The role of mentalizing in the relationship between schizotypal personality traits and state signs of psychosis risk captured by cognitive and perceptive basic symptoms.

Objective: Schizotypal traits and disturbances in mentalizing (the capacity to understand the mental states driving one's own and others' behaviors) have been implicated in increased vulnerability for psychosis. Therefore, we explored the associations linking schizotypal traits, mentalizing difficulties and their interactions to clinical high-risk for psychosis (CHR-P), as captured by the Basic Symptoms (BS) approach, during adolescence and young adulthood. Methods: Eighty-seven adolescents and young adults from the general population (46% male, 44% female; age: 14-23 years) were assessed with the Schizophrenia Proneness Interview (SPI-CY/A) for 11 perceptive and cognitive BS, with the Schizotypal Personality Questionnaire (SPQ) for schizotypal traits, and with the Reflective Functioning Questionnaire (RFQ) for self-reported mentalizing abilities. The RFQ evaluates the level of certainty (RFQc scale) and uncertainty (RFQu scale) with which individuals use mental state information to explain their own and others' behaviors. Results: Logistic regression models showed significant positive effects of the SPQ disorganization scale on perceptive BS and of the SPQ interpersonal scale on cognitive BS. Post-hoc analyses revealed that schizotypal features pertaining to odd speech and social anxiety, respectively, were associated with perceptive and cognitive BS. Furthermore, higher scores on the RFQu scale and lower scores on the RFQc scale independently explained the presence of cognitive BS. Finally, significant interaction effects between RFQc and SPQ odd speech on perceptive BS, and between RFQc and SPQ social anxiety on cognitive BS were found. Conclusion: Our findings suggest that schizotypal traits and mentalizing significantly relate both independently and through their interactions to the presence of cognitive and perceptive BS included in CHR-P criteria. Furthermore, mentalizing dysfunction may contribute in the relation between schizotypal traits and early state signs of CHR-P. Mentalizing may support both detection and early treatment of CHR-P among adolescents and young adults who present with trait risk for psychosis.

Self-Blame Mediates the Link between Childhood Neglect Experiences and Internalizing Symptoms in Low-Risk Adolescents.

Childhood neglect is the most common type of maltreatment, ranging from minor isolated incidents to consistent failures in emotional/physical caregiving. It has been associated with developmental impairments and considered a risk factor for the emergence of psychopathology, particularly internalizing disorders. This study aimed to explore individual differences in response to the continuum of severity of neglect in community adolescents, as well as the role of specific cognitive emotion regulation strategies (CERSs) as mediators between childhood neglect and current internalizing symptoms. Low-risk adolescents (12-19 years old; M age 15.88 years; N = 123; 64 Females) completed questionnaires assessing these experiences. We employed a regression model and a simple mediation analyses. Findings indicate a positive association between childhood neglect, internalizing behaviors, and the adoption of self-blame as CERS. Moreover, the use of self-blame in response to everyday stress partially mediated the relationship between neglect and internalizing behaviors (effect size: .28). Findings support the hypothesis that even in a low risk sample, neglect is associated with internalizing symptoms, and highlight the importance of assessing individual differences in the experience of neglect. Moreover, the mediation effect of the CERSs of self-blame might serve as a potential target for psychotherapeutic interventions aimed at reducing internalizing symptoms.

Cortical thickness of the insula and prefrontal cortex relates to externalizing behavior: Cross-sectional and prospective findings.

Externalizing behaviors (EBs) pertain to a diverse set of aggressive, antisocial, and potentially destructive behaviors directed toward the external environment. They range from nonclinical to clinical in severity, associated with opposition, aggression, hyperactivity, or impulsivity, and are considered a risk factor for the emergence of psychopathology later in adulthood. Focusing on community adolescents (N = 102; 49 female and 53 male adolescents; age range 12-19 years), this study aimed to explore the relations between EBs and the cortical thickness of regions of interest as well as to identify possible risk markers that could improve understanding of the EB construct. Using a mixed cross-sectional and prospective design (1-year follow-up), we report specific associations with cortical thickness of the left insular, right orbitofrontal, and left anterior cingulate cortex. Specifically, thinner left insular and right orbitofrontal cortex was associated with higher EBs, and thinner left anterior cingulate cortex predicted less reduction in EBs 1 year later. In addition, further examination of the aggression and rule-breaking subscales of the Youth/Adult Self-Report, used to assess EBs, revealed specific associations with insular subregions. Findings suggest that cortical structure morphology may significantly relate to the expression and maintenance of EBs within the general population of adolescents.

Associations between schizotypal personality features, mentalizing difficulties and thought problems in a sample of community adolescents.

AIM: Schizotypal trait expression and mentalizing impairments represent key factors associated with increased vulnerability for schizophrenia. In the current study, we analysed the nature of associations linking specific schizotypal personality features to mentalizing difficulties during adolescence. Furthermore, we examined the extent to which mentalizing difficulties mediate the relationship between schizotypal trait features and self-reported thought problems. METHODS: One hundred and five community adolescents (Mage = 15.72; SD = 1.91) completed a recently developed self-report measure of mentalizing (Reflective Functioning Questionnaire [RFQ]), evaluating the degree of certainty (RFQc-scale) and uncertainty (RFQu-scale) with which individuals utilize mental state information to understand their own and others' behaviour. High scores on the RFQu-scale reflect poor usage of mental state information, while high scores on the RFQc-scale capture adaptive levels of certainty about mental states. Self-report questionnaires were also used to assess schizotypal trait expression, thought problems and symptoms of anxiety/depression. RESULTS: Linear regression models indicated that schizotypal features of social anxiety and odd speech accounted for increased RFQu scores, while odd speech also accounted for reduced RFQc scores. RFQu partially mediated the effects of social anxiety and odd speech on the level of thought problems in the sample. CONCLUSIONS: Present findings suggest that schizotypal features that impede interpersonal communication during adolescence are linked to difficulties in mental state understanding. Our study also provides original data suggesting that the effects of social anxiety and odd speech on psychosis-risk may partially depend upon the level of mentalizing uncertainty. Mentalizing difficulties may constitute important clinical assessment and early prevention treatment targets in adolescents who demonstrate schizotypal features.

Self-Monitoring for speech and its links to age, cognitive effort, schizotypal trait expression and impulsivity during adolescence.

Introduction: Disruptions in self-monitoring processes represent key cognitive factors associated with schizophrenia spectrum disorders. In the current study, we assessed the effects of age and cognitive effort on self-monitoring for speech in adolescence, as well as its associations with personality dimensions pertaining to schizotypy and impulsivity.Methods: 121 community adolescents undertook a self-monitoring task that assesses the capacity to discriminate between self-generated overt and silent speech, for items requiring different levels of cognitive effort. Self-report measures were used to assess trait dimensions of schizotypy and impulsivity.Results: Cognitive effort, but not age, contributed to the overall rate of self-monitoring errors. Contrary to clinical psychosis and high risk samples, increased cognitive effort in healthy adolescents led to more internalising than externalising self-monitoring errors. Higher scores on the interpersonal dimension of schizotypy were associated with increases in the total rate of self-monitoring errors. No associations were found between positive schizotypy and externalising self-monitoring misattributions. Finally, trait impulsivity dimensions were not associated with self-monitoring performance.Conclusions: The present findings suggest that self-monitoring confusions may be linked to trait-risk for psychosis in adolescence. Future studies can prospectively assess whether the association between negative schizotypal traits and self-monitoring represents a distal marker of psychosis vulnerability.

The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a pragmatic, double-blind, placebo-controlled randomised trial.

BACKGROUND: Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response. METHODS: The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants. FINDINGS: Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication. INTERPRETATION: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder. FUNDING: National Institute for Health Research.

Patterns of source monitoring bias in incarcerated youths with and without conduct problems.

INTRODUCTION: Antisocial individuals present behaviours that violate the social norms and the rights of others. In the present study, we examine whether biases in monitoring the self-generated cognitive material might be linked to antisocial manifestations during adolescence. We further examine the association with psychopathic traits and conduct problems (CPs). METHODS: Sixty-five incarcerated adolescents (IAs; M age = 15.85, SD = 1.30) and 88 community adolescents (CAs; M age = 15.78, SD = 1.60) participated in our study. In the IA group, 28 adolescents presented CPs (M age = 16.06, SD = 1.41) and 19 did not meet the diagnostic criteria for CPs (M age = 15.97, SD = 1.20). Source monitoring was assessed through a speech-monitoring task, using items requiring different levels of cognitive effort; recognition and source-monitoring bias scores (internalising and externalising biases) were calculated. RESULTS: Between-group comparisons indicate greater overall biases and different patterns of biases in the source monitoring. IA participants manifest a greater externalising bias, whereas CA participants present a greater internalising bias. In addition, IA with CPs present different patterns of item recognition. CONCLUSIONS: These results indicate that the two groups of adolescents present different types of source-monitoring bias for self-generated speech. In addition, the IAs with CPs present impairments in item recognition. Future studies may examine the developmental implications of self-monitoring biases in the perseverance of antisocial behaviours from adolescence to adulthood.

A randomised controlled trial assessing the severity and duration of depressive symptoms associated with a clinically significant response to sertraline versus placebo, in people presenting to primary care with depression (PANDA trial): study protocol for a randomised controlled trial.

BACKGROUND: Depressive symptoms are usually managed within primary care and antidepressant medication constitutes the first-line treatment. It remains unclear at present which people are more likely to benefit from antidepressant medication. This paper describes the protocol for a randomised controlled trial (PANDA) to investigate the severity and duration of depressive symptoms that are associated with a clinically significant response to sertraline compared to placebo, in people presenting to primary care with depression. METHODS/DESIGN: PANDA is a randomised, double blind, placebo controlled trial in which participants are individually randomised to sertraline or placebo. Eligible participants are those who are between the ages of 18 to 74; have presented to primary care with depression or low mood during the past 2 years; have not received antidepressant or anti-anxiety medication in the 8 weeks prior to enrolment in the trial and there is clinical equipoise about the benefits of selective serotonin reuptake inhibitor (SSRI) medication. Participants who consent to participate in the trial are randomised to receive either sertraline or matching placebo, starting at 50 mg daily for 1 week, increasing to 100 mg daily for up to 11 weeks (with the option of increasing to 150 mg if required). Participants, general practitioners (GPs) and the research team will be blind to treatment allocation. The primary outcome will be depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9) at 6 weeks post randomisation, measured as a continuous outcome. Secondary outcomes include depressive symptoms measured with the PHQ-9 at 2 and 12 weeks as a continuous outcome and at 2, 6 and 12 weeks as a binary outcome; follow-up scores on depressive symptoms measured with the Beck Depression Inventory-II, anxiety symptoms measured by the Generalized Anxiety Disorder-7 and quality of life measured with the Euroqol-5D-5L and Short Form-12; emotional processing task scores measured at baseline, 2 and 6 weeks; and costs associated with healthcare use, time off work and personal costs. DISCUSSION: The PANDA trial uses a simple self-administered measure to establish the severity and duration of depressive symptoms associated with a clinically significant response to sertraline. The evidence from the trial will inform primary care prescribing practice by identifying which patients are more likely to benefit from antidepressants. TRIAL REGISTRATION: Controlled Trials ISRCTN Registry, ISRCTN84544741 . Registered on 20 March 2014. EudraCT Number: 2013-003440-22; Protocol Number: 13/0413 (version 6.1).

Attachment, Neurobiology, and Mentalizing along the Psychosis Continuum.

In this review article, we outline the evidence linking attachment adversity to psychosis, from the premorbid stages of the disorder to its clinical forms. To better understand the neurobiological mechanisms through which insecure attachment may contribute to psychosis, we identify at least five neurobiological pathways linking attachment to risk for developing psychosis. Besides its well documented influence on the hypothalamic-pituary-adrenal (HPA) axis, insecure attachment may also contribute to neurodevelopmental risk through the dopaminergic and oxytonergic systems, as well as bear influence on neuroinflammation and oxidative stress responses. We further consider the neuroscientific and behavioral studies that underpin mentalization as a suite of processes potentially moderating the risk to transition to psychotic disorders. In particular, mentalization may help the individual compensate for endophenotypical impairments in the integration of sensory and metacognitive information. We propose a model where embodied mentalization would lie at the core of a protective, resilience response mitigating the adverse and potentially pathological influence of the neurodevelopmental cascade of risk for psychosis.