La Ricerca

I am full professor and chair of Psychiatry, Department of Basic Medical Science, Neuroscience and Sense Organs, at the University of Bari, Italy where I head the Psychiatric Neuroscience Group. I am the former global head of Biomarkers and Clinical Imaging within the Neuroscience Department of Hoffman-La Roche, Basel Switzerland. I am board certified in psychiatry with extensive research and clinical experience in neuroimaging of neuropsychiatric disorders. As the head of the research groups in Bari and in Basel, my research has focused on using neuroimaging techniques to evaluate gene effects on brain function in healthy human subjects and in patients with neurological and psychiatric disorders. More specifically, my research has focused on translating genetic risk for several serious neuropsychiatric disorders into systems-level brain mechanisms and into predicting response to treatment with currently marketed drugs as well as identifying new targets for schizophrenia, bipolar disorder, autism spectrum disorders, Alzheimer’s Disease and Parkinson’s Disease.  

1)      A Bertolino, G Caforio, G Blasi, MP De Candia, V Latorre, V Petruzzella, M Altamura, G Nappi, S Papa, JH Callicott, VS Mattay, A Bellomo, T Scarabino, DR Weinberger, M Nardini: Interaction of COMT Val108/158 Met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry 2004, 161:1798-1805;2004

2)      Y. Zhang, A. Bertolino, L. Fazio, G. Blasi, A. Rampino, R. Romano, ML Lee, T. Xiao, A. Papp, D. Wang, W. Sadee: “Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory”. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20552-7. Epub 2007 Dec 11.

3)      G Blasi, C De Virgilio, A Papazacharias, P Taurisano, B Gelao, L Fazio, G Ursini, L Sinibaldi, I Andriola, R Masellis, R Romano, A Rampino, A Di Giorgio, L Lo Bianco, G Caforio, Francesco Piva, T Popolizio, C Bellantuono, O Todarello, JE Kleinman, G Gadaleta, DR Weinberger, A Bertolino. Converging evidence for the association of functional genetic variation in HTR2A with prefrontal physiology and olanzapine treatment. JAMA Psychiatry. 2013 Sep;70(9):921-30. doi: 10.1001/jamapsychiatry.2013.1378. PubMed PMID: 23842608.

4)      G Blasi, F Napolitano, G Ursini, A Di Giorgio, G Caforio, P Taurisano, L Fazio, B Gelao, MT Attrotto, L Colagiorgio, G Todarello, F Piva, A Papzacharias, R Masellis, M Mancini, A Porcelli, R Romano, A Rampino, T Quarto, M Giulietti, BK Lipska, JE Kleinman, T Popolizio, DR Weinberger, A Usiello, A Bertolino. GSK-3β genetic variation is associated with GSK-3βexpression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia. Am J Psychiatry, 2013 Aug 1;170(8):868-76. doi: 10.1176/appi.ajp.2012.12070908.

   Positions and Honors

Academic Appointments

1994-1995     Special Volunteer, Neuroimaging Branch, NINDS, NIH USA

1995-1996     Visiting Fellow, Clinical Brain Disorders Branch, NIMH, NIH USA

1997-1999     Visiting Scientist, Clinical Brain Disorders Branch, NIMH, NIH USA

1999-2004     Assistant Professor of Psychiatry, Clinica Psichiatrica II, Dept. of Neurology and Psychiatry, University of Bari, Italy

2005-2013  Associate Professor of Psychiatry, Clinica Psichiatrica, Dept. of Basic Medical Science, Neuroscience and Sense Organs, University of Bari, Italy

2010               Competition for Full Professorship in Psychiatry, Venia Legendi, University of Pavia, Italy

2012 -            Visiting Professor of Psychiatry, Institute of Psychiatry, King’s College, London, United Kingdom

2011-2013     Delegate for applied research of the Rector of the University of Bari, Italy

2013-2015     Global Head, Biomarkers and Clinical Imaging, Neuroscience, Opthalmology and Rare Diseases DTA, Hoffman-La Roche Ltd, Basel, Switzerland

2015- 2016    Associate Professor of Psychiatry, Clinica Psichiatrica, Dept. of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Italy

2016 – present Chairman, Department of Psychiatry, Azienda Ospedaliero Universitaria Consorziale Policlinico Bari, Bari, Italy

2016 – present Full Professor of Psychiatry, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy

 

Honors and Awards

2000               A. D’errico award for best paper published in 1999 from the Italian Society of Psychopathology

2003                    Vittorio F. Guidano Memorial Award from the International Society of Constructivism

  Contribution to Science

My principal contributions to science involve investigating the biological mechanisms of risk for schizophrenia. In particular, I am interested in how specific behavioral domains, including cognition and emotion, are related to genetic risk, imaging phenotypes, and treatment of schizophrenia.

I have pioneered the application of Proton Magnetic Resonance Spectroscopic Imaging (1H-MRSI) and Blood Oxygenated Level Dependent functional magnetic resonance imaging (BOLD-fMRI) to schizophrenia and other brain disorders.

a)  Bertolino A, Nawroz S, Mattay VS, Barnett AS, Duyn JH, Moonen CT, Frank JA, Tedeschi G, Weinberger DR. Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging. Am J Psychiatry. 1996 Dec;153(12):1554-63. PubMed PMID: 8942451.

b)     Bertolino A, Kumra S, Callicott JH, Mattay VS, Lestz RM, Jacobsen L, Barnett IS, Duyn JH, Frank JA, Rapoport JL, Weinberger DR. Common pattern of cortical pathology in childhood-onset and adult-onset schizophrenia as identified by proton magnetic resonance spectroscopic imaging. Am J Psychiatry. 1998 Oct;155(10):1376-83. PubMed PMID: 9766769.

c)     Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R, Goldberg TE, Weinberger DR. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex. 2000 Nov;10(11):1078-92. PubMed PMID: 11053229.

d)     Bertolino A, Esposito G, Callicott JH, Mattay VS, Van Horn JD, Frank JA, Berman KF, Weinberger DR. Specific relationship between prefrontal neuronal N-acetylaspartate and activation of the working memory cortical network in schizophrenia. Am J Psychiatry. 2000 Jan;157(1):26-33. Review. PubMed PMID: 10618009.

 I have conducted a line of scientific enquiry to shed new light on the neurodevelopmental pathophysiology of prefrontal abnormalities in schizophrenia demonstrating how they relate with the well known dopamine hypothesis.

a)     Bertolino A, Saunders RC, Mattay VS, Bachevalier J, Frank JA, Weinberger DR. Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: a proton magnetic resonance spectroscopic imaging study. Cereb Cortex. 1997 Dec;7(8):740-8. PubMed PMID: 9408038.

b)     Bertolino A, Roffman JL, Lipska BK, van Gelderen P, Olson A, Weinberger DR. Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. Cereb Cortex. 2002 Sep;12(9):983-90. PubMed PMID: 12183397.

c)     Bertolino A, Breier A, Callicott JH, Adler C, Mattay VS, Shapiro M, Frank JA, Pickar D, Weinberger DR. The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia. Neuropsychopharmacology. 2000 Feb;22(2):125-32. PubMed PMID: 10649825.

d)     Bertolino A, Knable MB, Saunders RC, Callicott JH, Kolachana B, Mattay VS, Bachevalier J, Frank JA, Egan M, Weinberger DR. The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia. Biol Psychiatry. 1999 Mar 15;45(6):660-7. PubMed PMID: 10187995.

 In the era preceding Genome Wide Association studies, I have led a group of scientists in establishing how variation in the gene coding for dopamine receptor D2 (DRD2) is associated with brain mechanisms involved in schizophrenia risk. More specifically, we have characterized how DRD2 genetic variation predicts splicing of the two major isoforms affecting prefrontal physiology during processing of working memory information and its relationship with steady-state striatal dopamine signaling. This gene has now received independent demonstration for its association with diagnosis of schizophrenia in the Genome Wide Association studies of the Psychiatric Genomics Consortium (Ripke et al, Nature 2014).

a)     Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee ML, Xiao T, Papp A, Wang D, Sadée W. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20552-7. Epub 2007 Dec 11. PubMed PMID: 18077373; PubMed Central PMCID: PMC2154469

b)     Bertolino A, Fazio L, Di Giorgio A, Blasi G, Romano R, Taurisano P, Caforio G, Sinibaldi L, Ursini G, Popolizio T, Tirotta E, Papp A, Dallapiccola B, Borrelli E, Sadee W. Genetically determined interaction between the dopamine transporter and the D2 receptor on prefronto-striatal activity and volume in humans. J Neurosci. 2009 Jan 28;29(4):1224-34. doi: 10.1523/JNEUROSCI.4858-08.2009. PubMed PMID: 19176830; PubMed Central PMCID: PMC2686116.

c)     Bertolino A, Fazio L, Caforio G, Blasi G, Rampino A, Romano R, Di Giorgio A, Taurisano P, Papp A, Pinsonneault J, Wang D, Nardini M, Popolizio T, Sadee W. Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia. Brain. 2009 Feb;132(Pt 2):417-25. doi: 10.1093/brain/awn248. Epub 2008 Oct 1. PubMed PMID: 18829695; PubMed Central PMCID: PMC2640212.

d)     Bertolino A, Taurisano P, Pisciotta NM, Blasi G, Fazio L, Romano R, Gelao B, Lo Bianco L, Lozupone M, Di Giorgio A, Caforio G, Sambataro F, Niccoli-Asabella A, Papp A, Ursini G, Sinibaldi L, Popolizio T, Sadee W, Rubini G. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. PLoS One. 2010 Feb 22;5(2):e9348. doi: 10.1371/journal.pone.0009348. PubMed PMID: 20179754; PubMed Central PMCID: PMC2825256.

 I have led a group of scientists in establishing a hierarchical, step-wise, translational genetics approach as a strategy to investigate how genetic variation in the dopamine D2 receptor molecular pathway translates into risk for prefrontal dysfunction, a well-known phenotype associated with schizophrenia, and response to treatment with antipsychotics.

a)     Blasi G, Napolitano F, Ursini G, Taurisano P, Romano R, Caforio G, Fazio L, Gelao B, Di Giorgio A, Iacovelli L, Sinibaldi L, Popolizio T, Usiello A, Bertolino A. DRD2/AKT1 interaction on D2 c-AMP independent signaling, attentional processing, and response to olanzapine treatment in schizophrenia. Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1158-63. doi: 10.1073/pnas.1013535108. Epub 2010 Dec 27. PubMed PMID: 21187413; PubMed Central PMCID: PMC3024671.

b)     Blasi G, Napolitano F, Ursini G, Di Giorgio A, Caforio G, Taurisano P, Fazio L, Gelao B, Attrotto MT, Colagiorgio L, Todarello G, Piva F, Papazacharias A, Masellis R, Mancini M, Porcelli A, Romano R, Rampino A, Quarto T, Giulietti M, Lipska BK, Kleinman JE, Popolizio T, Weinberger DR, Usiello A, Bertolino A. Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia. Am J Psychiatry. 2013 Aug;170(8):868-76. doi: 10.1176/appi.ajp.2012.12070908. PubMed PMID: 23598903.

c)     Blasi G, De Virgilio C, Papazacharias A, Taurisano P, Gelao B, Fazio L, Ursini G, Sinibaldi L, Andriola I, Masellis R, Romano R, Rampino A, Di Giorgio A, Lo Bianco L, Caforio G, Piva F, Popolizio T, Bellantuono C, Todarello O, Kleinman JE, Gadaleta G, Weinberger DR, Bertolino A. Converging evidence for the association of functional genetic variation in the serotonin receptor 2a gene with prefrontal function and olanzapine treatment. JAMA Psychiatry. 2013 Sep;70(9):921-30. doi: 10.1001/jamapsychiatry.2013.1378. PubMed PMID: 23842608.

d)     Blasi G, Selvaggi P, Fazio L, Antonucci LA, Taurisano P, Masellis R, Romano R, Mancini M, Zhang F, Caforio G, Popolizio T, Apud J, Weinberger DR, Bertolino A. Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics. Neuropsychopharmacology. 2015 Jun;40(7):1600-8. doi: 10.1038/npp.2015.5. Epub 2015 Jan 7. PubMed PMID: 25563748.

 I have led a group of investigators to assess how environmental factors may interact with genetic variation to modify risk for schizophrenia and associated prefrontal dysfunction. The first of these investigations has been referenced to as opening a new line of research defined as ‘imaging epigenetics’ because of the assessment of how DNA methylation interacts with genetic variation to affect human brain activity.

a)     Ursini G, Bollati V, Fazio L, Porcelli A, Iacovelli L, Catalani A, Sinibaldi L, Gelao B, Romano R, Rampino A, Taurisano P, Mancini M, Di Giorgio A, Popolizio T, Baccarelli A, De Blasi A, Blasi G, Bertolino A. Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity. J Neurosci. 2011 May 4;31(18):6692-8. doi: 10.1523/JNEUROSCI.6631-10.2011. PubMed PMID: 21543598.

b)     Colizzi M, Fazio L, Ferranti L, Porcelli A, Masellis R, Marvulli D, Bonvino A, Ursini G, Blasi G, Bertolino A. Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior. Neuropsychopharmacology. 2015 Feb;40(3):640-9. doi: 10.1038/npp.2014.213. Epub 2014 Aug 20. PubMed PMID: 25139064; PubMed Central PMCID: PMC4289952.

c)     Colizzi M, Iyegbe C, Powell J, Ursini G, Porcelli A, Bonvino A, Taurisano P, Romano R, Masellis R, Blasi G, Morgan C, Aitchison K, Mondelli V, Luzi S, Kolliakou A, David A, Murray RM, Bertolino A, Forti MD. Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis. Schizophr Bull. 2015 Mar 31. pii: sbv032. [Epub ahead of print] PubMed PMID: 25829376.

d)     Taurisano P, Blasi G, Romano R, Sambataro F, Fazio L, Gelao B, Ursini G, Lo Bianco L, Di Giorgio A, Ferrante F, Papazacharias A, Porcelli A, Sinibaldi L, Popolizio T, Bertolino A. DAT by perceived MC interaction on human prefrontal activity and connectivity during emotion processing. Soc Cogn Affect Neurosci. 2013 Dec;8(8):855-62. doi: 10.1093/scan/nss084. Epub 2012 Jul 27. PubMed PMID: 22842906; PubMed Central PMCID: PMC3831553.

Azioni sul documento

published on 25/07/2013 ultima modifica 09/04/2018