Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Different learning aberrations relate to delusion-like beliefs with different contents.

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control or that events in the world have specific personal meaning. We compare learning in two different cognitive tasks, probabilistic reversal learning and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that clinical high-risk status alone does not result in different behavioural results in the probabilistic reversal learning task but that an individual's level of paranoia is associated with excessive switching behaviour. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioural data to explore how latent parameters vary within individuals between tasks and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates in the probabilistic reversal learning task and the blocking task. Non-paranoid delusion-like belief conviction is instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which, given the transdiagnostic status of paranoia, might have differential utility in predicting psychosis.

The association between neighborhood-level social fragmentation and distressing psychotic-like experiences in early adolescence: the moderating role of close friends.

BACKGROUND: Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents. METHODS: Data were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends. RESULTS: Participants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted ß = 0.05; 95% CI: 0.01-0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted ß = -0.02; 95% CI: -0.04 to <-0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted ß = 0.07; 95% CI: 0.03-0.11). However, among those with more close friends, the association was non-significant (adjusted ß = 0.03; 95% CI: -0.01 to 0.07). CONCLUSIONS: Greater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach.

Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term "transdiagnostic" was widely used, the pathways to psychopathology emerge in a system involving equifinality and multifinality. Like most other psychological disorders, psychosis is associated with multiple domains of risk factors, both genetic and environmental, and there are many transdiagnostic developmental pathways that can lead to psychotic syndromes. In this article, we discuss our current understanding of heterogeneity in the etiology of psychosis and its implications for approaches to conceptualizing etiology and research. We highlight the need for examining risk factors at multiple levels and to increase the emphasis on transdiagnostic developmental trajectories as a key variable associated with etiologic subtypes. This will be increasingly feasible now that large, longitudinal datasets are becoming available and researchers have access to more sophisticated analytic tools, such as machine learning, which can identify more homogenous subtypes with the ultimate goal of enhancing options for treatment and preventive intervention.

Examining the Most Important Risk Factors for Predicting Youth Persistent and Distressing Psychotic-Like Experiences.

BACKGROUND: Persistence and distress distinguish more clinically significant psychotic-like experiences (PLEs) from those that are less likely to be associated with impairment and/or need for care. Identifying risk factors that identify clinically relevant PLEs early in development is important for improving our understanding of the etiopathogenesis of these experiences. Machine learning analyses were used to examine the most important baseline factors distinguishing persistent distressing PLEs. METHODS: Using Adolescent Brain Cognitive Development (ABCD) Study data on PLEs from 3 time points (ages 9-13 years), we created the following groups: individuals with persistent distressing PLEs (n = 305), individuals with transient distressing PLEs (n = 374), and individuals with low-level PLEs demographically matched to either the persistent distressing PLEs group (n = 305) or the transient distressing PLEs group (n = 374). Random forest classification models were trained to distinguish persistent distressing PLEs from low-level PLEs, transient distressing PLEs from low-level PLEs, and persistent distressing PLEs from transient distressing PLEs. Models were trained using identified baseline predictors as input features (i.e., cognitive, neural [cortical thickness, resting-state functional connectivity], developmental milestone delays, internalizing symptoms, adverse childhood experiences). RESULTS: The model distinguishing persistent distressing PLEs from low-level PLEs showed the highest accuracy (test sample accuracy = 69.33%; 95% CI, 61.29%-76.59%). The most important predictors included internalizing symptoms, adverse childhood experiences, and cognitive functioning. Models for distinguishing persistent PLEs from transient distressing PLEs generally performed poorly. CONCLUSIONS: Model performance metrics indicated that while most important factors overlapped across models (e.g., internalizing symptoms), adverse childhood experiences were especially important for predicting persistent distressing PLEs. Machine learning analyses proved useful for distinguishing the most clinically relevant group from the least clinically relevant group but showed limited ability to distinguish among clinically relevant groups that differed in PLE persistence.

Aspects of Area Deprivation Index in Relation to Hippocampal Volume Among Children.

Importance: Area deprivation index (ADI) has been shown to be associated with reduced hippocampal volume (HV) among youths. The social environment may interact with the association between ADI and HV. Objective: To investigate which aspects of ADI are uniquely associated with bilateral HV and whether school and family environments have moderating interactions in associations between ADI and HV. Design, Setting, and Participants: This cross-sectional study used data from the Adolescent Brain and Cognitive Development (ABCD) study. Participants aged 9 and 10 years were recruited from 21 sites in the US between September 2016 and August 2018. Data analysis was performed between March 2023 and April 2024. Exposures: ADI aspects were derived from participant primary home addresses provided by parents or guardians. Main Outcomes and Measures: HV was automatically segmented from structural brain images ascertained from magnetic resonance imaging. Multiple generalized linear mixed modeling tested associations between 9 indices of ADI and bilateral HV, with family groups and recruitment sites as random effects. After stepwise backward selection, models were adjusted for individual-level covariates, including age, sex, race and ethnicity, parental education, household income, and estimated intracranial volume. Results: This study included 10 114 participants aged 9 and 10 years (median [IQR] age, 9.92 [9.33-10.48] years; 5294 male [52.3%]; 200 Asian [2.0%], 1411 Black [14.0%], and 6655 White [65.8%]; 1959 Hispanic [19.4%]). After stepwise backward selection and adjusting for covariates, only the percentage of neighborhood-level single-parent households was associated with right HV (adjusted ß per 1-SD increase in single-parent households, -0.03; 95% CI, -0.06 to -0.01; P = .01). School environment interacted with neighborhood-level single-parent households in its association with right HV (adjusted ß per 1-SD increase in score, 0.02; 95% CI, 0.01 to 0.03; P = .003), such that there was an inverse association only among those at a school with the mean environment score (adjusted ß per 1% increase in single-parent households, -0.03; 95% CI, -0.05 to -0.01; P = .02) and worse (-1 SD score) school environment score (adjusted ß per 1% increase in single-parent households, -0.05; 95% CI, -0.09 to -0.01; P < .001) but not among those at better (+1 SD score) school environments. Conclusions and Relevance: In this study, an increased percentage of neighborhood-level single-parent households was associated with reduced right HV among children in schools with the mean or worse but not better environment score. These findings suggest that longitudinal research concerning the association of neighborhood-level characteristics and school environments with hippocampal development may be warranted to better understand complex interactions between various social factors and child neurodevelopment and mental health outcomes.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity.

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Longitudinal Trajectories of Premorbid Social and Academic Adjustment in Youth at Clinical High Risk for Psychosis: Implications for Conversion.

BACKGROUND AND HYPOTHESIS: Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the between-person level, which has constrained analyses of premorbid adjustment, clinical covariates, and conversion to psychosis. STUDY DESIGN: Growth-curve models examined longitudinal trajectories in retrospective reports of premorbid social and academic adjustment from youth at CHR (n = 498). Interaction models tested whether known covariates of premorbid adjustment problems (attenuated negative symptoms, cognition, and childhood trauma) were associated with different premorbid adjustment trajectories in converters vs non-converters (ie, participants who did/did not develop psychotic disorders within 2-year follow-up). STUDY RESULTS: Converters reported poorer social adjustment throughout the premorbid period. Converters who developed psychosis with an affective component reported poorer academic adjustment throughout the premorbid period than those who developed non-affective psychosis. Tentatively, baseline attenuated negative symptoms may have been associated with worsening social adjustment in the premorbid period for non-converters only. Childhood trauma impact was associated with fewer academic functioning problems among converters. Cognition effects did not differ based on conversion status. CONCLUSIONS: Premorbid social function is an important factor in risk for conversion to psychosis. Negative symptoms and childhood trauma had different relationships to premorbid functioning in converters vs non-converters. Mechanisms linking symptoms and trauma to functional impairment may be different in converters vs non-converters, suggesting possible new avenues for risk assessment.

The Complex Latent Structure of Attenuated Psychotic Symptoms: Hierarchical and Bifactor Models of SIPS Symptoms Replicated in Two Large Samples at Clinical High Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms. STUDY DESIGN: Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders. STUDY RESULTS: Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable. CONCLUSIONS: Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.

Sex differences in clinical presentation in youth at high risk for psychosis who transition to psychosis.

Sex differences have been observed in individuals with schizophrenia and for those at clinical high risk (CHR) for psychosis. However, specific differences in CHR individuals who transition to psychosis remain inconsistent and understudied. This study aimed to investigate sex differences in 156 CHR individuals who made the transition to psychosis. A wide range of demographics, positive and negative symptoms, depression, anxiety, social and role functioning, trauma, and substance use were assessed at baseline and symptoms and diagnoses at the time of transition. Fluctuations in positive and negative symptoms and different medications were also assessed. No sex differences were observed at baseline for those who later transitioned to psychosis. At transition, males were significantly more likely to be diagnosed as having schizophrenia or schizophreniform disorder and through the course of the study, males were more likely to be taking stimulants. Limitations in this study was the lack of longitudinal follow-up post transition. The study highlights the need for further research on sex differences in individuals who transition to psychosis. Understanding these differences can have implications for treatment and monitoring of CHR individuals.

Neurocognition in adolescents and young adults at clinical high risk for psychosis: Predictive stability for social and role functioning.

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning.

The hierarchical taxonomy of psychopathology in clinical high risk for psychosis: Validation and extension.

The Hierarchical Taxonomy of Psychopathology (HiTOP) consortium's transdiagnostic dimensional model of psychopathology has considerable support; however, this model has been underresearched in individuals at clinical high risk for psychosis (CHR-P), a population that may advance the model. CHR-P individuals not only have attenuated psychotic symptoms that vary in severity, but also have many comorbid diagnoses and varied clinical outcomes, including disorders with uncertain relations to HiTOP (e.g., obsessive-compulsive disorder). The present study used self-report and interview data from North American Prodrome Longitudinal Study-3 (710 CHR, 96 controls) to replicate the HiTOP model and test specific hypotheses regarding disorders with uncertain relations to its dimensions. Additionally, the present study examined the HiTOP model in relation to childhood trauma, declines in social functioning, and development of full psychosis. Confirmatory factor analysis indicated that the HiTOP model's fit was nearly adequate (e.g., comparative fit index = .89), though several theory-relevant modifications were indicated. Additionally, specific tests were conducted to gain a more fine-grained perspective on how disorders with less clear prior evidence were related to the HiTOP model. Notable findings from these analyses include bipolar spectrum disorders relating to the psychosis super spectrum (i.e., .39 loading), and obsessive-compulsive disorder showing a complex pattern of loadings (e.g., internalizing and psychosis). The final model parsimoniously accounted for childhood trauma (e.g., super spectra rs = .22-.32), associations with current functioning, and predicted future conversion to a psychotic disorder (e.g., super spectra R² = .13). Overall, these results inform the HiTOP model and suggest its promise for CHR-P research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study.

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

Robust Brain Correlates of Cognitive Performance in Psychosis and its Prodrome.

BACKGROUND: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state fMRI. We hypothesized a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. METHODS: The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the Human Connectome Project for Early Psychosis (n=183) to identify links between connectivity and ACPT performance. We then analyzed the North American Prodrome Longitudinal Study 2 (n=345), a multi-site prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and controls. RESULTS: Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p<.005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n=17). This finding was not observed in nonconverters (n=196) or controls (n=132). CONCLUSIONS: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.

Anomalías físicas menores y vulnerabilidad en jóvenes con un síndrome prodrómico / Minor physical anomalies and vulnerability in prodromal youth

Dado que tanto el cerebro como las características craneofaciales/de extremidades tienen su origen en la misma capa germinal durante la fase inicial de la gestación, la presencia posnatal de anomalías físicas menores (AFM) que afectan a estas características físicas puede ser indicativa de la existencia de defectos de la migración neural prenatal y, por consiguiente, de anomalías cerebrales en los individuos con psicosis. Sin embargo, hasta la fecha no se sabe qué síntomas y características de AFM pueden estar asociados, y de qué modo pueden reflejar esos marcadores la vulnerabilidad para desarrollar una psicosis en los adolescentes de alto riesgo. Esta información es especialmente crucial para comprender la susceptibilidad e informar las conceptualizaciones etiológicas, como el modelo de diátesis-estrés neural. En este estudio, se evaluó en 50 adolescentes con un síndrome prodrómico la presencia de AFM, el cortisol salivar, la función de memoria auditiva y visual, y los síntomas atenuados positivos, negativos y de desorganización. Los resultados indicaron que los participantes que presentaban unas AFM elevadas (n=25) se diferenciaban por un cortisol elevado, déficit de la memoria visual inmediata y tardía, y niveles más altos de síntomas prodrómicos de desorganización, en comparación con los participantes en los que había una menor incidencia de AFM. Esto fue respaldado por los análisis de correlación adicionales en los que se examinó a la totalidad de la muestra. Estas observaciones aportan un respaldo preliminar a la teoría de que las AFM pueden reflejar la vulnerabilidad del sistema del hipocampo en los pacientes prodrómicos (AU)

Because both the brain and craniofacial/limb features originate from the same germinal layer during early gestation, the postnatal presence of minor physical anomalies (MPAs) involving these physical features may be indicative of defects in prenatal neural migration and consequent brain abnormalities among individuals with psychosis. However, to date it is unknown what symptoms and characteristics MPAs may be associated with, or how these markers may reflect vulnerability among adolescents at high-risk for developing psychosis. This information is particularly vital for understanding susceptibility and informing etiological conceptualizations such as the neural diathesis-stress model. In this study, 50 adolescents with a prodromal syndrome were evaluated for MPAs, salivary cortisol, auditory and visual memory function, and attenuated positive, negative, and disorganized symptoms. Results indicated that the participants showing elevated MPAs (n=25) were distinguished by elevated cortisol, deficit immediate and delayed visual memory, and higher levels of disorganized prodromal symptoms when compared with those participants exhibiting a lower incidence of MPAs. This was supported by supplementary correlational analyses examining the entire sample. These findings provide preliminary support for a theory that MPAs may reflect hippocampal system vulnerability among prodromal patients (AU)