[Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders]. / Minderjährige in klinischen Prüfungen: Ethische Abwägungen ihres Einbezugs am Beispiel der indizierten Prävention psychotischer Erkrankungen.

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.

Predictors of help-seeking behaviour in people with mental health problems: a 3-year prospective community study.

BACKGROUND: The majority of people with mental illness do not seek help at all or only with significant delay. To reduce help-seeking barriers for people with mental illness, it is therefore important to understand factors predicting help-seeking. Thus, we prospectively examined potential predictors of help-seeking behaviour among people with mental health problems (N = 307) over 3 years. METHODS: Of the participants of a 3-year follow-up of a larger community study (response rate: 66.4%), data of 307 (56.6%) persons with any mental health problems (age-at-baseline: 16-40 years) entered a structural equation model of the influence of help-seeking, stigma, help-seeking attitudes, functional impairments, age and sex at baseline on subsequent help-seeking for mental health problems. RESULTS: Functional impairment at baseline was the strongest predictor of follow-up help-seeking in the model. Help-seeking at baseline was the second-strongest predictor of subsequent help-seeking, which was less likely when help-seeking for mental health problems was assumed to be embarrassing. Personal and perceived stigma, and help-seeking intentions had no direct effect on help-seeking. CONCLUSIONS: With only 22.5% of persons with mental health problems seeking any help for these, there was a clear treatment gap. Functional deficits were the strongest mediator of help-seeking, indicating that help is only sought when mental health problems have become more severe. Earlier help-seeking seemed to be mostly impeded by anticipated stigma towards help-seeking for mental health problems. Thus, factors or beliefs conveying such anticipated stigma should be studied longitudinally in more detail to be able to establish low-threshold services in future.

Psychometric properties of the Kessler psychological scales in a Swiss young-adult community sample indicate poor suitability for community screening for mental disorders.

AIM: The Kessler psychological distress scales (K10 and K6) are used as screening tools to assess psychological distress related to the likely presence of a mental disorder. Thus, we studied the psychometric properties of their German versions in a Swiss community sample to evaluate their potential usefulness to screen for mental disorders or relevant mental problems in the community and, relatedly, for low threshold transdiagnostic German-speaking services. METHODS: The sample consisted of 829 citizens of the Swiss canton Bern of age 19-43 years. K10/K6 were validated against mini-international neuropsychiatric interview (M.I.N.I.) diagnoses, questionnaires about health status and quality of life. Receiver operating characteristic (ROC) curve analyses were used to test for general discriminative ability and to select optimal cut-offs of the K10 and K6 for non-psychotic full-blown and subthreshold mental disorders. RESULTS: Cronbach's alphas were 0.81 (K10) and 0.70 (K6). ROC analyses indicated much lower optimal thresholds than earlier suggested; 10 for K10 and 6 for K6. At these thresholds, against M.I.N.I. diagnoses, Cohen's κ (≤0.173) and correspondence rates (≤58.14%) were insufficient throughout. Values were higher at the earlier suggested threshold, yet, at the cost of sensitivity that was below 0.5 in all but three, and below 0.3 in all but six cases. CONCLUSIONS: For the lack of sufficient validity and sensitivity, respectively, our findings suggest that both K10 and K6 would only be of limited use in a low-threshold transdiagnostic mental health service for young adults in Switzerland and likely other German-speaking countries.

Exploring the complex relationships between coping strategies, locus of control and self-esteem with psychopathology: structural equation modeling with a special focus on clinical high-risk of psychosis.

BACKGROUND: Coping strategies, competence, and locus of control (LOC) beliefs are important predictors of mental health (MH). However, research into their complex interactions has produced mixed results. Our study investigated them further in the previously unexplored context of clinical high-risk (CHR) of psychosis. METHODS: We tested six alternative structural equation models in a community sample (N = 523), hypothesizing a mediating role of coping and treating CHR symptoms as (i) an additional mediator or (ii) a specific outcome. Our measurement model included two latent factors of MH: (1) psychopathology (PP), consisting of presence of mental disorders, global and psychosocial functioning, and (2) self-rated health (SRH) status. RESULTS: In the model with the best Akaike Information Criterion and the latent factors as outcome variables, maladaptive coping completely mediated the impact of maladaptive LOC on PP and SRH. Additionally, CHR symptoms partially mediated the effect of maladaptive coping on PP and SRH in the community sample, as long as sex was not entered into the model. In the clinical sample (N = 371), the model did not support a mediation by CHR symptoms, despite significant pathways with both coping and MH outcomes; further, competence beliefs directly impacted SRH. CONCLUSIONS: Coping strategies are an important intervention target for MH promotion, especially in the community. In clinical populations, interventions focusing on coping strategies may improve CHR symptoms, thus potentially supporting better MH, especially SRH. Additionally, due to their mostly cascading effects on MH, improving competence and LOC beliefs may also promote psychological well-being.

The heterogeneity of attenuated and brief limited psychotic symptoms: association of contents with age, sex, country, religion, comorbidities, and functioning.

Introduction: The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. Method: A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. Result: We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. Conclusion: Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability.

Clinical high-risk criteria of psychosis in 8-17-year-old community subjects and inpatients not suspected of developing psychosis.

BACKGROUND: In children and adolescents compared to adults, clinical high-risk of psychosis (CHR) criteria and symptoms are more prevalent but less psychosis-predictive and less clinically relevant. Based on high rates of non-converters to psychosis, especially in children and adolescents, it was suggested that CHR criteria were: (1) Pluripotential; (2) A transdiagnostic risk factor; and (3) Simply a severity marker of mental disorders rather than specifically psychosis-predictive. If any of these three alternative explanatory models were true, their prevalence should differ between persons with and without mental disorders, and their severity should be associated with functional impairment as a measure of severity. AIM: To compare the prevalence and severity of CHR criteria/symptoms in children and adolescents of the community and inpatients. METHODS: In the mainly cross-sectional examinations, 8-17-year-old community subjects (n = 233) randomly chosen from the population register of the Swiss Canton Bern, and inpatients (n = 306) with primary diagnosis of attention-deficit/hyperactivity disorder (n = 86), eating disorder (n = 97), anxiety including obsessive-compulsive disorder (n = 94), or autism spectrum disorder (n = 29), not clinically suspected to develop psychosis, were examined for CHR symptoms/criteria. Positive items of the Structured Interview for Psychosis-Risk Syndromes (SIPS) were used to assess the symptomatic ultra-high-risk criteria, and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) was used to assess the 14 basic symptoms relevant to basic symptom criteria. We examined group differences in frequency and severity of CHR symptoms/criteria using χ 2 tests and nonparametric tests with Cramer's V and Rosenthal's r as effect sizes, and their association with functioning using correlation analyses. RESULTS: The 7.3% prevalence rate of CHR criteria in community subjects did not differ significantly from the 9.5% rate in inpatients. Frequency and severity of CHR criteria never differed between the community and the four inpatient groups, while the frequency and severity of CHR symptoms differed only minimally. Group differences were found in only four CHR symptoms: suspiciousness/persecutory ideas of the SIPS [χ 2 (4) = 9.425; P = 0.051, Cramer's V = 0.132; and Z = -4.281, P < 0.001; Rosenthal's r = 0.184], and thought pressure [χ 2 (4) = 11.019; P = 0.026, Cramer's V = 0.143; and Z = -2.639, P = 0.008; Rosenthal's r = 0.114], derealization [χ 2 (4) = 32.380; P < 0.001, Cramer's V = 0.245; and Z = -3.924, P < 0.001; Rosenthal's r = 0.169] and visual perception disturbances [χ 2 (4) = 10.652; P = 0.031, Cramer's V = 0.141; and Z = -2.822, P = 0.005; Rosenthal's r = 0.122] of the SPI-CY. These were consistent with a transdiagnostic risk factor or dimension, i.e., displayed higher frequency and severity in inpatients, in particular in those with eating, anxiety/obsessive-compulsive and autism spectrum disorders. Low functioning, however, was at most weakly related to the severity of CHR criteria/symptoms, with the highest correlation yielded for suspiciousness/persecutory ideas (Kendall's tau = -0.172, P < 0.001). CONCLUSION: The lack of systematic differences between inpatients and community subjects does not support suggestions that CHR criteria/symptoms are pluripotential or transdiagnostic syndromes, or merely markers of symptom severity.