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Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The field of digital mental health is rapidly expanding with digital tools being used in assessment, intervention, and supporting self-help. The application of digital mental health to hallucinations is, however, at a very early stage. This report from a working group of the International Consortium on Hallucinations Research considers particular synergies between the phenomenon of hallucinations and digital tools that are being developed. Highlighted uses include monitoring and managing intermittently occurring hallucinations in daily life; therapeutic applications of audio and video media including virtual and augmented reality; targeting verbal aspects of hallucinations; and using avatars to represent hallucinatory voices. Although there is a well-established Internet-based peer support network, digital resources for hallucinations have yet to be implemented in routine practice. Implementation may benefit from identifying how to market resources to the broad range of populations who experience hallucinations and identifying sustainable funding models. It is envisaged that digital tools will contribute to improved self-management and service provision for people experiencing hallucinations.

Auditory Hallucinations (AH) cause substantial suffering and dysfunction, yet remain poorly understood and modeled. Previous reports have linked AH to increases in negative emotions, suggesting a role for the autonomic nervous system (ANS) in underlying this link. Employing an Experience Sampling Method (ESM) approach, 40 individuals with schizophrenia completed a 36-hour ambulatory assessment of AH and cardiac autonomic regulation. Participants carried mobile electronic devices that prompted them to report 10 times/d the severity of their momentary AH, along with a Holter monitor that continuously recorded their cardiac autonomic regulation. The clocks of the devices and monitors were synchronized, allowing for high time-resolution temporal linking of the AH and concurrent autonomic data. Power spectral analysis was used to determine the relative vagal (parasympathetic) contribution to autonomic regulation during 5 minutes prior to each experience sample. The participants also completed interview-based measures of AH (SAPS; PSYRATS). The ESM-measured severity of AH was significantly correlated with the overall SAPS-indexed AH severity, along with the PSYRATS-indexed AH frequency, duration, loudness, degree of negative content, and associated distress. A mixed-effect regression model indicated that momentary increases in autonomic arousal, characterized by decreases in vagal input, significantly predicted increases in ESM-measured AH severity. Vagal input averaged over the 36-hour assessment displayed a small but significant inverse correlation with the SAPS-indexed AH. The results provide preliminary support for a link between ANS regulation and AH. The findings also underscore the highly dynamic nature of AH and the need to utilize high time-resolution methodologies to investigate AH., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Relational models of psychopathology propose that symptoms are dynamically connected and hypothesize that genetic and environmental influences moderate the strength of these symptom connections. Previous findings suggest that the interplay between hallucinations and delusions may play a crucial role in the development of psychotic disorder. The current study examined whether the connection between hallucinations and delusions is impacted by proxy genetic and environmental risk factors., Methods: Hallucinations and delusions at baseline and at 3-year follow-up were assessed in a sample of 1054 healthy siblings and 918 parents of 1109 patients with psychosis, and in 589 healthy controls (no familial psychosis risk). Environmental factors assessed were cannabis use, childhood trauma, and urbanicity during childhood. Logistic regression analyses tested whether familial psychosis risk predicted increased risk of delusions, given presence of hallucinations. Moderating effects of environmental factors on the hallucination-delusion association were tested in a similar fashion, restricted to the control and sibling groups., Results: The risk of delusions, given hallucinations, was associated with proxy genetic risk: 53% in parents, 47% in siblings, and 36% in controls. The hallucination-delusion association was stronger in those reporting cannabis use (risk difference: 32%) and childhood trauma (risk difference: 15%) although not all associations were statistically conclusive (respectively: p = .037; p = .054). A directionally similar but nonsignificant effect was found for urb anicity during childhood (risk difference: 14%, p =.357)., Conclusion: The strength of the connection between delusions and hallucinations is associated with familial and environmental risks for psychotic disorder, suggesting that specific symptom connections in the early psychosis psychopathology network are informative of underlying mechanisms., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Deficits in emotion processing are thought to underlie the key negative symptoms flat affect and anhedonia observed in psychotic disorders. This study investigated emotional experience and social behavior in the realm of daily life in a sample of patients with schizophrenia and schizoaffective disorder, stratified by level of negative symptoms., Methods: Emotional experience and behavior of 149 patients with schizophrenia and schizoaffective disorder and 143 controls were explored using the Experience Sampling Method., Results: Patients reported lower levels of positive and higher levels of negative affect compared with controls. High negative symptom patients reported similar emotional stability and capacity to generate positive affect as controls, whereas low negative symptom patients reported increased instability. All participants displayed roughly comparable emotional responses to the company of other people. However, in comparison with controls, patients showed more social withdrawal and preference to be alone while in company, particularly the high negative symptom group., Conclusions: This study revealed no evidence for a generalized hedonic deficit in patients with psychotic spectrum disorders. Lower rather than higher levels of negative symptoms were associated with a pattern of emotional processing which was different from healthy controls.

Background: Psychosis has been repeatedly suggested to be affected by increases in stress and arousal. However, there is a dearth of evidence supporting the temporal link between stress, arousal, and psychosis during "real-world" functioning. This paucity of evidence may stem from limitations of current research methodologies. Our aim is to the test the feasibility and validity of a novel methodology designed to measure concurrent stress and arousal in individuals with psychosis during "real-world" daily functioning., Method: Twenty patients with psychosis completed a 36-hour ambulatory assessment of stress and arousal. We used experience sampling method with palm computers to assess stress (10 times per day, 10 AM → 10 PM) along with concurrent ambulatory measurement of cardiac autonomic regulation using a Holter monitor. The clocks of the palm computer and Holter monitor were synchronized, allowing the temporal linking of the stress and arousal data. We used power spectral analysis to determine the parasympathetic contributions to autonomic regulation and sympathovagal balance during 5 minutes before and after each experience sample., Results: Patients completed 79% of the experience samples (75% with a valid concurrent arousal data). Momentary increases in stress had inverse correlation with concurrent parasympathetic activity (ρ = -.27, P < .0001) and positive correlation with sympathovagal balance (ρ = .19, P = .0008). Stress and heart rate were not significantly related (ρ = -.05, P = .3875)., Conclusion: The findings support the feasibility and validity of our methodology in individuals with psychosis. The methodology offers a novel way to study in high time resolution the concurrent, "real-world" interactions between stress, arousal, and psychosis. The authors discuss the methodology's potential applications and future research directions.

Objective: The aim of this study was to examine whether proneness to subjective cognitive failure (cognitive based mistakes) increases the risk for the development of symptoms of psychosis and to what degree any association was familial., Methods: At baseline, the Cognitive Failure Questionnaire (CFQ) and the Community Assessment of Psychic Experiences (CAPE) questionnaire were administered in a general population sample of genetically related individuals (n = 755). Individuals scoring high (>75th percentile) or average on the CAPE (between 40th and 60th percentile) (n = 488) were reinterviewed with the CAPE and Structured Interview for Schizotypy-Revised (SIS-R) at follow-up (mean interval = 7.7 months, SD = 4.8 months)., Results: Cross-trait, within-relative analysis showed a significant association between the CFQ and the negative dimension, assessed with both the CAPE and SIS-R, whereas no association was found between the CFQ and the positive dimension. Cross-trait, between-relative analyses showed no association between the CFQ in one relative and any of the dimensions of the subclinical psychosis phenotype in the other relative., Conclusion: Proneness to subjective cognitive failure possibly contributes to the development or persistence of negative symptoms and can be seen as potential risk factor for negative symptoms of psychosis. This overlap is due to individual effects rather than familial liability.

Not all individuals with experience of psychosis develop a need for care. The present study investigated differences in coping strategies and associated levels of perceived control over psychotic symptoms, in relation to need for care status. The influence of coping on need for care was assessed in 47 individuals incident for psychosis in a general population sample of 4,722. Need for care was associated with severity of psychotic experiences rather than associated distress, mean level of control, or average number of coping strategies used. Qualitative differences were apparent, however, in that those who resorted to the strategy of symptomatic coping (a coping strategy characterized by going along with and indulging in symptoms) experienced less control over their symptoms (odds ratio [OR] = 0.79, 95% confidence interval [CI]: 0.63-0.98) and had a higher probability of need for care (OR = 6.07, 95% CI: 1.94-18.95). The results suggest that qualitative differences in self-initiated coping modify the risk for need for care and subsequent patient status in those who experience psychotic symptoms and point to the possible importance of early coping-based interventions.

Flat affect is a core symptom of schizophrenia. To date, researchers have focused primarily on emotional expression. Only recently has the emotional experience of patients with schizophrenia been studied in laboratory settings. The goal of this study is to assess emotional experience in the complex world of daily life. A structured time-sampling technique, the Experience Sampling Method, was used to collect data. Schizophrenia subjects (n = 58) were compared to 65 nonpatient controls. Patients were divided into blunted and nonblunted subgroups on the basis of Brief Psychiatric Rating Scale (BPRS) behavioral ratings of flat affect. Schizophrenia subjects experienced more intense and more variable negative emotions than controls. For the positive emotions, we found less intensity and less variability in the schizophrenia subjects. No difference in patterns of affect was found between the blunted and the nonblunted schizophrenia subgroups. Our findings suggest that patients with schizophrenia are more emotionally active than has been assumed based on behavioral observations.

Systematic investigations into the experience of schizophrenic patients as they react and adapt to social environments are rare. Yet such information is extremely useful for understanding the psychopathology of schizophrenia, the planning of treatments, as well as for creating optimal treatment and living environments. In this study, dynamic fluctuations of mental state, social context, and experience in the daily life of schizophrenic patients were measured. Data were collected using the Experience Sampling Method on nine schizophrenic subjects and seven nonpsychiatric controls. Schizophrenic patients spent more time alone than normal--a difference that was largely created by the subsample of outpatients; hospitalized patients were less alone. As a group, the patients felt best when they were with one to three persons. The most troublesome condition reported was being alone or being in the company of more than three people. Three cases are presented to illustrate the individual variability of subjects' experience.