Neuroanatomical abnormalities in first-episode psychosis across independent samples: a multi-centre mega-analysis.

BACKGROUND: Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples. METHODS: Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. RESULTS: FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease - gyrus rectus - was negatively correlated with the severity of positive and negative symptoms. CONCLUSIONS: This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.

Machine Learning Approach to Inpatient Violence Risk Assessment Using Routinely Collected Clinical Notes in Electronic Health Records.

Importance: Inpatient violence remains a significant problem despite existing risk assessment methods. The lack of robustness and the high degree of effort needed to use current methods might be mitigated by using routinely registered clinical notes. Objective: To develop and validate a multivariable prediction model for assessing inpatient violence risk based on machine learning techniques applied to clinical notes written in patients' electronic health records. Design, Setting, and Participants: This prognostic study used retrospective clinical notes registered in electronic health records during admission at 2 independent psychiatric health care institutions in the Netherlands. No exclusion criteria for individual patients were defined. At site 1, all adults admitted between January 2013 and August 2018 were included, and at site 2 all adults admitted to general psychiatric wards between June 2016 and August 2018 were included. Data were analyzed between September 2018 and February 2019. Main Outcomes and Measures: Predictive validity and generalizability of prognostic models measured using area under the curve (AUC). Results: Clinical notes recorded during a total of 3189 admissions of 2209 unique individuals at site 1 (mean [SD] age, 34.0 [16.6] years; 1536 [48.2%] male) and 3253 admissions of 1919 unique individuals at site 2 (mean [SD] age, 45.9 [16.6] years; 2097 [64.5%] male) were analyzed. Violent outcome was determined using the Staff Observation Aggression Scale-Revised. Nested cross-validation was used to train and evaluate models that assess violence risk during the first 4 weeks of admission based on clinical notes available after 24 hours. The predictive validity of models was measured at site 1 (AUC = 0.797; 95% CI, 0.771-0.822) and site 2 (AUC = 0.764; 95% CI, 0.732-0.797). The validation of pretrained models in the other site resulted in AUCs of 0.722 (95% CI, 0.690-0.753) at site 1 and 0.643 (95% CI, 0.610-0.675) at site 2; the difference in AUCs between the internally trained model and the model trained on other-site data was significant at site 1 (AUC difference = 0.075; 95% CI, 0.045-0.105; P < .001) and site 2 (AUC difference = 0.121; 95% CI, 0.085-0.156; P < .001). Conclusions and Relevance: Internally validated predictions resulted in AUC values with good predictive validity, suggesting that automatic violence risk assessment using routinely registered clinical notes is possible. The validation of trained models using data from other sites corroborates previous findings that violence risk assessment generalizes modestly to different populations.

The role of self-serving cognitive distortions in reactive and proactive aggression.

BACKGROUND: Aggression is often divided into reactive and proactive forms. Reactive aggression is typically thought to encompass 'blaming others' and 'assuming the worst', while proactive aggression relates to 'self-centeredness' and 'minimising/mislabelling'. AIM: Our aim was to evaluate relationships between reactive and proactive aggression and cognitive distortions and to test whether changes in these cognitions relate to changes in aggression. METHODS: A total of 151 adolescents (60% boys; mean age 15.05 years, standard deviation 1.28) were enrolled in an evidence-based intervention to reduce aggression. Due to attrition and anomalous responses, the post-intervention sample involved 80 adolescents. Correlation and linear regression analyses were used to investigate the relationship between cognitive distortions and aggression. RESULTS: Blaming others was related to reactive aggression before the intervention, while all cognitive distortions were related to proactive aggression both pre- and post-intervention. Changes in reactive aggression were uniquely predicted by blaming others, while changes in proactive aggression were predicted by changes in cognitive distortions overall. CONCLUSION: To our knowledge, this study is the first to show a relationship between changes in cognitive distortions and changes in aggression. Treatment of reactive aggression may benefit from focusing primarily on reducing cognitive distortions involving misattribution of blame to others. Copyright © 2017 John Wiley & Sons, Ltd.

Transitioning to a Data Driven Mental Health Practice: Collaborative Expert Sessions for Knowledge and Hypothesis Finding.

The surge in the amount of available data in health care enables a novel, exploratory research approach that revolves around finding new knowledge and unexpected hypotheses from data instead of carrying out well-defined data analysis tasks. We propose a specification of the Cross Industry Standard Process for Data Mining (CRISP-DM), suitable for conducting expert sessions that focus on finding new knowledge and hypotheses in collaboration with local workforce. Our proposed specification that we name CRISP-IDM is evaluated in a case study at the psychiatry department of the University Medical Center Utrecht. Expert interviews were conducted to identify seven research themes in the psychiatry department, which were researched in cooperation with local health care professionals using data visualization as a modeling tool. During 19 expert sessions, two results that were directly implemented and 29 hypotheses for further research were found, of which 24 were not imagined during the initial expert interviews. Our work demonstrates the viability and benefits of involving work floor people in the analyses and the possibility to effectively find new knowledge and hypotheses using our CRISP-IDM method.

Treatment moderators of cognitive behavior therapy to reduce aggressive behavior: a meta-analysis.

Maladaptive aggression in adolescents is an increasing public health concern. Cognitive Behavior Therapy (CBT) is one of the most common and promising treatments of aggression. However, there is a lack of information on predictors of treatment response regarding CBT. Therefore, a meta-analysis was performed examining the role of predictors on treatment response of CBT. Twenty-five studies were evaluated (including 2,302 participants; 1,580 boys and 722 girls), and retrieved through searches on PubMed, PsycINFO and EMBASE. Effect sizes were calculated for studies that met inclusion criteria. Study population differences and specific CBT characteristics were examined for their explanatory power. There was substantial variation across studies in design and outcome variables. The meta-analysis showed a medium treatment effect for CBT to reduce aggression (Cohen'd = 0.50). No predictors of treatment response were found in the meta-analysis. Only two studies did examine whether proactive versus reactive aggression could be a moderator of treatment outcome, and no effect was found of this subtyping of aggression. These study results suggest that CBT is effective in reducing maladaptive aggression. Furthermore, treatment setting and duration did not seem to influence treatment effect, which shows the need for development of more cost-effective and less-invasive interventions. More research is needed on moderators of outcome of CBT, including proactive versus reactive aggression. This requires better standardization of design, predictors, and outcome measures across studies.

The cognitive and neural correlates of psychopathy and especially callous-unemotional traits in youths: a systematic review of the evidence.

It is unclear whether the concepts and findings of the underlying neurobiology of adult psychopathy apply to youths as well. If so, a life span approach to treatment should be taken. Because youths' brains are still developing, interventions at an early age may be far more effective in the long run. The aim of this systematic review is to examine whether the neurocognitive and neurobiological factors that underlie juvenile psychopathy, and specifically callous-unemotional (CU) traits, are similar to those underlying adult psychopathy. The results show that youths with CU traits show lower levels of prosocial reasoning, lower emotional responsivity, and decreased harm avoidance. Brain imaging studies in youths with CU traits are still rare. Available studies suggest specific neural correlates, such as a reduced response of the amygdala and a weaker functional connectivity between the amygdala and the ventromedial prefrontal cortex. These findings are largely in line with existing theories of adult psychopathy, such as the dual-hormone serotonergic hypothesis and the integrated emotions systems theory. We recommend that future studies investigate the role of oxytocin, invest in the study of neural mechanisms, and study the precursors, risk factors, and correlates of CU traits in early infancy and in longitudinal designs.

Development of schizotypal symptoms following psychiatric disorders in childhood or adolescence.

It was examined how juvenile psychiatric disorders and adult schizotypal symptoms are associated. 731 patients of the Department of Child and Adolescent Psychiatry of the University Medical Centre Utrecht, the Netherlands, with mean age of 12.1 years (SD = 4.0) were reassessed at the mean age of 27.9 years (SD = 5.7) for adult schizotypal symptoms using the Schizotypal Personality Questionnaire-Revised (Vollema, Schizophr Bull 26(3):565-575, 2000). Differences between 13 juvenile DSM categories and normal controls (n = 80) on adult schizotypal total and factor scores were analyzed, using (M)ANCOVA. Pervasive developmental disorders (PDD), attention deficit hyperactivity disorders (ADHD), deferred diagnosis, sexual and gender identity disorders and depressive disorders had higher SPQ total scores when compared to normal controls (p < 0.001). Higher levels of disorganized schizotypal symptoms were found for PDD, ADHD, and deferred diagnosis (p < 0.001). The same diagnostic groups showed higher level of negative schizotypal symptoms, which was likewise true for sexual and gender identity disorders, depressive disorders, disruptive disorders, and the category of 'Other conditions that may be a focus of clinical attention' (p < 0.001). No differences with normal controls were found for adult positive schizotypal symptoms (p < 0.110). The current findings are suggestive of the idea that psychiatric disorders in childhood or adolescence are a more general expression of a liability to schizophrenia spectrum pathology in future life. In addition, specific patterns of adult schizotypal symptomatology are associated with different types of juvenile psychiatric disorder.

Motor, emotional, and cognitive empathy in children and adolescents with autism spectrum disorder and conduct disorder.

It is unclear which aspects of empathy are shared and which are uniquely affected in autism spectrum disorder (ASD) and conduct disorder (CD) as are the neurobiological correlates of these empathy impairments. The aim of this systematic review is to describe the overlap and specificity of motor, emotional, and cognitive aspects of empathy in children and adolescents with ASD or CD. Motor and cognitive empathy impairments are found in both ASD and CD, yet the specificity seems to differ. In ASD facial mimicry and emotion recognition may be impaired for all basic emotions, whereas in CD this is only the case for negative emotions. Emotional empathy and the role of attention to the eyes therein need further investigation. We hypothesize that impaired motor and cognitive empathy in both disorders are a consequence of lack of attention to the eyes. However, we hypothesize major differences in emotional empathy deficits between ASD and CD, probably due to emotional autonomic and amygdala hyper-responsivity in ASD versus hypo-responsivity in CD, both resulting in lack of attention to the eyes.

Conduct disorders.

Conduct disorder (CD) is a frequently occurring psychiatric disorder characterized by a persistent pattern of aggressive and non-aggressive rule breaking antisocial behaviours that lead to considerable burden for the patients themselves, their family and society. This review paper updates diagnostic and therapeutic approaches to CD in the light of the forthcoming DSM-5 definition. The diagnostic criteria for CD will remain unchanged in DSM-5, but the introduction of a specifier of CD with a callous-unemotional (CU) presentation is new. Linked to this, we discuss the pros and cons of various other ways to subtype aggression/CD symptoms. Existing guidelines for CD are, with few exceptions, already of a relatively older date and emphasize that clinical assessment should be systematic and comprehensive and based on a multi-informant approach. Non-medical psychosocial interventions are recommended as the first option for the treatment of CD. There is a role for medication in the treatment of comorbid syndromes and/or in case of insufficient response to psychosocial interventions and severe and dangerous aggressive and violent behaviours.

Callous-unemotional traits as a cross-disorders construct.

PURPOSE: Callous-unemotional (CU) traits are currently viewed as the defining signs and symptoms of juvenile psychopathy. It is unclear, however, whether CU traits have validity only in the context of conduct disorder (CD) as proposed by Frick and Moffitt (A proposal to the DSM-V childhood disorders and the ADHD and disruptive behavior disorders work groups to include a specifier to the diagnosis of conduct disorder based on the presence of callous-unemotional traits, American Psychiatric Association, Washington, DC, 2010), or also outside CD, either in combination with other forms of psychopathology or as a stand-alone construct. METHODS: The current review systematically studied the existent literature on CU traits in juveniles to examine their validity inside and outside CD according to the framework regarding the validity of a psychiatric diagnosis provided by Robins and Guze (Am J Psychiatry 126:983-987, 1970). RESULTS: Inside youth with conduct problems, and CD specifically, it seems that CU traits meet the Robins and Guze criteria. As many of the reviewed studies included youth with ODD and ADHD as well, there are indications the same might be true for ODD and ADHD, although probably to a lesser extent. In other disorders, CU traits may be present as well, but their role is not firmly established. As stand-alone construct, data are lacking or are scarce on all of the above-mentioned criteria. CONCLUSIONS: CU traits are a useful specifier in CD, and possibly also in disruptive behaviour disorders (DBDs) more generally. High CU traits outside DBDs exist but it is as yet unknown if there is a clinical need for defining CU traits as a stand-alone construct.

Cerebrospinal fluid D-serine and glycine concentrations are unaltered and unaffected by olanzapine therapy in male schizophrenic patients.

N-Methyl D-aspartate (NMDA)-receptor hypofunction has been implicated in the pathophysiology of schizophrenia and D-serine and glycine add-on therapy to antipsychotics has shown beneficial effects in schizophrenic patients. Nevertheless, previous studies have not shown consistently altered D-serine concentrations in cerebrospinal fluid (CSF) of schizophrenic patients. To confirm and extend these results, CSF concentrations of both endogenous NMDA-receptor co-agonists d-serine and glycine and their common precursor L-serine were analyzed simultaneously in 17 healthy controls and 19 schizophrenic patients before and 6 weeks after daily olanzapine (10 mg) treatment. CSF D-serine, L-serine and glycine concentrations and their relative ratios were similar between schizophrenic patients and controls and no differences were observed before and after olanzapine therapy. Thus, the NMDA-receptor hypofunction hypothesis in schizophrenia is not explained by olanzapine therapy-dependent absolute or relative decreases in CSF D-serine and glycine concentrations in this series of male patients, thereby not providing convenient markers for the disorder.