Search

The aim of this study was to examine the neurocognitive deficits associated with the first episode of major depressive disorder (recent onset depression, ROD) in adolescents as compared to adult patients. Cross-sectional neurocognitive data from the baseline assessments of the PRONIA study with N = 650 (55.31% females) were analyzed. Based on a principal component analysis of eleven neurocognitive tests, we constructed an overall neurocognitive performance (NP) score. We examined mean score differences in NP between the groups of healthy controls (HC) and ROD and between adolescents (15-21 years) and adults (22-40 years) within a GLM approach. This accounts for unbalanced data with focus on interaction effects while controlling for effects of medication and educational years. Our results show lower NP for the ROD as compared to the HC group (d = - 0.29, p = .046) and lower NP for the adolescent group as compared to the adult group (d = - 0.29; p < .039). There was no interaction between these two group effects (F = 1.11; p = .29). Our findings suggest that the detrimental effect of ROD on neurocognitive functioning is comparable in adolescent and adult patients, since lower scores in adolescent patients are explained by effects of age and education. Neurocognitive impairment is an under addressed issue in clinical treatment guidelines for adolescent MDD. We suggest efficient monitoring in clinical practice by using an aggregate of the Digit Symbol Substitution Test and the Trail Making Test B, which highly correlated with the overall score of NP (r = 0.82)., (© 2024. The Author(s).)

Background: Chronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes, reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in people with enduring illness, but few have explored inflammatory changes. We sought to identify an inflammatory signal and the associated brain function underlying anhedonia among young people with recent-onset psychosis and recent-onset depression., Methods: Resting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from 108 (mean [SD] age = 26.2 [6.2] years; female = 50) participants with recent-onset psychosis (n = 53) and recent-onset depression (n = 55) from the European Union/Seventh Framework Programme-funded PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Time series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and a functional connectivity model were developed to classify participants into an anhedonic group or a normal hedonic group., Results: A repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic recent-onset psychosis/recent-onset depression groups with a balanced accuracy of 63.9% and an area under the curve of 0.61. The functional connectivity model produced a balanced accuracy of 55.2% and an area under the curve of 0.57. Anhedonic group assignment was driven by higher levels of interleukin 6, S100B, and interleukin 1 receptor antagonist and lower levels of interferon gamma, in addition to connectivity within the precuneus and posterior cingulate., Conclusions: We identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Altered hippocampal morphology and metabolic pathology, but also hippocampal circuit dysfunction, are established phenomena seen in psychotic disorders. Thus, we tested whether hippocampal subfield volume deficits link with deviations in glucose metabolism commonly seen in early psychosis, and whether the glucose parameters or subfield volumes change during follow-up period using one-year longitudinal study design of 78 first-episode psychosis patients (FEP), 48 clinical high-risk patients (CHR) and 83 controls (CTR). We also tested whether hippocampal morphology and glucose metabolism relate to clinical outcome. Hippocampus subfields were segmented with Freesurfer from 3T MRI images and parameters of glucose metabolism were determined in fasting plasma samples. Hippocampal subfield volumes were consistently lower in FEPs, and findings were more robust in non-affective psychoses, with strongest decreases in CA1, molecular layer and hippocampal tail, and in hippocampal tail of CHRs, compared to CTRs. These morphometric differences remained stable at one-year follow-up. Both non-diabetic CHRs and FEPs had worse glucose parameters compared to CTRs at baseline. We found that, insulin levels and insulin resistance increased during the follow-up period only in CHR, effect being largest in the CHRs converting to psychosis, independent of exposure to antipsychotics. The worsening of insulin resistance was associated with deterioration of function and symptoms in CHR. The smaller volume of hippocampal tail was associated with higher plasma insulin and insulin resistance in FEPs, at the one-year follow-up. Our longitudinal study supports the view that temporospatial hippocampal subfield volume deficits are stable near the onset of first psychosis, being more robust in non-affective psychoses, but less prominent in the CHR group. Specific subfield defects were related to worsening glucose metabolism during the progression of psychosis, suggesting that hippocampus is part of the circuits regulating aberrant glucose metabolism in early psychosis. Worsening of glucose metabolism in CHR group was associated with worse clinical outcome measures indicating a need for heightened clinical attention to metabolic problems already in CHR., (© 2024. The Author(s).)

Background: Birth cohort studies have shown that adverse childhood experiences (ACEs) are associated with all-cause mortality. The effect of ACEs on premature mortality among working-age people is less clear and may differ between the genders., Objective: In this prospective population study, we investigated the association of ACEs with all-cause mortality in a working-age population., Participants and Methods: In a representative Finnish population study, Health 2000, individuals aged 30 to 64 years were interviewed in 2000, and their deaths were registered until 2020. At baseline, the participants (n = 4981, 2624 females) completed a questionnaire that included 11 questions on ACEs and questions on tobacco smoking, alcohol abuse, self-reported health and sufficiency of income. All-cause mortality was analysed by Cox regression analysis., Results: Of the ACEs, financial difficulties, parental unemployment and individual's own chronic illness were associated with mortality. High number (4+) of ACEs was significantly associated with all-cause mortality in females (HR 2.11, p < 0.001), not in males. Poor health behaviour, self-reported health and low income were the major predictors of mortality in both genders. When the effects of these factors were controlled, childhood family conflicts associated with mortality in both genders., Conclusions: Among working-age people, females seem to be sensitive to the effects of numerous adverse childhood experiences, exhibiting higher premature all-cause mortality. Of the individual ACEs, family conflicts may increase risk of premature mortality in both genders. The effect of ACEs on premature mortality may partly be mediated via poor adult health behaviour and low socioeconomic status., What Is Already Known: In birth cohort studies, adverse childhood experiences (ACEs) have been associated with all-cause mortality. In working-age people, the association of ACEs with premature mortality is less clear and may differ between the genders., What This Study Adds: In working-age people, high number of ACEs associate with all-cause premature mortality in females, not in males. The effect of ACEs on premature mortality may partly be mediated via poor adult health behaviour, self-reported health and low socioeconomic status., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Timely outpatient follow-up and readmission after discharge are common quality indicators in psychiatric care, but their association varies in previous research. We aimed to examine whether the impact of outpatient follow-up and other factors on readmission risk evolves over time in people with non-affective psychotic disorder (NAP)., Methods: The Finnish Quality of Care Register includes all people diagnosed with NAP since January 2010. Here, we followed patients with a hospital discharge between 2017 and 2021 until readmission, death, or up to 365 days. Time of the first outpatient follow-up appointment, length of stay (LOS), number of previous hospitalizations, psychosis diagnosis, substance use disorder (SUD), residential status, economic activity, gender, age, year, and region were included. Follow-up time was divided into five periods: week 1, weeks 2-4, weeks 5-13, weeks 14-25, and weeks 26-52, and each period was analyzed separately with Cox regression., Results: Of the 29 858 discharged individuals, 54.1% had an outpatient follow-up within a week. A total of 10 623 (35.6%) individuals were readmitted. Short LOS increased the readmission risk in the first four weeks, whereas lack of outpatient follow-up raised the risk (adjusted HRs between 1.15 (95% CI 1.04-1.26) and 1.53 (1.37-1.71) in weeks 5-52. The number of previous hospitalizations remained a consistent risk factor throughout the follow-up, while SUD increased risk after 4 weeks and living without family after 13 weeks., Conclusions: Risk factors of readmission vary over time. These temporal patterns must be considered when developing outpatient treatment programs.

The Finnish Quality of Psychosis Care Register assesses nonaffective psychosis (NAP) care, acknowledging treatment outside specialized psychiatric services. This approach, while providing a holistic view, raises concerns about diagnostic inaccuracies. Here, we studied situations where the register-based diagnosis might be inaccurate, and whether the first episode can be reliably identified using a 14-year wash-out period. People with first register-based NAP (ICD-10 F20-F29) between years 2010 and 2018 and without NAP diagnoses in 1996-2009 were identified from the Care Register for Health Care. A diagnosis of NAP was deemed unreliable before age 7, when dementia preceded NAP diagnosis, and when a NAP diagnosis had been assigned at admission or during psychiatric hospitalization but was not confirmed by discharge diagnosis. Despite a 14-year follow-back the first register diagnosis may miss the first treatment episode in older patients. Register-based studies on psychotic disorders should pay attention to exclusion criteria and to the definition of treatment onset., (© 2024. The Author(s).)

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 (N ROP  = 79, N ROD  = 30, N CHR  = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (N ROP  = 61, N ROD  = 100, N CHR  = 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 (BAC impaired  = 58.5%; BAC spared  = 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&#95;web/ . Clinical trial registry number: DRKS00005042., (© 2023. The Author(s).)

Clinical and neuroimaging data has been increasingly used in recent years to disentangle heterogeneity of treatment response to cognitive training (CT) and predict which individuals may achieve the highest benefits. CT has small to medium effects on improving cognitive and social functioning in recent onset psychosis (ROP) patients, who show the most profound cognitive and social functioning deficits among psychiatric patients. We employed multivariate pattern analysis (MVPA) to investigate the potential of cognitive data to predict social functioning improvement in response to 10 h of CT in patients with ROP. A support vector machine (SVM) classifier was trained on the naturalistic data of the Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study sample to predict functioning in an independent sample of 70 ROP patients using baseline cognitive data. PRONIA is a part of a FP7 EU grant program that involved 7 sites across 5 European countries, designed and conducted with the main aim of identifying (bio)markers associated with an enhanced risk of developing psychosis in order to improve early detection and prognosis. Social functioning was predicted with a balanced accuracy (BAC) of 66.4% (Sensitivity 78.8%; Specificity 54.1%; PPV 60.5%; NPV 74.1%; AUC 0.64; P = 0.01). The most frequently selected cognitive features (mean feature weights > ± 0.2) included the (1) correct number of symbol matchings within the Digit Symbol Substitution Test, (2) the number of distracting stimuli leading to an error within 300 and 200 trials in the Continuous Performance Test and (3) the dynamics of verbal fluency between 15 and 30 s within the Verbal Fluency Test, phonetic part. Next, the SVM classifier generated on the PRONIA sample was applied to the intervention sample, that obtained 54 ROP patients who were randomly assigned to a social cognitive training (SCT) or treatment as usual (TAU) group and dichotomized into good (GF-S ≥ 7) and poor (GF-S < 7) functioning patients based on their level of Global Functioning-Social (GF-S) score at follow-up (FU). By applying the initial PRONIA classifier, using out-of-sample cross-validation (OOCV) to the sample of ROP patients who have undergone the CT intervention, a BAC of 59.3% (Sensitivity 70.4%; Specificity 48.1%; PPV 57.6%; NPV 61.9%; AUC 0.63) was achieved at T0 and a BAC of 64.8% (Sensitivity 66.7%; Specificity 63.0%; PPV 64.3%; NPV 65.4%; AUC 0.66) at FU. After SCT intervention, a significant improvement in predicted social functioning values was observed in the SCT compared to TAU group (P ≤0.05; ES[Cohens' d] = 0.18). Due to a small sample size and modest variance of social functioning of the intervention sample it was not feasible to predict individual response to SCT in the current study. Our findings suggest that the use of baseline cognitive data could provide a robust individual estimate of future social functioning, while prediction of individual response to SCT using cognitive data that can be generated in the routine patient care remains to be addressed in large-scale cognitive training trials., Competing Interests: Declaration of Competing Interest This study was supported by EU-FP7 project PRONIA (Personalized Prognostic Tools for Early Psychosis Management) under the Grant Agreement No° 602152 (PI: NK), NARSAD Young Investigator Award of the Brain & Behavior Research Foundation No° 28474 (PI: LK-I) and LMU excellent (LKI). NK, JK and RKRA are currently honorary speakers for Otsuka/Lundbeck. RU received grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion. C Pantelis was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (1105825), an aNHMRC L3 Investigator Grant (1196508), and NHMRC-EU grant (1075379). SSH is supported by NIH National Institute of Mental Health, grant T32MH122394. The remaining authors including members of the PRONIA consortium have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Adverse childhood experiences (ACEs) associate with various mental disorders, including personality features. Our understanding of how ACEs influence alexithymia features in the general population is limited. In a prospective population setting, we studied whether ACEs associate with alexithymia, and the role of sex and emotional symptoms in this association. Methods: In a Finnish population-based prospective study, 3,142 individuals aged between 30 and 64 years completed eleven ACE questions and the Toronto Alexithymia Scale in 2000 and 2011, and the Hopkins Symptoms Checklist in 2011. The effect of ACEs on alexithymia and its subdomains - difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT) in 2000 and 2011 - was analysed using repeated measures ANOVA. Results: The number of ACEs and their main component, childhood social disadvantage, associated positively with total alexithymia scores and its subdomains DIF and DDF, and negatively with EOT. After controlling for the effect of depression and anxiety, the strength of these associations was reduced, but the effect of social disadvantage on DIF and EOT remained significant in females. Childhood family conflicts associated positively with DIF in males and negatively with EOT in females. Additionally, maternal mental problems associated positively with DIF and DDF in females. Discussion: In the general population, ACEs, particularly social disadvantage, are associated with adult alexithymia features. Alexithymia features, detectable from youth, may predispose individuals to emotional disturbances caused by childhood adversities. The effect of family conflicts and maternal mental problems on alexithymia features varies between sexes.

Background: Formal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level., Methods: Two hundred thirty-three individuals with recent-onset psychosis were drawn from the multisite European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multiband fractional amplitude of low frequency fluctuations, gray matter volume and white matter volume data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up., Results: Cross-sectionally, multivariate patterns of gray matter volume within the salience, dorsal attention, visual, and ventral attention networks separated the FThD severity subgroups (balanced accuracy [BAC] = 60.8%). Longitudinally, distributed activations/deactivations within all fractional amplitude of low frequency fluctuation sub-bands (BAC slow-5  = 73.2%, BAC slow-4  = 72.9%, BAC slow-3  = 68.0%), gray matter volume patterns overlapping with the cross-sectional ones (BAC = 62.7%), and smaller frontal white matter volume (BAC = 73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multimodal balanced accuracy of BAC = 77%., Conclusions: We report the first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open up avenues for the development of neuroimaging-based diagnostic, prognostic, and treatment options for the early recognition and management of FThD and associated poor outcomes., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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.

Background: Neurocognitive deficits are a core feature of psychosis and depression. Despite commonalities in cognitive alterations, it remains unclear if and how the cognitive deficits in patients at clinical high risk for psychosis (CHR) and those with recent-onset psychosis (ROP) are distinct from those seen in recent-onset depression (ROD)., Aims: This study was carried out within the European project 'Personalized Prognostic Tools for Early Psychosis Management', and aimed to characterise the cognitive profiles of patients with psychosis or depression., Method: We examined cognitive profiles for patients with ROP ( n = 105), patients with ROD ( n = 123), patients at CHR ( n = 116) and healthy controls ( n = 372) across seven sites in five European countries. Confirmatory factor analysis identified four cognitive factors independent of gender, education and site: speed of processing, attention and working memory, verbal learning and spatial learning., Results: Patients with ROP performed worse than healthy controls in all four domains ( P < 0.001), whereas performance of patients with ROD was not affected ( P > 0.05). Patients at CHR performed worse than healthy controls in speed of processing ( P = 0.001) and spatial learning ( P = 0.003), but better than patients with ROP across all cognitive domains (all P ≤ 0.01). CHR and ROD groups did not significantly differ in any cognitive domain. These findings were independent of comorbid depressive symptoms, substance consumption and illness duration., Conclusions: These results show that neurocognitive abilities are affected in CHR and ROP, whereas ROD seems spared. Although our findings may support the notion that those at CHR have a specific vulnerability to psychosis, future studies investigating broader transdiagnostic risk cohorts in longitudinal designs are needed.

Introduction: A sense of mastery refers to beliefs about having control over one's life and has been found to protect health and buffer the effect of stressful experiences., Methods: We investigated sense of mastery in first-episode psychosis (FEP) patients and population controls at baseline and at one-year follow-up. Pearlin and Schooler's Sense of Mastery scale was completed by 322 participants at baseline and by 184 participants at follow-up., Results: People having experienced FEP reported lower mastery than controls at both time points, but a modest increase was seen in patients at follow-up. The strongest correlates of high baseline mastery in FEP were lower depressive symptoms and higher perceived social support, whereas positive or negative psychotic symptoms did not associate with mastery. Current depressive symptoms also correlated with mastery at the follow-up point, and change in depressive symptoms correlated with change in mastery. Higher mastery at treatment entry predicted remission of psychotic symptoms one year later. Sense of mastery was also found to mediate the association of perceived social support with depressive symptoms., Discussion: The usefulness of mastery measures should be further tested for estimations of patient prognosis in early psychosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lindgren, Therman, From, Hietala, Laurikainen, Salokangas and Suvisaari.)

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., Competing Interests: NK reported receiving grants from the European Union (EU) during the conduct of the study and having a patent to US20160192889A1 issued. SR reported receiving grants from the European Commission during the conduct of the study. AR-R reported receiving grants from the EU during the conduct of the study. CA reported receiving non-financial support from Sunovion Pharmaceuticals, Inc. and H. Lundbeck A/S outside the submitted manuscript. JH reported receiving personal fees from Orion Company, Ltd., Otsuka Pharmaceutical Co, Ltd., and H. Lundbeck A/S and European College of Neuropsychopharmacology Congress participation support from Takeda Pharmaceutical Company Limited during the conduct of the study. FS-L reported receiving grants from the Swiss National Foundation during the conduct of the study. CP reported receiving grants from Australian National Health and the Medical Research Council during the conduct of the study and personal fees from H. Lundbeck A/S and Australia Pty Ltd outside the submitted manuscript. RU reported receiving personal fees from Sunovion Pharmaceuticals, Inc, outside the submitted manuscript. EM reported having a patent to US20160192889A1 licensed. TL reported receiving funding from the Koeln Fortune Program/Faculty of Medicine, University of Cologne (No. 370/2020). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Theisen, Rosen, Meisenzahl, Koutsouleris, Lichtenstein, Ruhrmann, Kambeitz, Kambeitz-Ilankovic, Riecher-Rössler, Chisholm, Upthegrove, Antonucci, Bertolino, Pigoni, Salokangas, Pantelis, Wood, Lencer, Falkai, Hietala, Brambilla, Schmidt, Andreou, Borgwardt, Osman and Schultze-Lutter.)

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.

Background: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia., Methods: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects., Results: There was a 3-year later age at onset for females ( P  < .001) and lower rates of negative symptoms ( P  < .01) and higher depression/anxiety measures ( P  < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages ( P  = .001). No significant effects were found concerning duration of illness., Discussion: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states., (© 2022. The Author(s).)

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 (R 2  = 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abnormal glucose and lipid metabolism is common in antipsychotic-naive first-episode patients with schizophrenia, but it is unclear whether these changes can already be seen in premorbid or prodromal period, before the first psychotic episode. We examined insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride trajectories in children and adolescents (9-18 years old), who were later diagnosed with schizophrenia, any non-affective psychosis (NAP) or affective disorder (AD). The study population consisted of a general population-based cohort "The Cardiovascular Risk in Young Finns Study", started in 1980 (n = 3596). Psychiatric diagnoses were derived from the Health Care Register up to the year 2018. Multivariate statistical analysis indicated no significant differences in insulin or lipid levels in children and adolescents who later developed schizophrenia (n = 41) compared to the cohort control group (n = 3202). In addition, no changes in these parameters were seen in the NAP (n = 74) or AD (n = 156) groups compared to the controls, but lower triglyceride levels in childhood/adolescence associated with earlier diagnosis of psychotic disorder in the NAP group. Taken together, our results do not support any gross-level insulin or lipid changes during childhood and adolescence in individuals with later diagnosis of schizophrenia-spectrum disorder. Since changes in glucose and lipid metabolism can be observed in neuroleptic-naive patients with schizophrenia, we hypothesize that the more marked metabolic changes develop during the prodrome closer to the onset of the first psychotic episode. The findings have relevance for studies on developmental hypotheses of schizophrenia., (© 2022. The Author(s).)

Background: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures., Methods: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470)., Results: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures., Conclusions: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnostically and improve development of stratified treatments., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Importance: The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far., Objective: To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD)., Design, Setting, and Participants: This study included 1870 individuals from 5 cohorts, including (1) patients with bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022., Main Outcomes and Measures: Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery., Results: Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22 of 102 [21.6%]) than the temporo-limbic AD patterns (28 of 157 [17.8%] and 3 of 102 [2.9%], respectively). bvFTD expression was predicted by high body mass index, psychomotor slowing, affective disinhibition, and paranoid ideation (R2 = 0.11). The schizophrenia pattern was expressed in 92 of 108 patients (85.5%) with bvFTD and was linked to the C9orf72 variant, oligoclonal banding in the cerebrospinal fluid, cognitive impairment, and younger age (R2 = 0.29). bvFTD and schizophrenia pattern expressions forecasted 2-year psychosocial impairments in patients with CHR and were predicted by polygenic risk scores for frontotemporal dementia, AD, and schizophrenia. Findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients with nonrecovery from those with preserved recovery., Conclusions and Relevance: Neurobiological links may exist between bvFTD and psychosis focusing on prefrontal and salience system alterations. Further transdiagnostic investigations are needed to identify shared pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectra.

Extrapyramidal (EP) symptoms such as tremor, rigidity, and bradykinesia are common side effects of most antipsychotics, and may associate with impaired performance in neurocognitive testing. We studied EP symptoms in first-episode psychosis (FEP; n = 113). Cognitive testing and EP symptoms (three items of the Simpson-Angus Scale) were assessed at baseline and follow-up (mean follow-up time 12 months). Mild EP symptoms were present at treatment onset in 40% of the participants. EP symptoms were related with lower performance in neurocognitive testing at baseline and at follow-up, especially among those with nonaffective psychotic disorder, and especially in tasks requiring speed of processing. No associations between EP symptoms and social cognition were detected. In linear regression models, when positive and negative symptom levels and chlorpromazine equivalents were accounted for, baseline EP symptoms were associated with worse baseline global neurocognition and visuomotor performance. Baseline EP symptoms also longitudinally predicted global, verbal, and visuomotor cognition. However, there were no cross-sectional associations between EP symptoms and cognitive performance at follow-up. In sum, we found both cross-sectional and longitudinal associations between EP symptoms and neurocognitive task performance in the early course of psychosis. Those without EP symptoms at the start of treatment had higher baseline and follow-up neurocognitive performance. Even mild EP symptoms may represent early markers of long-term neurocognitive impairment., (© 2022. The Author(s).)

Objectives: Selection bias is a concern in studies on psychotic disorders due to high dropout rates and many eligibility criteria for inclusion. We studied how representative the first-episode psychosis study sample in the Turku Early Psychosis Study (TEPS) was., Methods: We screened 3772 consecutive admissions to the clinical psychiatric services of Turku Psychiatry, Finland, between October 2011 and June 2016. A total of 193 subjects had first-episode psychosis and were suitable for TEPS. Out of 193 subjects, 101 participated (PA) and 92 did not participate (NPA) in TEPS due to refusal or contact problems. We retrospectively used patient register data to study whether NPA and PA groups differed in terms of clinical outcomes during 1-year follow-up., Results: In overall sample, the NPA group had a significantly higher rate of discontinuation of clinical treatment than the PA group (48.9 % vs 29.7 %, p = 0.01). In the hospital-treated subsample chi-square tests did not indicate statistically significant differences between the NPA and PA groups in the rate of involuntary care (69.7 % vs 62.7 %, p = 0.34), coercive measures (36.0 % vs 22.7 %, p = 0.06), and readmissions during the follow-up (41.5 % vs 33.8 %, p = 0.31), respectively., Conclusion: The differences in clinical outcomes and treatment characteristics in the non-participating and participating groups were relatively modest. The results do not support a major sample selection bias that would complicate the interpretation of results in this first-episode psychosis study., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures., Objective: To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural imaging data from early psychosis and depression stages., Design, Setting, and Participants: A multisite, naturalistic, longitudinal cohort study (10 sites in 5 European countries; including major follow-up intervals at 9 and 18 months) with a referred patient sample of those with clinical high risk for psychosis (CHR-P), recent-onset psychosis (ROP), recent-onset depression (ROD), and healthy controls were recruited between February 1, 2014, to July 1, 2019. Data were analyzed between January 2020 and January 2022., Main Outcomes and Measures: A nonnegative matrix factorization technique separately decomposed clinical (287 variables) and parcellated brain structural volume (204 gray, white, and cerebrospinal fluid regions) data across CHR-P, ROP, ROD, and healthy controls study groups. Stability criteria determined cluster number using nested cross-validation. Validation targets were compared across subgroup solutions (premorbid, longitudinal, and schizophrenia polygenic risk scores). Multiclass supervised machine learning produced a transferable solution to the validation sample., Results: There were a total of 749 individuals in the discovery group and 610 individuals in the validation group. Individuals included those with CHR-P (n = 287), ROP (n = 323), ROD (n = 285), and healthy controls (n = 464), The mean (SD) age was 25.1 (5.9) years, and 702 (51.7%) were female. A clinical 4-dimensional solution separated individuals based on positive symptoms, negative symptoms, depression, and functioning, demonstrating associations with all validation targets. Brain clustering revealed a subgroup with distributed brain volume reductions associated with negative symptoms, reduced performance IQ, and increased schizophrenia polygenic risk scores. Multilevel results distinguished between normative and illness-related brain differences. Subgroup results were largely validated in the external sample., Conclusions and Relevance: The results of this longitudinal cohort study provide stratifications beyond the expression of positive symptoms that cut across illness stages and diagnoses. Clinical results suggest the importance of negative symptoms, depression, and functioning. Brain results suggest substantial overlap across illness stages and normative variation, which may highlight a vulnerability signature independent from specific presentations. Premorbid, longitudinal, and genetic risk validation suggested clinical importance of the subgroups to preventive treatments.

Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant variables rather than specific psychiatric symptoms. We employed a new data-driven method (Orthogonal Projective Non-Negative Matrix Factorization) to delineate novel gyrification-based networks of structural covariance in 308 healthy controls. Gyrification within the networks was then compared to 713 patients with recent onset psychosis or depression, and at clinical high-risk. Associations with diagnosis, symptoms, cognition, and functioning were investigated using linear models. Results demonstrated 18 novel gyrification networks in controls as verified by internal and external validation. Gyrification was reduced in patients in temporal-insular, lateral occipital, and lateral fronto-parietal networks (pFDR < 0.01) and was not moderated by illness group. Higher gyrification was associated with better cognitive performance and lifetime role functioning, but not with symptoms. The findings demonstrated that gyrification can be parsed into novel brain networks that highlight generalized illness effects linked to developmental vulnerability. When combined, our study widens the window into the etiology of psychiatric risk and its expression in adulthood., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the lower end of the normal distribution of individual differences in social functioning., Methods: We used a machine learning classifier to test for the presence of a previously validated brain structural pattern associated with impaired social outcome in CHR-P (CHR-outcome-neurosignature) in the neuroimaging profiles of individuals from two non-clinical samples (total n = 1763) and examined its association with social function, psychopathology and cognition., Results: Although the CHR-outcome-neurosignature could be detected in a subset of the non-clinical samples, it was not associated was adverse social outcomes or higher psychopathology levels. However, participants whose neuroanatomical profiles were highly aligned with the CHR-outcome-neurosignature manifested subtle disadvantage in fluid (P FDR  = 0.004) and crystallized intelligence (P FDR  = 0.01), cognitive flexibility (P FDR  = 0.02), inhibitory control (P FDR  = 0.01), working memory (P FDR  = 0.0005), and processing speed (P FDR  = 0.04)., Conclusions: We provide evidence of divergence in brain structural underpinnings of social dysfunction derived from a psychosis-risk enriched population when applied to non-clinical samples. This approach appears promising in identifying brain mechanisms bound to psychosis through comparisons of patient populations to non-clinical samples with the same neuroanatomical profiles., Competing Interests: Drs Koutsouleris and Meisenzahl hold issued patent US20160192889A1 (‘Adaptive pattern recognition for psychosis risk modelling’). Dr. Upthegrove reported receiving personal fees from Sunovion Pharmaceuticals, Inc, outside the submitted work. Dr. Hietala reported receiving personal fees from Orion Company, Ltd, Otsuka Pharmaceutical Co, Ltd, and H. Lundbeck A/S, outside the submitted work. No other disclosures were reported., (© 2022 The Authors.)

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 (p fdr < 0.001) and role (p fdr  < 0.001) functioning, as well as worse neurocognitive performance in semantic (p fdr < 0.001) and phonological verbal fluency (p fdr  < 0.001), short-term verbal memory (p fdr  = 0.002) and abstract thinking (p fdr  = 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., (© 2021. The Author(s).)

Background: The childhood adverse experiences (CAEs) are common in the general population and very common among help-seekers. Particularly, sexual and physical abuse have received a great attention in research and public media. Prevalence of CAEs and their association with attitudes towards others and psychiatric disorders were investigated., Methods: The Trauma And Distress Scale (TADS) was fulfilled by people of the general population (GP; n  = 692) and by patients attending primary (PrC) and psychiatric outpatient (PsC) care ( n  = 415)., Results: In GP, 51% reported emotional and 50% physical neglect, and 37% emotional, 23% physical 23% and 6% sexual abuse. In PsC, the corresponding figures were 82%, 73%, 68%, 37% and 17% respectively. The CAEs had a strong tendency to cumulate into same participants: 30% of GP and 66% of PsC reported three or more CAEs. In GP, participant who reported emotional neglect felt that other people had a negative attitude towards them. In the combined PrC and PsC sample, emotional neglect had a specific effect on depression, anxiety and substance abuse., Conclusions: Emotional neglect is the most frequently reported CAE and associates with attitudes towards other people and the occurrence of psychiatric symptoms and disorders in adulthood. The findings received support the attachment theory launched by Bowlby and emphasise the importance of understanding emotional atmosphere that individuals are facing in their childhood and adolescence.

Continued cannabis use (CCu) is an important predictor for poor long-term outcomes in psychosis and clinically high-risk patients, but no generalizable model has hitherto been tested for its ability to predict CCu in these vulnerable patient groups. In the current study, we investigated how structured clinical and cognitive assessments and structural magnetic resonance imaging (sMRI) contributed to the prediction of CCu in a group of 109 patients with recent-onset psychosis (ROP). We tested the generalizability of our predictors in 73 patients at clinical high-risk for psychosis (CHR). Here, CCu was defined as any cannabis consumption between baseline and 9-month follow-up, as assessed in structured interviews. All patients reported lifetime cannabis use at baseline. Data from clinical assessment alone correctly classified 73% (p < 0.001) of ROP and 59 % of CHR patients. The classifications of CCu based on sMRI and cognition were non-significant (ps > 0.093), and their addition to the interview-based predictor via stacking did not improve prediction significantly, either in the ROP or CHR groups (ps > 0.065). Lower functioning, specific substance use patterns, urbanicity and a lack of other coping strategies contributed reliably to the prediction of CCu and might thus represent important factors for guiding preventative efforts. Our results suggest that it may be possible to identify by clinical measures those psychosis-spectrum patients at high risk for CCu, potentially allowing to improve clinical care through targeted interventions. However, our model needs further testing in larger samples including more diverse clinical populations before being transferred into clinical practice., (© 2022. The Author(s).)

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.

Background: Functional recovery of patients with clinical and subclinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known about how these factors predict functional outcomes in the same models. We investigated functional outcomes and their predictors in patients with first-episode psychosis (FEP) or a confirmed or nonconfirmed clinical high risk of psychosis (CHR-P vs. CHR-N)., Methods: Altogether, 130 patients with FEP, 60 patients with CHR-P and 47 patients with CHR-N were recruited and extensively examined at baseline (T0) and 9 (T1) and 18 (T2) months later. Global Assessment of Functioning (GAF) at T0, T1 and T2 and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcomes were predicted using multivariate repeated ANOVA., Results: During follow-up, the GAF score improved significantly in patients with FEP and CHR-P but not in patients with CHR-N. A single marital status, low basic education level, poor work situation, disorganization symptoms, perceptual deficits, and poor premorbid adjustment in patients with FEP, disorganization symptoms and poor premorbid adjustment in patients with CHR-P, and a low basic education level, poor work situation and general symptoms in patients with CHR-N predicted poor functional outcomes. Psychotic symptoms at T1 in patients with FEP and psychotic and depression symptoms at T1 and anxiety symptoms at T2 in patients with CHR-P were associated with poor functioning., Conclusions: In patients with FEP and CHR-P, poor premorbid adjustment and disorganization symptomatology are common predictors of the functional outcome, while a low education level and poor work situation predict worse functional outcomes in patients with FEP and CHR-N. Interventions aimed at improving the ability to work and study are most important in improving the functioning of patients with clinical or subclinical psychosis., (© 2021. The Author(s).)