E-Clinical High Risk for Psychosis: Viewpoint on Potential of Digital Innovations for Preventive Psychiatry.
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SUBMITTER: Reilly T
PROVIDER: S-EPMC6915798 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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E-Clinical High Risk for Psychosis: Viewpoint on Potential of Digital Innovations for Preventive Psychiatry.
Reilly Thomas T Mechelli Andrea A McGuire Philip P Fusar-Poli Paolo P Uhlhaas Peter J PJ
JMIR mental health 20191003 10
E-mental health is an emerging area of research that has the potential to overcome some of the current barriers to progress in working with people at clinical high risk for psychosis (CHR-P). This article provides an overview of how e-mental health could be used in the detection, prediction, and treatment in the CHR-P population. Specifically, we evaluate e-detection, e-prediction, and e-therapeutics for this clinical population. E-mental health holds great promise to improve current management ...[more]
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Project description:BackgroundPsychiatry has long needed a better and more scalable way to capture the dynamics of behavior and its disturbances, quantitatively across multiple data channels, at high temporal resolution in real time. By combining 24/7 data-on location, movement, email and text communications, and social media-with brain scans, genetics, genomics, neuropsychological batteries, and clinical interviews, researchers will have an unprecedented amount of objective, individual-level data. Analyzing these data with ever-evolving artificial intelligence could one day include bringing interventions to patients where they are in the real world in a convenient, efficient, effective, and timely way. Yet, the road to this innovative future is fraught with ethical dilemmas as well as ethical, legal, and social implications (ELSI).ObjectiveThe goal of the Ethics Checklist is to promote careful design and execution of research. It is not meant to mandate particular research designs; indeed, at this early stage and without consensus guidance, there are a range of reasonable choices researchers may make. However, the checklist is meant to make those ethical choices explicit, and to require researchers to give reasons for their decisions related to ELSI issues. The Ethics Checklist is primarily focused on procedural safeguards, such as consulting with experts outside the research group and documenting standard operating procedures for clearly actionable data (eg, expressed suicidality) within written research protocols.MethodsWe explored the ELSI of digital health research in psychiatry, with a particular focus on what we label "deep phenotyping" psychiatric research, which combines the potential for virtually boundless data collection and increasingly sophisticated techniques to analyze those data. We convened an interdisciplinary expert stakeholder workshop in May 2020, and this checklist emerges out of that dialogue.ResultsConsistent with recent ELSI analyses, we find that existing ethical guidance and legal regulations are not sufficient for deep phenotyping research in psychiatry. At present, there are regulatory gaps, inconsistencies across research teams in ethics protocols, and a lack of consensus among institutional review boards on when and how deep phenotyping research should proceed. We thus developed a new instrument, an Ethics Checklist for Digital Health Research in Psychiatry ("the Ethics Checklist"). The Ethics Checklist is composed of 20 key questions, subdivided into 6 interrelated domains: (1) informed consent; (2) equity, diversity, and access; (3) privacy and partnerships; (4) regulation and law; (5) return of results; and (6) duty to warn and duty to report.ConclusionsDeep phenotyping research offers a vision for vastly more effective care for people with, or at risk for, psychiatric disease. The potential perils en route to realizing this vision are significant; however, and researchers must be willing to address the questions in the Ethics Checklist before embarking on each leg of the journey.
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Project description:The presence of a positive family relationship has been suggested as a protective factor from parental stress and from the development of full-blown psychosis. However, to date, there is limited research on family functioning in adolescents with psychosis and at clinical high risk for psychosis (CHR-P). This study is aimed at comparing family functioning and perceived stress in parents of adolescents with either CHR-P, early onset psychosis (EOP), or other psychiatric disorders (no CHR-P). As a secondary aim, it will correlate family functioning with parental perceived stress in order to find critical targets of intervention. We conducted a Reporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD)-compliant, real-world, cross-sectional study. One-hundred and eleven adolescents aged 12-17 who access the institute of hospitalization and care with scientific character (IRCCS) Mondino Foundation Neuropsychiatric services (Pavia, Italy) between 2017 and 2020 and their parents (n = 222) were included. Sociodemographic characteristics of adolescents and their parents were collected. Family functioning was evaluated through the Family Adaptability and Cohesion Evaluation Scale-IV (FACES-IV) and the level of stress through the Perceived Stress Scale (PSS). Twenty adolescents had EOP, 38 had CHR-P, and 59 had no CHR-P. In total, 2.6% of CHR-P adolescents were adopted, 76.3% had separated-divorced parents, and 34.2% of parents had a depressive disorder. Among the FACES-IV sub-scale, maternal rigidity was progressively increased from no-CHR-P to CHR-P to EOP group, with statistical differences between EOP and the other two groups (p = 0.01). CHR-P mothers and fathers showed a high level of PSS values, without group difference. Lastly, PSS values correlated positively with the Rigidity, Disengagement, and Chaos scale of FACES-IV and negatively with the Communication scale (p < 0.05). Our results suggest that family functioning has a central role and could represent a worthwhile target of intervention for adolescents at CHR-P, leading the way to new preventive approaches.
| S-EPMC9051044 | biostudies-literature
Project description:Clinical outcomes vary among youths at clinical high risk for psychosis (CHR-P), with approximately 20% progressing to full-blown psychosis over 2 to 3 years and 30% achieving remission. Recent research efforts have focused on identifying biomarkers that precede psychosis onset and enhance the accuracy of clinical outcome prediction in CHR-P individuals, with the ultimate goal of developing staged treatment approaches based on the individual's level of risk. Identifying such biomarkers may also facilitate progress toward understanding pathogenic mechanisms underlying psychosis onset, which may support the development of mechanistically informed early interventions for psychosis. In recent years, electroencephalography-based event-related potential measures with established sensitivity to schizophrenia have gained traction in the study of CHR-P and its clinical outcomes. In this review, we describe the evidence for event-related potential abnormalities in CHR-P and discuss how they inform our understanding of information processing deficits as vulnerability markers for emerging psychosis and as indicators of future outcomes. Among the measures studied, P300 and mismatch negativity are notable because deficits predict conversion to psychosis and/or CHR-P remission. However, the accuracy with which these and other measures predict outcomes in CHR-P has been obscured in the prior literature by the tendency to only report group-level differences, underscoring the need for inclusion of individual predictive accuracy metrics in future studies. Nevertheless, both P300 and mismatch negativity show promise as electrophysiological markers of risk for psychosis, as target engagement measures for clinical trials, and as potential translational bridges between human studies and animal models focused on novel drug development for early psychosis.
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Project description:Individuals diagnosed with psychotic disorders exhibit abnormalities in the perception of expressive behaviors, which are linked to symptoms and visual information processing domains. Specifically, literature suggests these groups have difficulties perceiving gestures that accompany speech. While our understanding of gesture perception in psychotic disorders is growing, gesture perception abnormalities and clues about potential causes and consequences among individuals meeting criteria for a clinical high-risk (CHR) syndrome is limited. Presently, 29 individuals with a CHR syndrome and 32 healthy controls completed an eye-tracking gesture perception paradigm. In this task, participants viewed an actor using abstract and literal gestures while presenting a story and eye gaze data (eg, fixation counts and total fixation time) was collected. Furthermore, relationships between fixation variables and both symptoms (positive, negative, anxiety, and depression) and measures of visual information processing (working memory and attention) were examined. Findings revealed that the CHR group gazed at abstract gestures fewer times than the control group. When individuals in the CHR group did gaze at abstract gestures, on average, they spent significantly less time fixating compared to controls. Furthermore, reduced fixation (ie, count and time) was related to depression and slower response time on an attentional task. While a similar pattern of group differences in the same direction appeared for literal gestures, the effect was not significant. These data highlight the importance of integrating gesture perception abnormalities into vulnerability models of psychosis and inform the development of targeted treatments for social communicative deficits.
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Project description:Motor deficits appear prior to psychosis onset, provide insight into vulnerability as well as mechanisms that give rise to emerging illness, and are predictive of conversion. However, to date, the extant literature has often targeted a complex abnormality (e.g., gesture dysfunction, dyskinesia), or a single fundamental domain (e.g., accuracy) but rarely provided critical information about several of the individual components that make up more complex behaviors (or deficits). This preliminary study applies a novel implicit motor task to assess domains of motor accuracy, speed, recognition, and precision in individuals at clinical high risk for psychosis (CHR-p). Sixty participants (29 CHR-p; 31 healthy volunteers) completed clinical symptom interviews and a novel Serial Interception Sequence Learning (SISL) task that assessed implicit motor sequence accuracy, speed, precision, and explicit sequence recognition. These metrics were examined in multilevel models that enabled the examination of overall effects and changes in motor domains over blocks of trials and by positive/negative symptom severity. Implicit motor sequence accuracy, speed, and explicit sequence recognition were not detected as impacted in CHR-p. When compared to healthy controls, individuals at CHR-p were less precise in motor responses both overall (d = 0.91) and particularly in early blocks which normalized over later blocks. Within the CHR-p group, these effects were related to positive symptom levels (t = - 2.22, p = 0.036), such that individuals with higher symptom levels did not improve in motor precision over time (r's = 0.01-0.05, p's > 0.54). CHR-p individuals showed preliminary evidence of motor precision deficits but no other motor domain deficits, particularly in early performance that normalized with practice.
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Project description:Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n=138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis.
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Project description:Several studies have demonstrated that youth at clinical high risk (CHR) of developing psychosis have a high prevalence of comorbid psychiatric disorders. Less is known about the impact of comorbid diagnoses on later conversion to psychosis and the change over time. The aim of this study was to determine the frequency and distribution of psychiatric diagnoses at baseline and over time in the North American Prodrome Longitudinal Study (NAPLS 2) and the role of comorbid diagnoses in conversion to psychosis. The NAPLS 2 sample consisted of 744 CHR youth and 276 healthy controls. Only 21% of the CHR group did not have a comorbid diagnosis with many have 2-3 DSM-IV comorbid diagnoses. The most common diagnoses were anxiety and depressive disorders, which did improve over time. The only diagnosis at baseline that differentiated the converters from the non-converters was cannabis misuse. Comorbidity, except for cannabis use, was essentially independent of clinical outcome. It is possible that those with comorbid diagnoses are preferentially the help-seeking individuals that present for help in our clinics and research projects and that those who are at risk but do not have a comorbid diagnosis may not be seeking help in the prodromal phase.
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Project description:The current study examined the presence of abnormalities in cortical grey-matter (GM) in a sample of clinical high-risk (CHR) participants and examined relationships with psychosocial functioning and neurocognition. CHR-participants (n = 114), participants who did not fulfil CHR-criteria (CHR-negative) (n = 39) as well as a group of healthy controls (HC) (n = 49) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. No significant differences in GM-thickness and intensity were observed in CHR-participants compared to CHR-negative and HC. Circumscribed abnormalities in GM-intensity were found in the visual and frontal cortex of CHR-participants. Moreover, small-to-moderate correlations were observed between GM-intensity and neuropsychological deficits in the CHR-group. The current data suggest that CHR-participants may not show comprehensive abnormalities in GM. We discuss the implications of these findings for the pathophysiological theories of early stage-psychosis as well as methodological issues and the impact of different recruitment strategies.
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Project description:Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I-V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy controls. We also explored the association between mitochondrial function and brain microglial activation and glutathione levels using a translocator protein 18 kDa [18F]FEPPA PET scan and 1H-MRS scan, respectively. There were no significant differences in mitochondrial complex function and lactate/pyruvate levels between CHR and healthy controls. In the CHR group, mitochondrial complex III function (r = -0.51, p = 0.008) and lactate levels (r = 0.61, p = 0.004) were associated with prodromal negative symptoms. As previously reported, there were no significant differences in microglial activation and glutathione levels between groups, however, mitochondrial complex IV function was inversely related to microglial activation in the hippocampus in CHR (r = -0.42, p = 0.04), but not in healthy controls. In conclusion, alterations in mitochondrial function are not yet evident in CHR, but may relate to the severity of prodromal symptoms, particularly negative symptoms.
| S-EPMC5906614 | biostudies-literature
Project description:AimsThe clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis.Methods"Preferred Reporting Items for Systematic reviews and Meta-Analyses" and "Meta-analysis Of Observational Studies in Epidemiology"-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS).ResultsTwenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges' g = 1.410, 95% confidence interval (CI) 1.002-1.818]; negative psychotic symptoms (Hedges' g = 0.683, 95% CI 0.371-0.995); depressive symptoms (Hedges' g = 0.844, 95% CI 0.371-1.317); and functioning (Hedges' g = 0.776, 95% CI 0.463-1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3-58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges' g = 0.706, 95% CI 0.091-1.322) and functioning (Hedges' g = 0.623, 95% CI 0.375-0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = -0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = -0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies.ConclusionsClinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.
| S-EPMC8786617 | biostudies-literature