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Morphological abnormalities of subcortical structures have been consistently reported along the schizophrenia clinical spectrum, and they may play an important role in the pathophysiology of psychosis. However, the question arises whether these subcortical features are consequences of medication and illness chronicity, or if they contribute to the vulnerability to develop schizophrenia spectrum disorders. If some of the subcortical abnormalities could be evidenced in community adolescents expressing higher schizotypal traits (psychometric schizotypy), they could potentially shed light on vulnerability markers. To date, very few studies have examined the link between psychometric schizotypy and volumes of subcortical regions, and none of them have used a longitudinal design. This study sets out to investigate developmental trajectories of subcortical volumes in 110 community adolescents (12 to 20 years old), for whom MRI-scans were acquired over a period of 5 years, reaching a total of 297 scans. Analyses were conducted using Freesurfer, and schizotypal traits were measured with the Schizotypal Personality Questionnaire (SPQ). Using mixed model regression analyses following a region-of-interest approach, we observed differential linear developmental trajectories in four subcortical structures when comparing higher versus lower scorers on the disorganized schizotypy dimension (bilateral hippocampus, left-lateral ventricle and left-pallidum) and the negative schizotypy dimension (bilateral pallidum, and right-thalamus). All results survived a threshold of p < .05 (FDR-corrected) while covarying for the effect of other psychological problems (externalized and internalized psychopathology). These results indicate that expression of higher levels of negative and disorganized schizotypy during adolescence was associated with neural markers linking schizotypy personality features to schizophrenia spectrum disorders., Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The 22q11.2 deletion syndrome (22q11DS) is one of the highest known risk factors for schizophrenia and recent findings have highlighted the clinical relevance of ultra-high risk (UHR) criteria in this population. However, studies in other at-risk populations have shown that the presence of negative symptoms (NS) is also of clinical relevance in predicting transition to psychosis. The present study examined in detail the presence and course of NS in 22q11DS, as well as their value in predicting transition to psychosis., Methods: A total of 111 participants aged between 8 and 33 years were assessed with the Structured Interview for Psychosis-Risk Syndromes (SIPS). A follow-up assessment was available for 89 individuals., Results: Core NS of at least moderate severity were present in 50.5% of the sample and were more severe in individuals meeting UHR criteria. They predominantly remained stable over time and their emergence between baseline and follow-up assessment was associated with significant functional decline. Some NS were significant predictors of conversion to psychosis and the emergence/persistence of psychosis risk., Conclusions: Altogether, these findings highlight that NS are core manifestations of psychosis in individuals with 22q11DS that strongly impact global functioning. The presence of NS should be a primary target of early therapeutic intervention in this population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Schizotypal traits are expressions of underlying vulnerability to psychotic disorders which have a potential impact on mental health status, neurocognition, quality of life, and daily functioning. To date, little research has examined epidemiologic landscape of schizotypal traits at the cross-national level. Our aim was to study the expression of schizotypal traits by sex, age, and country in a combined sample gathered from 12 countries., Methods: A total of 27,001 participants completed the Schizotypal Personality Questionnaire (SPQ). The mean age of participants was 22.12 (SD=6.28); 37.5% (n=10,126) were males., Results: Schizotypal traits varied according to sex, age, and country. Females scored higher than males in the positive dimension, whereas males scored higher in the disorganization dimension. By age, a significant decrease in the positive schizotypal traits was observed. Epidemiological expression of schizotypal traits varied by country. Moreover, several interactions by sex, age, and country were found., Conclusions: This pattern is similar to those found in patients with psychosis and psychotic-like experiences. These findings provide new insights and the opportunity to explore the phenotypic expression of schizotypal traits at cross-national level., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Schizotypal Personality Questionnaire-Brief (SPQ-B) was developed with the aim of examining variations in healthy trait schizotypy, as well as latent vulnerability to psychotic-spectrum disorders. No previous study has studied the cross-cultural validity of the SPQ-B in a large cross-national sample. The main goal of the present study was to analyze the reliability and the internal structure of SPQ-B scores in a multinational sample of 28,426 participants recruited from 14 countries. The mean age was 22.63years (SD=7.08; range 16-68years), 37.7% (n=10,711) were men. The omega coefficients were high, ranging from 0.86 to 0.92 for the total sample. Confirmatory factor analysis revealed that SPQ-B items were grouped either in a theoretical structure of three first-order factors (Cognitive-Perceptual, Interpersonal, and Disorganized) or in a bifactor model (three first-order factors plus a general factor of schizotypal personality). In addition, the results supported configural but not strong measurement invariance of SPQ-B scores across samples. These findings provide new information about the factor structure of schizotypal personality, and support the validity and utility of the SPQ-B, a brief and easy tool for assessing self-reported schizotypal traits, in cross-national research. Theoretical and clinical implications for diagnostic systems, psychosis models, and cross-national mental health strategies are derived from these results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates. If this is the case, temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high-density (204 channel) EEG to explore between-group microstate differences in 30 adolescents with 22q11DS and 28 age-matched controls. We found an increased presence of one microstate class (class C) in the 22q11DS adolescents with respect to controls that was associated with positive prodromal symptoms (hallucinations). A previous across-age study showed that the class C microstate was more present during adolescence and a combined EEG-fMRI study associated the class C microstate with the salience resting state network, a network known to be dysfunctional in schizophrenia. Therefore, the increased class C microstates could be indexing the increased risk of 22q11DS individuals to develop schizophrenia if confirmed by our ongoing longitudinal study comparing both the adult 22q11DS individuals with and without schizophrenia, as well as schizophrenic individuals with and without 22q11DS., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Clinical and phenomenological accounts of schizophrenia suggest that impairments in self-reflective processes significantly contribute to psychopathological expression. Recent imaging studies observe atypical cerebral activation patterns during self-reflection, especially around the cortical midline structures, both in psychosis-prone adults and individuals with schizophrenia. Given that self-reflection processes consolidate during adolescence, and that early transient expression of psychosis (positive schizotypy) also arises during this period, the present study sought to examine whether atypical cerebral activation during self-reflection task could be associated with early schizotypic expression during adolescence. Forty-two neurotypical adolescent participants (19 females) aged from 12 to 19 (15.92±1.9) underwent a self-reflection task using functional neuroimaging (fMRI), where they had to evaluate trait adjectives (1 to 4 ratings) about themselves or their same sex best friend. The Schizotypal Personality Questionnaire (SPQ) was employed to assess positive schizotypic expression. Results showed that positive schizotypy in adolescents significantly correlated with cortical midline activation patterns in the dorsomedial prefrontal cortex (dmPFC) and the posterior cingulate cortex (PCC), as well as the dorsolateral PFC and the lingual gyrus. The results are consistent with previous imaging literature on self-reflection and schizophrenia. They further highlight that the relationship between self-reflection processes and positive schizotypy operates at the trait level of expression and can be observed as early as adolescence., (Copyright © 2013 Elsevier B.V. All rights reserved.)

While schizotypal features are common during adolescence, they can also signal increased risk for the onset of schizophreniform disorders. Most studies with adolescents find that hallucination and delusion-like symptoms (positive schizotypal features) best predict future psychopathology. Still, the developmental process of positive schizotypy remains elusive, specifically with regards to 1) its relationships to negative and disorganization schizotypal dimensions; 2) its associations to maladaptive functioning during adolescence. This longitudinal study aimed to further characterize these relationships, thereby delineating "early and broadly defined psychosis risk mental states" (Keshavan et al., 2011). The current study presents the 3-year course of schizotypal trait expression in 34 clinical adolescents aged 12 to 18 years consulting for non-psychotic difficulties. Schizotypal expression was assessed twice using the Schizotypal Personality Questionnaire, accompanied by an examination of internalizing/externalizing problems using the Achenbach scales. Cross-sectional and longitudinal analyses were conducted to assess the expression and course of schizotypal dimensions; mediation analyses were further employed to highlight the developmental interactions promoting the maintenance of positive schizotypal expression. The results reveal that positive schizotypy, and more specifically unusual perceptual experiences, significantly declined during the study interval. Disorganization features were found to mediate the relationships between the negative and positive dimensions of schizotypy within and across evaluations. Somatic complaints and attentional difficulties further strengthened the expression of positive schizotypy during the study interval. These results suggest that the relationship between disorganization features and positive schizotypy may play a central role in establishing risk for psychosis during adolescence., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Atypical functional connectivity in the maturing brains of 22q11.2 deletion syndrome (22q11DS) may contribute to the expression of early psychotic symptoms commonly reported by these youths. This study's objective was to examine functional connectivity in cerebral networks at rest (Resting-State Networks; RSNs) and their relationship to symptomatic and neuropsychological characteristics putting them at very high risk factor for developing psychosis. Twenty-seven adolescents with 22q11DS and 33 typically developing control adolescents matched for age, gender and handedness underwent an 8-minute resting state functional MRI session. RSNs identification procedure employed Independent Component Analysis (ICA). We tested for potential group differences in functional connectivity within-networks. Then, we examined relationships between network connectivity and symptomatic/neuropsychological characteristics in the 22q11DS group. A total of nine resting-state networks were identified. Between-group differences suggested both increased and decreased functional connectivity in the 22q11DS group, involving the default-mode, sensorimotor, visuo-spatial, and high level visual networks. Finally, atypical connectivity in the default-mode network, specifically within the left superior frontal gyrus region, correlated with prodromal symptom intensity and neuropsychological performances in the 22q11DS group. The results suggest that atypical functional connectivity may sustain both increased vulnerability to psychosis and characteristic cognitive impairments in 22q11DS., (Copyright © 2012 Elsevier B.V. All rights reserved.)

22q11.2 deletion syndrome (22q11DS) is associated with an increased susceptibility to develop schizophrenia. Despite a large body of literature documenting abnormal brain structure in 22q11DS, cerebral changes associated with brain maturation in 22q11DS remained largely unexplored. To map cortical maturation from childhood to adulthood in 22q11.2 deletion syndrome, we used cerebral MRI from 59 patients with 22q11DS, aged 6 to 40, and 80 typically developing controls; three year follow-up assessments were also available for 32 patients and 31 matched controls. Cross-sectional cortical thickness trajectories during childhood and adolescence were approximated in age bins. Repeated-measures were also conducted with the longitudinal data. Within the group of patients with 22q11DS, exploratory measures of cortical thickness differences related to COMT polymorphism, IQ, and schizophrenia were also conducted. We observed deviant trajectories of cortical thickness changes with age in patients with 22q11DS. In affected preadolescents, larger prefrontal thickness was observed compared to age-matched controls. Afterward, we observed greater cortical loss in 22q11DS with a convergence of cortical thickness values by the end of adolescence. No compelling evidence for an effect of COMT polymorphism on cortical maturation was observed. Within 22q11DS, significant differences in cortical thickness were related to cognitive level in children and adolescents, and to schizophrenia in adults. Deviant trajectories of cortical thickness from childhood to adulthood provide strong in vivo cues for a defect in the programmed synaptic elimination, which in turn may explain the susceptibility of patients with 22q11DS to develop psychosis.

Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk for developing schizophrenia: half of affected adolescents report transient psychotic experiences and up to 30% of adults are diagnosed with schizophrenia. Prospective studies have shown that psychotic symptoms in childhood are predictive of later schizophreniform disorders. The current study aimed to define the prevalence and correlates of psychotic symptoms (PS) in young children and adolescents with 22q11DS. Forty-three children and adolescents with 22q11DS (mean age = 10.62+/-11.19) participated in this study. The occurrence of PS and their neuropsychological and behavioral correlates were investigated through semi-structured interviews and standardized measures. Psychotic symptoms were reported in 28% of the total sample and 17% of pre-adolescent children, and associated with decreased verbal IQ scores [F(1) = 4.41, p = 0.042]. Compared to young patients without PS, young patients with PS were perceived by their parents as more anxious-depressed [F(1) = 4.76, p = 0.035] and withdrawn [F(1) = 7.63, p = 0.009], with reduced adaptive socialization skills [F(1) = 6.88, p = 0.012]. Results suggest that psychotic manifestations are present earlier than typically reported in youngsters with 22q11DS and are accompanied by reduced verbal IQ performance and decreased adaptative social skills. The symptomatic, neuropsychological and behavioral characteristics observed in the current study may constitute central markers of increased risk for psychosis in 22q11DS.