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Author: Alessia Luoni (19)


Jan
2018

To date, gene-environment (GxE) interaction studies in depression have been limited to hypothesis-based candidate genes, since genome-wide (GWAS)-based GxE interaction studies would require enormous datasets with genetics, environmental, and clinical variables. We used a novel, cross-species and cross-tissues "omics" approach to identify genes predicting depression in response to stress in GxE interactions. We integrated the transcriptome and miRNome profiles from the hippocampus of adult rats exposed to prenatal stress (PNS) with transcriptome data obtained from blood mRNA of adult humans exposed to early life trauma, using a stringent statistical analyses pathway.

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Jan
2018

A growing body of evidence supports the idea that drugs targeting the glutamate system may represent a valuable therapeutic alternative in major depressive disorders (MDD). The rapid and prolonged mood elevating effect of the NMDA receptor (NMDAR) antagonist ketamine has been studied intensely. However, its clinical use is hampered by deleterious side-effects, such as psychosis.

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Dec
1969

Prenatal stress (PNS) might affect the developmental programming of adult chronic diseases such as metabolic and mood disorders. The molecular mechanisms underlying such regulations may rely upon long-term changes in stress-responsive effectors such as Brain-Derived Neurotrophic Factor (BDNF) that can affect neuronal plasticity underlying mood disorders and may also play a role in metabolic regulation. Based upon previous data, we hypothesized that PNS might lead to greater vulnerability to an obesogenic challenge experienced at adulthood.

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Jun
2017

Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation.

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Feb
2018

The evidence underlying the so-called glutamatergic hypothesis ranges from NMDA receptor hypofunction to an imbalance between excitatory and inhibitory circuits in specific brain structures. Among all glutamatergic system components, metabotropic receptors play a main role in regulating neuronal excitability and synaptic plasticity. Here, we investigated, using qRT-PCR and western blot, consequences in the hippocampus and prefrontal/frontal cortex (PFC/FC) of mice with a genetic deletion of the metabotropic glutamate receptor 5 (mGlu5), addressing key components of the GABAergic and glutamatergic systems.

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Nov
2016

The emergence of psychiatric disorders relies on the interaction between genetic vulnerability and environmental adversities. Several studies have demonstrated a crucial role for epigenetics (e.g.

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Apr
2015

Prenatal stress (PNS) is a risk factor for the development of neuropsychiatric disorders. This study was aimed at assessing, in a rodent model, changes in gene expression profiles and behavioral output as a result of PNS, during periadolescence, a critical developmental period for the onset of psychopathology. Social behavior was studied in a standardized social interaction paradigm and the expression of Brain-Derived Neurotrophic Factor (Bdnf), a marker of neuronal plasticity, and of inhibitory and excitatory mechanisms (Na(+)-K(+)-2Cl(-) and K(+)-Cl(-) cotransporters ratio, NKCC1/KCC2) was analyzed.

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Dec
1969

The impact of early physical and social environments on life-long pathological phenotypes is well known and there is now compelling evidence that stressful experiences during gestation or early in life can lead to enhanced susceptibility to mental illness. Here, we discuss the data from preclinical studies aimed at investigating the molecular consequences of the exposure to stressful events during prenatal or early postnatal life that might contribute to later psychopathology. Particularly, we will discuss the existence of age windows of vulnerability to environmental conditions during brain maturation using as examples several studies performed with different animal models.

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Oct
2014

Major depression is associated with several alterations, including reduced neuronal plasticity and impaired synaptic function, which represent an important target of pharmacological intervention.
In the present study, we have investigated the ability of the antipsychotic drug lurasidone to modulate behavioral and neuroplastic alterations in the chronic mild stress model of depression.
Rats that show reduced sucrose consumption after 2 weeks of chronic mild stress have reduced expression of the pool of Bdnf transcripts with the long 3' untranslated region (3'-UTR) that may be targeted to the synaptic compartment, suggesting the contribution of the neurotrophin to the behavioral dysfunction produced by chronic mild stress.

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Dec
1969

The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g.

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Apr
2014

Lurasidone is a novel second generation antipsychotic drug characterized by a multi-receptor profile. Besides the high affinity for 5-HT2A and D2 receptors, it is also characterized by potent 5-HT7 receptor antagonism, which may be beneficial for mood and cognition. Considering that dose-dependent changes in receptor occupancy may differentially impact gene transcription, we aimed at investigating the effects of acute and chronic treatments with different doses of lurasidone (1, 3 and 10mg/kg) in rats on the expression of the activity-regulated genes Arc, Zif268 and Npas4, which are markers of neuronal activation and are also associated with neuroadaptive mechanisms.

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Apr
2014

Adolescence is characterized by important molecular and anatomical changes with relevance for the maturation of brain circuitry and cognitive function. This time period is of critical importance in the emergence of several neuropsychiatric disorders accompanied by cognitive impairment, such as affective disorders and schizophrenia. The molecular mechanisms underlying these changes at neuronal level during this specific developmental stage remains however poorly understood.

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Feb
2014

Despite the rapid control of schizophrenic symptoms is due to the ability of antipsychotic drugs (APDs) to block D2 receptors in the mesolimbic pathway, it is now well-established that the therapeutic effects rely on adaptive mechanisms set in motion by their long-term administration. Such neuroplastic mechanisms depend on the pharmacological profile of the drug employed, with marked differences existing between first and second generation APDs. On these bases, the major accomplishment of this work was to investigate neuroadaptive changes set in motion by repeated treatment with aripiprazole, a novel APD that is unique for being a partial agonist at dopamine D2 receptors.

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May
2013

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms mediating these effects are poorly understood. Here we identify the glucocorticoid receptor (GR) target gene, serum- and glucocorticoid-inducible kinase 1 (SGK1), as one such mechanism. Using a human hippocampal progenitor cell line, we found that a small molecule inhibitor for SGK1, GSK650394, counteracted the cortisol-induced reduction in neurogenesis.

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Apr
2013

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. We, therefore, investigated the molecular signaling pathways mediating the effects of cortisol on proliferation, neuronal differentiation, and astrogliogenesis, in an immortalized human hippocampal progenitor cell line. In addition, we examined the molecular signaling pathways activated in the hippocampus of prenatally stressed rats, characterized by persistently elevated glucocorticoid levels in adulthood.

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Jul
2013

Second-generation antipsychotics (SGA) are multi-target agents widely used for the treatment of schizophrenia and bipolar disorder that also hold potential for the treatment of impaired emotional control, thanks to their diverse receptor profiles as well as their potential in modulating neuroadaptive changes in key brain regions. The aim of this study was thus to establish the ability of lurasidone, a novel SGA characterized by a multi-receptor signature, to modulate behavioural and molecular defects associated with a genetic model of impaired emotional control, namely serotonin transporter knockout (SERT KO) rats. At behavioural level, we found that chronic lurasidone treatment significantly increased fear extinction in SERT KO rats, but not in wild-type control animals.

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May
2012

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial.

Trials 2012 May 30;13:73. Epub 2012 May 30.
Mirella Ruggeri, Chiara Bonetto, Antonio Lasalvia, Giovanni De Girolamo, Angelo Fioritti, Paola Rucci, Paolo Santonastaso, Giovanni Neri, Francesca Pileggi, Daniela Ghigi, Maurizio Miceli, Silvio Scarone, Angelo Cocchi, Stefano Torresani, Carlo Faravelli, Christa Zimmermann, Anna Meneghelli, Carla Cremonese, Paolo Scocco, Emanuela Leuci, Fausto Mazzi, Massimo Gennarelli, Paolo Brambilla, Sarah Bissoli, Maria Elena Bertani, Sarah Tosato, Katia De Santi, Sara Poli, Doriana Cristofalo, Michele Tansella, , Mirella Ruggeri, Maria Elena Mirella, Sarah Bissoli, Chiara Bonetto, Doriana Cristofalo, Katia De Santi, Antonio Lasalvia, Silvia Lunardi, Valentina Negretto, Sara Poli, Sarah Tosato, Maria Grazia Zamboni, Mario Ballarin, Giovanni De Girolamo, Angelo Fioritti, Giovanni Neri, Francesca Pileggi, Paola Rucci, Luisella Bocchio Chiavetto, Catia Scasselatti, Roberta Zanardini, Paolo Brambilla, Marcella Bellani, Alessandra Bertoldo, Veronica Marinelli, Valentina Negretto, Cinzia Perlini, Gianluca Rambaldelli, Antonio Lasalvia, Mariaelena Bertani, Sarah Bissoli, Lorenza Lazzarotto, Sonia Bardella, Francesco Gardellin, Dario Lamonaca, Antonio Lasalvia, Marco Lunardon, Renato Magnabosco, Marilena Martucci, Stylianos Nicolau, Francesco Nifosì, Michele Pavanati, Massimo Rossi, Carlo Piazza, Gabriella Piccione, Alessandra Sala, Annalisa Sale, Benedetta Stefan, Spyridon Zotos, Mirko Balbo, Ileana Boggian, Enrico Ceccato, Rosa Dall'Agnola, Francesco Gardellin, Barbara Girotto, Claudia Goss, Dario Lamonaca, Antonio Lasalvia, Roberta Leoni, Alessia Mai, Annalisa Pasqualini, Michele Pavanati, Carlo Piazza, Gabriella Piccione, Stefano Roccato, Alberto Rossi, Annalisa Sale, Stefania Strizzolo, Spyridon Zotos, Anna Urbani, Flavia Ald, Barbara Bianchi, Paola Cappellari, Raffaello Conti, Laura De Battisti, Ermanna Lazzarin, Silvia Merlin, Giuseppe Migliorini, Tecla Pozzan, Lucio Sarto, Stefania Visonà, Andrea Brazzoli, Antonella Campi, Roberta Carmagnani, Sabrina Giambelli, Annalisa Gianella, Lino Lunardi, Davide Madaghiele, Paola Maestrelli, Lidia Paiola, Elisa Posteri, Loretta Viola, Valentina Zamberlan, Marta Zenari, Sarah Tosato, Martina Zanoni, Giovanni Bonadonna, Mariacristina Bonomo, Paolo Santonastaso, Carla Cremonese, Paolo Scocco, Angela Veronese, Patrizia Anderle, Andrea Angelozz, Isabelle Amalric, Gabriella Baron, Enrico Bruttomesso Fabio Candeago, Franco Castelli, Maria Chieco, Carla Cremonese, Enrico Di Costanzo, Mario Derossi, Michele Doriguzzi, Osvaldo Galvano, Marcello Lattanz, Roberto Lezzi, Marisa Marcato, Alessandro Marcolin, Franco Marini, Manlio Matranga, Donato Scalabrin, Maria Zucchetto, Flavio Zadro, Giovanni Austoni, Maria Bianco, Francesca Bordino, Filippo Dario, Alessandro De Risio, Aldo Gatto, Simona Granà, Emanuele Favero, Anna Franceschin, Silvia Friederici, Vanna Marangon, Michela Pascolo, Luana Ramon, Paolo Scocco, Angela Veronese, Stefania Zambolin, Rossana Riolo, Antonella Buffon, Carla Cremonese, Elena Di Bortolo, Silvia Friederici, Stefania Fortin, Marisa Marcato, Francesco Matarrese, Simona Mogni, Novella Codemo, Alessio Russi, Alessandra Silvestro, Elena Turella, Paola Viel, Anna Dominoni, Lorenzo Andreose, Mario Boemio, Loretta Bressan, Arianna Cabbia, Elisabetta Canesso, Romina Cian, Claudia Dal Piccol, Maria Manuela Dalla Pasqua, Anna Di Prisco, Lorena Mantellato, Monica Luison, Sandra Morgante, Mirna Santi, Moreno Sacillotto, Mauro Scabbio, Patrizia Sponga, M Luisa Sguotto, Flavia Stach, M Grazia Vettorato, Giorgio Martinello, Francesca Dassiè, Stefano Marino, Linda Cibiniel, Ilenia Masetto, Marisa Marcato, Oscar Cabianca, Amalia Valente, Livio Caberlotto, Alberto Passoni, Patrizia Flumian, Luigino Daniel, Massimo Gion, Stanziale Stanziale, Flora Alborino, Vladimiro Bortolozzo, Lucio Bacelle, Leonarda Bicciato, Daniela Basso, Filippo Navaglia, Fabio Manoni, Mauro Ercolin, Giovanni Neri, Franco Giubilini, Massimiliano Imbesi, Emanuela Leuci, Fausto Mazzi, Enrico Semrov, Castel S Giovanni, Valli Taro e Ceno, Polo Ovest, Silvio Anelli, Mario Amore, Laura Bigi, Welsch Britta, Giovanna Barazzoni Anna, Uobes Bonatti, Maria Borziani, Isabella Crosato, Raffaele Galluccio, Margherita Galeotti, Mauro Gozzi, Vanna Greco, Emanuele Guagnini, Stefania Pagani, Malvasi Maccherozzi, Francesco Marchi, Ermanno Melato, Elena Mazzucchi, Franco Marzullo, Pietro Pellegrini, Nicoletta Petrolini, Paolo Volta, Silvio Anelli, Franca Bonara, Elisabetta Brusamonti, Roberto Croci, Ivana Flamia, Francesca Fontana, Romina Losi, Fausto Mazzi, Roberto Marchioro, Stefania Pagani, Luigi Raffaini, Luca Ruju, Antonio Saginario, M Grazia Tondelli, Donatella Marrama, Lucia Bernardelli, Federica Bonacini, Annaluisa Florindo, Marina Merli, Patrizia Nappo, Lorena Sola, Ornella Tondelli, Matteo Tonna, M Teresa Torre, Morena Tosatti, Gloria Venturelli, Daria Zampolla, Antonia Bernardi, Cinzia Cavalli, Lorena Cigala, Cinzia Ciraudo, Antonia Di Bari, Lorena Ferri, Fabiana Gombi, Sonia Leurini, Elena Mandatelli, Stefano Maccaferri, Mara Oroboncoide, Barbara Pisa, Cristina Ricci, Enrica Poggi, Corrado Zurlini, Monica Malpeli, Rossana Colla, Elvira Teodori, Luigi Vecchia, Rocco D'Andrea, Tommaso Trenti, Paola Paolini, Fausto Mazzi, Paolo Carpeggiani, Francesca Pileggi, Daniela Ghigi, Mariateresa Gagliostro, Michela Pratelli, Paola Rucci, S Lazzaro, Antonio Antonelli, Luana Battistini, Francesca Bellini, Eva Bonini, Caterina Bruschi Rossella Capelli, Cinzia DiDomizio, Chiara Drei, Giuseppe Fucci, Alessandra Gualandi, Maria Rosaria Grazia, Anna M Losi, Federica Mazzanti Paola Mazzoni, Daniela Marangoni, Giuseppe Monna, Marco Morselli, Alessandro Oggioni, Silvio Oprandi, Walter Paganelli, Morena Passerini, Maria Piscitelli, Gregorio Reggiani, Gabriella Rossi, Federica Salvatori, Simona Trasforini, Carlo Uslenghi, Simona Veggetti, Giovanna Bartolucci, Rosita Baruffa, Francesca Bellini, Raffaella Bertelli, Lidia Borghi, Patrizia Ciavarella, Cinzia DiDomizio, Giuseppe Monna, Alessandro Oggioni, Elisabetta Paltrinieri, Francesco Rizzardi, Piera Serra, Damiano Suzzi, Uslenghi Carlo, Maria Piscitelli, Paolo Arienti, Fabio Aureli, Rosita Avanzi, Vincenzo Callegari, Alessandra Corsino, Paolo Host, Rossella Michetti, Michela Pratelli, Francesco Rizzo, Paola Simoncelli, Elena Soldati, Eraldo Succi, Massimo Bertozzi, Elisa Canetti, Luca Cavicchioli, Elisa Ceccarelli, Stefano Cenni, Glenda Marzola, Vanessa Gallina, Carla Leoni, Andrea Olivieri, Elena Piccolo, Sabrina Ravagli, Rosaria Russo, Daniele Tedeschini, Marina Verenini, Walter Abram, Veronica Granata, Alessandro Curcio, Giovanni Guerra, Samuela Granini, Lara Natali, Enrica Montanari, Fulvia Pasi, Umbertina Ventura, Stefania Valenti, Masi Francesca, Rossano Farneti, Paolo Ravagli, Romina Floris, Otello Maroncelli, Gianbattista Volpones, Donatella Casali, Maurizio Miceli, Andrea Bencini, Massimo Cellini, Luca De Biase, Leonardo Barbara, Liedl Charles, Cristina Pratesi, Andrea Tanini, Massimo Cellini, Maurizio Miceli, Riccardo Loparrino, Cristina Pratesi, Cinzia Ulivelli, Cristina Cussoto, Nico Dei, Enrico Fumanti, Manuela Pantani, Gregorio Zeloni, Rossella Bellini, Roberta Cellesi, Nadia Dorigo, Patrizia Gullì, Luisa Ialeggio, Maria Pisanu, Graziella Rinaldi, Angela Konze, Angelo Cocchi, Anna Meneghelli, Mario Bianco, Litta Modignani, Maria Frova, Emiliano Monzani, Alberto Zanobio, Marina Malagoli, Roberto Pagani, Simona Barbera, Carla Morganti, Emiliano Monzani, Elisabetta Sarzi Amadè, Virginia Brambilla, Anita Montanari, Giori Caterina, Carmelo Lopez, Alessandro Marocchi, Andrea Moletta, Maurizio Sberna, M Teresa Cascio, Silvio Scarone, Maria Laura Manzone, Barbera Barbara, Luisa Mari, Maria L Manzone, Edoardo Razzini, Yvonne Bianchi, M Rosa Pellizzer, Antonella Verdecchia, M Gabriella Sferrazza, M Laura Manzone, Rosa Pismataro, Gian Vico Melzi D'Eril, Alessandra Barassi, Rosana Pacciolla, Gloria Faraci, Stefano Torresani, Bolzano Rosmini, Fabio Carpi, Margit Soelva, Monica Anderlan, Michele De Francesco, Efi Duregger, Stefano Torresani, Carla Vettori, Sabrina Doimo, Erika Kompatscher, Margit Soelva, Stefano Torresani, Michael Forer, Helene Kerschbaumer, Anna Gampe, Maira Nicoletti, Chiara Acerbi, Daniele Aquilino, Silvia Azzali, Luca Bensi, Sarah Bissoli, Davide Cappellari, Elisa Casana, Nadia Campagnola, Elisa Dal Corso, Elisabetta Di Micco, Erika Gobbi, Laura Ferri, Erika Gobbi, Laura Mairaghi, Sara Malak, Luca Mesiano, Federica Paterlini, Michela Perini, Elena Maria Puliti, Rosaria Rispoli, Elisabetta Rizzo, Chiara Sergenti, Manuela Soave, Andrea Alpi, Laura Bislenghi, Tiziana Bolis, Francesca Colnaghi, Simona Fascendini, Silvia Grignani, Anna Meneghelli, Giovanni Patelli, Carlo Faravelli, Silvia Casale, Christa Zimmermann, Giuseppe Deledda, Claudia Goss, Mariangela Mazzi, Michela Rimondini, Massimo Gennarelli, Catia Scassellati, Cristian Bonvicini, Sara Longo, Luisella Bocchio Chiavetto, Roberta Zanardini, Mariacarla Ventriglia, Rosanna Squitti, Giovanni Frisoni, Michela Pievani, Matteo Balestrieri, Paolo Brambilla, Cinzia Perlini, Veronica Marinelli, Marcella Bellani, Gianluca Rambaldelli, Alessandra Bertoldo, Manfredo Atzori, Fausto Mazzi, Paolo Carpeggiani, Alberto Beltramello, Franco Alessandrini, Francesca Pizzini, Giada Zoccatelli, Maurizio Sberna, Angela Konze, Pierluigi Politi, Enzo Emanuele, Natascia Brondino, Gianvito Martino, Alessandra Bergami, Roberto Zarbo, Marco Andrea Riva, Fabio Fumagalli, Raffaella Molteni, Francesca Calabrese, Gianluigi Guidotti, Alessia Luoni, Flavia Macchi, Stefania Artioli, Marco Baldetti, Milena Bizzocchi, Donatella Bolzon, Elisa Bonello, Giorgia Cacciari, Claudia Carraresi, M Teresa Cascio, Gabriele Caselli, Karin Furlato, Sara Garlassi, Alessandro Gavarini, Silvia Lunardi, Fabio Macchetti, Valentina Marteddu, Giorgia Plebiscita, Sara Poli, Stefano Totaro, Paul Bebbington, Max Birchwood, Paola Dazzan, Elisabeth Kuipers, Graham Thornicroft, Carmine Pariante, Steve Lawrie, Carmine Pariante, Jair C Soares
Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services.
The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design.

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Feb
2012

Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity.

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Mar
2012

It is known that long-term treatment with antipsychotic drugs (APDs) produces neuroadaptive changes through the modulation of different proteins that, by enhancing neuronal plasticity and cellular resiliency, may improve core disease symptoms. The aim of this study was to investigate the ability of chronic treatment with the novel antipsychotic lurasidone to modulate BDNF expression in hippocampus and prefrontal cortex, under basal conditions or in response to an acute stress, a major precipitating element in psychiatric disorders. By means of real-time PCR, we found that (1) chronic lurasidone treatment increases total BDNF mRNA levels in rat prefrontal cortex and, to less extent, in hippocampus; (2) the modulation of BDNF mRNA levels in response to acute swim stress in lurasidone-treated rats was markedly potentiated in hippocampus, and to less extent in prefrontal cortex, through the selective regulation of different neurotrophin isoforms.

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