Universidad del Desarrollo

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Premorbid school performance trajectories in patients with treatment-resistant schizophrenia prescribed clozapine in the public health system in Chile: a case-control study, 2007–2020
(Cambridge University Press (CUP), 2025)
Jose Conejeros-Pavez
;
Javiera Vasquez
;
Camila Diaz
;
Cristian Mena
;
UNDURRAGA FOURCADE, JUAN PABLO
Background The premorbid phase of treatment-resistant schizophrenia (TRS) may reveal underlying mechanisms and inform early interventions. According to the neurodevelopmental hypothesis, treatment resistance may be linked to pronounced developmental impairments. We examined school grades and attendance trajectories in children who later developed TRS.Methods This case-control study analyzed school grade point average and attendance among all individuals born after 1990 and started on clozapine in Chile's public health system as a proxy for TRS. Control groups included children later diagnosed with treatment-responsive schizophrenia, bipolar disorder, and unaffected classmates. Linear mixed models accounted for individual and school-level confounders.Results We included 1072 children (9929 observations, 29.3% female) subsequently diagnosed with TRS, 323 (2802 observations, 25.7% female) with schizophrenia, 175 (1784 observations, 53.8% female) bipolar disorder, and 273,260 (533,335 observations, 47% female) unaffected classmates. Children who later developed TRS had worse grades across levels than their classmates (-0.26 SD [-0.2, -0.4]), but not treatment-responsive schizophrenia. All severe mental illness groups showed grade declines in later school levels, with TRS showing steeper linear decline than treatment-responsive schizophrenia (groupxage of -0.03; 95%CI -0.04, -0.01) and steeper quadratic decline than bipolar disorder (groupxage 2 of -0.005; -0.01, -0.001). Attendance declined over time in the two groups developing schizophrenia compared to their classmates. Those developing TRS experienced the sharpest drop (groupxage compared to schizophrenia -0.03; -0.05, -0.01 and bipolar disorder -0.027; -0.049, -0.006).Conclusions TRS may stem from a more aggressive pathological process or pronounced late-maturation abnormality, rather than an early premorbid impairment, suggesting an intervention target.
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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
;
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
;
Alejandro Jara
;
Néstor Muñoz
;
Carlos Milovic
;
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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Gender, age and geographical representation over the past 50 years of schizophrenia research
(2022)
Luz María Alliende
;
Leticia S. Czepielewski
;
David Aceituno
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Carmen Paz Castañeda
;
Camila Diaz
15Scopus© Citations 5

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