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Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.Methods: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins. © 2012 Orešič et al.; licensee BioMed Central Ltd.

This study aimed to examine alexithymic features and associations between alexithymia and psychiatric symptoms among adolescents living in a closed institution because of severe behavioral problems. Forty-seven adolescents (29 boys and 18 girls) aged 15 to 18 years completed the 20-item Toronto Alexithymia Scale (TAS-20) Questionnaire and the Youth Self-Report, whereas their foster parents completed the Child Behavior Checklist. The TAS-20 scores of the participants were compared with those of an extensive population sample (N = 6000) matched by age and birth year. Reform school adolescents are significantly more alexithymic than the control group, and the TAS-20 scores are correlated with numerous psychiatric problems, mainly in the internalizing spectrum, but also with thought problems and self-reported aggression. Promoting abilities in identifying and describing feelings is important when treating delinquent adolescents. [ABSTRACT FROM AUTHOR]

Studies of the prodromal stage of schizophrenia show that the late prepsychotic phase is associated with mild neuropsychological deficits that parallel those of schizophrenia. However, it is still unclear whether this association is present across the whole range of symptoms of psychosis-proneness, or specific to the extreme groups. In this study, the linear associations between dimensions of psychosis-proneness (as measured by the 92-item Prodromal Questionnaire) and performance on 20 neuropsychological measures were assessed in a group of 71 nonpsychotic adolescent psychiatric patients. A structure of positive, negative and disorganized prodromal symptom dimensions was found, replicating earlier findings. No symptom dimension was significantly associated with neuropsychological performance, even when corrected for nonspecific psychological distress. These findings suggest that the association between symptoms and neuropsychological performance is specific to high levels of symptoms or to the truly prodromal subpopulation. The results also highlight the importance of simultaneous assessment of affective state. [ABSTRACT FROM AUTHOR]

Background: Subclinical psychotic-like experiences (PLEs) are common among general population adolescents but have been found to correlate with various problems in well-being. Due to limited sample sizes these effects have not been well differentiated by sex and age., Methods: Using a nationally representative survey of almost 160,000 adolescents, we studied endorsement and correlates of PLEs by sex among middle adolescence pupils (ages 14-16) and late adolescence students (ages 16-20). PLEs were investigated with three questionnaire items: auditory and visual hallucinatory experiences and suspicious thought content, using a frequency response scale., Results: Weekly PLEs were reported by 14 % of the adolescents, more often in females (17 %) than males (11 %) and in the younger age group (17 %) compared to the older adolescents (10 %). A latent PLE factor represented the three assessed PLEs with good fit. Factor scores were highest for the younger females and lowest for the older males. The PLE factor correlated with two latent factors of other well-being, namely living environment ("adversity", loading most heavily on parental mental abuse; r = 0.63), and concurrent mental health ("distress", loading most heavily on depressive symptoms; r = 0.50). Adversity was associated especially strongly with PLEs in 14-16-year-old males., Conclusions: This cross-sectional study reaching the whole 14-20 age group in schools in Finland offers data on the meaning and relevance of PLEs as general markers of vulnerability. Many adolescents experience PLEs recurrently and these experiences are associated with a wide variety of burden in the adolescent's everyday life., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: High levels of mental health problems among young people were reported during the COVID-19 pandemic, but studies of the post-pandemic period are scarce. We assessed mental health problems among Finnish youth before, during, and after the COVID-19 pandemic using nationwide population-based samples. Our aim was to examine in which direction the heightened levels of adolescent mental health problems have developed after the pandemic., Methods: In this national, repeated cross-sectional, population-based study in Finland, we recruited students at lower and upper secondary level (aged 13-20 years) who were taking part in the Finnish School Health Promotion (SHP) survey in 2015-23 (119 681-158 897 participants per round). The SHP is based on total sampling and conducted biennially between March and May. Self-reports covered the seven-item Generalized Anxiety Disorder Scale; the two-item Patient Health Questionnaire for depression; the Mini Social Phobia Inventory for social anxiety; the Short Warwick-Edinburgh Mental Wellbeing Scale for mental wellbeing; loneliness; the Sick, Control, One Stone, Fat, Food measure for disordered eating; and suicidality (suicidal ideation, deliberate self-harm, and suicide attempts). Scales were dichotomised using validated cutoffs. Presence of any and comorbid mental health problems was assessed. Logistic (for dichotomised outcomes) and linear (for Short Warwick-Edinburgh Mental Wellbeing Scale) mixed effects models were used to analyse the effect of survey year on mental health, controlling for sociodemographic background factors and stratified by gender and school level. Cisgender and transgender youth were compared., Findings: Between 2015 and 2023, the SHP study recruited 722 488 students (371 634 [51·6%] girls and 348 857 [48·4%] boys) with a mean age of 15·8 years (SD 1·3) who were either in the eighth and ninth grades of comprehensive school or the first and second years of general and vocational upper secondary schools in Finland. The proportion of participants with generalised anxiety, depression, and social anxiety symptoms above the cutoff increased from pre-COVID-19 levels to 2021 and remained at these higher levels in 2023 among all study groups. Among girls in lower secondary education, prevalence of generalised anxiety, depression, and social anxiety symptoms increased from 2021 to 2023, as did social anxiety among girls in upper secondary education. Among boys, the proportion with social anxiety symptoms decreased between 2021 and 2023. Mental wellbeing scores decreased in all groups between 2021 and 2023, and disordered eating increased in girls, and in boys in lower secondary education. Suicidality increased in girls but not in boys. Loneliness was the only measure to show improvement in all groups from 2021 to 2023. In 2023, 55 895 (72·6%) of 76 994 girls and 22 718 (32·8%) of 69 205 boys reported at least one mental health problem, and 37 250 (48·4%) girls and 9442 (13·6%) boys reported comorbid mental health problems. Among both transfeminine and transmasculine youth, the prevalence of generalised anxiety and depression symptoms decreased from 2021 to 2023, but compared with cisgender youth, the proportions were significantly higher throughout., Interpretation: The effects of the COVID-19 pandemic on youth mental health could be long lasting. In this study, the substantial change for the better among transgender youth was a positive exception. Providing adequate support and treatment for young people with poor mental health is essential, but solutions to the mental health crisis need to address a wider societal perspective and should be developed in partnership with young people., Funding: NordForsk, Research Council of Finland., Translations: For the Finnish and Swedish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, artificial intelligence training, and similar technologies.)

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1β) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation., (© 2024. The Author(s).)

Background: The research on adverse childhood experiences (ACEs) has deepened our understanding of the long-lasting and cumulative effects of childhood adversities. However, the instruments measuring ACEs have several shortcomings, including limited item coverage, collapsing of items and response options, simplistic scoring, and inadequate psychometric assessments., Objective: To design and conduct preliminarily psychometric testing for a brief new self-report instrument-the THL Adverse Childhood Experiences questionnaire (ACE-THL)-with a comprehensive set of clearly formulated items and appropriate response options., Methods: A previously published process model was applied to develop the ACE-THL questionnaire, which was validated by cognitive interviews (N = 20). Interviewers and interviewees completed the questionnaire separately for a cross-informant comparison. In a separate survey panel validation, the respondents filled out the ACE-THL twice, two weeks apart (N = 513, with 426 in the follow-up). Interview data were used to improve item clarity, and test-retest reliability and structural validity were assessed with repeated survey data., Results: The final 14-item questionnaire, including 12 ACE items and two items measuring protective experiences, was highly acceptable to the respondents. In the factor analysis of the quantitative data, a sufficiently single-dimensional construct was found, remaining stable in retesting two weeks later. The internal consistency (omega) of the a priori one-dimensional model was 0.89 and 0.90 at baseline and follow-up, respectively. The high test-retest reliability (mean score rank order correlation 0.93) of the ACE-THL indicated that the probed perceptions of childhood experiences are stable., Conclusion: Based on the initial validation, the 14-item ACE-THL questionnaire is a reliable and valid instrument to measure adverse childhood experiences, as well as protective experiences., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: Psychosis-Like Experiences (PLEs) and depressive symptoms are correlated in clinical adolescent populations. However, symptom-level associations between the two phenomena are not clear., Methods: We analysed factor structures of a PLE instrument, the Prodromal Questionnaire-Brief (PQ-B), based on dimensions of positive symptoms of schizophrenia, and a depression measurement instrument, the Beck Depression Inventory (BDI-21A) and performed a network analysis of item-level associations between the two measures. The sample consisted of 417 adolescents (range 13-18 years of age, mean 14.9 years, 72.4% females) entering secondary psychiatric services at Helsinki metropolitan area, Finland., Results: Confirmatory factor analysis resulted in adequately fitting 2-factor solution, one for PQ-B and one for BDI-21, with a strong correlation coefficient of 0.605 between the two factors. In the network analysis, PQ-B and BDI-21 both formed their own clusters, and two significant pathways were estimated between PQ-B and BDI-21 clusters: 1. the association between paranoid thinking and distorted body image, and 2. the association between somatic preoccupation and worry about problems of one's mind., Conclusions: Even though on a general, factor level, PLEs and depressive symptoms were strongly correlated, unique associations between symptoms of the two constructs were sparse. These findings should be considered in the psychiatric assessment and in the care of adolescents., (© 2023 John Wiley & Sons Australia, Ltd.)

This article reports the psychometric properties of both full and the abbreviated (Short) Warwick-Edinburgh Mental Well-being Scales (WEMWBS; SWEMWBS) in the Finnish general population. A large cross-sectional dataset (N = 5,335) was collected as part of the nationally representative FinHealth Study in 2017. Exploratory and confirmatory factor analyses of the data evaluated one-, two-, three-, and bi-factorial solutions with a split-half approach. McDonald's omega was used to assess internal consistency and convergent validity was evaluated using four established mental health and well-being scales (BDI-6, GHQ-12, MHI-5, EUROHIS-QOL8). Contrary to previous findings, our results supported a three-factor model of the full scale with separate, yet highly correlated, mental, social, and eudemonic well-being factors. For the SWEMWBS, the bi-factor model showed the best fit, with a strong general mental well-being factor and a weaker specific eudemonic well-being factor. In this sampling context, the social aspect of mental well-being may be considered a separable construct from other mental well-being dimensions and the shorter 7-item version might thus be a preferable option when assessing overall mental well-being., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships, or any other relationship that could be construed as a potential conflict of interest or affect their ability to present data objectively., (Copyright © 2023. Published by Elsevier B.V.)

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.)

Background: Several psychological symptoms in adolescence associate with later development of psychosis. However, it is unclear which symptoms specifically predict psychotic disorders rather than psychiatric disorders in general. We conducted a prospective study comparing how specific adolescent psychotic-like symptoms, predicted psychotic and non-psychotic hospital-treated psychiatric disorders in the population-based Northern Finland Birth Cohort 1986 (NFBC1986)., Methods: At age 15-16 years, 6632 members of the NFBC1986 completed the PROD-screen questionnaire. New hospital-treated mental disorders of the NFBC1986 participants were detected between age 17 and 30 years from the Finnish Care Register for Health Care. Multiple covariates were used in the analysis., Results: During the follow-up, 1.1% of the participants developed a psychotic and 3.2% a non-psychotic psychiatric disorder. Three symptoms were specifically associated with onset of psychosis compared to non-psychotic psychiatric disorders: 'Difficulty in controlling one's speech, behaviour or facial expression while communicating' (adjusted OR 4.00; 95% CI 1.66-9.92), 'Difficulties in understanding written text or heard speech' (OR 2.25; 1.12-4.51), and 'Difficulty or uncertainty in making contact with other people' (OR 2.20; 1.03-4.67). Of these, the first one remained statistically significant after Bonferroni correction for multiple comparisons., Conclusion: To our knowledge, this is the first general-population-based prospective study exploring psychiatric symptoms predicting the onset of hospital-treated first-episode psychosis in comparison to non-psychotic disorders. We found three symptoms related with difficulties in social interaction which predicted onset of psychosis. This is a novel finding and should be replicated., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Alarming levels of emotional symptoms among youth were reported during the COVID-19 pandemic. Studies assessing these figures against the pre-pandemic developments are rare. We examined the trend of generalized anxiety (GA) in adolescents in the 2010s and the effect of the COVID-19 pandemic against this trend., Methods: Data from the Finnish School Health Promotion study with 750,000 participants aged 13-20 between 2013 and 2021 was analyzed using GAD-7 to measure self-reported GA (cut-off ≥10). Inquiries were made about remote learning arrangements. Effects of time and COVID-19 were analyzed with logistic regression., Results: Among females, an increasing trend in GA between 2013 and 2019 was found (OR per year 1.05), and the prevalence increased from 15.5 % to 19.7 %. Among males, the trend was decreasing (OR = 0.98), with prevalence from 6.0 % to 5.5 %. Increase in GA from 2019 to 2021 was stronger in females (19.7 % to 30.2 %) than males (5.5 % to 7.8 %), while the effect of COVID-19 on GA was equally strong (OR = 1.59 vs. OR = 1.60) against the pre-pandemic trends. Remote learning was associated with elevated levels of GA, especially among those with unmet needs for learning support., Limitations: The design of repeated cross-sectional surveys doesn't allow analyses of within individual changes., Conclusions: Given the pre-pandemic trends of GA, the COVID-19 effect on it appeared equal in both sexes. The increasing pre-pandemic trend among adolescent females and the strong effect of COVID-19 on GA among both sexes warrants constant monitoring of mental health of the youth in the aftermath of the COVID-19 pandemic., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background : Sexual and physical abuse have been associated with long-term systemic alterations such as low-grade inflammation and changes in brain morphology that may be reflected in the metabolome. However, data on the metabolic consequences of sexual and physical abuse remain scarce. Objective : This pilot study sought to investigate changes in the metabolite profile related to sexual and physical abuse in depressed adolescent psychiatric outpatients. Method : The study included 76 patients aged 14-18 years, whose serum samples were analysed with a targeted metabolite profiling methodology. We estimated the associations between metabolite concentrations and the Trauma and Distress Scale (TADS) Sexual and Physical Abuse factor scores using three linear regression models (one unadjusted and two adjusted) per metabolite and trauma type pair. Additional variables in the two adjusted models were 1) the lifestyle indicators body mass index, tobacco use, and alcohol use, and 2) depression scores and the chronicity of depression. Results : TADS Sexual Abuse scores associated positively with homogentisic acid, as well as cystathionine, and negatively with choline in linear regression analysis, whereas TADS Physical Abuse scores associated negatively with AMP, choline, γ-glutamyl cysteine and succinate, and positively with D-glucuronic acid. Conclusions : This pilot study did not include a healthy control group for comparison and the cohort was relatively small. Nevertheless, we observed alterations in metabolites related to one-carbon metabolism, mitochondrial dysfunction, oxidative stress, and inflammation in depressed patients with a history of sexual or physical abuse.

Background: Several multivariate algorithms have been developed for predicting psychosis, as attempts to obtain better prognosis prediction than with current clinical high-risk (CHR) criteria. The models have typically been based on samples from specialized clinics. We evaluated the generalizability of 19 prediction models to clinical practice in an unselected adolescent psychiatric sample., Methods: In total, 153 adolescent psychiatric patients in the Helsinki Prodromal Study underwent an extensive baseline assessment including the SIPS interview and a neurocognitive battery, with 50 participants (33%) fulfilling CHR criteria. The adolescents were followed up for 7 years using comprehensive national registers. Assessed outcomes were (1) any psychotic disorder diagnosis ( n = 18, 12%) and (2) first psychiatric hospitalization ( n = 25, 16%) as an index of overall deterioration of functioning., Results: Most models improved the overall prediction accuracy over standard CHR criteria (area under the curve estimates ranging between 0.51 and 0.82), although the accuracy was worse than that in the samples used to develop the models, also when applied only to the CHR subsample. The best models for transition to psychosis included the severity of positive symptoms, especially delusions, and negative symptoms. Exploratory models revealed baseline negative symptoms, low functioning, delusions, and sleep problems in combination to be the best predictor of psychiatric hospitalization in the upcoming years., Conclusions: Including the severity levels of both positive and negative symptomatology proved beneficial in predicting psychosis. Despite these advances, the applicability of extended psychosis-risk models to general psychiatric practice appears limited.

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).)

Aims: Increased mental health problems during the COVID-19 pandemic have become a major concern among young adults. Our aim was to understand which COVID-19-related questions predicted mental well-being during the outbreak., Methods: Two cross-sectional datasets were used. The primary dataset was collected in May 2020 ( n = 1001), during the initial COVID-19 outbreak, and the secondary in April 2019 ( n = 10866), before the pandemic. Mental well-being was assessed with the Short Warwick-Edinburgh Mental Well-Being Scale. Relationships between mental well-being and COVID-19-related questions were investigated with lasso regression. As an exploratory analysis, two-way ANOVAs were used to compare mental well-being before and during the outbreak., Results: Higher levels of mental well-being were associated with lower levels of academic stress and COVID-19-related worry, along with a higher satisfaction with the procedures and information provided by the higher education institutions and the government. COVID-19-related symptoms and infections did not have an impact on students' mental well-being during the outbreak. Small to moderate effect sizes across the time points were detected, indicating an overall decrease in mental well-being across age and gender during the outbreak., Conclusions: COVID-19 had an impact on higher education students' mental well-being. Higher education institutes may play a crucial role in protecting their students' well-being during uncertain times.

Psychotic-like experiences (PLEs) have been identified as risk markers for psychotic disorders and may indicate an individual's susceptibility to mental disorders in general. We examined whether 23 PLEs (assessed with M-CIDI questionnaire) reported in young adulthood (n = 1313) predict subsequent psychotic or any mental disorders in the general population. We also investigated whether these possible associations are explained by general psychological distress assessed with the General Health Questionnaire-12 (GHQ-12). The register follow-up period spanned 10-12 years. In Cox regression models, PLEs predicted subsequent psychotic disorders (n = 12) when the effects of age, sex, education, and marital status were adjusted for, but not when general psychological distress was added to the model. Having any mental disorders during follow-up (n = 91) was predicted by PLEs reported at a younger age, when controlling for age, sex, education, marital status, and general psychological distress. In line with earlier results in other age groups, PLEs can be seen as a sign of vulnerability to not just psychotic but all mental disorders during the following years also among young adults in the general population. PLEs were a predictive marker of general psychopathology independently from general psychological distress., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to examine the factor structure of the Adolescent Dissociative Experiences Scale (A-DES) questionnaire with item response theory (IRT) methods, including an assessment of measurement invariance with differential item functioning (DIF) analysis. Three abbreviated versions of the A-DES (with 20, 10, and 5 items) were constructed based on the IRT and DIF statistics. The respondents in this population-based study (N = 4,072) were 12- to 19-year-old Finnish junior and senior high school students. A one-factor model of the A-DES was best supported, and the original theoretical four-factor model showed poor fit. The A-DES turned out to have high measurement invariance with respect to age, gender, transgender tendencies, having multiple friends, the use of illegal substances, and experience of being bullied. Compared to the full 30-item A-DES, abbreviated versions of the questionnaire retained acceptable information value and empirical reliability in the clinically relevant range of symptomatology. Further psychometric studies are needed especially with regards to clinical use.

Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)-derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron-astrocyte co-cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ., (© 2021 The Authors. GLIA published by Wiley Periodicals LLC.)

Objectives: Cognitive impairment is frequent in multiple sclerosis (MS) as approximately half of the patients manifest some degree of cognitive impairment. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been designed for brief cognitive evaluation. The purpose of the study was to validate the BICAMS along with the Finnish versions of one self-rating questionnaire each for cognition and fatigue., Methods: A total of 65 MS patients and 45 healthy controls (HC) were assessed with the BICAMS, the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), and the Fatigue Scale for Motor and Cognitive Functions (FSMC) twice, approximately within nine days., Results: MS patients scored markedly lower than the HCs on each of the three tests of the BICAMS. Of the patients, 60% scored at least 1.5 SD below the mean of the HCs on at least one test; 49% on the SDMT, 26% on the CVLT-II, and 28% on the BVMT-R. Correlation coefficients for the repeated measurement were between 0.75 and 0.89 for the three tests in the whole study sample. MS patients reported more cognitive symptoms and more fatigue than the HCs. Cronbach's alpha was 0.94 for the MSNQ and 0.98 for the FSMC. Correlation coefficient for the repeated measurement was 0.91 for the MSNQ and between 0.92 and 0.94 for the FSMC scores for the whole study sample., Conclusions: The present study supports the validity of the Finnish version of the BICAMS. The SDMT was the most sensitive of the three BICAMS tests and showed cognitive impairment in half of the patients. The Finnish versions of the MSNQ and the FSMC proved useful tools in approaching concerns related to cognition and fatigue., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

The molecular pathophysiological mechanisms underlying schizophrenia have remained unknown, and no treatment exists for primary prevention. We used Ingenuity Pathway Analysis to analyze canonical and causal pathways in two different datasets, including patients from Finland and USA. The most significant findings in canonical pathway analysis were observed for glutamate receptor signaling, hepatic fibrosis, and glycoprotein 6 (GP6) pathways in the Finnish dataset, and GP6 and hepatic fibrosis pathways in the US dataset. In data-driven causal pathways, ADCYAP1, ADAMTS, and CACNA genes were involved in the majority of the top 10 pathways differentiating patients and controls in both Finnish and US datasets. Results from a Finnish nation-wide database showed that the risk of schizophrenia relapse was 41% lower among first-episode patients during the use of losartan, the master regulator of an ADCYAP1, ADAMTS, and CACNA-related pathway, compared to those time periods when the same individual did not use the drug. The results from the two independent datasets suggest that the GP6 signaling pathway, and the ADCYAP1, ADAMTS, and CACNA-related purine, oxidative stress, and glutamatergic signaling pathways are among primary pathophysiological alterations in schizophrenia among patients with European ancestry. While no reproducible dopaminergic alterations were observed, the results imply that agents such as losartan, and ADCYAP1/PACAP -deficit alleviators, such as metabotropic glutamate 2/3 agonist MGS0028 and 5-HT7 antagonists - which have shown beneficial effects in an experimental Adcyap1 -/- mouse model for schizophrenia - could be potential treatments even before the full manifestation of illness involving dopaminergic abnormalities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

We have previously reported a replicable association between variants at the PDE4D gene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations underlying these previous findings, we sequenced 1.5 Mb of the PDE4D genomic locus in 20 families (consisting of 96 individuals and 79 independent chromosomes), followed by two stages of genotyping across 6668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4570 SNPs across the PDE4D gene, with 380 associated to schizophrenia (p ≤ 0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor-binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort (combined statistics for rs35278 p = 0.0012; OR = 1.18, 95% CI: 1.06-1.32; and rs165940 p = 0.0016; OR = 1.27, 95% CI: 1.13-1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p = 0.025, OR = 1.18, 95% CI: 1.07-1.30) and cognitive domains of major mental illnesses (g-score p = 0.044, β = -0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, β = -0.044) and verbal working memory (p = 0.0062, β = -0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels of PDE4D in the cerebellum (p-value = 0.04; m-value = 0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at the PDE4D locus in the Finnish population, increasing risk broadly to psychotic disorders.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia., Competing Interests: EH, ED, GM, JB, NB, MB, AC, CC, DD, TD, GD, MG, AG, CG, HH, CH, VJ, RK, JK, GK, CM, AM, DM, KM, CM, IN, DQ, AR, BR, DS, ST, TT, JV, JW, EV, GB, LS, JM No competing interests declared, MD M Di Forti reports personal fees from Janssen, outside the submitted work. FG Fiona Gaughran has received honoraria from Lundbeck, Otsuka, and Sunovion. She has a family member with professional links to Lilly and GSK, including shares. KK Kaarina Kowalec has consulted with Emerald Lake Safety Ltd. (2017-2018) and has received speaker honoraria from Biogen/Fraser Health Multiple Sclerosis Clinic (2018). Both are unrelated to the work published here. JM James MacCabe has received research funding from H Lundbeck. MO Michael C O'Donovan is supported by a collaborative research grant from Takeda Pharmaceuticals. Takeda played no part in the conception, design, implementation, or interpretation of this study. PS PF Sullivan reports the following potentially competing financial interests. Current: Lundbeck (advisory committee, grant recipient). Past three years: Pfizer (scientific advisory board). DC David A Collier is a full time employee and stockholder of Eli Lilly and Company. RM Robin M Murray reports personal fees from Janssen, Lundbeck, Sunovion, Recordati and Otsuka, (© 2021, Hannon et al.)

Valid measurement of group differences in self-reported psychotic-like experiences (PLEs) requires knowing any group-specific measurement properties of the instruments. We investigated the measurement invariance of the 21-item Prodromal Questionnaire-Brief (PQ-B) questionnaire across gender, ethnic minority/majority status, and presence of depressive symptoms in two different US non-clinical undergraduate samples ( N = 1,099). For each item, endorsement of the experience and the associated distress were combined for analysis. A unidimensional model of the PQ-B fit the data well. Across genders, the PQ-B showed configural and metric, but not full scalar invariance; there were statistically significant differences in eight thresholds of six items, most being higher endorsement thresholds for self-identified females. Partial scalar invariance was also found for ethnic status, with five thresholds of three items being higher for the minority participants. For depressive symptomatology, defined as the top quintile by the Beck Depression Inventory-II, partial scalar invariance required dropping one item, after which there were statistically significant differences only in two response thresholds. Overall, a wide range of PLE questionnaire items were found to be robust to gender and ethnicity effects, strengthening confidence in found group differences in PLEs. Although full scalar invariance could not be ascertained for any of the group comparisons, the few found scalar differences across groups were small, with minimal impact on group PLE estimates. However, since PLEs are easily conceptually entangled with depression symptoms, similar items should be considered for exclusion if separable constructs are the target of investigation., 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 © 2021 Lång, Mittal, Schiffman and Therman.)

Background: Autism and schizophrenia spectrum disorders both represent severely disabling neurodevelopmental disorders with marked impairments in social functioning. Despite an increased incidence of psychosis in autism, and substantial overlap in symptoms and cognitive markers, it is unclear whether such phenotypes are specifically related to risk for psychosis or perhaps reflect more general, idiosyncratic autism traits. The attenuated psychosis syndrome (APS) is primarily defined by the presence of attenuated psychotic symptoms, which currently constitute the best and most-replicated clinical predictors of psychosis, and are common in clinical youth with and without autism. The aims of this study were to test the hypothesis that facial affect processing is impaired in adolescents with APS and to explore whether such deficits are more indicative of psychotic or autistic phenotypes on a categorical and dimensional level., Materials and Method: Fifty-three adolescents with APS and 81 typically developing controls (aged 12-18) were included. The APS group consisted of adolescents with (n = 21) and without (n = 32) a diagnosis of autism spectrum disorder. Facial affect recognition was assessed with the Amsterdam Neuropsychological Tasks using a cascade model of cognitive processing, in which disturbances in "lower-level" cognitive abilities (pattern recognition), affect "higher-level" cognitive processes (face recognition and facial affect recognition). For associations with schizotypal and autistic-like traits the Schizotypal Personality Questionnaire and Social Communication Questionnaire were used in a confirmatory item factor analysis framework., Results: Contrary to expectation, APS in adolescents was not associated with impairments in pattern, face, or facial affect recognition. However, the APS group with autism spectrum disorder showed a general latency in response time to social and non-social stimuli. Dimensionally assessed schizotypal and autistic-like traits did not predict the accuracy or the speed of face or facial affect recognition., Conclusion: Facial affect processing performance was not associated with APS in adolescence and represents an unlikely early vulnerability marker for psychosis. APS individuals with a more autistic-like profile were characterized by slower responses to social- and non-social stimuli, suggesting that the combined effect of APS and autism spectrum disorder on cognition is larger than for APS alone., (Copyright © 2020 Maat, Therman, Swaab and Ziermans.)

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen's d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = -0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [ 11 C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V T ) of [ 11 C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen's d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

Background: The Cambridge Depersonalization Scale (CDS) characterizes the quality, frequency, and duration of dissociative symptoms. While the psychometric properties of the CDS have been evaluated in primary dissociative disorder, this has been insufficiently addressed among other psychiatric patient groups such as patients with a bipolar disorder (BD)., Methods: Outpatients with variable mood (n = 73) responded to a survey that assessed dissociative symptoms and other characteristics. We used factor analysis and McDonald's omega to evaluate psychometric properties of the CDS, and correlations with other characteristics., Results: Previously suggested multifactorial models of the CDS were not supported, but the single-dimensional model fit both dichotomized (p = 0.31, CFI = 0.99, RMSEA = 0.02, ECV 70%) and trichotomized CDS responses (p = 0.06, CFI = 0.96, RMSEA = 0.04, ECV 47%). The CDS showed high internal consistency (ω = 0.96). CDS factor scores correlated with symptom severity on the Quick Inventory for Depressive Symptoms (QIDS-SR-16) (ρ = 0.59), the Social Phobia Inventory (ρ = 0.52), the American Association of Psychiatry Severity measure for Panic Disorders (ρ = 0.46), the Childhood Trauma Questionnaire (ρ = 0.44), and the Trauma Screening Questionnaire (ρ = 0.53). Two abbreviated versions of the CDS, retaining the best 14 or 7 items were proposed., Limitations: The sample size remained moderate., Conclusions: The CDS is a psychometrically sound, unidimensional measure with clinical impact to detect and characterize dissociative symptoms in BD patients. Establishing the reliability and validity of the abbreviated scales for screening necessitates further study., Competing Interests: Declaration of Competing Interest Dr. Serge Beaulieu has received funding from Astra-Zeneca, Bristol-Myers-Squibb, Lundbeck, Otsuka, Sunovion; he has been a consultant or part of an advisory board for Allergan, Astra Zeneca, BMS, Forest Laboratories, Janssen-Ortho, Lundbeck, Merck, Otsuka, Pfizer, and Sunovion; he was part of the speaker bureau for Allergan, Astra Zeneca, BMS, Janssen-Ortho, Lundbeck, Otsuka, Pfizer, Purdue, and Sunovion. Maija Lindgren has received speaker honorarium from Lundbeck. No other authors have conflicts of interest. None of the funding sources participated in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication., (Copyright © 2019. Published by Elsevier B.V.)

It has remained unclear why schizophrenia typically manifests after adolescence and which neurobiological mechanisms are underlying the cascade leading to the actual onset of the illness. Here we show that the use of induced pluripotent stem cell-derived neurons of monozygotic twins from pairs discordant for schizophrenia enhances disease-specific signal by minimizing genetic heterogeneity. In proteomic and pathway analyses, clinical illness is associated especially with altered glycosaminoglycan, GABAergic synapse, sialylation, and purine metabolism pathways. Although only 12% of all 19,462 genes are expressed differentially between healthy males and females, up to 61% of the illness-related genes are sex specific. These results on sex-specific genes are replicated in another dataset. This implies that the pathophysiology differs between males and females, and may explain why symptoms appear after adolescence when the expression of many sex-specific genes change, and suggests the need for sex-specific treatments.

Background: We investigated whether psychosis risk symptoms predicted psychiatric service use using seven-year register follow-up data., Methods: Our sample included 715 adolescents aged 15-18, referred to psychiatric care for the first time. Psychosis risk symptoms were assessed with the Prodromal Questionnaire (PQ) at the beginning of the treatment. We assessed the power of the overall PQ as well as its positive, negative, general, and disorganized psychosis risk symptom factors in predicting prolonged service use. Baseline psychiatric diagnoses (grouped into 7 categories) were controlled for. Based on both inpatient and outpatient psychiatric treatment after baseline, adolescents were divided into three groups of brief, intermittent, and persistent service use., Results: Stronger symptoms on any PQ factor as well as the presence of a mood disorder predicted prolonged service use. All of the PQ factors remained significant predictors when adjusted for baseline mood disorder and multimorbidity., Conclusions: In a prospective follow-up of a large sample using comprehensive mental health records, our findings indicate that assessing psychosis risk symptoms in clinical adolescent settings at the beginning of treatment could predict long-term need for care beyond diagnostic information. Our findings replicate the previous findings that positive psychosis risk symptoms are unspecific markers of severity of psychopathology. Also psychosis risk symptoms of the negative, disorganization, and general clusters are approximately as strongly associated with prolonged psychiatric service use in the upcoming years., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Aim: Recent evidence from psychosis risk studies of preselected samples suggests that early functional impairment may be a vulnerability marker for psychosis. We investigated whether functional impairment predicted later risk of psychotic disorder and psychiatric hospitalizations in adolescents at entry to general psychiatric services., Methods: A total of 154 adolescents, aged 15 to 18 years, were recruited to the study at entry to general adolescent psychiatric services in Helsinki, Finland. Structured Interview for Prodromal Syndrome and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorder for DSM-IV, Clinical version interviews were used to assess psychotic-like symptoms, psychosis risk and psychiatric diagnoses. Of the adolescents, 46 met the criteria for clinical high risk status. The level of functioning was assessed with Global Functioning Social, Role and Psychological scales. The adolescents were followed for 3 to 9 (median = 5) years via a hospital discharge register. Cox regression analyses were used to examine whether baseline functioning predicted psychotic disorders and psychiatric hospitalizations when controlling for the effect of psychosis risk symptoms., Results: Impairments in social, role or psychological functioning did not predict psychotic disorders beyond risk symptoms. Impairment in psychological functioning was the only significant predictor of any psychiatric hospitalization after adjusting for positive psychosis risk symptom severity and level of social and role functioning., Conclusions: Psychosis was predicted by psychotic-like experiences at entry to psychiatric services. No aspect of functioning predicted psychosis in adolescents, which is likely to be explained by the low incidence of psychosis transitions. Severe mental disorders as assessed by psychiatric hospitalizations were predicted by more severe symptomatology as assessed by the psychological functioning scale., (© 2017 John Wiley & Sons Australia, Ltd.)

Deficiencies in theory of mind (ToM) are common in psychosis and may largely explain impaired social functioning. Currently, it is unclear whether impairments in ToM are explained by the more general cognitive deficits related to psychosis or whether ToM is impaired in psychosis independently of other cognitive deficits. This study examined ToM using the Hinting Task in young adults (n = 66) with first-episode psychosis and matched controls (n = 62). The participants were administered a broad neuropsychological assessment. Participants with psychosis performed worse than controls on the Hinting Task. However, 75% of the variance between the groups was explained by general cognitive deficits, especially impaired processing speed and episodic memory. Hinting Task performance of the best functioning patient group did not differ from that of the control group. When the psychosis group was divided according to diagnosis, the Hinting Task difference between individuals with schizophrenia and controls remained significant even when general cognitive performance was controlled for, suggesting specific verbal ToM deficits in schizophrenia. In contrast, those with other psychotic disorders did not differ from controls. Our results suggest that ToM deficits can be seen in early phases of psychotic disorders, schizophrenia in particular, and are partly independent of other cognitive functions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1 , NDE1 , NDEL1 , PDE4B and PDE4D , the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 ( p = 3.0 × 10 -8 ), located on a non-coding exon of NDE1 Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment., (© 2017 The Authors.)

Aim: We explored whether cognitive performance, and verbal learning in particular, predicts psychosis or psychiatric hospitalizations among unselected first-admission adolescent patients in general psychiatric care., Methods: Up to 152 adolescents aged 15-18 were interviewed with the SIPS, tested with a cognitive test battery in the beginning of their psychiatric treatment, and followed for a maximum of 9 years (median 4.5 years)., Results: The composite factors of processing speed, verbal performance and visuospatial performance did not predict psychosis (n = 7) or all-cause psychiatric hospitalizations (n = 26) beyond psychosis risk symptoms. However, those who developed psychosis performed worse on California Verbal Learning Test (CVLT) compared to other adolescents. Lower scores of CVLT immediate recall predicted psychosis (P = .003, HR = 1.13 per CVLT point decrease). However, when general verbal ability was adjusted for, CVLT did not reach significance., Conclusions: Impaired verbal list learning may predict psychosis also among adolescent psychiatric patients not preselected for psychosis risk suspicion., (© 2015 Wiley Publishing Asia Pty Ltd.)

Aim: We investigated the associations between clinical high-risk for psychosis (CHR), psychotic-like symptoms and suicidality among adolescent psychiatric patients., Methods: The sample consisted of 54 CHR and 107 non-CHR psychiatric patients aged 15-18 in Helsinki, Finland, who were assessed at the beginning of their psychiatric treatment with the Structured Interview for Prodromal Syndromes (SIPS). Current suicidality was measured with the Beck Depression Inventory (item 9), while lifetime suicidality was evaluated from all available data, including patient files. The participants were followed for 2.8-8.9 years via the national hospital discharge register, with the follow-up outcome being intentional self-harm. Data on suicides were also gathered from the Causes of Death statistics., Results: Only 30.5% of the adolescents had no suicidal ideation at the beginning of their treatment. CHR risk state and SIPS-assessed delusions, suspiciousness, and hallucinations were associated with higher current suicidality. Of the 154 adolescents with register follow-up, there were five (3.2%) with intentional self-harm resulting in hospital treatment, all female. CHR status was not associated with self-harm. Current suicidality, familial risk of psychosis, and SIPS decreased expression of emotions were associated with self-harm during follow-up. In a Cox regression analysis model among girls, only decreased expression of emotions remained a significant predictor of intentional self-harm. Baseline suicidality measures were not associated with transitions to psychosis., Conclusions: CHR status was associated with higher current suicidality but did not predict follow-up intentional self-harm in treatment-seeking adolescents. Decreased expression of emotions may indicate higher risk of intentional self-harm in adolescent treatment-seeking girls., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: Schizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia, there remains uncertainty about the causal genes involved in disease pathogenesis and how their function is regulated., Results: We performed a multi-stage epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in a total of 1714 individuals from three independent sample cohorts. We have identified multiple differentially methylated positions and regions consistently associated with schizophrenia across the three cohorts; these effects are independent of important confounders such as smoking. We also show that epigenetic variation at multiple loci across the genome contributes to the polygenic nature of schizophrenia. Finally, we show how DNA methylation quantitative trait loci in combination with Bayesian co-localization analyses can be used to annotate extended genomic regions nominated by studies of schizophrenia, and to identify potential regulatory variation causally involved in disease., Conclusions: This study represents the first systematic integrated analysis of genetic and epigenetic variation in schizophrenia, introducing a methodological approach that can be used to inform epigenome-wide association study analyses of other complex traits and diseases. We demonstrate the utility of using a polygenic risk score to identify molecular variation associated with etiological variation, and of using DNA methylation quantitative trait loci to refine the functional and regulatory variation associated with schizophrenia risk variants. Finally, we present strong evidence for the co-localization of genetic associations for schizophrenia and differential DNA methylation.

Background: The Symptom Checklist-90 (SCL-90) is a questionnaire that is widely used to measure subjective psychopathology. In this study we investigated the psychometric properties of the SCL-90 among adolescent inpatients and community youth matched on age and gender., Methods: The final SCL-90 respondents comprised three subsets: 201 inpatients at admission, of whom 152 also completed the instrument at discharge, and 197 controls. The mean age at baseline was 15.0 years (SD 1.2), and 73 % were female. Differential SCL-90 item functioning between the three subsets was assessed with an iterative algorithm, and the presence of multidimensionality was assessed with a number of methods. Confirmatory factor analyses for ordinal items compared three latent factor models: one dimension, nine correlated dimensions, and a one-plus-nine bifactor model. Sensitivity to change was assessed with the bifactor model's general factor scores at admission and discharge. The accuracy of this factor in detecting the need for treatment used, as a gold standard, psychiatric diagnoses based on clinical records and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime (K-SADS-PL) interview., Results: Item measurement properties were largely invariant across subsets under the unidimensional model, with standardized factor scores at admission being 0.04 higher than at discharge and 0.06 higher than those of controls. Determination of the empirical number of factors was inconclusive, reflecting a strong main factor and some multidimensionality. The unidimensional factor model had very good fit, but the bifactor model offered an overall improvement, though subfactors accounted for little item variance. The SCL-90s ability to identify those with and without a psychiatric disorder was good (AUC = 83 %, Glass's Δ = 1.4, Cohen's d = 1.1, diagnostic odds ratio 12.5). Scores were also fairly sensitive to change between admission and discharge (AUC 72 %, Cohen's d = 0.8)., Conclusions: The SCL-90 proved mostly unidimensional and showed sufficient item measurement invariance, and is thus a useful tool for screening overall psychopathology in adolescents. It is also applicable as an outcome measure for adolescent psychiatric patients. SCL-90 revealed significant gender differences in subjective psychopathology among both inpatients and community youth.

The aim of the present study was to compare change in functioning, affective symptoms and level of psychosis-risk symptoms in symptomatic adolescents who were treated either in an early intervention programme based on a need-adapted Family- and Community-orientated integrative Treatment Model (FCTM) or in standard adolescent psychiatric treatment (Treatment As Usual, TAU). 28 pairs were matched by length of follow-up, gender, age, and baseline functioning. At one year after the start of treatment, the matched groups were compared on change in functioning (GAF-M), five psychosis-risk dimensions of the Structured Interview for Psychosis-Risk Syndromes (SIPS), and self-reported anxiety, depression, and hopelessness symptoms (BAI, BDI-II, BHS). FCTM was more effective in improving functioning (20% vs. 6% improvement on GAF-M), as well as self-reported depression (53% vs. 14% improvement on BDI-II) and hopelessness (41% vs. 3% improvement on BHS). However, for psychosis-risk symptoms and anxiety symptoms, effectiveness differences between treatment models did not reach statistical significance. To conclude, in the present study, we found greater improvement in functioning and self-reported depression and hopelessness among adolescents who received a need-adapted Family- and Community-orientated integrative Treatment than among those who were treated in standard adolescent psychiatry., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Psychotic-like experiences (PLEs) are sub-psychotic expressions of the psychosis continuum. Several studies have suggested multifactorial models, including a bifactor model, of the putative PLEs assessed with the popular Community Assessment of Psychic Experiences (CAPE) questionnaire. Our confirmatory results in a gender-balanced population of adolescents and young adults support a three-factor Paranoia-Delusions-Hallucinations structure of PLEs, which excludes Grandiosity and Common Paranormal Beliefs. The best latent models achieved excellent fit when taking the categorical nature of the responses into consideration., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: We performed a whole-genome expression study to clarify the nature of the biological processes mediating between inherited genetic variations and cognitive dysfunction in schizophrenia., Method: Gene expression was assayed from peripheral blood mononuclear cells using Illumina Human WG6 v3.0 chips in twins discordant for schizophrenia or bipolar disorder and control twins. After quality control, expression levels of 18,559 genes were screened for association with the California Verbal Learning Test (CVLT) performance, and any memory-related probes were then evaluated for variation by diagnostic status in the discovery sample (N = 190), and in an independent replication sample (N = 73). Heritability of gene expression using the twin design was also assessed., Results: After Bonferroni correction (p < 2.69 × 10-6), CVLT performance was significantly related to expression levels for 76 genes, 43 of which were differentially expressed in schizophrenia patients, with comparable effect sizes in the same direction in the replication sample. For 41 of these 43 transcripts, expression levels were heritable. Nearly all identified genes contain common or de novo mutations associated with schizophrenia in prior studies., Conclusion: Genes increasing risk for schizophrenia appear to do so in part via effects on signaling cascades influencing memory. The genes implicated in these processes are enriched for those related to RNA processing and DNA replication and include genes influencing G-protein coupled signal transduction, cytokine signaling, and oligodendrocyte function., ((c) 2015 APA, all rights reserved).)

Symptoms of the psychotic type are relatively common in young persons, but seldom result in the development of an actual psychotic disorder. Psychotic-like symptoms in the young are, however, associated with more severe psychiatric symptoms and a less favorable prognosis, whereby their identification is important in psychiatric treatment. A symptom-oriented approach is important in the treatment: instead of the possible risk of psychosis, focus will be on the actual situation, taking the total symptom picture and the person's life situation into consideration. Cognitive psychotherapy is the recommended first-line treatment for psychotic-like symptoms.

The Prodromal Questionnaire (PQ) identifies psychiatric help-seekers in need of clinical interviews to diagnose psychosis risk. However, some providers use the PQ alone to identify risk. Therefore, we tested its predictive utility among 731 adolescent psychiatric help-seekers, with a 3-9-year register-based follow-up. Nine latent factors corresponded well with postulated subscales. Depersonalization predicted later hospitalization with a psychosis diagnosis (HR 1.6 per SD increase), and Role Functioning predicted any psychiatric hospitalization (HR 1.3). Published cut-off scores were poor predictors of psychosis; endorsement rates were very high for most symptoms. Therefore, we do not recommend using the PQ without second-stage clinical interviews., (Copyright © 2014 Elsevier B.V. All rights reserved.)