On neuroimaging correlates of aggression in psychoses

Introduction. Aggressive behaviour in persons with a psychotic disorder is clinically highly relevant because of its impact on patients' families, society and caregivers - also, it increases stigmatization of psychiatric patients in general. The neurobiological processes triggering aggression in psychoses are little known. A comprehension of these underlying mechanisms could enhance the predictability and prevention of violent acts and permit a specialized and more individualized patient treatment - also, this could drastically reduce stigmatization. Here, we investigated the neurobiological underpinnings of aggression in psychoses by means of magnetic resonance imaging. Methods. We performed two systematic reviews examining results on structural and functional magnetic resonance imaging correlates of aggression in persons with psychoses in order to synthesize the current knowledge in this field. Also, we calculated an effect size analysis on structural correlates of aggression in psychoses. Then, we conducted a voxel-based morphometry (VBM) study investigating correlates of an agitated-aggressive syndrome in early psychoses. Results. We systematically reviewed twelve studies on structural magnetic resonance imaging correlates of aggression in psychoses including a total of 314 patients and 96 healthy control participants (HC). Qualitative analyses showed lower volumes of whole brain (WB), prefrontal regions, temporal lobe, hippocampus, thalamus, and cerebellum, and larger volumes of the lateral ventricles, amygdala and putamen in violent (VS) as opposed to non-violent schizophrenia persons (NVS). In the quantitative effect size analyses, violent persons with schizophrenia exhibited a significantly lower WB volume than HC (p = 0.004) and than non-violent persons with schizophrenia (p = 0.007). Our systematic review on functional magnetic resonance imaging correlates of aggression in psychoses included twelve studies with 236 patients and 92 HC. During the n-back tasks, VS as opposed to NVS hypoactivated their inferior parietal lobe. When anticipating shock, VS versus NVS hyperactivated their medial prefrontal gyrus, cuneus, middle temporal gyrus and middle occipital gyrus. When viewing negative emotional pictures, VS versus NVS hyperactivated the middle frontal gyrus, inferior frontal gyrus, anterior cingulate, lingual gyrus, precentral gyrus, globus pallidus, mid-cingulate, and precuneus. In our study examining VBM correlates in early psychoses we found reduced lingual gyrus volumes in persons with early psychoses with an agitated-aggressive syndrome as opposed to HC. Conclusion. We found nonsystematic structural and functional correlates of aggression in psychoses. In total, only very little studies on the neurobiological underpinnings of aggression in psychoses have been conducted. There have been no attempts to replicate any of the observed findings in the published literature. Focusing on future directions, we recommend that authors adhere to clear definitions of aggression, measurements of psychopathology, comorbidities and medication. In particular, replication studies would allow for a better synthesis of the findings. Furthermore, there are no studies on affective psychoses or early psychoses. Our pilot study on VBM correlates of aggression in early psychoses provides a first hint towards the hypothesis that the lingual gyrus volume may be inversely correlated with an agitated-aggressive syndrome in early stages of psychoses

Functional Neuroimaging Correlates of Aggression in Psychosis: A Systematic Review With Recommendations for Future Research

Background and methods: Aggression in psychosis is clinically important. We systematically compiled the evidence on functional correlates of aggression in psychosis searching PubMed, EMBASE, ScienceDirect, and PsycINFO until September 2017. We included studies reporting functional brain imaging correlates of aggression comparing: (1) affective or non-affective psychosis groups with a history of violence or with aggression operationalized using questionnaires, (2) affective or non-affective psychosis groups with a history of violence or with aggression operationalized using questionnaires to controls, (3) affective or non-affective psychosis groups with a history of violence or with aggression operationalized using questionnaires to controls with diagnoses other than affective or non-affective psychoses. We applied no language restriction and required patients to have a DSM or ICD diagnosis of affective or non-affective psychosis.Results: Our sample consisted of 12 studies with 334 patients and 113 controls. During n-back tasks, violent (VS) as opposed to non-violent persons with schizophrenia (NVS) hypoactivated their inferior parietal lobe. When anticipating shock, VS vs. NVS hyperactivated their medial prefrontal gyrus, cuneus, middle temporal gyrus, and middle occipital gyrus. When viewing negative emotional pictures, VS vs. NVS hyperactivated the middle frontal gyrus, inferior frontal gyrus, anterior cingulate, lingual gyrus, precentral gyrus, globus pallidus, mid-cingulate, and precuneus.Limitations: Due to the small number of available studies, sample overlap, and insufficient reporting of relevant moderators we could not conduct a meta-analysis.Conclusions: We found non-systematic functional correlates of aggression in schizophrenia. Only few studies using varied paradigms and often overlapping samples have been conducted. There have been no attempts to replicate any of the observed findings in the published literature. Focusing on future directions, we recommend that authors adhere to clear definitions of aggression, measurements of psychopathology, comorbidities, and medication. In particular, replication studies would allow for a better synthesis of the findings.PROSPERO Registration Number: CRD4201604857

Traces of trauma – a multivariate pattern analysis of childhood trauma, brain structure and clinical phenotypes

Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research

Structural Magnetic Resonance Imaging Correlates of Aggression in Psychosis: A Systematic Review and Effect Size Analysis

Background:; Aggression in psychoses is of high clinical importance, and volumetric MRI techniques have been used to explore its structural brain correlates.; Methods:; We conducted a systematic review searching EMBASE, ScienceDirect, and PsycINFO through September 2017 using thesauri representing aggression, psychosis, and brain imaging. We calculated effect sizes for each study and mean Hedge's g for whole brain (WB) volume. Methodological quality was established using the PRISMA checklist (PROSPERO: CRD42014014461).; Results:; Our sample consisted of 12 studies with 470 patients and 155 healthy controls (HC). After subtracting subjects due to cohort overlaps, 314 patients and 96 HC remained. Qualitative analyses showed lower volumes of WB, prefrontal regions, temporal lobe, hippocampus, thalamus and cerebellum, and higher volumes of lateral ventricles, amygdala, and putamen in violent vs. non-violent people with schizophrenia. In quantitative analyses, violent persons with schizophrenia exhibited a significantly lower WB volume than HC (; p; = 0.004), and also lower than non-violent persons with schizophrenia (; p; = 0.007).; Conclusions:; We reviewed evidence for differences in brain volume correlates of aggression in persons with schizophrenia. Our results point toward a reduced whole brain volume in violent as opposed to non-violent persons with schizophrenia. However, considerable sample overlap in the literature, lack of reporting of potential confounding variables, and missing research on affective psychoses limit our explanatory power. To permit stronger conclusions, further studies evaluating structural correlates of aggression in psychotic disorders are needed

Table_1_Structural Magnetic Resonance Imaging Correlates of Aggression in Psychosis: A Systematic Review and Effect Size Analysis.DOCX

<p>Background: Aggression in psychoses is of high clinical importance, and volumetric MRI techniques have been used to explore its structural brain correlates.</p><p>Methods: We conducted a systematic review searching EMBASE, ScienceDirect, and PsycINFO through September 2017 using thesauri representing aggression, psychosis, and brain imaging. We calculated effect sizes for each study and mean Hedge's g for whole brain (WB) volume. Methodological quality was established using the PRISMA checklist (PROSPERO: CRD42014014461).</p><p>Results: Our sample consisted of 12 studies with 470 patients and 155 healthy controls (HC). After subtracting subjects due to cohort overlaps, 314 patients and 96 HC remained. Qualitative analyses showed lower volumes of WB, prefrontal regions, temporal lobe, hippocampus, thalamus and cerebellum, and higher volumes of lateral ventricles, amygdala, and putamen in violent vs. non-violent people with schizophrenia. In quantitative analyses, violent persons with schizophrenia exhibited a significantly lower WB volume than HC (p = 0.004), and also lower than non-violent persons with schizophrenia (p = 0.007).</p><p>Conclusions: We reviewed evidence for differences in brain volume correlates of aggression in persons with schizophrenia. Our results point toward a reduced whole brain volume in violent as opposed to non-violent persons with schizophrenia. However, considerable sample overlap in the literature, lack of reporting of potential confounding variables, and missing research on affective psychoses limit our explanatory power. To permit stronger conclusions, further studies evaluating structural correlates of aggression in psychotic disorders are needed.</p

Structural Magnetic Resonance Imaging Correlates of Aggression in Psychosis: A Systematic Review and Effect Size Analysis

Background: Aggression in psychoses is of high clinical importance, and volumetric MRI techniques have been used to explore its structural brain correlates.Methods: We conducted a systematic review searching EMBASE, ScienceDirect, and PsycINFO through September 2017 using thesauri representing aggression, psychosis, and brain imaging. We calculated effect sizes for each study and mean Hedge's g for whole brain (WB) volume. Methodological quality was established using the PRISMA checklist (PROSPERO: CRD42014014461).Results: Our sample consisted of 12 studies with 470 patients and 155 healthy controls (HC). After subtracting subjects due to cohort overlaps, 314 patients and 96 HC remained. Qualitative analyses showed lower volumes of WB, prefrontal regions, temporal lobe, hippocampus, thalamus and cerebellum, and higher volumes of lateral ventricles, amygdala, and putamen in violent vs. non-violent people with schizophrenia. In quantitative analyses, violent persons with schizophrenia exhibited a significantly lower WB volume than HC (p = 0.004), and also lower than non-violent persons with schizophrenia (p = 0.007).Conclusions: We reviewed evidence for differences in brain volume correlates of aggression in persons with schizophrenia. Our results point toward a reduced whole brain volume in violent as opposed to non-violent persons with schizophrenia. However, considerable sample overlap in the literature, lack of reporting of potential confounding variables, and missing research on affective psychoses limit our explanatory power. To permit stronger conclusions, further studies evaluating structural correlates of aggression in psychotic disorders are needed

Validation of the Bullying Scale for Adults - Results of the PRONIA-study

Background: Bullying as a specific subtype of adverse life events is a major risk factor for poor mental health. Although many questionnaires on bullying are available, so far none covers bullying retrospectively throughout school and working life. To close this gap, the Bullying Scale for Adults (BSA) was designed. Methods: Based on data of 622 participants from five European countries collected in the prospective multicenter Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study, we investigated whether the BSA is a reliable and valid measurement for bullying and whether there is a difference across different diagnostic groups of early mental disorders (recent onset depressive/psychotic patients, patients at clinical high-risk of psychosis) and healthy controls. Results: Bullying experiences were significantly less frequent in healthy controls than in patient groups, with no significant differences between the three clinical groups. The BSA exhibited a high item scale discrimination (r > .3) and very good internal consistency (Cronbach's alpha = .93). Four factors were identified: 1. Sexual harassment, 2. Emotional Abuse, 3. Physical Abuse, 4. Problems at school. The highly significant correlation between bullying, and childhood adversities and trauma (r = .645, p < .001) indicated good concurrent validity. Discussion: The BSA is the first validated questionnaire that, in retrospective, reliably records various aspects of bullying (incl. its consequences) not only throughout childhood but also working life. It can be used to assess bullying as a transdiagnostic risk factor of mental disorders in different mental disorders, esp. psychosis and depression

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.</p