Sibylle Metzler

Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

IMPORTANCE Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

Pre-reflective and reflective self-reference: A spatiotemporal EEG analysis

Functional imaging studies consistently support the role of the medial prefrontal cortex to be a part of a functional network of reflective self-awareness. The current study introduces a new linguistic task which (1) directly compares self-reference and other-reference, and (2) separates pre-reflective from reflective aspects of self-awareness. Twenty-six healthy volunteers evaluated trait adjectives in reference to the self or a close friend while a continuous 30-channel EEG was recorded. Low-resolution brain electromagnetic tomography (LORETA) was used for statistical brain imaging. As expected, the direct comparison of self-reference to other-reference revealed the MPFC to be significant and strongly more active during the self-reference condition. Pre-reflective aspects of self seem to be implemented to a greater degree in the ventral, reflective aspects of the self in dorsal parts of the MPFC. In the pre-reflective self condition, brain areas that receive homeostatic afferents from somatic and visceral sensation of the body such as the insula and the somatosensory cortex were strongly activated as early as 134 ms after stimulus onset. The right inferior parietal lobe seems to be involved in self-referential processing in general.

Stigma as a stressor and transition to schizophrenia after one year among young people at risk of psychosis

According to stress-vulnerability models, social stressors contribute to the onset of schizophrenia. Stigma and discrimination associated with mental illness may be a stressor for young people at risk of psychosis even prior to illness onset, but quantitative longitudinal data on this issue are lacking. We examined the cognitive appraisal of stigma-related stress as predictor of transition to schizophrenia among young people at risk of psychosis. In Zürich, Switzerland, 172 participants between 13 and 35years old and with either high or ultra-high risk of psychosis or risk of bipolar disorder were included. With 71 dropouts, transition was assessed during 12months among 101 participants of whom 13 converted to schizophrenia. At baseline, the cognitive appraisal of stigma as a stressor was measured by self-report, based on the primary appraisal of stigma as harmful and the secondary appraisal of resources to cope with stigma. Positive and negative symptoms were examined using the Positive and Negative Syndrome Scale. Compared with participants who did not convert to schizophrenia, converters had significantly more positive (p<.001) and negative (p<.001) symptoms and reported higher levels of stigma-related harm (p=.003) and stress (p=.009) at baseline. More perceived harm due to stigma at baseline predicted transition to schizophrenia (odds ratio 2.34, 95%-CI 1.19-4.60) after adjusting for age, gender, symptoms and functioning. Stigma stress may increase the risk of transition to schizophrenia. Research is needed on interventions that reduce public negative attitudes towards young people at risk and that support individuals at risk to cope with stigma-related stress.

Longitudinal course of self-labeling, stigma stress and well-being among young people at risk of psychosis.

Stigma may undermine the well-being of young people at risk of psychosis. We therefore measured self-labeling, stigma variables and well-being at baseline and again one year later among 77 at-risk participants. An increase in self-labeling during this period predicted heightened stigma stress after one year and a decrease in stigma stress predicted better well-being at follow-up, controlling for symptoms, psychiatric comorbidity and sociodemographic variables. Besides early intervention programmes, strategies are needed to reduce the public stigma associated with at-risk status and to support young people at risk to better cope with self-labeling and stigma stress.

Temporal variability and spatial diffusion of the N2 event-related potential in high-functioning patients with schizophrenia

Recent theories of schizophrenia have proposed a fundamental instability of information processing on a neurophysiological level, which can be measured as an increase in latency variability of event-related potentials (ERPs). If this reflects a fundamental deficit of the schizophrenic illness, it should also occur in high-functioning patients. These patients have also been observed to show a more diffuse activation pattern in neuroimaging studies, which is thought to reflect compensatory processes to maintain task performance. In the present study we investigated temporal variability and spatial diffusion of the visual N2 component in a group of high-functioning patients with preserved cognitive performance. 28 patients with schizophrenia and 28 control participants matched for gender, age and education participated in the study. Subjects performed a visual Go/Nogo task, while event-related potentials were obtained. Trial-to-trial latency variability was calculated with a Wavelet-based method. Patients with schizophrenia showed a robust increase in N2 latency variability at electrodes Fz and Cz in all task conditions. Regarding spatial distribution healthy participants showed a focused fronto-central N2 peak. In contrast, patients with schizophrenia showed a more diffuse pattern and additional negative peaks over lateral electrodes in the Nogo condition. These results clearly show that even in high-functioning patients with schizophrenia a higher temporal variability of ERPs can be observed. This provides support for temporal instability of information processing as a fundamental deficit associated with schizophrenia. The more diffuse scalp distribution might reflect processes that compensate for this instability when cognitive control is required.

Stigma and suicidal ideation among young people at risk of psychosis after one year

Suicidality is common among individuals at risk of psychosis. Emerging findings suggest that mental illness stigma contributes to suicidality. However, it is unclear whether stigma variables are associated with suicidality among young people at risk of psychosis. This longitudinal study assessed perceived public stigma and the cognitive appraisal of stigma as a stressor (stigma stress) as predictors of suicidal ideation among individuals at risk of psychosis over the period of one year. One hundred and seventy-two participants between 13 and 35 years of age were included who were at high or ultra-high risk of psychosis or at risk of bipolar disorder. At one-year follow-up, data were available from 73 completers. In multiple logistic regressions an increase of stigma stress (but not of perceived stigma) over one year was significantly associated with suicidal ideation at one-year follow-up, controlling for age, gender, symptoms, comorbid depression and suicidal ideation at baseline. Interventions to reduce public stigma and stigma stress could therefore improve suicide prevention among young people at risk of psychosis.

Evaluation of trait adjectives and ego pathology in schizophrenia: An N400 study

The N400, an event-related brain potential (ERP), can be triggered by semantic or arithmetic violations in visual or auditory stimulus material. Schizophrenia patients exhibit an altered N400 presumably resulting from impaired semantic memory associative networks. The present study investigates, whether an altered N400 can also be found in semantic violations of the own self-concept. We use simple descriptive sentences to combine semantics with the self-concept in order to explore differences and possible deficits in schizophrenia patients. Schizophrenia patients and controls were shown trait adjectives in reference to themselves. Participants had to decide if the presented trait adjective was congruent or incongruent with their own self-concept. Only in controls, the N400 was significantly more negative in the incongruent compared to the congruent condition. Controls seemed to profit from a stable self-concept as they were faster in judging if a given trait was descriptive for the self than for someone else, which might result from processes related to the self-reference effect. Interestingly, in schizophrenia patients, the higher the scores for ego pathology were, the smaller the N400 effect turned out to be. The diminished N400 effect is probably associated with a disturbed self-concept in schizophrenia.

F30. SMARTPHONE APPLICATION “ROBIN”: FEASIBILITY, ENGAGEMENT AND SATISFACTION OF A SMARTPHONE APPLICATION APPROACH TO SUPPORT TREATMENT OF (ATTENUATED) PSYCHOTIC SYMPTOMS IN ADOLESCENTS

Abstract Background There is increasing interest in using mobile technologies such as smartphones application in mental health care. First research results from the use of smartphone applications in the treatment of psychotic disorders are promising. Current analysis showed, that especially young people would be interested in smartphone applications within treatment settings. However, there is a lack of investigations in this population. There is also little known about mobile technologies in the work with attenuated psychotic symptoms. To address these gaps, we developed “Robin”, a specific smartphone application to support the therapy of adolescents with attenuated or full-blown psychotic symptoms. The smartphone application targets medication adherence, real-time symptom assessment and provides help coping with symptoms and stressful situations in daily life. Methods Based on existing literature and our clinical expertise within a specialized outpatient care for adolescents with (attenuated) psychotic symptoms, a first modular version of the app was developed and adapted after first pilot investigations with patients (N=7, Age 14–18) and therapists (N=10). Participants of the pilot investigation completed a questionnaire regarding usability and acceptance of the application. Furthermore, we investigated how the patients used the application in their daily life by analyzing the user data from the application. In September 2017, the development of the smartphone application has been finalized and we have started with a systematic clinical evaluation study for testing the efficiency of the app. The application is only used in combination with psychotherapy in our university hospital for child and adolescent psychiatry. Results The data from our pilot investigation showed, that “Robin” was accepted by clinicians and patients. All clinicians said they would like to use the application to enrich their therapeutic approaches. All patients in the pilot project used the application in their daily life. Especially modules with information about symptoms and coping strategies were frequently used. Since September 2017, first patients have been included to the systematic evaluation study. In Florence 2018, we will present first data from this study about feasibility, engagement and subjectively perceived benefit of the smartphone application. Discussion The first feedbacks from the pilot investigation were encouraging. The findings were used to improve and adapt the application. Since September 2017, the application is used in psychotherapy and an evaluation study has started. This is one of the first clinical trials to test the efficacy of a specific application developed for adolescents with psychotic and with attenuated psychotic symptoms.

S33. ETRO - A PROSPECTIVE FOLLOW-UP STUDY OF THE COMBINED TREATMENT APPROACH “ROBIN” FOR ADOLESCENTS WITH HIGH RISK FOR DEVELOPING A PSYCHOTIC DISORDER: THERAPY MODULES ENHANCED BY A SMARTPHONE APPLICATION

Abstract Background The most promising strategy in targeted prevention of psychotic disorders is to treat the at risk-symptoms in the pre-psychotic period. Although high risk-symptoms for psychotic disorder are common in adolescence and associated with a marked reduction in functioning, the evidence base required to guide effective interventions for adolescents at risk and even first-episode psychosis is limited. The clinicians from the early intervention center in Zurich have developed the treatment approach “Robin” (standardized manual and smartphone App) for adolescents with high risk for developing a psychotic disorder. The manual is targeting at risk-symptoms, comorbid disorders, improvement of quality of life and daily functioning. The therapy modules are based on evidence based treatment strategies in adults with a high risk and recommendations for adolescents with first episodes of psychosis. It follows the guidelines on early intervention in clinical psychosis high risk states of the European Association for Psychiatry. The intervention also includes a smartphone application for supporting the patients between sessions. This application targets real-time symptom assessment, medication adherence, and provides coping strategies for dealing with symptoms of psychosis and daily life hurdles. Methods The clinical intervention study ETRo is designed as a naturalistic controlled trial. The goal is to compare efficacy of a 16-week intervention in patients with at-risk symptoms (age range 13–18) with an active control group (treatment as usual). Power calculations conducted in collaboration with a statistician determined the recruitment goal of 30 participants in the treatment condition. Participants from a former early recognition study (N=62, Age: 13–18 years, Ø 15.06) are included for the control condition. For the intervention condition, help seeking adolescents with APS-Symptoms, aged 13–18, are being recruited during a three year time period. Within this prospective study, at-risk symptoms and data for comorbid symptoms, functioning, self-efficacy, and quality of life are collected at six time points (baseline, during the treatment period, immediately after intervention and 6, 12 and 24 months later). Results Since August 2017, first participants have been included and their treatment has started. In Florence, we will present our first results. This will include implementation of the treatment program and first findings of treatment period. Discussion Even though young patients with at-risk symptoms may profit best of specialised treatment approaches, little is known about age-appropriate treatment strategies in this vulnerable age group. This is one of the first controlled trials to test the efficacy of a specific treatment program for minor patients with attenuated psychotic symptoms.