Exploring the interplay between psychotic experiences, functional somatic symptoms and health anxiety in childhood and adolescence - A longitudinal cohort study.

BACKGROUND: Similarities exist between contemporary explanatory models underlying psychosis development, functional somatic symptoms, and health anxiety. The current study aimed to examine the potential interplay between psychotic experiences (and alternate measures of anomalous self-experiences and aberrant attribution of salience) and functional somatic symptoms on the outcome of health anxiety in youths. METHODS: In a prospective general-population birth cohort, the Copenhagen Child Cohort 2000 (CCC2000), data from two time-points were available for 1122 individuals. We assessed the associations between psychotic experiences and functional somatic symptoms with health anxiety both cross-sectionally at ages 11- and 16-years, and longitudinally from age 11 to 16. Further, we examined if there was an interaction between these two domains on the outcome of health anxiety using the interaction contrast ratio. RESULTS: Functional somatic symptoms and psychotic experiences were strongly cross-sectionally associated with health anxiety at both ages 11 and 16, even after adjustment for general psychopathology. In the longitudinal analyses, functional somatic symptoms, and psychotic experiences at age 11 were not individually associated with health anxiety at age 16 but having both functional somatic symptoms and psychotic experiences was: odds ratio 3.90, 95%CI 1.7-8.9, with suggestion of evidence for interaction beyond the additive effects. This association was attenuated after adjustment for general psychopathology: odds ratio 2.6, 95 % CI 1.0-6.4. CONCLUSION: The strong associations between the domains support the idea of possible overlapping mechanisms underlying psychotic experiences, functional somatic symptoms, and health anxiety.

The relationship between childhood trauma, psychotic symptoms, and cognitive schemas in patients with schizophrenia, their siblings, and healthy controls: results from the EU-GEI study.

BACKGROUND: The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms. METHODS: Seven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale. RESULTS: Patients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood emotional abuse and neglect were more common in siblings than controls. CT was related to negative cognitive schemas toward self/others in patients, siblings, and controls. We found that negative schemas about self-mediated the relationship between emotional abuse and thought withdrawal and thought broadcasting. Approximately 33.9% of the variance in these symptoms was explained by the mediator. It also mediated the relationship between sexual abuse and persecutory delusions in SCZ. CONCLUSIONS: Our findings suggest that childhood abuse and neglect are more common in patients with schizophrenia than their siblings and healthy controls, and have different impacts on clinical domains which we searched. The relationship between CT and positive symptoms seems to be mediated by negative cognitive schemas about self in schizophrenia.

Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study.

BACKGROUND: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. METHODS: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. RESULTS: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. CONCLUSIONS: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

The Frequency of Design Studies Targeting People With Psychotic Symptoms and Features in Mental Health Care Innovation: Secondary Analysis of a Systematic Review.

This study examined and reflected on the frequency of people with psychotic symptoms and features as the target population in design studies for mental health care innovation.

Population Salutogenesis-The Future of Psychiatry?

This Viewpoint discusses the potential of salutogenesis, or emphasis on health- and wellness-promoting practices, as a public health approach to mitigate increasing levels of mental illness and distress.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding.

The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRSN), in interaction with bullying, parental bonding, and childhood adversity. Data were derived from a general population adolescent and young adult twin cohort. The final sample consisted of 202 monozygotic and 436 dizygotic twins and 319 twin pairs. The Short Eysenck Personality questionnaire was used to measure neuroticism. PRSN was trained on the results from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB) cohorts, yielding two different PRSN. Multilevel mixed-effects models were used to analyze the main and interacting associations of PRSN, childhood adversity, bullying, and parental bonding style with neuroticism. We found no evidence of gene-environment correlation. PRSN thresholds of .005 and .2 were chosen, based on GPC and UKB datasets, respectively. After correction for confounders, all the individual variables were associated with the expression of neuroticism: both PRSN from GPC and UKB, childhood adversity, maternal bonding, paternal bonding, and bullying in primary school and secondary school. However, the results indicated no evidence for gene-environment interaction in this cohort. These results suggest that genetic vulnerability on the one hand and negative life events (childhood adversity and bullying) and positive life events (optimal parental bonding) on the other represent noninteracting pathways to neuroticism.

Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation.

BACKGROUND: Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. STUDY DESIGN: We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. STUDY RESULTS: Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. CONCLUSIONS: We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other's effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia.

Prevalence, time trends, and correlates of major depressive episode and other psychiatric conditions among young people amid major social unrest and COVID-19 in Hong Kong: a representative epidemiological study from 2019 to 2022.

Background: Hong Kong is among the many populations that has experienced the combined impacts of social unrest and the COVID-19 pandemic. Despite concerns about further deteriorations in youth mental health globally, few epidemiological studies have been conducted to examine the prevalence and correlates of major depressive episode (MDE) and other major psychiatric disorders across periods of population-level changes using diagnostic interviews. Methods: We conducted a territory-wide household-based epidemiological study from 2019 to 2022 targeting young people aged 15-24 years. MDE, generalised anxiety disorder (GAD), panic disorder (PD), and bipolar disorder (BD) were assessed using the Composite International Diagnostic Interview-Screening Scales in 3340 young people. Psychotic disorders were assessed by experienced psychiatrists according to the DSM. Help-seeking patterns were also explored. Findings: 16.6% had any mental disorder (13.7% 12-month MDE, 2.3% BD, 2.1% GAD, 1.0% PD, 0.6% psychotic disorder). The prevalence of MDE increased from 13.2% during period 1 (May 2019-June 2020) to 18.1% during period 2 (July-December 2020), followed by 14.0% during period 3 (January-June 2021) and 13.2% during period 4 (July 2021-June 2022). Different stressors uniquely contributed to MDE across periods: social unrest-related stressors during period 1, COVID-19 stressors during period 2, and personal stressors during periods 3-4. Lower resilience, loneliness, frequent nightmares, and childhood adversity were consistently associated with MDE. Compared to other conditions, those with MDE showed the lowest service utilisation rate (16.7%). Perceiving services to "cost too much" and "talked to friends or relatives instead" were among the major reasons for not seeking help. MDE was also significantly associated with poorer functioning and health-related quality of life. Interpretation: MDE can be sensitive to population-level changes, although its persistently elevated prevalence across the study period is of concern. Efforts to mitigate their impacts on youth mental health alongside personal risk factors are needed. Further work is required to increase the availability and acceptability of youth-targeted mental health services. Funding: Food and Health Bureau (HKSAR Government).

Gender differences in the associations between childhood adversity and psychopathology in the general population.

PURPOSE: To explore gender differences of the associations between childhood adversity (CA) subtypes and psychiatric symptoms in the general population. METHODS: Data of 791 participants were retrieved from a general population twin cohort. The Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire were used to assess overall psychopathology with nine symptom domains scores and total CA with exposure to five CA subtypes, respectively. The associations between CA and psychopathology were analyzed in men and women separately and were subsequently compared. RESULTS: Total CA was associated with total SCL-90 and all symptom domains without significant gender differences. However, the analyses of CA subtypes showed that the association between emotional abuse and total SCL-90 was stronger in women compared to men [χ2(1) = 4.10, P = 0.043]. Sexual abuse was significantly associated with total SCL-90 in women, but emotional neglect and physical neglect were associated with total SCL-90 in men. Exploratory analyses of CA subtypes and SCL-90 subdomains confirmed the pattern of gender-specific associations. In women, emotional abuse was associated with all symptom domains, and sexual abuse was associated with all except phobic anxiety and interpersonal sensitivity. In men, emotional neglect was associated with depression, and physical neglect was associated with phobic anxiety, anxiety, interpersonal sensitivity, obsessive-compulsive, paranoid ideation, and hostility subdomains. CONCLUSION: CA is a trans-syndromal risk factor regardless of gender. However, differential associations between CA subtypes and symptom manifestation might exist. Abuse might be particularly associated with psychopathology in women, whereas neglect might be associated with psychopathology in men.

The use of experiential knowledge in the role of a psychiatrist.

Introduction: There is increasing interest in the use of experiential knowledge and the development of experiential expertise in mental health. Yet, little is known about how best to use this expertise in the role of a psychiatrist. Objective: This study aims to gain insight into the concerns of psychiatrists using their lived experiences with mental health distress as a source of knowledge for patients, colleagues and themselves. Materials and method: Eighteen psychiatrists with lived experience as patients in mental health care were interviewed with a semi-structured questionnaire. The interviews were analyzed using qualitative narrative thematic analysis. Findings: The majority of the respondents use their lived experience implicitly in the contact with patients, which makes the contact more equal and strengthens the treatment relationship. When explicitly using experiential knowledge in the contact with patients, thought should be given at forehand to its purpose, timing and dosage. Recommendations are that the psychiatrist should be able to reflect on his/her lived experience from a sufficient distance and should take patient factors into account. When working in a team, it is advisable to discuss the use of experiential knowledge in advance with the team. An open organizational culture facilitates the use of experiential knowledge and safety and stability in the team are vital. Current professional codes do not always offer the space to be open. Organizational interests play a role, in the degree of self-disclosure as it can lead to conflict situations and job loss. Respondents unanimously indicated that the use of experiential knowledge in the role of a psychiatrist is a personal decision. Self-reflection and peer supervision with colleagues can be helpful to reflect on different considerations with regard to the use of experiential knowledge. Conclusion: Having personal lived experiences with a mental disorder affects the way psychiatrists think about and performs the profession. The perception of psychopathology becomes more nuanced and there seems to be an increased understanding of the suffering. Even though harnessing experiential knowledge makes the doctor-patient relationship more horizontal it remains unequal because of the difference in roles. However, if adequately used, experiential knowledge can enhance the treatment relationship.

The Involvement of Service Users and People With Lived Experience in Mental Health Care Innovation Through Design: Systematic Review.

BACKGROUND: Mental health care faces challenges that not only necessitate innovation but also require the involvement of service users and people with lived experience in developing and evaluating mental health care services. As the development of digital interventions is becoming more prevalent, design approaches are increasingly finding their way into mental health. There is evidence that these approaches can successfully integrate user experience into mental health services. However, there is no clear overview of the studies conducted and the lessons learned concerning the involvement of service users and people with lived experience. OBJECTIVE: In this systematic review, we aimed to provide an overview of the involvement of service users and people with lived experience in mental health care services through design approaches and to synthesize the advantages of design approaches in mental health care. METHODS: The following 5 databases were searched for relevant abstracts: PsycINFO, PubMed, Web of Science, Scopus, and Embase. In addition, 2 health design journal archives, Design for Health and The Journal of Health Design, were searched. To categorize the results, we collected the reported added value from the included articles and conducted a thematic synthesis in which the themes were developed from the retrieved data. The themes were discussed, revised, and checked until saturation was achieved. RESULTS: We included and categorized 33 papers. Most studies involved service users, primarily adults, and used various design approaches. Most of these studies aimed to design or evaluate digital interventions. Service users and people with lived experience were involved in different roles but never as decision makers. Studies that used co-design approaches exhibited the highest levels of involvement. Various added values were reported, including tailoring and testing interventions and digital interventions, improving engagement and collaboration, gathering the needs of stakeholders, and empowering participants as resourceful actors. The challenges reported were maintaining participants' continued participation throughout the study, managing the iterative nature of design, providing a safe space, balancing insights from design and medical science, and navigating design processes in medical environments. CONCLUSIONS: This systematic review provides an overview of the studies that used design approaches to involve service users and people with lived experience in mental health care innovation. Design approaches have advantages in mental health care innovation, offering added value and having manageable challenges. Future studies using design approaches in mental health care should involve participants as partners and decision makers and report on collaboration in a systematic and clear manner.

Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.

BACKGROUND: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. METHODS: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. FINDINGS: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. INTERPRETATION: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries.

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study.

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood.

Context v. algorithm: evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis.

BACKGROUND: A transdiagnostic and contextual framework of 'clinical characterization', combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis. METHODS: Prediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions. RESULTS: Any prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model. CONCLUSION: A transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology.

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

BACKGROUND: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. METHODS: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. RESULTS: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). CONCLUSIONS: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.

Clinician and patient perspectives on the ontology of mental disorder: a qualitative study.

Background: Psychiatry may face an "identity crisis" regarding its very foundations. The lack of consensus regarding the theoretical grounds of psychiatry as a discipline has its epicenter in the discussion about the Diagnostic and Statistical Manual (DSM). A growing number of academics considers the manual broken and a growing number of patients voice concern. Despite the huge body of critique, 90% of Randomized Trials are based on DSM definitions of mental disorder. Therefore, the question regarding the ontology of mental disorder remains: what is a mental disorder, exactly? Aims: We aim to identify ontologies that live among patients and clinicians, evaluate the degree of consistency and coherence between clinician and patient views and contribute to the establishment of a novel ontological paradigm of mental disorder that is aligned with patients' and clinicians' perspectives. Method: Eighty participants (clinicians/patients/clinicians with lived experience) were interviewed using a semi-structured interview, exploring their ideas on the ontology of mental disorder. This question was approached from different angles which led to comprising the interview schedule into different topics: "concept of disorder," "representation by DSM," "what is treated," "what is recovered," and "the right outcome measure." Interviews were transcribed and analyzed using inductive Thematic Analysis. Results: From all subthemes and main themes, a typology was constructed in which six, not necessarily mutually exclusive, ontological domains were identified: mental disorder as (1) disease, (2) functional impairment, (3) loss of adaptation, (4) existential problem, (5) highly subjective phenomenon, and (6) deviation from social norms. Common ground for the sample groups was that mental disorder is about functional impairment. Although about a fourth of sample clinicians holds an ontological concept of disease, only a small percentage of patients and none of the clinicians with lived experience adhered to an ontological concept of disease. The sample clinicians most often understand mental disorder to be a highly subjective phenomenon, and individuals with lived experience (patients and clinicians) most often understand mental (dis)order to be adaptational in nature: an (im)balance of burden in relation to strengths, skills, and recourses. Conclusion: The ontological palette is more diverse than what is taught about mental disorder in dominant scientific and educational discourse. There is a need to diversify the current, dominant ontology and make room for other ontologies. Investment is required in the development, elaboration and coming of age of these alternative ontologies, allowing them to reach their full potential and act as drivers of a landscape of promising novel scientific and clinical approaches.

Adjusting for population stratification in polygenic risk score analyses: a guide for model specifications in the UK Biobank.

The current study was conducted to provide a general guidance for model specifications in polygenic risk score (PRS) analyses of the UK Biobank, such as adjusting for covariates (i.e. age, sex, recruitment centers, and genetic batch) and the number of principal components (PCs) that need to be included. To cover behavioral, physical and mental health outcomes, we evaluated three continuous outcomes (BMI, smoking, drinking) and two binary outcomes (Major Depressive Disorder and educational attainment). We applied 3280 (656 per phenotype) different models including different sets of covariates. We evaluated these different model specifications by comparing regression parameters such as R2, coefficients, and P values, as well as ANOVA tests. Findings suggest that only up to three PCs appears to be sufficient for controlling population stratification for most outcomes, whereas including other covariates (particularly age and sex) appears to be more essential for model performance.