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4. Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice

Author

Cortés,Bastián I., Meza,Rodrigo C., Ancatén-González,Carlos, Ardiles,Nicolás M., Aránguiz,María-Ignacia, Tomita,Hideaki, Kaplan,David R., Cornejo,Francisca, Nunez-Parra,Alexia, Moya,Pablo R., Chávez,Andrés E., Cancino,Gonzalo I., Cortés,Bastián I., Meza,Rodrigo C., Ancatén-González,Carlos, Ardiles,Nicolás M., Aránguiz,María-Ignacia, Tomita,Hideaki, Kaplan,David R., Cornejo,Francisca, Nunez-Parra,Alexia, Moya,Pablo R., Chávez,Andrés E., and Cancino,Gonzalo I.

Published
2024

5. Effects of Dietary Fiber, Phenolic Compounds, and Fatty Acids on Mental Health: Possible Interactions with Genetic and Epigenetic Aspects.

Author

Lutz, Mariane, Moya, Pablo R., Gallorio, Sofía, Ríos, Ulises, and Arancibia, Marcelo

Abstract

Scientific evidence shows that dietary patterns are a key environmental determinant of mental health. Dietary constituents can modify epigenetic patterns and thus the gene expression of relevant genetic variants in various mental health conditions. In the present work, we describe some nutrigenomic effects of dietary fiber, phenolic compounds (plant secondary metabolites), and fatty acids on mental health outcomes, with emphasis on their possible interactions with genetic and epigenetic aspects. Prebiotics, through their effects on the gut microbiota, have been associated with modulation in the neuroendocrine response to stress and the facilitation of the processing of positive emotions. Some of the genetic and epigenetic mechanisms include the serotonin neurotransmitter system (TPH1 gene) and the brain-derived neurotrophic factor (inhibition of histone deacetylases). The consumption of phenolic compounds exerts a positive role in neurocognitive domains. The evidence showing the involvement of genetic and epigenetic factors comes mainly from animal models, highlighting the role of epigenetic mechanisms through miRNAs and methyltransferases as well as the effect on the expression of apoptotic-related genes. Long-chain n-3 fatty acids (EPA and DHA) have been mainly related to psychotic and mood disorders, but the genetic and epigenetic evidence is scarce. Studies on the genetic and epigenetic basis of these interactions need to be promoted to move towards a precision and personalized approach to medicine. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

Author

Moya, Pablo R, Dodman, Nicholas H, Timpano, Kiara R, Rubenstein, Liza M, Rana, Zaker, Fried, Ruby L, Reichardt, Louis F, Heiman, Gary A, Tischfield, Jay A, King, Robert A, Galdzicka, Marzena, Ginns, Edward I, and Wendland, Jens R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Anxiety Disorders, Brain Disorders, Serious Mental Illness, Neurosciences, Clinical Research, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adult, Antigens, CD, Blotting, Western, Cadherins, DNA Mutational Analysis, Genotype, HEK293 Cells, Humans, Mutation, Missense, Obsessive-Compulsive Disorder, Phenotype, Psychiatric Status Rating Scales, Tourette Syndrome, Transfection, N-cadherin, CDH2, rare gene variants, canine compulsive disorder, obsessive-compulsive disorder, Tourette disorder, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N=1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P=0.014, OR=6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders.

Published
2013

7. Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression

Author

Delgado-Acevedo, Claudia, Estay, Sebastián F., Radke, Anna K., Sengupta, Ayesha, Escobar, Angélica P., Henríquez-Belmar, Francisca, Reyes, Cristopher A., Haro-Acuña, Valentina, Utreras, Elías, Sotomayor-Zárate, Ramón, Cho, Andrew, Wendland, Jens R., Kulkarni, Ashok B., Holmes, Andrew, Murphy, Dennis L., Chávez, Andrés E., and Moya, Pablo R.

Published
2019
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9. Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol

Author

Crowley, James J, Cappi, Carolina, Ochoa-Panaifo, Marcos E, Frederick, Renee M, Kook, Minjee, Wiese, Andrew D, Rancourt, Diana, Atkinson, Elizabeth G, Giusti-Rodriguez, Paola, Anderberg, Jacey L, Abramowitz, Jonathan S, Adorno, Victor R, Aguirre, Cinthia, Alves, Gustavo S, Alves, Gilberto S, Ancalade, NaEshia, Arellano Espinosa, Alejandro A, Arnold, Paul D, Ayton, Daphne M, Barbosa, Izabela G, Barón Castano, Laura Marcela, Barrera, Cynthia N, Belén Prieto, María, Berardo, María Celeste, Berrones, Dayan, Best, John R, Bigdeli, Tim B, Burton, Christie L, Callahan, Jennifer L, Carneiro, Maria Cecília B, Cepeda, Sandra L, Chazelle, Evelyn, Chire, Jessica M, Churruca Munoz, Macarena, Claisse Quiroz, Pamela, Cobite, Journa, Comer, Jonathan S, Costa, Daniel L, Crosbie, Jennifer, Cruz, Victor O, Dager, Guillermo, Daza, Luisa F, de la Rosa-Gómez, Anabel, del Río, Daniela, Delage, Fernanda Z, Dreher, Carolina B, Fay, Lucila, Fazio, Tomas, Ferrão, Ygor A, Ferreira, Gabriela M, Figueroa, Edith G, Fontenelle, Leonardo F, Forero, Diego A, Fragoso, Daniele TH, Gadad, Bharathi S, Garrison, Sheldon R, González, Andres, Gonzalez, Laura D, González, Marco A, Gonzalez-Barrios, Polaris, Goodman, Wayne, Guintivano, Jerry, Guttfreund, Daniel G, Guzick, Andrew G, Halvorsen, Matthew W, Hovey, Joseph D, Janssen-Aguilar, Reinhard, Jensen, Matias, Jimenez Reynolds, Alexandra Z, Juárez Lujambio, Joali Alexandra, Khalfe, Nasim, Knutsen, Madison A, Lack, Caleb, Lanzagorta, Nuria, Lima, Monicke O, Longhurst, Melanie O, Lozada Martinez, David A, Luna, Elba S, Marques, Andrea H, Martinez, Molly, Matos, Maria de Los Angeles, Maye, Caitlyn E, McGuire, Joseph F, Menezes, Gabriela, Minaya, Charlene, Miño, Tomás, Mithani, Sara M, Montes de Oca, Circe, Morales-Rivero, Alonso, Moreira-de-Oliveira, Maria E, Morris, Olivia J, Muñoz, Sandra I, Naqqash, Zainab, Núñez Bracho, Ambar A, Núñez Bracho, Belinda E, Ochoa Rojas, Maria Corina, Olavarria Castaman, Luis A, Ortega, Iliana, Patel, Darpan I, Patrick, Ainsley K, Paz y Mino, Mariel, Perales Orellana, Jose L, Perdigão Stumpf, Bárbara, Peregrina, Tamara, Pérez Duarte, Tania, Piacsek, Kelly L, Placencia, Maritza, Quarantini, Lucas C, Quarantini-Alvim, Yana, Ramos, Renato T, Ramos, Iaroslava C, Ramos, Vanessa R, Ramsey, Kesley A, Ray, Elise V, Richter, Margaret A, Riemann, Bradley C, Rivas, Juan C, Rosario, Maria C, Ruggero, Camilo J, Ruiz-Chow, Angel A, Ruiz-Velasco, Alejandra, Sampaio, Aline S, Saraiva, Leonardo C, Schachar, Russell J, Schneider, Sophie C, Schweissing, Ethan J, Seligman, Laura D, Shavitt, Roseli G, Soileau, Keaton J, Stewart, S. Evelyn, Storch, Shaina B, Strouphauer, Emily R, Timpano, Kiara R, Treviño-de la Garza, Beatriz, Vargas-Medrano, Javier, Vásquez, María I, Vidal Martinez, Guadalupe, Weinzimmer, Saira A, Yanez, Mauricio A, Zai, Gwyneth, Zapata-Restrepo, Lina M, Zappa, Luz M, Zepeda-Burgos, Raquel M, Zoghbi, Anthony W, Miguel, Euripedes C, Rodriguez, Carolyn I, Martinez Mallen, Mayra C, Moya, Pablo R, Borda, Tania, Moyano, María Beatriz, Mattheisen, Manuel, Pereira, Stacey, Lázaro-Muñoz, Gabriel, Martinez-Gonzalez, Karen G, Pato, Michele T, Nicolini, Humberto, and Storch, Eric A

Subjects
Article
Abstract

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org ). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Published
2023

11. Implications of Physical Exercise on Episodic Memory and Anxiety: The Role of the Serotonergic System.

Author

Illesca-Matus, Ricardo, Ardiles, Nicolás M., Munoz, Felipe, and Moya, Pablo R.

Subjects
EPISODIC memory, MEMORY, COGNITIVE ability, ANXIETY, ANXIETY disorders
Abstract

There is a growing interest in investigating the effects of physical exercise on cognitive performance, particularly episodic memory. Similarly, an increasing number of studies in recent decades have studied the effects of physical activity on mood and anxiety disorders. Moreover, the COVID-19 pandemic has raised awareness of the importance of regular physical activity for both mental and physical health. Nevertheless, the exact mechanisms underlying these effects are not fully understood. Interestingly, recent findings suggest that the serotonergic system may play a key role in mediating the effects of physical exercise on episodic memory and anxiety. In this review, we discuss the impact of physical exercise on both episodic memory and anxiety in human and animal models. In addition, we explore the accumulating evidence that supports a role for the serotonergic system in the effects of physical exercise on episodic memory and anxiety. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Correction: Behavioral and synaptic alterations relevant to obsessivecompulsive disorder in mice with increased EAAT3 expression

Author

Delgado-Acevedo, Claudia, Estay, Sebastián F., Radke, Anna K., Sengupta, Ayesha, Escobar, Angélica P., Henríquez-Belmar, Francisca, Reyes, Cristopher A., Haro-Acuña, Valentina, Utreras, Elías, Sotomayor-Zárate, Ramón, Cho, Andrew, Wendland, Jens R., Kulkarni, Ashok B., Holmes, Andrew, Murphy, Dennis L., Chávez, Andrés E., and Moya, Pablo R.

Published
2019
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15. Protein kinase B (AKT) upregulation and Thy-1-αvβ3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

Author

Pérez-Núñez, Ramón, Chamorro, Alejandro, González, María Fernanda, Contreras, Pamela, Artigas, Rocío, Corvalán, Alejandro H., van Zundert, Brigitte, Reyes, Christopher, Moya, Pablo R., Avalos, Ana María, Schneider, Pascal, Quest, Andrew F. G., and Leyton, Lisette

Subjects
PROTEIN kinase B, CONNEXIN 43, GLIOSIS, PI3K/AKT pathway, TRANSGENIC mice, KINASES
Abstract

Background: In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvβ3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. Methods: Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). Results: The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. Conclusions: Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis. [ABSTRACT FROM AUTHOR]

Published
2023
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18. A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder

Author

Wendland, Jens R., Moya, Pablo R., Timpano, Kiara R., Anavitarte, Adriana P., Kruse, Matthew R., Wheaton, Michael G., Ren-Patterson, Renee F., and Murphy, Dennis L.

Subjects
Obsessive-compulsive disorder -- Research, Obsessive-compulsive disorder -- Genetic aspects, Haplotypes -- Research, Gene expression -- Research, Health, Psychology and mental health
Published
2009

25. El maltrato infantil y su rol en el curso clínico de pacientes con trastorno bipolar

Author

Ríos, Ulises, Moya, Pablo R., Urrejola, Óscar, Hermosilla, Jimena, Gonzalez, René, Muñoz, Paulina, Moran, Javier, Solervicens, Paula, and Jiménez, Juan Pablo

Subjects
Bipolar Disorder, Cognition, Suicide, Attempted, Child Abuse, Psychological Trauma
Abstract

Background: A history of child abuse is common and has a significant impact in the clinical course of patients diagnosed with bipolar disorders (BD). Aims: To assess the frequency of child abuse experiences in patients BD type I and to evaluate its association with clinical course and cognitive functioning variables. Material and Methods: 117 patients with BD aged 45 ± 14 years (66% women) answered the Childhood Trauma Questionnaire (CTQ). The clinical course (illness onset, history of suicide attempts and number of hospitalizations) was obtained from medical records. Cognitive functioning was evaluated through social and non-social cognition tasks. Results: 64% of participants reported some type of child abuse. This variable was associated with an early onset of the disease (Odds ratio (OR) = 3.3; p < 0.02), increased risk of suicide attempts (OR = 2.4; p < 0.04) and specific disturbances in social cognitive tasks. Conclusions: Our study supports evidence of a common history of child abuse in patients with BD. Although child abuse predicts a worse clinical course, major clinical practice guidelines, as well as research designs, do not highlight this evidence.

Published
2020

28. Esquizofrenia resistente: Definiciones e Implicancias del concepto de Esquizofrenia Resistente a tratamiento

Author

Pizarro-Galleguillos, Benjamín, Waissbluth, Cavieres, Álvaro, Moya, Pablo R, and Bustamante, M. Leonor

Subjects
Treatment resistant, Resistencia a tratamiento, Antipsychotics, Clozapina, Antipsicóticos, Clozapine
Abstract

Resumen La esquizofrenia (EQZ) es una entidad clínica altamente heterogénea. Determina un severo impacto en la calidad de vida de los pacientes y un alto costo para la sociedad. Los antipsicóticos son la primera línea de tratamiento, sin embargo, hasta un tercio de los pacientes presentaran una esquizofrenia resistente a tratamiento (ERT). Se ha propuesto que la ERT podría corresponder a un grupo neurobiológicamente distinto de la enfermedad con una arquitectura genética particular y no solo al extremo del espectro de severidad de la misma. A pesar de ello, actualmente no existe consenso en la literatura en torno a la definición de ERT. En este trabajo presentamos una revisión de diferentes definiciones de ERT centrándonos principalmente en las guías clínicas publicadas. Además se discuten las alternativas terapéuticas en ERT y, finalmente, se proponen perspectivas futuras en torno a la necesidad de desarrollar predictores de respuesta a antipsicóticos de primera y segunda línea, así como también la posibilidad de comprender la neurobiología de la ERT. Schizophrenia (SZ) is a highly heterogeneous clinical entity. It causes a severe disruption in quality of life, and it imposes a significant burden to society. Antipsychotics are the first line treatment, however up to a 30% of the patients will present resistance to treatment. Treatment resistant schizophrenia (TRS) could be a neurobiologically distinct disorder and not merely an extremely severe form of SZ. However, there is no consensus in the literature as to the definition of TRS. In the present work we review different definitions of TRS, mainly from clinical guidelines. Furthermore, we discuss therapeutic alternatives for TRS and suggest future perspectives regarding the identification of response predictors and understanding the neurobiology of TRS.

Published
2019

32. Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats

Author

Pérez, Miguel Ángel, primary, Morales, Camila, additional, Santander, Odra, additional, García, Francisca, additional, Gómez, Isabel, additional, Peñaloza-Sancho, Valentín, additional, Fuentealba, Pablo, additional, Dagnino-Subiabre, Alexies, additional, Moya, Pablo R., additional, and Fuenzalida, Marco, additional

Published
2019
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34. Latin American Trans‐ancestry INitiative for OCD genomics (LATINO): Study protocol

Author

Crowley, James J., Cappi, Carolina, Ochoa‐Panaifo, Marcos E., Frederick, Renee M., Kook, Minjee, Wiese, Andrew D., Rancourt, Diana, Atkinson, Elizabeth G., Giusti‐Rodriguez, Paola, Anderberg, Jacey L., Abramowitz, Jonathan S, Adorno, Victor R, Aguirre, Cinthia, Alves, Gilberto S, Alves, Gustavo S, Ancalade, NaEshia, Anderberg, Jacey L, Arellano Espinosa, Alejandro A, Arnold, Paul D, Atkinson, Elizabeth G, Ayton, Daphne M, Barbosa, Izabela G, Castano, Laura Marcela Barón, Barrera, Cynthia N, Berardo, María Celeste, Berrones, Dayan, Best, John R, Bigdeli, Tim B, Borda, Tania, Burton, Christie L, Buxbaum, Joseph D, Callahan, Jennifer L, Cappi, Carolina, Carneiro, Maria Cecília B, Cepeda, Sandra L, Chazelle, Evelyn, Chire, Jessica M, Munoz, Macarena Churruca, Quiroz, Pamela Claisse, Cobite, Journa, Comer, Jonathan S, Costa, Daniel L, Crosbie, Jennifer, Crowley, James J, Cruz, Victor O, Dager, Guillermo, Daza, Luisa F, Rosa‐Gómez, Anabel, Río, Daniela, Delage, Fernanda Z, Dreher, Carolina B, Fay, Lucila, Fazio, Tomas, Ferrão, Ygor A, Ferreira, Gabriela M, Figueroa, Edith G, Fontenelle, Leonardo F, Forero, Diego A, Fragoso, Daniele TH, Frederick, Renee M, Gadad, Bharathi S, Garrison, Sheldon R, Giusti‐Rodriguez, Paola, Gonzalez, Laura D, González, Andres, González, Marco A, Gonzalez‐Barrios, Polaris, Goodman, Wayne, Grice, Dorothy E, Guintivano, Jerry, Guttfreund, Daniel G, Guzick, Andrew G, Halvorsen, Matthew W, Hovey, Joseph D, Huang, Hailiang, Irreño‐Sotomonte, Jonathan, Janssen‐Aguilar, Reinhard, Jensen, Matias, Jimenez Reynolds, Alexandra Z, Lujambio, Joali Alexandra Juárez, Khalfe, Nasim, Knutsen, Madison A, Kook, Minjee, Lack, Caleb, Lanzagorta, Nuria, Lázaro‐Muñoz, Gabriel, Lima, Monicke O, Longhurst, Melanie O, Lozada Martinez, David A, Luna, Elba S, Marques, Andrea H, Martinez, Molly, Martinez Mallen, Mayra C, Martinez‐Gonzalez, Karen G, Los Angeles Matos, Maria, Mattheisen, Manuel, Maye, Caitlyn E, McGuire, Joseph F, Menezes, Gabriela, Miguel, Euripedes C, Minaya, Charlene, Miño, Tomás, Mithani, Sara M, Oca, Circe Montes, Morales‐Rivero, Alonso, Moreira‐de‐Oliveira, Maria E, Morris, Olivia J, Moya, Pablo R, Moyano, María Beatriz, Muñoz, Sandra I, Naqqash, Zainab, Nicolini, Humberto, Núñez Bracho, Ambar A, Núñez Bracho, Belinda E, Rojas, Maria Corina Ochoa, Ochoa‐Panaifo, Marcos E, Olavarria Castaman, Luis A, Balmaceda, Trinidad Olivos, Ortega, Iliana, Patel, Darpan I, Pato, Michele T, Patrick, Ainsley K, Mino, Mariel Paz y, Perales Orellana, Jose L, Stumpf, Bárbara Perdigão, Peregrina, Tamara, Pereira, Stacey, Duarte, Tania Pérez, Piacsek, Kelly L, Placencia, Maritza, Prieto, María Belén, Quarantini, Lucas C, Quarantini‐Alvim, Yana, Ramos, Iaroslava C, Ramos, Renato T, Ramos, Vanessa R, Ramsey, Kesley A, Rancourt, Diana, Ray, Elise V, Richter, Margaret A, Riemann, Bradley C, Rivas, Juan C, Rodriguez, Carolyn I, Rosario, Maria C, Ruggero, Camilo J, Ruiz‐Chow, Angel A, Ruiz‐Velasco, Alejandra, Sagarnaga, Melisa N, Sampaio, Aline S, Saraiva, Leonardo C, Schachar, Russell J, Schneider, Sophie C, Schweissing, Ethan J, Seligman, Laura D, Shavitt, Roseli G, Soileau, Keaton J, Stewart, S. Evelyn, Storch, Eric A, Storch, Shaina B, Strouphauer, Emily R, Cuevas, Vissente Tapia, Timpano, Kiara R, Garza, Beatriz Treviño‐de, Vallejo‐Silva, Alexie, Vargas‐Medrano, Javier, Vásquez, María I, Martinez, Guadalupe Vidal, Weinzimmer, Saira A, Wiese, Andrew D, Yanez, Mauricio A, Zai, Gwyneth, Zapata‐Restrepo, Lina M, Zappa, Luz M, Zepeda‐Burgos, Raquel M, Zoghbi, Anthony W, Sampaio, Aline Santos, Hounie, Ana Gabriela, Ribeiro, Ana Paula, Souza e Silva, Angela Rodrigues, Martinho, Ariane Fadel, Stumpf, Bárbara Luciane Perdigão, Melo Fadel, Bianca Torres Mendonça, Porto, Camila Vale, Chacur, Carina Freitas, Loureiro, Carla Pereira, Dreher, Carolina Blaya, Cappi, Carolina, Bortoncello, Cristiane Flôres, Conceição Costa, Daniel Lucas, Fragoso, Daniele Tamae Hashimoto, Miguel, Euripedes Constantino, Delage, Fernanda Zetola, Cervone, Flávia, Menezes, Gabriela Bezerra, Souza Barros, Gabriela Cirqueira, Ferreira, Gabriela Mourão, Alves, Gilberto Sousa, Alves, Gustavo Santiago, Caminha, Hugo, Barbosa, Izabela Guimarães, Cenci, Jaqueline, Muhlbauer, Julia Fernandes Eigenheer, Silva, Juliana Rigue, Saraiva, Leonardo Cardoso, Costa Fontenelle, Leonardo Franklin, Camba Lopez, Lígia S., Faro, Livi Ferreira Testoni, Moreira, Luan Pinheiro Domingues, Laurito, Luana Dumans, Castro Quarantini, Lucas, Samezima, Luciana Midori, Santos Martins, Luiz Felipe Guimarães, Oliveira, Marcos Vinícius Sousa, Mathis, Maria Alice, Lopes, Maria Carolina Paraíso, Carneiro, Maria Cecília, Rosário, Maria Conceição, Oliveira, Maria Eduarda Ismerio Moreira, Pinho, Marina Martorelli, Oliveira Lima, Monicke, Nagano, Nádia, Danna, Patrycia Chedid, Silva, Pedro Pereira Fortes, Jesus Cardoso, Raquel Fernandes, Christo, Renan Barbosa, Avila, Richard Chuquel Silveira, Radins, Rodrigo Bolsson, Shavitt, Roseli Gedanke, Santos Ribeiro, Samara, Silveira Meirelles, Tatiane Veríssimo, Aguiar, Thays Mendes, Silva Sousa, Theresa Kerolayne, Vieira, Thiago Blanco, Ramos, Vanessa Rogério, Vasconcellos, Veronica Huhne, Alvim, Yana Quarantini, Ferrão, Ygor Arzeno, Abramowitz, Jonathan S., Adorno, Victor R., Aguirre, Cinthia, Alves, Gilberto S., Alves, Gustavo S., Ancalade, NaEshia, Arellano Espinosa, Alejandro A., Arnold, Paul D., Ayton, Daphne M., Barbosa, Izabela G., Castano, Laura Marcela Barón, Barrera, Cynthia N., Berardo, María Celeste, Berrones, Dayan, Best, John R., Bigdeli, Tim B., Burton, Christie L., Buxbaum, Joseph D., Callahan, Jennifer L., Carneiro, Maria Cecília B., Cepeda, Sandra L., Chazelle, Evelyn, Chire, Jessica M., Munoz, Macarena Churruca, Quiroz, Pamela Claisse, Cobite, Journa, Comer, Jonathan S., Costa, Daniel L., Crosbie, Jennifer, Cruz, Victor O., Dager, Guillermo, Daza, Luisa F., Rosa‐Gómez, Anabel, Río, Daniela, Delage, Fernanda Z., Dreher, Carolina B., Fay, Lucila, Fazio, Tomas, Ferrão, Ygor A., Ferreira, Gabriela M., Figueroa, Edith G., Fontenelle, Leonardo F., Forero, Diego A., Fragoso, Daniele T. H., Gadad, Bharathi S., Garrison, Sheldon R., González, Andres, Gonzalez, Laura D., González, Marco A., Gonzalez‐Barrios, Polaris, Goodman, Wayne K., Grice, Dorothy E., Guintivano, Jerry, Guttfreund, Daniel G., Guzick, Andrew G., Halvorsen, Matthew W., Hovey, Joseph D., Huang, Hailiang, Irreño‐Sotomonte, Jonathan, Janssen‐Aguilar, Reinhard, Jensen, Matias, Jimenez Reynolds, Alexandra Z., Lujambio, Joali Alexandra Juárez, Khalfe, Nasim, Knutsen, Madison A., Lack, Caleb, Lanzagorta, Nuria, Lima, Monicke O., Longhurst, Melanie O., Lozada Martinez, David A., Luna, Elba S., Marques, Andrea H., Martinez, Molly S., Los Angeles Matos, Maria, Maye, Caitlyn E., McGuire, Joseph F., Menezes, Gabriela, Minaya, Charlene, Miño, Tomás, Mithani, Sara M., Oca, Circe Montes, Morales‐Rivero, Alonso, Moreira‐de‐Oliveira, Maria E., Morris, Olivia J., Muñoz, Sandra I., Naqqash, Zainab, Núñez Bracho, Ambar A., Núñez Bracho, Belinda E., Rojas, Maria Corina Ochoa, Olavarria Castaman, Luis A., Balmaceda, Trinidad Olivos, Ortega, Iliana, Patel, Darpan I., Patrick, Ainsley K., Paz y Mino, Mariel, Perales Orellana, Jose L., Stumpf, Bárbara Perdigão, Peregrina, Tamara, Duarte, Tania Pérez, Piacsek, Kelly L., Placencia, Maritza, Prieto, María Belén, Quarantini, Lucas C., Quarantini‐Alvim, Yana, Ramos, Renato T., Ramos, Iaroslava C., Ramos, Vanessa R., Ramsey, Kesley A., Ray, Elise V., Richter, Margaret A., Riemann, Bradley C., Rivas, Juan C., Rosario, Maria C., Ruggero, Camilo J., Ruiz‐Chow, Angel A., Ruiz‐Velasco, Alejandra, Sagarnaga, Melisa N., Sampaio, Aline S., Saraiva, Leonardo C., Schachar, Russell J., Schneider, Sophie C., Schweissing, Ethan J., Seligman, Laura D., Shavitt, Roseli G., Soileau, Keaton J., Stewart, S. Evelyn, Storch, Shaina B., Strouphauer, Emily R., Cuevas, Vissente Tapia, Timpano, Kiara R., Garza, Beatriz Treviño‐de, Vallejo‐Silva, Alexie, Vargas‐Medrano, Javier, Vásquez, María I., Martinez, Guadalupe Vidal, Weinzimmer, Saira A., Yanez, Mauricio A., Zai, Gwyneth, Zapata‐Restrepo, Lina M., Zappa, Luz M., Zepeda‐Burgos, Raquel M., Zoghbi, Anthony W., Miguel, Euripedes C., Rodriguez, Carolyn I., Martinez Mallen, Mayra C., Moya, Pablo R., Borda, Tania, Moyano, María Beatriz, Mattheisen, Manuel, Pereira, Stacey, Lázaro‐Muñoz, Gabriel, Martinez‐Gonzalez, Karen G., Pato, Michele T., Nicolini, Humberto, and Storch, Eric A.

Abstract

Obsessive‐compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long‐sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans‐ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans‐ancestry genomic analyses to accelerate the identification of OCD risk loci, fine‐map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Published
2024
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35. Esquizofrenia resistente: Definiciones e Implicancias del concepto de Esquizofrenia Resistente a tratamiento

Author

Pizarro-Galleguillos,Benjamín, Waissbluth,Óscar, Cavieres,Álvaro, Moya,Pablo R, Bustamante,M. Leonor, Pizarro-Galleguillos,Benjamín, Waissbluth,Óscar, Cavieres,Álvaro, Moya,Pablo R, and Bustamante,M. Leonor

Abstract

Resumen La esquizofrenia (EQZ) es una entidad clínica altamente heterogénea. Determina un severo impacto en la calidad de vida de los pacientes y un alto costo para la sociedad. Los antipsicóticos son la primera línea de tratamiento, sin embargo, hasta un tercio de los pacientes presentaran una esquizofrenia resistente a tratamiento (ERT). Se ha propuesto que la ERT podría corresponder a un grupo neurobiológicamente distinto de la enfermedad con una arquitectura genética particular y no solo al extremo del espectro de severidad de la misma. A pesar de ello, actualmente no existe consenso en la literatura en torno a la definición de ERT. En este trabajo presentamos una revisión de diferentes definiciones de ERT centrándonos principalmente en las guías clínicas publicadas. Además se discuten las alternativas terapéuticas en ERT y, finalmente, se proponen perspectivas futuras en torno a la necesidad de desarrollar predictores de respuesta a antipsicóticos de primera y segunda línea, así como también la posibilidad de comprender la neurobiología de la ERT.

Published
2019

36. Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression

Author

Delgado-Acevedo, Claudia, primary, Estay, Sebastián F., additional, Radke, Anna K., additional, Sengupta, Ayesha, additional, Escobar, Angélica P., additional, Henríquez-Belmar, Francisca, additional, Reyes, Cristopher A., additional, Haro-Acuña, Valentina, additional, Utreras, Elías, additional, Sotomayor-Zárate, Ramón, additional, Cho, Andrew, additional, Wendland, Jens R., additional, Kulkarni, Ashok B., additional, Holmes, Andrew, additional, Murphy, Dennis L., additional, Chávez, Andrés E., additional, and Moya, Pablo R., additional

Published
2018
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37. Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice

Author

González,Luis F., Henríquez-Belmar,Francisca, Delgado-Acevedo,Claudia, Cisternas-Olmedo,Marisol, Arriagada,Gloria, Sotomayor-Zárate,Ramón, Murphy,Dennis L., Moya,Pablo R., González,Luis F., Henríquez-Belmar,Francisca, Delgado-Acevedo,Claudia, Cisternas-Olmedo,Marisol, Arriagada,Gloria, Sotomayor-Zárate,Ramón, Murphy,Dennis L., and Moya,Pablo R.

Abstract

Background Obsessive–compulsive disorder (OCD) is a severe neuropsychiatric condition affecting 1–3% of the worldwide population. OCD has a strong genetic component, and the SLC1A1 gene that encodes neuronal glutamate transporter EAAT3 is a strong candidate for this disorder. To evaluate the impact of reduced EAAT3 expression in vivo, we studied male EAAT3 heterozygous and wild-type littermate mice using a battery of behavioral paradigms relevant to anxiety (open field test, elevated plus maze) and compulsivity (marble burying), as well as locomotor activity induced by amphetamine. Using high-performance liquid chromatography, we also determined tissue neurotransmitter levels in cortex, striatum and thalamus—brain areas that are relevant to OCD. Results Compared to wild-type littermates, EAAT3 heterozygous male mice have unaltered baseline anxiety-like, compulsive-like behavior and locomotor activity. Administration of acute amphetamine (5 mg/kg intraperitoneally) increased locomotion with no differences across genotypes. Tissue levels of glutamate, GABA, dopamine and serotonin did not vary between EAAT3 heterozygous and wild-type mice. Conclusions Our results indicate that reduced EAAT3 expression does not impact neurotransmitter content in the corticostriatal circuit nor alter anxiety or compulsive-like behaviors.

Published
2017

38. Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats

Author

Espinosa, Pedro, primary, Silva, Roxana A., additional, Sanguinetti, Nicole K., additional, Venegas, Francisca C., additional, Riquelme, Raul, additional, González, Luis F., additional, Cruz, Gonzalo, additional, Renard, Georgina M., additional, Moya, Pablo R., additional, and Sotomayor-Zárate, Ramón, additional

Published
2016
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41. Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT2A and 5-HT2C receptors

Author

Acuña-Castillo, Claudio, Villalobos, Claudio, Moya, Pablo R, Sáez, Patricio, Cassels, Bruce K, and Huidobro-Toro, J Pablo

Subjects
Patch-Clamp Techniques, Propylamines, In Vitro Techniques, Nitro Compounds, Serotonin Receptor Agonists, Structure-Activity Relationship, Xenopus laevis, Receptors, Serotonin, Papers, Phenethylamines, Ethylamines, Oocytes, Receptor, Serotonin, 5-HT2C, Animals, Female, Receptor, Serotonin, 5-HT2A, Serotonin Antagonists
Abstract

The pharmacological profile of a series of (+/-)-2,5-dimethoxy-4-(X)-phenylisopropylamines (X=I, Br, NO(2), CH(3), or H) and corresponding phenylethylamines, was determined in Xenopus laevis oocytes injected with cRNA coding for rat 5-HT(2A) or 5-HT(2C) receptors. The efficacy and relative potency of these drugs were determined and compared to classical 5-HT(2) receptor agonists and antagonists. The rank order of agonist potency at the 5-HT(2A) receptor was: alpha-methyl-5-HT=5-HTm-CPPMK-212; at the 5-HT(2C) receptor the order was: 5-HTalpha-methyl-5-HTMK-212m-CPP. All these compounds were full agonists at the 5-HT(2C) receptor, but alpha-methyl-5-HT and m-CPP showed lower efficacy at the 5-HT(2A) receptor. 4-(4-Fluorobenzoyl)-1-(4-phenylbutyl)piperidine (4F 4PP) was 200 times more potent as a 5-HT(2A) antagonist than at 5-HT(2C) receptors. Conversely, RS 102221 was 100 times more potent as a 5-HT(2C) antagonist, confirming their relative receptor selectivities. The phenylisopropylamines were partial agonists at the 5-HT(2A) receptor, with I(max) relative to 5-HT in the 22+/-7 to 58+/-15% range; the corresponding phenylethylamines had lower or undetectable efficacies. All these drugs had higher efficacies at 5-HT(2C) receptors; DOI was a full 5-HT(2C) agonist. 2C-I and the other phenylethylamines examined showed relative efficacies at the 5-HT(2C) receptor ranging from 44+/-10% to 76+/-16%. 2C-N was a 5-HT(2) receptor antagonist; the mechanism was competitive at the 5-HT(2A), but non-competitive at the 5-HT(2C) receptor. The antagonism was time-dependent at the 5-HT(2C) receptor but independent of pre-incubation time at the 5-HT(2A) receptor subtype. The alpha-methyl group determines the efficacy of these phenylalkylamines at the 5-HT(2A) and 5-HT(2C) receptors.

Published
2002

42. Improving Amphetamine Therapeutic Selectivity: N,N‐dimethyl‐MTA has Dopaminergic Effects and does not Produce Aortic Contraction

Author

Sotomayor‐Zárate, Ramón, primary, Jara, Pablo, additional, Araos, Patricio, additional, Vinet, Raúl, additional, Quiroz, Gabriel, additional, Renard, Georgina M., additional, Espinosa, Pedro, additional, Hurtado‐Guzmán, Claudio, additional, Moya, Pablo R., additional, Iturriaga‐Vásquez, Patricio, additional, Gysling, Katia, additional, and Reyes‐Parada, Miguel, additional

Published
2013
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44. In a Model of Batten Disease, Palmitoyl Protein Thioesterase-1 Deficiency Is Associated with Brown Adipose Tissue and Thermoregulation Abnormalities

Author

Khaibullina, Alfia, primary, Kenyon, Nicholas, additional, Guptill, Virginia, additional, Quezado, Martha M., additional, Wang, Li, additional, Koziol, Deloris, additional, Wesley, Robert, additional, Moya, Pablo R., additional, Zhang, Zhongjian, additional, Saha, Arjun, additional, Mukherjee, Anil B., additional, and Quezado, Zenaide M.N., additional

Published
2012
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45. 4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding EffectsIn Vivo

Author

Sotomayor-Zárate, Ramón, primary, Quiroz, Gabriel, additional, Araya, Katherine A., additional, Abarca, Jorge, additional, Ibáñez, María R., additional, Montecinos, Alejandro, additional, Guajardo, Carlos, additional, Núñez, Gabriel, additional, Fierro, Angélica, additional, Moya, Pablo R., additional, Iturriaga-Vásquez, Patricio, additional, Gómez-Molina, Cristóbal, additional, Gysling, Katia, additional, and Reyes-Parada, Miguel, additional

Published
2012
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