Research Topics - Genetics of Cognition

Higher-order Cognitive Processes

The cognitive control of behavior, including the selection and execution of goal-directed actions, is a highly heritable trait and a major determinant of our health and well-being. Alterations in cognitive control are shared common features of different psychiatric and neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and bipolar disorder. Notably, cognitive deficits in these disorders are currently considered the main source of disability, having the most critical impact on the daily life of the patients and their relatives, on public health and long-term outcomes.

Our first scientific effort is to develop effective preclinical tools to study higher-order cognitive abilities with high translational validity from/to humans, while taking advantage of the outstanding advanced molecular and mechanistic tools available for mice. Importantly, we are interested in how cognitive functions change in males and females throughout development. The domains we are most focused on: working memory, attentional control, executive functions and flexibility.

[PAPERS] Higher-order Cognitive Processes

Related papers

Ciampoli M, Scheggia D, Papaleo F*. Automatic Intra-/Extra-Dimensional Attentional Set-Shifting Task in Adolescent Mice. Frontiers in Behavioral Neuroscience. 2021 Jul 19;15:704684. doi: 10.3389/fnbeh.2021.704684. *Corresponding author
Leggio GM, Torrisi SA, Mastrogiacomo R, Mauro D, Chisari M, Devroye C, Scheggia D, Nigro M, Geraci F, Pintori N, Giurdanella G, Costa L, Bucolo C, Ferretti V, Sortino MA, Ciranna L, De Luca MA, Mereu M, Managò F, Salomone S, Drago F, Papaleo F*. The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans. Molecular Psychiatry. 2021 Apr;26(4):1272-1285. doi: 10.1038/s41380-019-0511-4. *Corresponding author
Leggio GM, Torrisi SA, Mastrogiacomo R, Mauro D, Chisari M, Devroye C, Scheggia D, Nigro M, Geraci F, Pintori N, Giurdanella G, Costa L, Bucolo C, Ferretti V, Sortino MA, Ciranna L, De Luca MA, Mereu M, Managò F, Salomone S, Drago F, Papaleo F*. The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans. Molecular Psychiatry. 2019 Sep 6. doi: 10.1038/s41380-019-0511-4. *Corresponding author
Contarini G, Ferretti V, Papaleo F*. Acute Administration of URB597 Fatty Acid Amide Hydrolase Inhibitor Prevents Attentional Impairments by Distractors in Adolescent Mice. Frontiers in Pharmacology. 2019 Jul 19;10:787. doi: 10.3389/fphar.2019.00787.
Morè L, Lauterborn JC, Papaleo F*, Brambilla R. Enhancing cognition through pharmacological and environmental interventions: examples from preclinical models of neurodevelopmental disorders. Neurosci Biobehav Rev. 2019 Apr 10. doi: 10.1016/j.neubiorev.2019.02.003. [Epub ahead of print] Review. *Corresponding author.
Scheggia D, Mastrogiacomo R, Mereu M, Sannino S, Straub RE, Armando M, Managò F, Guadagna S, Piras F, Zhang F, Kleinman JE, Hyde TM, Kaalund SS, Pontillo M, Orso G, Caltagirone C, Borrelli E, De Luca MA, Vicari S, Weinberger DR, Spalletta G, Papaleo F*. Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment. Nature Communications. 2018 Jun 11;9(1):2265. doi:10.1038/s41467-018-04711-w. *Corresponding author.
Carr GV, Maltese F, Sibley DR, Weinberger DR, Papaleo F*. The Dopamine D5 Receptor Is Involved in Working Memory. Frontiers in Pharmacology. 2017. Oct 6;8:666. doi: 10.3389/fphar.2017.00666. *Corresponding author.
Ciampoli M, Contarini G, Mereu M, Papaleo F*. Attentional Control in Adolescent Mice Assessed with a Modified Five Choice Serial Reaction Time Task. Scientific Reports. 2017 Aug 30;7(1):9936. doi: 10.1038/s41598-017-10112-8. *Corresponding author.
Scheggia D, Zamberletti E, Realini N, Mereu M, Contarini G, Ferretti V, Managò F, Margiani G, Brunoro R, Rubino T, De Luca MA, Piomelli D, Parolaro D, Papaleo F*. Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex. Molecular Psychiatry. 2018 Apr;23(4):1040-1050. doi:10.1038/mp.2017.126. Epub 2017 Jun20. *Corresponding author.
Sannino S, Padula MC, Managò F, Schaer M, Schneider M, Armando M, Scariati E, Sloan-Bena F, Mereu M, Pontillo M, Vicari S, Contarini G, Chiabrera C, Pagani M, Gozzi A, Eliez S, Papaleo F*. Adolescence is the starting point of sex-dichotomous COMT genetic effects. Transl Psychiatry. 2017 May 30;7(5):e1141. doi: 10.1038/tp.2017.109. *Corresponding author.
Mereu M, Contarini G, Buonaguro EF, Latte G, Managò F, Iasevoli F, de Bartolomeis A, Papaleo F*. Dopamine transporter (DAT) genetic hypofunction in mice produces alterations consistent with ADHD but not schizophrenia or bipolar disorder. Neuropharmacology. 2017 Jul 15;121:179-194. doi:10.1016/j.neuropharm.2017.04.037. Epub 2017 Apr 26. *Corresponding author.
Huang H, Guadagna S, Mereu M, Ciampoli M, Pruzzo G, Ballard T, Papaleo F*. A schizophrenia relevant 5-Choice Serial Reaction Time Task for mice assessing broad monitoring, distractibility and impulsivity. Psychopharmacology (Berl). 2017 Jul;234(13):2047-2062. doi:10.1007/s00213-017-4611-z. Epub 2017 Apr 5. *Corresponding author.
Managò F, Mereu M, Mastwal S, Mastrogiacomo R, Scheggia D, Emanuele M, De Luca MA, Weinberger DR, Wang KH, Papaleo F*. Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia. Cell Rep. 2016 Aug 23;16(8):2116-28. doi: 10.1016/j.celrep.2016.07.044. *Corresponding author.
Carr GV, Chen J, Yang F, Ren M, Yuan P, Tian Q, Bebensee A, Zhang GY, Du J, Glineburg P, Xun R, Akhile O, Akuma D, Pickel J, Barrow JC, Papaleo F, Weinberger DR. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. Molecular Psychiatry. 2016 Nov;21(11):1517-1526. doi: 10.1038/mp.2015.219.
Papaleo F, Yang F, Paterson C, Palumbo S, Carr GV, Wang Y, Floyd K, Huang W, Thomas CJ, Chen J, Weinberger DR, Law AJ. Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model. J Neurosci. 2016 Apr 27;36(17):4859-75. doi: 10.1523/JNEUROSCI.4632-15.2016.
Scheggia D, Papaleo F*. An Operant Intra-/Extra-dimensional Set-shift Task for Mice. J Vis Exp. 2016 Jan 22;(107). doi: 10.3791/53503. *Corresponding author.
Papaleo F*, Sannino S, Piras F, Spalletta G. Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia. Eur Neuropsychopharmacol. 2015 Dec;25(12):2349-63. doi: 10.1016/j.euroneuro.2015.10.005. *Corresponding author.
Sannino S, Gozzi A, Cerasa A, Piras F, Scheggia D, Manago F, Damiano M, Galbusera A, Erickson LC, Tonelli DDT, Bifone A, Tsaftaris SA, Caltagirone C, Weinberger DR, Spalletta G, Papaleo F*. COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans. Cerebral Cortex 2015; Sep;25(9):2529-41. doi: 10.1093/cercor/bhu053. Epub 2014 Mar 21. *Corresponding author.
Papaleo F*, Burdick MC, Callicott JH, Weinberger DR. Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans. Molecular Psychiatry. 2014 Mar;19(3):311-6. doi: 10.1038/mp.2013.133. Epub 2013 Oct 22. *Corresponding author.
Scheggia D, Bebensee A, Weinberger DR, Papaleo F*. The Ultimate Intra/Extradimensional Attentional Set-Shifting Task for Mice. Biol Psychiatry. 2014 Apr 15;75(8):660-70. doi: 10.1016/j.biopsych.2013.05.021. Epub 2013 Jun 28. *Corresponding author.
Carr GV, Jenkins KA, Weinberger DR, Papaleo F*. Loss of dysbindin-1 in mice impairs reward-based operant learning by increasing impulsive and compulsive behavior. Behav Brain Res. 2013 Mar 15;241:173-84. doi: 10.1016/j.bbr.2012.12.021. Epub 2012 Dec 20. *Corresponding author.
Papaleo F*, Erickson L, Liu G, Chen J, Weinberger DR. Effects of sex and COMT genotype on environmentally modulated cognitive control in mice. PNAS. 2012 Dec 4;109(49):20160-5. doi: 10.1073/pnas.1214397109. Epub 2012 Nov 19. *Corresponding author.
Papaleo F*, Yang F, Garcia S, Chen J, Lu B, Crawley JN, Weinberger DR. Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Molecular Psychiatry 2012 Jan; 17(1):85-98. doi: 10.1038/mp.2010.106. Epub 2010 Oct 19. *Corresponding author.
Papaleo F*, Silverman JL, Aney J, Tian Q, Barkan CL, Chadman KK, Crawley JN. Working memory deficits, increased anxiety-like traits and seizure susceptibility in BDNF overexpressing mice. Learning & Memory. 2011 Jul 26;18(8):534-44. Print 2011 Aug. *Corresponding author.
Papaleo F*, Lipska BK, Weinberger DR. Mouse models of genetic effects on cognition: Relevance to schizophrenia. Neuropharmacology. 2012 Mar;62(3):1204-20. Epub 2011 May 5.*Corresponding author.
Papaleo F, Crawley JN, Song J, Lipska BK, Pickel J, Weinberger DR, Chen J. Genetic dissection of the role of Catechol-O-Methyltransferase in cognition and stress reactivity in mice. J. Neurosci. 2008 Aug 27; 28(35):8709-23. doi: 10.1523/JNEUROSCI.2077-08.2008.

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Social Cognition

In social species, high-level cognitive functions are strongly interconnected with social abilities and social context. Social interactions depend on our ability to decipher expressions of emotions in others. This biological process, defined as “social cognition”, has profound implications in everyone’s life. Consistently, disturbances in this domain are early and distinctive features of many psychiatric and neurodevelopmental disorders including autism spectrum disorders and schizophrenia. However, despite the deleterious impact on the everyday life of these subjects, social cognitive impairments still miss an effective treatment.

We focus on addressing the cellular mechanisms underlying the ability to discriminate conspecifics based on positive or negative emotional states, and the correlation of these processes with other forms of social behaviors. We are particularly interested on the implication and interplay of different cell types (neurons and glial cells) and systems, such as neuropeptides (e.g. oxytocin, corticotropin releasing factor, somatostatin), and neurotransmitters (e.g. dopamine, endocannabinoids).

[PAPERS] Social Cognition

Related papers

Scheggia D, La Greca F, Maltese F, Chiacchierini G, Italia M, Molent C, Bernardi F, Carrano N, Zianni E, Gardoni F, Diluca M, Papaleo F. Reciprocal cortico-amygdala connections regulate prosocial and selfish choices in mice. Nature Neuroscience. 2022. In Press.
Maltese F, Papaleo F*. Oxytocin Discrepancies in Social Dynamics. Neuron. 2020 Aug 19;107(4):591-593. doi: 10.1016/j.neuron.2020.07.027. *Corresponding author.
Scheggia D, Papaleo F*. Social Neuroscience: Rats Can Be Considerate to Others. Current Biology. 2020 Mar 23;30(6):R274-R276. doi: 10.1016/j.cub.2020.01.093. *Corresponding author.
Scheggia D, Managò F, Maltese F, Bruni S, Nigro M, Dautan D, Latuske P, Contarini G, Gomez-Gonzalo M, Requie LM, Ferretti V, Castellani G, Mauro D, Bonavia A, Carmignoto G, Yizhar O, Papaleo F*. Somatostatin interneurons in the prefrontal cortex control affective state discrimination in mice. Nature Neuroscience. 2020 Jan;23(1):47-60. doi: 10.1038/s41593-019-0551-8. Epub 2019 Dec 16. *Corresponding author.
Ferretti V, Maltese F, Contarini G, Nigro M, Bonavia A, Huang H, Morelli G, Scheggia D, Managò F, Castellani G, Cancedda L, Chini B, Grinevich V, Papaleo F*. Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice. Current Biology. 2019. 29, 1–16 June 17, doi.org/10.1016/j.cub.2019.04.070. *Corresponding author.
Ferretti V, Papaleo F*. Understanding others: emotion recognition abilities in humans and other animals. Genes, Brain Behavior. 2018. Dec13:e12544. doi:10.1111/gbb.12544. *Corresponding author.
Szczurkowska J, Pischedda F, Pinto B, Managò F, Haas CA, Summa M, Bertorelli R, Papaleo F, Schäfer MK, Piccoli G, Cancedda L. NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice. Brain. 2018 Jul 27. doi: 10.1093/brain/awy190.
Managò F & Papaleo F*. Schizophrenia: What’s Arc Got to Do with It? Frontiers in Behavioral Neuroscience. 2017. Sep 20; 11:181. doi: 10.3389/fnbeh.2017.00181. *Corresponding author.
Galbusera A, De Felice A, Stefano G, Bassetto G, Maschietto M, Nishimori K, Chini B, Papaleo F, Vassanelli S, Gozzi A. Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates. Neuropsychopharmacology. 2017 Jun;42(7):1420-1434. doi: 10.1038/npp.2016.283. Epub 2016 Dec 20.
Managò F, Mereu M, Mastwal S, Mastrogiacomo R, Scheggia D, Emanuele M, De Luca MA, Weinberger DR, Wang KH, Papaleo F*. Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia. Cell Rep. 2016 Aug 23;16(8):2116-28. doi: 10.1016/j.celrep.2016.07.044. *Corresponding author.
Papaleo F, Yang F, Paterson C, Palumbo S, Carr GV, Wang Y, Floyd K, Huang W, Thomas CJ, Chen J, Weinberger DR, Law AJ. Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model. J Neurosci. 2016 Apr 27;36(17):4859-75. doi: 10.1523/JNEUROSCI.4632-15.2016.
Huang H, Papaleo F*. Genetic modulation of oxytocin's effects in social functioning. Ann Transl Med. 2015 Dec;3(22):348. doi: 10.3978/j.issn.2305-5839.2015.09.36. *Corresponding author.
Huang H, Michetti C, Busnelli M, Managò F, Sannino S, Scheggia D, Giancardo L, Sona D, Murino V, Chini B, Luisa Scattoni M, Papaleo F*. Chronic and Acute Intranasal Oxytocin Produce Divergent Social Effects in Mice. Neuropsychopharmacology. 2014 Apr;39(5):1102-14. doi: 10.1038/npp.2013.310. Epub 2013 Nov 4. *Corresponding author.
Giancardo L, Sona D, Huang H, Sannino S, Managò F, Scheggia D, Papaleo F*, Murino V. Automatic visual tracking and social behaviour analysis with multiple mice. PLoS One. 2013 Sep 16;8(9):e74557. doi: 10.1371/journal.pone.0074557. *Corresponding author.

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Genetics

Psychiatric and neurodevelopmental disorders such as schizophrenia, autism spectrum disorders, ADHD, and bipolar disorder are characterized by a strong genetic component and a robust correlation with cognitive/social dysfunctions. From a therapeutic perspective, “diagnostics” boundaries in psychiatry might be refined by genetically informed analyses and/or overcome by a focus on basic dimensions of functioning. Notably, diagnostic- and empirically-based therapeutics often produce inefficient and highly variable responses, especially for cognitive and social deficits. Clinical guidelines strongly recommend adapting treatments to each individual case but, so far, no biomarkers exist to implement personalized treatments.

We aim to provide new knowledge on the mechanistic bases of the unpredictable variability of treatment efficacy in cognitive and social processes, by considering the impact of genetic variations, critical developmental periods and sex differences. In particular, we test specific hypotheses regarding functional common genetic variants, epistatic interactions or specific copy number variants syndromes, with high penetrance in the development of schizophrenia, autism and ADHD (e.g. 22q11.2, 16p11.2).

[PAPERS] Genetics

Related papers

Leggio GM, Torrisi SA, Mastrogiacomo R, Mauro D, Chisari M, Devroye C, Scheggia D, Nigro M, Geraci F, Pintori N, Giurdanella G, Costa L, Bucolo C, Ferretti V, Sortino MA, Ciranna L, De Luca MA, Mereu M, Managò F, Salomone S, Drago F, Papaleo F*. The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans. Molecular Psychiatry. 2019 Sep 6. doi: 10.1038/s41380-019-0511-4. *Corresponding author.
Szczurkowska J, Pischedda F, Pinto B, Managò F, Haas CA, Summa M, Bertorelli R, Papaleo F, Schäfer MK, Piccoli G, Cancedda L.NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice. Brain. 2018 Jul 27. doi: 10.1093/brain/awy190.
Scheggia D, Mastrogiacomo R, Mereu M, Sannino S, Straub RE, Armando M, Managò F, Guadagna S, Piras F, Zhang F, Kleinman JE, Hyde TM, Kaalund SS, Pontillo M, Orso G, Caltagirone C, Borrelli E, De Luca MA, Vicari S, Weinberger DR, Spalletta G, Papaleo F*.Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment. Nature Communications. 2018 Jun 11;9(1):2265. doi:10.1038/s41467-018-04711-w. *Corresponding author.
Carr GV, Maltese F, Sibley DR, Weinberger DR, Papaleo F*. The Dopamine D5 Receptor Is Involved in Working Memory. Frontiers in Pharmacology. 2017. Oct 6;8:666. doi: 10.3389/fphar.2017.00666. *Corresponding author.
Amato D, Vernon AC, Papaleo F. Dopamine, the antipsychotic molecule: a perspective on mechanisms underlying antipsychotic response variability. Neuroscience & Biobehavioral Reviews. 2018 Feb;85:146-159. doi: 10.1016/j.neubiorev.2017.09.027. Epub 2017 Sep 29.
Managò F & Papaleo F*. Schizophrenia: What’s Arc Got to Do with It? Frontiers in Behavioral Neuroscience. 2017. Sep 20; 11:181. doi: 10.3389/fnbeh.2017.00181. *Corresponding author.
Ciampoli M, Contarini G, Mereu M, Papaleo F*. Attentional Control in Adolescent Mice Assessed with a Modified Five Choice Serial Reaction Time Task. Scientific Reports. 2017 Aug 30;7(1):9936. doi: 10.1038/s41598-017-10112-8. *Corresponding author.
Scheggia D, Zamberletti E, Realini N, Mereu M, Contarini G, Ferretti V, Managò F, Margiani G, Brunoro R, Rubino T, De Luca MA, Piomelli D, Parolaro D, Papaleo F*. Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex. Molecular Psychiatry. 2018 Apr;23(4):1040-1050. doi:10.1038/mp.2017.126. Epub 2017 Jun20. *Corresponding author.
Sannino S, Padula MC, Managò F, Schaer M, Schneider M, Armando M, Scariati E, Sloan-Bena F, Mereu M, Pontillo M, Vicari S, Contarini G, Chiabrera C, Pagani M, Gozzi A, Eliez S, Papaleo F*. Adolescence is the starting point of sex-dichotomous COMT genetic effects. Transl Psychiatry. 2017 May 30;7(5):e1141. doi: 10.1038/tp.2017.109. *Corresponding author.
Mereu M, Contarini G, Buonaguro EF, Latte G, Managò F, Iasevoli F, de Bartolomeis A, Papaleo F*. Dopamine transporter (DAT) genetic hypofunction in mice produces alterations consistent with ADHD but not schizophrenia or bipolar disorder. Neuropharmacology. 2017 Jul 15;121:179-194. doi:10.1016/j.neuropharm.2017.04.037. Epub 2017 Apr 26. *Corresponding author.
Contarino A, Kitchener P, Vallée M, Papaleo F, Piazza PV. CRF1 receptor-deficiency increases cocaine reward. Neuropharmacology. 2017 May 1;117:41-48. doi: 10.1016/j.neuropharm.2017.01.024. Epub 2017 Jan 27.
Managò F, Mereu M, Mastwal S, Mastrogiacomo R, Scheggia D, Emanuele M, De Luca MA, Weinberger DR, Wang KH, Papaleo F*. Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia. Cell Rep. 2016 Aug 23;16(8):2116-28. doi: 10.1016/j.celrep.2016.07.044. *Corresponding author.
Carr GV, Chen J, Yang F, Ren M, Yuan P, Tian Q, Bebensee A, Zhang GY, Du J, Glineburg P, Xun R, Akhile O, Akuma D, Pickel J, Barrow JC, Papaleo F, Weinberger DR. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. Molecular Psychiatry. 2016 Nov;21(11):1517-1526. doi: 10.1038/mp.2015.219.
Papaleo F, Yang F, Paterson C, Palumbo S, Carr GV, Wang Y, Floyd K, Huang W, Thomas CJ, Chen J, Weinberger DR, Law AJ. Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model. J Neurosci. 2016 Apr 27;36(17):4859-75. doi: 10.1523/JNEUROSCI.4632-15.2016.
Huang H, Papaleo F*. Genetic modulation of oxytocin's effects in social functioning. Ann Transl Med. 2015 Dec;3(22):348. doi: 10.3978/j.issn.2305-5839.2015.09.36. *Corresponding author.
Papaleo F*, Sannino S, Piras F, Spalletta G. Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia. Eur Neuropsychopharmacol. 2015 Dec;25(12):2349-63. doi: 10.1016/j.euroneuro.2015.10.005. *Corresponding author.
Sannino S, Gozzi A, Cerasa A, Piras F, Scheggia D, Manago F, Damiano M, Galbusera A, Erickson LC, Tonelli DDT, Bifone A, Tsaftaris SA, Caltagirone C, Weinberger DR, Spalletta G, Papaleo F*. COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans. Cerebral Cortex 2015; Sep;25(9):2529-41. doi: 10.1093/cercor/bhu053. Epub 2014 Mar 21. *Corresponding author.
Papaleo F*, Burdick MC, Callicott JH, Weinberger DR. Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans. Molecular Psychiatry. 2014 Mar;19(3):311-6. doi: 10.1038/mp.2013.133. Epub 2013 Oct 22. *Corresponding author.
Carr GV, Jenkins KA, Weinberger DR, Papaleo F*. Loss of dysbindin-1 in mice impairs reward-based operant learning by increasing impulsive and compulsive behavior. Behav Brain Res. 2013 Mar 15;241:173-84. doi: 10.1016/j.bbr.2012.12.021. Epub 2012 Dec 20. *Corresponding author.
Papaleo F*, Erickson L, Liu G, Chen J, Weinberger DR. Effects of sex and COMT genotype on environmentally modulated cognitive control in mice. PNAS. 2012 Dec 4;109(49):20160-5. doi: 10.1073/pnas.1214397109. Epub 2012 Nov 19. *Corresponding author.
Scheggia D, Sannino S, Scattoni ML, Papaleo F*. COMT as a drug target for cognitive functions and dysfunctions. CNS & Neurological Disorders-Drug Targets. 2012 May;11(3):209-21. Review. *Corresponding author.
Ingallinesi M, Rouibi K, Le Moine C, Papaleo F, Contarino A. CRF₂ receptor-deficiency eliminates opiate withdrawal distress without impairing stress-coping. Molecular Psychiatry. 2012 Dec;17(12):1283-94. doi: 10.1038/mp.2011.119. Epub 2011 Sep 27.
Papaleo F*, Yang F, Garcia S, Chen J, Lu B, Crawley JN, Weinberger DR. Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Molecular Psychiatry 2012 Jan; 17(1):85-98. doi: 10.1038/mp.2010.106. Epub 2010 Oct 19. *Corresponding author.
Papaleo F*, Lipska BK, Weinberger DR. Mouse models of genetic effects on cognition: Relevance to schizophrenia. Neuropharmacology. 2012 Mar;62(3):1204-20. Epub 2011 May 5.*Corresponding author.
Papaleo F, Weinberger DR. Dysbindin and Schizophrenia: It’s dopamine and glutamate all over again. Biological Psychiatry. 2011 January 1; 69(1): 2-4.
Papaleo F, Crawley JN, Song J, Lipska BK, Pickel J, Weinberger DR, Chen J. Genetic dissection of the role of Catechol-O-Methyltransferase in cognition and stress reactivity in mice. Neurosci. 2008 Aug 27; 28(35):8709-23. doi: 10.1523/JNEUROSCI.2077-08.2008.
Papaleo F, Kitchener P, Contarino A. Disruption of the CRF/CRF₁ receptor stress system exacerbates the somatic signs of opiate withdrawal. Neuron. 2007 Feb 15;53(4):577-589.
Contarino A and Papaleo F. The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal. PNAS. 2005 Dec 20; 102(51):18649-18654.

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Immune-brain Communication

Immune System-Brain Communication

Increasing evidence is strengthening the hypothesis that immune vulnerability and altered inflammatory responses might play a pivotal role in the pathophysiology of neurodevelopmental disorders such as autism, ADHD, and schizophrenia. In particular, early alterations in immune activity have been linked with aberrant developmental trajectories in cognitive and social processes.

We aim to investigate the immune-brain communication as the base of alterations in cognitive and social processes, as well as treatment responses. In particular, we study copy number variants microdeletion syndromes with robust penetrance in the development of schizophrenia, autism and ADHD (e.g. 22q11.2, 16p11.2), as a unique opportunity to address the interplay between genetic- and immune-vulnerability in the development of cognitive and social alterations.

[PAPERS] Immune-brain Communication

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Castellani G, Contarini G, Mereu M, Albanesi E, Devroye C, D'Amore C, Ferretti V, De Martin S, Papaleo F. Dopamine-Mediated Immunomodulation affects Choroid Plexus Function. Brain Behav Immun. 2019 Jun 5. doi: 10.1016/j.bbi.2019.06.006. [Epub ahead of print]

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Higher-order Cognitive Processes

[PAPERS] Higher-order Cognitive Processes

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[PAPERS] Social Cognition

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[PAPERS] Genetics

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Immune-brain Communication

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