Person: Undurraga, Juan
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Publication Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis(2023) García Saborit, Marisleydis; Jara, Alejandro; Muñoz, Néstor; Milovic, Carlos; Tepper, Angeles; Alliende, Luz María; Mena, Carlos; Iruretagoyena, Bárbara; Ramírez-Mahaluf, Juan Pablo; Díaz, Camila; Nachar, Ruben; Castañeda, Carmen Paz; González, Alfonso; Undurraga, Juan; Crossley, Nicolás; Tejos, CristianBackground: 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. Methods: 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. Results: 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. Conclusions: 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.Publication Country-level gender inequality is associated with structural differences in the brains of women and men(2023) Zugman, André; Alliende, Luz María; Medel, Vicente; Bethlehem, Richard A.I.; Seidlitz, Jakob; Ringlein, Grace; Arango, Celso; Arnatkevičiūtė, Aurina; Asmal, Laila; Bellgrove, Mark; Benegal, Vivek; Bernardo, Miquel; Billeke, Pablo; Bosch-Bayard, Jorge; Bressan, Rodrigo; Busatto, Geraldo F.; Castro, Mariana N.; Chaim-Avancini, Tiffany; Compte, Albert; Costanzi, Monise; Czepielewsk, Leticia; Dazzan, Paola; Fuente-Sandoval, Camilo de la; Forti, Marta Di; Díaz-Caneja, Covadonga M.; Díaz-Zuluaga, Ana María; Ples, Stefan Du; Duran, Fabio L. S.; Fittipaldi, Sol; Fornito, Alex; Freimer, Nelson B.; Gadelha, Ary; Gama, Clarissa S.; Garani, Ranjini; Garcia-Rizo, Clemente; Gonzalez Campo, Cecilia; Gonzalez-Valderrama, Alfonso; Guinjoan, Salvador; Holla, Bharath; Undurraga, JuanGender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.Publication Clinicians’ preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders around the world: a survey from the ISBD Lithium task force(2023) Hidalgo‑Mazzei, Diego; Mantingh, Tim; Pérez de Mendiola, Xavier; Samalin, Ludovic; Undurraga, Juan; Strejilevich, Sergio; Severus, Emanuel; Bauer, Michael; González-Pinto, Ana; Nolen, Willem A.; Young, Allan H.; Vieta, EduardBackground Lithium has long been considered the gold‑standard pharmacological treatment for the maintenance treatment of bipolar disorders (BD) which is supported by a wide body of evidence. Prior research has shown a steady decline in lithium prescriptions during the last two decades. We aim to identify potential factors explaining this decline across the world with an anonymous worldwide survey developed by the International Society for Bipolar Disorders (ISBD) Task Force “Role of Lithium in Bipolar Disorders” and distributed by diverse academic and professional international channels. Results A total of 886 responses were received of which 606 completed the entire questionnaire while 206 completed it partially. Respondents were from 43 different countries comprising all continents. Lithium was the most preferred treatment option for the maintenance of BD patients (59%). The most relevant clinical circumstances in which lithium was the preferred option were in patients with BD I (53%), a family history of response (18%), and a prior response during acute treatment (17%). In contrast, Lithium was not the preferred option in case of patients´ negative beliefs and/or attitudes towards lithium (13%), acute side‑effects or tolerability problems (10%) and intoxication risk (8%). Clinicians were less likely to prefer lithium as a first option in BD maintenance phase when practising in developing economy countries [X2 (1, N = 430) = 9465, p = 0.002) ] and private sectors [X2 (1, N = 434) = 8191, p = 0.004)]. Conclusions Clinicians’ preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders appear to be affected by both the patients’ beliefs and the professional contexts where clinicians provide their services. More research involving patients is needed for identifying their attitudes toward lithium and factors affecting its use, particularly in developing economies.Publication Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I(2023) Varo, Cristina; Amoretti, Silvia; Sparacino, Giulio; Jiménez, Esther; Solé, Brisa; Bonnin, Caterina Del Mar; Montejo, Laura; Serra, Maria; Torrent, Carla; Salagre, Estela; Benabarre, Antoni; Salgado-Pineda, Pilar; Montoro Salvatierra, Irene; Sáiz, Pilar A.; García-Portilla, María Paz; Sánchez-Gistau, Vanessa; Pomarol-Clotet, Edith; Ramos-Quiroga, Josep Antoni; Pacchiarotti, Isabella; García-Rizo, Clemente; Undurraga, Juan; Reinares, María; Martinez-Aran, Anabel; Vieta, Eduard; Verdolini, NormaBackground Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. Methods The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. Results In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (S.E.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, S.E. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β = −0.293, p = 0.034) and verbal memory performance (β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. Conclusions Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.Publication Intra and inter-individual variability in functional connectomes of patients with First Episode of Psychosis(2023) Tepper, Angeles; Vásquez Núñez, Javiera; Ramirez-Mahaluf, Juan Pablo; Aguirre, Juan Manuel; Barbagelata, Daniella; Maldonado, Elisa; Díaz Dellarossa, Camila; Nachar, Ruben; González-Valderrama, Alfonso; Undurraga, Juan; Goñi, Joaquín; Crossley, NicolásPatients with Schizophrenia may show different clinical presentations, not only regarding inter-individual comparisons but also in one specific subject over time. In fMRI studies, functional connectomes have been shown to carry valuable individual level information, which can be associated with cognitive and behavioral variables. Moreover, functional connectomes have been used to identify subjects within a group, as if they were fingerprints. For the particular case of Schizophrenia, it has been shown that there is reduced connectome stability as well as higher inter-individual variability. Here, we studied inter and intra-individual heterogeneity by exploring functional connectomes’ variability and related it with clinical variables (PANSS Total scores and antipsychotic’s doses). Our sample consisted of 30 patients with First Episode of Psychosis and 32 Healthy Controls, with a test–retest approach of two resting-state fMRI scanning sessions. In our patients’ group, we found increased deviation from healthy functional connectomes and increased intragroup inter-subject variability, which was positively correlated to symptoms’ levels in six subnetworks (visual, somatomotor, dorsal attention, ventral attention, frontoparietal and DMN). Moreover, changes in symptom severity were positively related to changes in deviation from healthy functional connectomes. Regarding intra-subject variability, we were unable to replicate previous findings of reduced connectome stability (i.e., increased intra-subject variability), but we found a trend suggesting that result. Our findings highlight the relevance of variability characterization in Schizophrenia, and they can be related to evidence of Schizophrenia patients having a noisy functional connectome.