p.

Group housing of gestating sows benefits their welfare by allowing them freedom of movement and the opportunity for social interaction. However, social life could also bring disadvantages for individuals who receive direct aggression or are displaced from the feeder. The aim of this study was to investigate associations between social behaviour, body condition and live weight. Gestating sows (n=298) were investigated on a commercial farm. Sows were housed in mixed parity groups where two single space, ad libitum trough feeders served 12 animals. Sows were weighed, body condition scored and had their back fat layer measured at mixing, 4 weeks after insemination and again before farrowing. Social status was estimated based on the numbers of won and lost agonistic interactions at mixing and at the end of gestation. In addition, tear staining was scored before the farrowing and reproductive performance data were collected. With the aid of video recordings, 100 to 150 interactions per group were observed. Winning percentage at mixing and at the end of gestation were associated (Plt;0.05) and appeared relatively stable within individuals. Tear staining scores and litter sizes were not associated with winning percentage at the end of gestation. However, live weight, relative weight, body condition and back fat thickness were associated with winning percentage (Plt;0.05), giving heavier animals an advantage. Low winning percentage related to lower live weight gain, probably due to poorer success in competition for feed. Live weight within a mixed parity group could be used as a proxy measure for social status. Sows with low body condition score and submissive sows might need special attention with regard to group dynamics and housing to alleviate the effects of competition in group housing.

Anatomical, cognitive and behavioral sex differences are widely recognized in many species. It has been proposed that some of these differences might result from the organizing effects of prenatal sex steroids. In humans, males usually exhibit higher levels of physical aggression and prowess. In this study, we analyze the relationship between second-to-fourth digit (2D:4D) ratiosa proxy for prenatal androgen levelsand foul play and sporting performance in a sample of junior soccer players from a professional Uruguayan soccer club. Our results show that the most aggressive players (i.e., those awarded one or more red cards) have a more masculine finger pattern (lower 2D:4D ratio), while no relationship could be found between sporting performance and 2D:4D ratios. The results are discussed in the context of previous findings. Aggr. Behav. 42:417-426, 2016. (c) 2015 Wiley Periodicals, Inc.

Research suggests that restrictive measures are widely used on adolescents with mild intellectual disabilities. In the Netherlands, restrictive measures are defined as all measures that limit the freedom of a person. In most countries, legislation and policies that seek to reduce the use of restrictive measures focus on seclusion and mechanical and physical restraints. The study aimed to investigate the extent to which restrictive practices are used in the care of adolescents with mild intellectual disabilities while also exploring the attitudes of support staff toward these interventions. A survey study was done among a nationally representative Dutch research sample consisting of support staff. A structured questionnaire was completed by 195 staff members (response of 68.7%) working in settings providing care for people with intellectual disabilities. The measures generally used by staff members who work with adolescents with mild intellectual disabilities involved restricting the freedom of movement and so‐called social restrictions (such as limiting the use of mobile phones). Nearly all respondents considered restrictive measures to be justified in the case of danger, physical aggression, or sexually abusive behavior (87.8–96.8%). Frequently mentioned reasons for using restrictive measures were averting or avoiding danger (90.4 and 83.0%, respectively) and calming the adolescent (63.8%). Although seclusion and mechanical and physical restraints were generally considered most intrusive, staff members were aware that social restrictions could also be instrusive. The fact that current policies do not address these measures makes support staff question the lawfulness of their actions. As well as staff training to reduce the use of restrictive measures, rules, and legislation are also needed to clarify the options and limits to using such measures in the professional care of adolescents with mild intellectual disabilities.

Contains fulltext : 194962.pdf (Publisher’s version ) (Open Access) Self-injurious behavior (SIB) is one of the most detrimental behaviors for the person showing it, as well as for their environment. Nevertheless, structured clinical assessments of SIB are scarce. Staff completed a Self-Harm Scale (SHS) every time they witnessed SIB in clients with an intellectual disability (ID) and co-occurring psychopathology (N= 33). Descriptive statistics were conducted to explore the nature of the incidents of SIB and the characteristics of the people involved in the incidents. In 41 weeks, 104 SIB incidents were reported for 8 out of 33 clients (24%). Incidents were most prevalent on Mondays (23%). As far as the methods of SIB concerned, cutting was the most used method (63%). Clients who showed SIB differed significantly from clients who did not on gender, having a personality disorder and communicative abilities. This study was one of the few that used an incident-based record form to report SIB by direct observation. It is hoped that the SHS helps to gain more information about SIB, to improve individualized interventions. Further research is necessary to determine the psychometric properties and clinical utility of the scale. 16 p.

Background: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of aggression to aberrant serotonergic neurotransmission. We determined possible associations between 6 serotonergic neurotransmission-related gene variants and severe criminal offenses. Methods: Male Russian prisoners who were convicted for murder (n = 117) or theft (n = 77) were genotyped for variants of the serotonin transporter (5HTTLPR), tryptophan hydroxylase, tryptophan-2,3-dioxygenase, or type 2C (5-HT2C) receptor genes and compared with general-population male controls (n = 161). Prisoners were psychologically phenotyped using the Buss-Durkee Hostility Inventory and the Beck Depression Inventory. Results: No differences were found between murderers and thieves either concerning genotypes or concerning psychological measures. Comparison of polymorphism distribution between groups of prisoners and controls revealed highly significant associations of 5HTTLPR and 5-HTR2C (rs6318) gene polymorphisms with being convicted for criminal behavior. Conclusions: The lack of biological differences between the 2 groups of prisoners indicates that the studied 5HT-related genes do not differentiate between the types of crimes committed.

Executive function and intelligence are negatively associated with aggression, yet the role of executive function has rarely been examined in the context of school bullying. We studied whether different domains of executive function and non-verbal intelligence are associated with bullying involvement in early elementary school. The association was examined in a population-based sample of 1,377 children. At age 4 years we assessed problems in inhibition, shifting, emotional control, working memory and planning/organization, using a validated parental questionnaire (the BRIEF-P). Additionally, we determined child non-verbal IQ at age 6 years. Bullying involvement as a bully, victim or a bully-victim in grades 1-2 of elementary school (mean age 7.7 years) was measured using a peer-nomination procedure. Individual bullying scores were based on the ratings by multiple peers (on average 20 classmates). Analyses were adjusted for various child and maternal socio-demographic and psychosocial covariates. Child score for inhibition problems was associated with the risk of being a bully (OR per SD = 1.35, 95%CI: 1.09-1.66), victim (OR per SD = 1.21, 95%CI: 1.00-1.45) and a bully-victim (OR per SD = 1.55, 95%CI: 1.10-2.17). Children with higher non-verbal IQ were less likely to be victims (OR = 0.99, 95%CI: 0.98-1.00) and bully-victims (OR = 95%CI: 0.93-0.98, respectively). In conclusion, our study showed that peer interactions may be to some extent influenced by children's executive function and non-verbal intelligence. Future studies should examine whether training executive function skills can reduce bullying involvement and improve the quality of peer relationships.