Michele Tortora Pato

Professor, Psychiatry & the Behavioral Sciences
Clinical Sciences Center
and Zilkha Neurogenetic Institute
Keck School of Medicine

Research Topics

  1. Genetics
  2. Psychotic Disorders
  3. OCD
  4. Population Studies

Research Overview

Michele Pato and her husband and collaborator Carlos Pato have an ongoing interest in the genetics of complex phenotypes such as psychotic disorders, schizophrenia and bipolar disorder, as well as obsessive-compulsive disorder. Trying to understand the genetics of these complex diseases has been extremely difficult, given inherent genetic variability and variability in the disorders themselves.That is why our team decided to focus our efforts on a population strategy?one designed to ?decrease the amount of variability in our study population.? The Azores and Madeira island archipelagos?landforms that did not have a native population, and so were settled virtually from scratch by the Portuguese in the 1400s, were an ideal setting for our work. These are isolated islands that were populated by design, and you can go back 500 years to look at the families there and look over the centuries how new families added to this genetic pool. Basically, we?re just taking advantage of a natural history experiment that goes back 500 years.

Today, we have about 3,500 subjects that we continue to follow over time. We?re tracking their histories, following their families and attempting to predict who is at risk?and see how that genetic risk, combined with non-genetic variables, together determine whether a child goes on to develop one of these illnesses.

We are also pioneering techniques for using microarray gene expression studies to pursue potential diagnostic and screening tests for these mental-health disorders and have also been looking at whole-genome linkage studies and family-based association studies to better understand the genetics of schizophrenia and bipolar disorder.

Selected Publications

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Pato CN, Middleton FA, Gentile KL, Morley CP, Medeiros HM, Macedo A, Azevedo MH, Pato MT, "Genetic linkage to chromosome 6q22 is a consistent finding in Portuguese subpopulations and may generalize to broader populations."  Am J Med Genet B Neuropsychiatr Genet. 2005 Apr 5;134(1):119-21

PatoCN, PatoMT, DalyM, VernerA, KirbyA, HudsonT, MedeirosH, MorleyCP, MacedoA, DouradoA, CoelhoI, ValenteJ, SoaresMJ, Carlos Paz Ferreira, Celia Carvalho, KennedyJL, AzevedoMH, SklarP, "Genome Scan and linkage for Bipolar Disorder in Portuguese Island Populations." American J. of Medical Genetics;127B(1):30-4, 2004

Middleton FA, Pato MT,Gentile KL, McGann L, Brown AM, Trauzzi M, Diab H, Morley CP, Medeiros HM, Macedo A, Azevedo MH, Pato CN, "Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches." Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136(1):12-25

Petryshen TL, Middleton FA, Tahl AR, Rockwell GN, Purcell S, Aldinger KA, Kirby A, Morley CP, McGann L, Gentile KL, Medeiros HM, Carvalho C, Macedo A, Albus M, Maier W, Trixler M, Eichhammer P, Azevedo MH, Schwab SG, Wildenauer DB, Pato MT, Pato CN, Daly MJ, Sklar P, "Genetic Investigation of chromosome 5q GABAa Receptor subunit genes in schizophrenia," Mol Psychiatry. 2005 Dec;10(12):105

Freedman ML, Reich DE, Penney K, McDonald G, Patterson N, Gabriel S, Topol EJ, Smoller JW, Pato CN, Pato MT,  Petryshen T, Kolonel L, Sklar P, Lander ES, Henderson B, Hirschhorn J, Altshuler D,  "The impact of population stratification on genetic association studies" Nature Genetics, 2004 Apr;36(4):388-93. Epub 2004 Mar 28

MiddletonFA,  PatoMT, Gentile KL, Morley CP, Zhao X, Eisner A, Brow A, Petryshen TL, Kirby AN, Medeiros H, Carvalho C, Macedo A, Dourado A, Coelho I, Valente J, Soares MJ, Ferreira CP,  Lei M, , Azevedo MH, Kennedy JL,  Daly MJ, Sklar P, Pato CN, "Genome-wide linkage analysis of bipolar disorder using high density single nucleotide polymorphism (snp) genotyping arrays: A comparison with microsatellite markers and finding of significant linkage to chromosome 6q22"  Am J Hum Genet. 2004 May;74(5):886-97. Epub 2004 Apr 01.

SklarP, PatoCN, DalyM, VernerA, KirbyA, HudsonT, MedeirosH, MorleyCP, MacedoA, DouradoA, CoelhoI, ValenteJ, SoaresMJ, Carlos Paz Ferreira, Celia Carvalho, KennedyJL, AzevedoMH, LanderE, PatoMT, "Genetic Linkage for  Schizophrenia and Psychosis in Portuguese Island Populations." Molecular Psychiatry ,9, 213-218. 2004

Pato MT, Pato CN:  "Teaching Research Basics to all Residents: 10 years of Experience."  Academic Psychiatry 25: 77-81 (2001).

Pato MT, Pigott TA, Hill JL, Grover G, Bernstein SE and Murphy DL:  "Clomipramine vs Buspirone in OCD:  A Controlled Trial."  Am J. Psychiatry  148:1, 1991.

Pato MT, Zohar-Kadouch R, Zohar J and Murphy DL:  "Return of Symptoms After Discontinuation of Clomipramine in Patients with Obsessive-Compulsive Disorder."  Am. J. Psychiatry  45:1521-1525, 1988.