Disentangling heterogeneity of psychosis expression in the general population: sex-specific moderation effects of environmental risk factors on symptom networks.

BACKGROUND: Psychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called 'symptom network'. Differences in demographics, as well as exposure to adversities and risk factors, may produce substantial heterogeneity in symptom networks, highlighting potential etiological divergence in psychosis risk. METHODS: To explore this idea in a data-driven way, we employed a novel recursive partitioning approach in the 2007 English National Survey of Psychiatric Morbidity (N = 7242). We sought to identify 'network phenotypes' by explaining heterogeneity in symptom networks through potential moderators, including age, sex, ethnicity, deprivation, childhood abuse, separation from parents, bullying, domestic violence, cannabis use, and alcohol. RESULTS: Sex was the primary source of heterogeneity in symptom networks. Additional heterogeneity was explained by interpersonal trauma (childhood abuse and domestic violence) in women and domestic violence, cannabis use, ethnicity in men. Among women, especially those exposed to early interpersonal trauma, an affective loading within psychosis may have distinct relevance. Men, particularly those from minority ethnic groups, demonstrated a strong network connection between hallucinatory experiences and persecutory ideation. CONCLUSION: Symptom networks of psychosis expression in the general population are highly heterogeneous. The structure of symptom networks seems to reflect distinct sex-related adversities, etiologies, and mechanisms of symptom-expression. Disentangling the complex interplay of sex, minority ethnic group status, and other risk factors may help optimize early intervention and prevention strategies in psychosis.

The non-specific nature of mental health and structural brain outcomes following childhood trauma.

BACKGROUND: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure. METHODS: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry. RESULTS: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found. CONCLUSIONS: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

Prevalence of cognitive impairments and strengths in the early course of psychosis and depression.

BACKGROUND: Studies investigating cognitive impairments in psychosis and depression have typically compared the average performance of the clinical group against healthy controls (HC), and do not report on the actual prevalence of cognitive impairments or strengths within these clinical groups. This information is essential so that clinical services can provide adequate resources to supporting cognitive functioning. Thus, we investigated this prevalence in individuals in the early course of psychosis or depression. METHODS: A comprehensive cognitive test battery comprising 12 tests was completed by 1286 individuals aged 15-41 (mean age 25.07, s.d. 5.88) from the PRONIA study at baseline: HC (N = 454), clinical high risk for psychosis (CHR; N = 270), recent-onset depression (ROD; N = 267), and recent-onset psychosis (ROP; N = 295). Z-scores were calculated to estimate the prevalence of moderate or severe deficits or strengths (>2 s.d. or 1-2 s.d. below or above HC, respectively) for each cognitive test. RESULTS: Impairment in at least two cognitive tests was as follows: ROP (88.3% moderately, 45.1% severely impaired), CHR (71.2% moderately, 22.4% severely impaired), ROD (61.6% moderately, 16.2% severely impaired). Across clinical groups, impairments were most prevalent in tests of working memory, processing speed, and verbal learning. Above average performance (>1 s.d.) in at least two tests was present for 40.5% ROD, 36.1% CHR, 16.1% ROP, and was >2 SDs in 1.8% ROD, 1.4% CHR, and 0% ROP. CONCLUSIONS: These findings suggest that interventions should be tailored to the individual, with working memory, processing speed, and verbal learning likely to be important transdiagnostic targets.

Ecological momentary assessment (EMA) combined with unsupervised machine learning shows sensitivity to identify individuals in potential need for psychiatric assessment.

Ecological momentary assessment (EMA), a structured diary assessment technique, has shown feasibility to capture psychotic(-like) symptoms across different study groups. We investigated whether EMA combined with unsupervised machine learning can distinguish groups on the continuum of genetic risk toward psychotic illness and identify individuals with need for extended healthcare. Individuals with psychotic disorder (PD, N = 55), healthy individuals (HC, N = 25) and HC with first-degree relatives with psychosis (RE, N = 20) were assessed at two sites over 7 days using EMA. Cluster analysis determined subgroups based on similarities in longitudinal trajectories of psychotic symptom ratings in EMA, agnostic of study group assignment. Psychotic symptom ratings were calculated as average of items related to hallucinations and paranoid ideas. Prior to EMA we assessed symptoms using the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experience (CAPE) to characterize the EMA subgroups. We identified two clusters with distinct longitudinal EMA characteristics. Cluster 1 (NPD = 12, NRE = 1, NHC = 2) showed higher mean EMA symptom ratings as compared to cluster 2 (NPD = 43, NRE = 19, NHC = 23) (p < 0.001). Cluster 1 showed a higher burden on negative (p < 0.05) and positive (p < 0.05) psychotic symptoms in cross-sectional PANSS and CAPE ratings than cluster 2. Findings indicate a separation of PD with high symptom burden (cluster 1) from PD with healthy-like rating patterns grouping together with HC and RE (cluster 2). Individuals in cluster 1 might particularly profit from exchange with a clinician underlining the idea of EMA as clinical monitoring tool.

Using combined environmental-clinical classification models to predict role functioning outcome in clinical high-risk states for psychosis and recent-onset depression.

BACKGROUND: Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning. AIMS: We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample. METHOD: Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD). RESULTS: Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD. CONCLUSIONS: Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.

Does childhood trauma predict schizotypal traits? A path modelling approach in a cohort of help-seeking subjects.

Schizotypy constitutes a susceptibility to beneficial and deleterious schizotypal traits, ranging from coping mechanisms to schizotypal personality disorder on a psychosis continuum. Growing evidence indicates a relationship between childhood adversity and trauma and schizotypy. However, the exact influence of childhood adversity and trauma on schizotypy and its relation to sex is not sufficiently understood. Therefore, we investigated sex-adjusted connections between childhood adversity and trauma subdomains (emotional/physical/sexual abuse, emotional/physical neglect) and positive (magical ideation, perceptual aberration) as well as negative schizotypy (physical/social anhedonia). In total, 240 outpatients of the Early Detection and Intervention Centre of the University Hospital Cologne were assessed with the Trauma and Distress Scale for childhood adversity and trauma and the Wisconsin Schizotypy Scales for schizotypy. Path analyses were performed to investigate sex-adjusted correlations. The well-fitting path model of the total sample linked emotional abuse to magical ideation (p = 0.03; SE = 0.20) and emotional neglect to social anhedonia (p = 0.01; SE = 0.26). In females, physical abuse predicted magical ideation (p = 0.01; SE = 0.33), while emotional neglect forecasted physical anhedonia (p = 0.03; SE = 0.34) and social anhedonia (p = 0.03; SE = 0.32). In males, sexual abuse predicted perceptive aberration (p = 0.04; SE = 0.19) and emotional abuse forecasted magical ideation (p = 0.03; SE = 0.27). Overall, the significance of sex-specific interrelations between trauma and schizotypy were highlighted. Magical ideation and perceptive aberration occurred prominently in the absence of negative and disorganized schizotypy, thus positive schizotypy could be discussed as a beneficial expression of coping with emotional, physical and sexual abuse. Furthermore, emotional neglect should be addressed particularly to prevent deleterious negative schizotypy in females.Trial registration number (20-1243), date of registration (May 19th 2020), retrospectively registered.

The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study.

BACKGROUND: Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition. METHODS: 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). RESULTS: The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (pfdr < 0.001) and role (pfdr < 0.001) functioning, as well as worse neurocognitive performance in semantic (pfdr < 0.001) and phonological verbal fluency (pfdr < 0.001), short-term verbal memory (pfdr = 0.002) and abstract thinking (pfdr = 0.010), in comparison to FTD-Low group. CONCLUSIONS: Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.

Detailed clinical phenotyping and generalisability in prognostic models of functioning in at-risk populations.

Personalised prediction of functional outcomes is a promising approach for targeted early intervention in psychiatry. However, generalisability and resource efficiency of such prognostic models represent challenges. In the PRONIA study (German Clinical Trials Register: DRKS00005042), we demonstrate excellent generalisability of prognostic models in individuals at clinical high-risk for psychosis or with recent-onset depression, and substantial contributions of detailed clinical phenotyping, particularly to the prediction of role functioning. These results indicate that it is possible that functioning prediction models based only on clinical data could be effectively applied in diverse healthcare settings, so that neuroimaging data may not be needed at early assessment stages.

Relationships between childhood trauma and perceived stress in the general population: a network perspective.

BACKGROUND: Experiences of childhood trauma (CT) are associated with increased psychological vulnerability. Past research suggests that CT might alter stress processing with a subsequent negative impact on mental health. However, it is currently unclear how different domains of CT exert effects on specific subjective experiences of stress during adulthood. METHODS: In the present study, we used network analysis to explore the complex interplay between distinct domains of CT and perceived stress in a large, general-population sample of middle-aged adults (N = 1252). We used a data-driven community-detection algorithm to identify strongly connected subgroups of items within the network. To assess the replicability of the findings, we repeated the analyses in a second sample (N = 862). Combining data from both samples, we evaluated network differences between men (n = 955) and women (n = 1159). RESULTS: Results indicate specific associations between distinct domains of CT and perceived stress. CT domains reflecting a dimension of deprivation, i.e. experiences of neglect, were associated exclusively to a stress network community representing low perceived self-efficacy. By contrast, CT associated with threat, i.e. experiences of abuse, was specifically related to a stress community reflecting perceived helplessness. Our results replicated with high accordance in the second sample. We found no difference in network structure between men and women, but overall a stronger connected network in women. CONCLUSIONS: Our findings emphasize the unique role of distinct domains of CT in psychological stress processes in adulthood, implying opportunities for targeted interventions following distinct domains of CT.

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.

Sex differences in symptomatology of psychosis-risk patients and in prediction of psychosis.

Sex differences may be important for understanding underlying pathophysiological mechanisms and developing effective preventions and treatments of mental disorders. Despite sex differences in the onset of psychosis, patients at clinical high risk for psychosis (CHR) are underinvestigated for sex effects, especially with respect to models for prediction of conversion to psychosis. We studied psychopathological sex differences in referrals to a German early detection service and in its subgroup of converters and examined sex-specific psychopathological prediction models. In 152 male and 90 female referrals (88% at CHR; 35% converters), symptoms assessed with the Structured Interview for Psychosis-Risk Syndromes were investigated for sex differences using effect sizes. Sex-specific prediction models of psychosis were separately generated using Cox regressions with a LASSO operator. We found different small sex effects (0.10 < Rosenthal's r < 0.30) in the referral and in the converter sample. In the referral sample, exclusively, males showed more pronounced symptoms (all negative symptoms incl. reduced stress tolerance, grandiosity, and disorganized communication); in converters, females experienced more pronounced perceptual abnormalities, bizarre thinking, and odd behaviors, while males expressed and experienced emotions to a lower degree. Furthermore, sexes differed in psychosis-predictive symptoms: "suspiciousness" and "disorganized communication" were prominent in prediction of psychosis in males, whereas "trouble with focus and attention" was so in females. While most sex differences in patients attending an early detection service seem to reflect general differences that are not specifically related to psychosis, others might be psychosis-specific. These results can inform the development of more individualized and effective interventions for CHR patients based on more precise sex-specific prediction models.

[Social Anxiety in individuals with clinical high-risk state for psychosis]. / Soziale Ängste im klinischen Hochrisikostadium für Psychosen.

In recent years an increased comorbidity of schizophrenic disorders with anxiety disorders has been reported. Thus, among patients with a disorder from the schizophrenia spectrum, a general anxiety disorder was found in 38.3 % of patients, with 14.9 % of these with social phobia (SP). Especially social anxiety (SA) is of particular importance because it is often associated with depression and can contribute to psychosocial disabilities in patients with psychosis.Anxiety disorders already seem to occur prior to the first psychotic manifestation in the clinical high-risk state (CHR). Therefore, the questions arise as to whether this comorbidity is also dominated by SP in this patient group and, if so, what its consequences are on early detection and prevention of psychotic disorders. To clarify these questions, the present paper provides a systematic review of all published studies on social anxiety (SA) in the CHR.A total of 124 studies were included comprising 1702 CHR individuals, 445 healthy controls, 67 relatives / siblings of patients with psychotic disorders and 95 patients with a psychosis. In the most meaningful study, anxiety disorders were generally highly significant in CHR individuals (51 %) compared to control subjects from the normal population (4 %). Among those with anxiety disorders, 14.4 % suffered from SP compared to 0.36 % in normal controls and thus SP was almost as frequent as the prevalence of this type of anxiety disorders in the schizophrenic spectrum (14.9 %). Also, the degree of SA in CHR individuals (SIAS score = 34.4, SD = 6.11) (SIAS-Score = 22.1, SD = 8.7), measured with the Social Interaction and Anxiety Scale (SIAS) in 9 studies, was almost as high as in psychotic patients (SIAS score = 35.0, SD = 9.56) and healthy controls (SIAS score = 14.,6; SD = 7,28). This degree of SA was also related to the attenuated psychotic symptomatology of the CHR individuals. However, the only study investigating the relationship between SA and a possible transition to a first psychotic manifestation did not reveal any predictive power. The feared psychosocial loss of function, which is already present in CHR, seems to be connected not only to the strong SA, but also to the similarly frequent comorbid depressive disorders.Moreover, one study has already provided some evidence that it is promising to address the SA as well as functional impairments in the CHR through newly developed specialized cognitive behavioural therapies.

The apolipoprotein N-acyl transferase Lnt is dispensable for growth in Acinetobacter species.

Directing the flow of protein traffic is a critical task faced by all cellular organisms. In Gram-negative bacteria, this traffic includes lipoproteins. Lipoproteins are synthesized as precursors in the cytoplasm and receive their acyl modifications upon export across the inner membrane. The third and final acyl chain is added by Lnt, which until recently was thought to be essential in all Gram-negatives. In this report, we show that Acinetobacter species can also tolerate a complete loss-of-function mutation in lnt. Absence of a fully functional Lnt impairs modification of lipoproteins, increases outer membrane permeability and susceptibility to antibiotics, and alters normal cellular morphology. In addition, we show that loss of lnt triggers a global transcriptional response to this added cellular stress. Taken together, our findings provide new insights on and support the growing revisions to the Gram-negative lipoprotein biogenesis paradigm.

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness.

Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (NROP = 61, NROD = 100, NCHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. CLINICAL TRIAL REGISTRY NAME: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042.

Alterations of Functional Connectivity Dynamics in Affective and Psychotic Disorders.

BACKGROUND: Patients with psychosis and patients with depression exhibit widespread neurobiological abnormalities. The analysis of dynamic functional connectivity (dFC) allows for the detection of changes in complex brain activity patterns, providing insights into common and unique processes underlying these disorders. METHODS: We report the analysis of dFC in a large sample including 127 patients at clinical high risk for psychosis, 142 patients with recent-onset psychosis, 134 patients with recent-onset depression, and 256 healthy control participants. A sliding window-based technique was used to calculate the time-dependent FC in resting-state magnetic resonance imaging data, followed by clustering to reveal recurrent FC states in each diagnostic group. RESULTS: We identified 5 unique FC states, which could be identified in all groups with high consistency (mean r = 0.889 [SD = 0.116]). Analysis of dynamic parameters of these states showed a characteristic increase in the lifetime and frequency of a weakly connected FC state in patients with recent-onset depression (p < .0005) compared with the other groups and a common increase in the lifetime of an FC state characterized by high sensorimotor and cingulo-opercular connectivities in all patient groups compared with the healthy control group (p < .0002). Canonical correlation analysis revealed a mode that exhibited significant correlations between dFC parameters and clinical variables (r = 0.617, p < .0029), which was associated with positive psychosis symptom severity and several dFC parameters. CONCLUSIONS: Our findings indicate diagnosis-specific alterations of dFC and underline the potential of dynamic analysis to characterize disorders such as depression and psychosis and clinical risk states.

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.

Disentangling the impact of childhood abuse and neglect on depressive affect in adulthood: A machine learning approach in a general population sample.

BACKGROUND: Different types of childhood maltreatment (CM) are key risk factors for psychopathology. Specifically, there is evidence for a unique role of emotional abuse in affective psychopathology in children and youth; however, its predictive power for depressive symptomatology in adulthood is still unknown. Additionally, emotional abuse encompasses several facets, but the strength of their individual contribution to depressive affect has not been examined. METHOD: Here, we used a machine learning (ML) approach based on Random Forests to assess the performance of domain scores and individual items from the Childhood Trauma Questionnaire (CTQ) in predicting self-reported levels of depressive affect in an adult general population sample. Models were generated in a training sample (N = 769) and validated in an independent test sample (N = 466). Using state-of-the-art methods from interpretable ML, we identified the most predictive domains and facets of CM for adult depressive affect. RESULTS: Models based on individual CM items explained more variance in the independent test sample than models based on CM domain scores (R2 = 7.6 % vs. 6.4 %). Emotional abuse, particularly its more subjective components such as reactions to and appraisal of the abuse, emerged as the strongest predictors of adult depressive affect. LIMITATIONS: Assessment of CM was retrospective and lacked information on timing and duration. Moreover, reported rates of CM and depressive affect were comparatively low. CONCLUSIONS: Our findings corroborate the strong role of subjective experience in CM-related psychopathology across the lifespan that necessitates greater attention in research, policy, and clinical practice.

Transdiagnostic Psychopathology in a Help-Seeking Population of an Early Recognition Center for Mental Disorders: Protocol for an Experience Sampling Study.

BACKGROUND: Prevention in psychiatry provides a promising way to address the burden of mental illness. However, established approaches focus on specific diagnoses and do not address the heterogeneity and manifold potential outcomes of help-seeking populations that present at early recognition services. Conceptualizing the psychopathology manifested in help-seeking populations from a network perspective of interacting symptoms allows transdiagnostic investigations beyond binary disease categories. Furthermore, modern technologies such as smartphones facilitate the application of the Experience Sampling Method (ESM). OBJECTIVE: This study is a combination of ESM with network analyses to provide valid insights beyond the established assessment instruments in a help-seeking population. METHODS: We will examine 75 individuals (aged 18-40 years) of the help-seeking population of the Cologne early recognition center. For a maximally naturalistic sample, only minimal exclusion criteria will be applied. We will collect data for 14 days using a mobile app to assess 10 transdiagnostic symptoms (ie, depressive, anxious, and psychotic symptoms) as well as distress level 5 times a day. With these data, we will generate average group-level symptom networks and personalized symptom networks using a 2-step multilevel vector autoregressive model. Additionally, we will explore associations between symptom networks and sociodemographic, risk, and resilience factors, as well as psychosocial functioning. RESULTS: The protocol was designed in February 2020 and approved by the Ethics Committee of the University Hospital Cologne in October 2020. The protocol was reviewed and funded by the Köln Fortune program in September 2020. Data collection began in November 2020 and was completed in November 2021. Of the 258 participants who were screened, 93 (36%) fulfilled the inclusion criteria and were willing to participate in the study. Of these 93 participants, 86 (92%) completed the study. The first results are expected to be published in 2022. CONCLUSIONS: This study will provide insights about the feasibility and utility of the ESM in a help-seeking population of an early recognition center. Providing the first explorative phenotyping of transdiagnostic psychopathology in this population, our study will contribute to the innovation of early recognition in psychiatry. The results will help pave the way for prevention and targeted early intervention in a broader patient group, and thus, enable greater intended effects in alleviating the burden of psychiatric disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35206.

(Attenuated) hallucinations join basic symptoms in a transdiagnostic network cluster analysis.

Hallucinations are considered characteristic symptoms of psychosis and part of the 'psychosis superspectrum' of the Hierarchical Taxonomy Of Psychopathology (HiTOP) initiative. To gain insight into their psychopathological relevance, we studied their dimensional placement within a single dense transdiagnostic network constituting of basic symptoms as well as of attenuated and frank psychotic, and related symptoms. Newman's modularity analysis was used to detect symptom clusters in an earlier generated network (Jimeno, N., et al., 2020. Main symptomatic treatment targets in suspected and early psychosis: New insights from network analysis. Schizophr. Bull. 46, 884-895. https://doi.org/10.1093/schbul/sbz140). The constituting 86 symptoms were assessed with the Schizophrenia Proneness Instrument, Adult version (SPI-A), the Structured Interview for Psychosis-Risk Syndromes (SIPS), and the Positive And Negative Syndrome Scale (PANSS) in three adult samples of an early detection service: clinical high-risk (n = 203), first-episode psychosis (n = 153), and major depression (n = 104). Three clusters were detected: "subjective disturbances", "positive symptoms and behaviors", and "negative and anxious-depressive symptoms". The predominately attenuated hallucinations of both SIPS and PANSS joined the basic symptoms in "subjective disturbances", whereas other positive symptoms entered "positive symptoms and behaviors". Our results underline the importance of insight in separating true psychotic hallucinations from other hallucinatory experiences that, albeit phenomenologically similar are still experienced with some insight, i.e., are present in an attenuated form. We conclude that, strictly, hallucinations held with any degree of insight should not be used to diagnose transition to or presence of frank psychoses and, relatedly, to justify antipsychotic medication.

Relationships between global functioning and neuropsychological predictors in subjects at high risk of psychosis or with a recent onset of depression.

OBJECTIVE: Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational functioning, and cognition. METHODS: 102 CHR subjects and 110 patients with recent onset depression (ROD) were recruited. Global assessment of functioning (GAF) related to symptoms (GAF-S) and disability (GAF-D). and global functioning social (GF-S) and role (GF-R), at baseline and of the previous month and year, and a set of neurocognitive measures, were used for classification and regression. RESULTS: Neurocognitive measures related to GF-R at baseline (r = 0.20, p = 0.004), GF-S at present (r = 0.14, p = 0.042) and of the past year (r = 0.19, p = 0.005), for GAF-F of the past month (r = 0.24, p < 0.001) and GAF-D of the past year (r = 0.28, p = 0.002). Classification reached values of balanced accuracy of 61% for GF-R and GAF-D. CONCLUSION: We found that neurocognition was related to psychosocial functioning. More specifically, a deficit in executive functions was associated to poor social and occupational functioning.