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Childhood socioemotional development and growth mindset preceding schizophrenia: case–control study using prospectively collected data
(Royal College of Psychiatrists, 2026-04-06)
Javiera Vasquez-Nuñez
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José Conejeros
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Camila Díaz-Dellarrossa
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Cristian Mena
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UNDURRAGA FOURCADE, JUAN PABLO
<jats:sec id="S2056472426110047_as1"> <jats:title>Background</jats:title> <jats:p>Understanding premorbid socioemotional trajectories in schizophrenia is crucial for early identification and potential primary prevention. Studies in adults with schizophrenia suggest similar socioemotional premorbid difficulties, but are limited by their retrospective design.</jats:p> </jats:sec> <jats:sec id="S2056472426110047_as2"> <jats:title>Aims</jats:title> <jats:p>To contribute new insights into the premorbid socioemotional characteristics of schizophrenia, beyond the biases of retrospective studies, this research investigates three educational socioemotional dimensions in children who later developed the disorder.</jats:p> </jats:sec> <jats:sec id="S2056472426110047_as3"> <jats:title>Method</jats:title> <jats:p> We conducted a case–control study using prospectively collected data, examining childhood differences in perceived parental support, self-esteem and school motivation, and growth mindset (intelligence can improve through effort) among individuals who later developed schizophrenia ( <jats:italic>n</jats:italic> = 341) and their classmates ( <jats:italic>n</jats:italic> = 20 567). We constructed <jats:italic>z</jats:italic> -normalised indicators based on standardised national tests administered in fourth, eighth and tenth grades in Chile. Mixed linear models accounted for repeated measures and adjusted for educational level, gender, grade point average, school and year. </jats:p> </jats:sec> <jats:sec id="S2056472426110047_as4"> <jats:title>Results</jats:title> <jats:p> Children later diagnosed with schizophrenia reported less parental educational support compared with their classmates ( <jats:italic>β</jats:italic> = −0.276, 95% CI −0.388 to −0.163). Only girls who later developed schizophrenia reported lower self-esteem and school motivation than their peers ( <jats:italic>β</jats:italic> = −0.290, 95% CI −0.498 to −0.131). Contrary to our hypothesis, children who later developed schizophrenia showed a higher growth mindset ( <jats:italic>β</jats:italic> = 0.287, 95% CI 0.077–0.497). </jats:p> </jats:sec> <jats:sec id="S2056472426110047_as5"> <jats:title>Conclusions</jats:title> <jats:p>Our results suggest that premorbid socioemotional characteristics in schizophrenia are detectable in childhood and may vary by gender. These findings highlight the potential of educational settings as platforms for preventive interventions aimed at enhancing parental support and monitoring students’ psycho-emotional well-being, while acknowledging gender-specific developmental trajectories and heterogeneity in premorbid functioning.</jats:p> </jats:sec>
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Longitudinal changes in striatocortical connectivity in first-episode psychosis associated with the emergence of treatment resistance
(Springer Science and Business Media LLC, 2025-08-16)
Angeles Tepper
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Javiera Vásquez
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Camila Díaz Dellarossa
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Juan Pablo Ramirez-Mahaluf
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Juan Aguirre
1
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Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia
(2021)
Barbara Iruretagoyena
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Carmen Paz Castañeda
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Cristian Mena
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Camila Diaz
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Ruben Nachar
7Scopus© Citations 10
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Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis
(2023)
Marisleydis García Saborit
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Alejandro Jara
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Néstor Muñoz
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Carlos Milovic
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Angeles Tepper
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.</jats:p> </jats:sec>
Scopus© Citations 1 1
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Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities
(2020)
Nicolas A. Crossley
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Andre Zugman
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Francisco Reyes-Madrigal
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Leticia S. Czepielewski
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Mariana N. Castro
<jats:title>Summary</jats:title><jats:sec id="S0007125020001439_sec_a1"><jats:title>Background</jats:title><jats:p>Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a2"><jats:title>Aims</jats:title><jats:p>We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a3" sec-type="methods"><jats:title>Method</jats:title><jats:p>This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a4" sec-type="results"><jats:title>Results</jats:title><jats:p>A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (<jats:italic>P</jats:italic> = 0.006). Controls showed a positive correlation between total grey matter volume and income (<jats:italic>R</jats:italic> = 0.14, <jats:italic>P</jats:italic> = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (<jats:italic>R</jats:italic> = −0.076, <jats:italic>P</jats:italic> = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a5" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.</jats:p></jats:sec>
Scopus© Citations 10 1
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Intra and inter-individual variability in functional connectomes of patients with First Episode of Psychosis
(2023)
Ángeles Tepper
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Javiera Vásquez Núñez
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Juan Pablo Ramirez-Mahaluf
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Juan Manuel Aguirre
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Daniella Barbagelata
Scopus© Citations 1 2
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Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
(2022)
Juan P Ramirez-Mahaluf
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Ángeles Tepper
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Luz Maria Alliende
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Carlos Mena
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Carmen Paz Castañeda
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Hypothesis</jats:title> <jats:p>Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Design</jats:title> <jats:p>Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Results</jats:title> <jats:p>We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.</jats:p> </jats:sec>
Scopus© Citations 17 1
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Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome
(2021)
Ángeles Tepper
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Analía Cuiza
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Luz María Alliende
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Carlos Mena
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Juan Pablo Ramirez-Mahaluf
<jats:title>Abstract</jats:title> <jats:p>22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.</jats:p>
1Scopus© Citations 6
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Differences of affective and non-affective psychoses in early intervention services from Latin America
(2022)
Raphael O. Cerqueira
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Carolina Ziebold
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Daniel Cavalcante
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Giovany Oliveira
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Javiera Vásquez
Scopus© Citations 8 8
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Duration of untreated psychosis and acute remission of negative symptoms in a South American first-episode psychosis cohort
(2017)
Alfonso González-Valderrama
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Carmen Paz Castañeda
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Cristián Mena
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Juan Undurraga
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Pilar Mondaca
16Scopus© Citations 15

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