Download PDF
Pharmacopsychiatry 2008; 41: S2-S18
DOI: 10.1055/s-2008-1081461
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Systems Biology and Psychiatry – Modeling Molecular and Cellular Networks of Mental Disorders

F. Tretter 1 , M. Albus 2
  • 1Department of Addictions Isar Amper Clincis, Clinic Munich East, Haar/Munich, Germany
  • 2Dîrector, Isar Amper Clincis, Clinic Munich East, Haar/Munich, Germany
Further Information

Publication History

Publication Date:
28 August 2008 (online)

Also available at
    Permissions and Reprints

Abstract

Biological psychiatry has more and more directed it's focus on the involvement of genes and molecules in mental health and disease. On these levels, new approaches in other medical fields are noticed that are collectively dubbed “Systems Biology”. Conceptually, this new paradigm tries to view molecular interactions in cellular networks as dynamic, self-organizing events that eventually result in an ordered maintenance of the whole system. A great deal of applied mathematics is required in systems biology to set up and carry out computer modeling and simulation. In terms of psychiatric research, developing “systems biology of the neuron” could become a pivotal achievement for a better understanding of mental illness on the molecular level. A brief outline of imminent tasks and links between systems biology and biological psychiatry is presented.

References

  • 1 Abbott L, Regehr WG. Synaptic computation.  Nature. 2004;  431 ((7010)) 796-803
    CrossrefPubMedGoogle Scholar
  • 2 Abbott L, Varela J, Sen K, Nelson SB. Synaptic depression and cortical gain control.  Science. 1997;  275 220-224
    PubMedGoogle Scholar
  • 3 Ahn AC, Tewari M, Poon CS, Phillips RS. The limits of reductionism in medicine: could systems biology offer an alternative?.  PLoS Med. 2006;  3 ((6)) e208
    CrossrefPubMedGoogle Scholar
  • 4 Ahn AC, Tewari M, Poon CS, Phillips RS. The clinical applications of a systems approach.  PLoS Med. 2006;  3 ((7)) e209
    CrossrefPubMedGoogle Scholar
  • 5 Alon U. Systems Biology – Design principles of biological circuits. New York: Chapman & Hall 2007
  • 6 Andreasen N. Brave new brain – Conquering Mental Illness in the Era of The Genome. New York: Oxford University Press 2004
  • 7 Arbib MA, Grethe JS. Computing the brain: A guide to neuroinformatics. San Diego: Academic Press 2001
  • 8 Arbib MA. (Ed). The Handbook of Brain Theory and Neural Networks, 2nd ed. Cambridge, MA: MIT Press 2002
  • 9 Ashby WR. Introduction to Cybernetics. New York : Chapman & Hall 1956
  • 10 Baldi P, Brunak S. Bioinformatics. A practical guide to the analysis of genes and proteins. New York: Wiley 1999
  • 11 Bender W, Albus M, Möller HJ, Tretter F. Towards systemic theories in biological psychiatry.  Pharmacopsychiatry. 2006;  39 ((Suppl.1)) 4-9
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Benoit-Marand M, Borrelli E, Gonomn F. Inhibition of dopamine release via presynaptic D2 receptors: time course and functional characteristics in vivo.  J Neuroscience. 2001;  21 9134-9141
    PubMedGoogle Scholar
  • 13 Bertalanffy LV. Modern Theories of Development: An Introduction to Theoretical Biology. New York: Oxford University Press 1933
  • 14 Bertalanffy LV. General system theory. New York: Braziller 1968
  • 15 Bhave SV, Hornbaker C, Phang TL, Saba L, Lapadat R, Kechris K, Gaydos J, MacGoldrick D, Dolbey A, Leach S, Soriano B, Ellington A, Ellington E, Jones K, Mangion J, Belknap JK, Williams RW, Hunter LE, Hoffman PL, Tabakoff B. The PhenoGen informatics website: tools for analyses of complex traits.  BMC Genet. 2007;  8 59
    CrossrefPubMedGoogle Scholar
  • 16 Boccara N. Modeling complex systems. Berlin: Springer 2004
  • 17 Bunge M. Philosophy of Science. 2 Vol. London: Transaction Publishers 1998
  • 18 Cardelli L. Abstract machines of systems biology. Transactions on Computational Systems Biology. III, LNBI 3737. Berlin: Springer 2005: 145-168
  • 19 Cohen JD, Servan-Schreiber D. A theory of dopamine function and its role in cognitive deficits in schizophrenia.  Schizophrenia Bulletin. 1993;  19 85-104
    PubMedGoogle Scholar
  • 20 Conrad ED, Tyson JJ. Modeling molecular interaction networks with nonlinear ordinary differential equations. In: Szallasi Z, Stelling J, Periwal V (Eds). System modeling in cellular biology. Cambridge, MA: MIT Press 2006: 97-124
    Google Scholar
  • 21 Cragg SJ, Rice ME. DAncing past the DAT at a DA synapse.  TRENDS in Neurosciences. 2004;  27
    PubMedGoogle Scholar
  • 22 Davis KM, Wu JY. Role of glutamatergic and GABAergic systems in alcoholism.  J Biomed Sci. 2001;  8 ((1)) 7-19
    CrossrefPubMedGoogle Scholar
  • 23 Dayan P, Abbott L. Theoretical Neuroscience. Computational and mathematical modeling of neural systems. Cambridge, MA: MIT Press 2005
  • 24 Dayan P, Williams J. Putting computation back into computational modeling.  Pharmacopsychiatry. 2006;  39 ((Suppl.1)) S50-S51
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Dennett DC. Sweet dreams. Philosophical obstacles to a science of consciousness. Cambridge, MA: MIT Press 2006
  • 26 Durstewitz D. A few important points about dopamine's role in neural network dynamics.  Pharmacopsychiatry. 2006;  39 ((Suppl.1)) S1-S88
    PubMedGoogle Scholar
  • 27 Edelman GM, Tononi G. A universe of consciousness. How matter becomes imagination. New York: Basic books 2000
  • 28 Eigen M. Molekulare Selbstorganisation und Evolution (Self organization of matter and the evolution of biological macro molecules.).  Naturwissenschaften Bd. 1971;  58 ((10)) 465-523
    PubMedGoogle Scholar
  • 29 Eigen M, Schuster P. The Hypercycle – A Principle of Natural Self-Organization. Berlin: Springer 1979
  • 30 Fernandez E, Schlappe R, Girault J-A, Le Novere N. DARPP-32 is a robust integrator of dopamine and glutamate signals.  PLoS Computational Biology. 2006;  2 ((12)) e176
    CrossrefPubMedGoogle Scholar
  • 31 Feynman R. The Character of Physical Law (Messenger Lectures, 1964). Cambridge, MA: MIT Press 2001
  • 32 Finney A, Hucka M, Borstewin J, Keating SM, Shapiro BE, Matthews J, Kovitz BL, Schilstra MJ, Funahashi A, Doyle J, Kitano H. Software Infrastructure for effective communication and reuse of computational models. In: Szallasi Z, Periwal V, Stelling J (Eds). System, modelling in Cellular Biology. Cambridge, MA: MIT Press 2006: 355-378
    Google Scholar
  • 33 Fishwick . (Ed) Handbook of dynamic system modeling. New York: Chapman & Hall 2007
  • 34 FMRE, Federal Ministery of Research and Education . , 2006. Systems Biology. www.bmbf.e/pub/systembiologie.pdf,http://www.forschung.bmbf.de/press/785.php
  • 35 Forrester J. Urban dynamics. Cambridge, MA: MIT Press 1961
  • 36 Gallinat J, Obermayer K, Heinz A. Systems Neurobiology of the dysfunctional brain.  Pharmacopsychiatry. 2007;  40 ((Suppl.1)) S40-S44
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Gebicke-Haerter P. Expression profiling methods used in drug abuse research.  Addict Biol. 2005;  10 ((1)) 37-46
    PubMedGoogle Scholar
  • 38 Gebicke-Haerter PJ. Expression profiling in brain disorders and beyond.  Nihon Shinkei Seishin Yakurigaku Zasshi.. 2006;  26 ((1)) 1-10
    PubMedGoogle Scholar
  • 39 Gross R, Löffler M. Prinzipien der Medizin. Heidelberg: Springer 1997
  • 40 Haken H. Synergetics. An introduction. Berlin: Springer 1983
  • 41 Haubold B, Wiehe T. Introduction to computational biology. Basel: Birkhäuser 2006
  • 42 Hodgkin AL, Huxley AF. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo.  J Physol Lond. 1952;  117 500-544
    PubMedGoogle Scholar
  • 43 Hofmann RE, MacGlashan TH. Using a speech perception neural network computer simulation to contrast neuroanatomic versus neuromodulatory models of auditory hallucinations.  Pharmacopsychiatry. 2006;  39 ((Suppl.1)) S54-S64
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Holst EV, Mittelstaedt H. Das Reafferenzprinzip.  Naturwissenschaften. 1950;  37 464-476
    CrossrefPubMedGoogle Scholar
  • 45 Huang S, Wikswo J. Dimensions of systems biology.  Rev Physiol Biochem Pharmacol. 2006;  81-104
    PubMedGoogle Scholar
  • 46 Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins.  J Mol Biol. 1961;  3 318-356
    PubMedGoogle Scholar
  • 47 Kell DB, Knowles JD. The role of modeling in systems biology. In: Szallasi Z, Stelling J, Periwal V (Eds). System modeling in cellular biology. Cambridge, MA: MIT Press 2006: 3-18
  • 48 Kitano H. Perspective on Systems Biology.  New generation Computing. 2000;  18 199-216
    CrossrefPubMedGoogle Scholar
  • 49 Kitano H. Systems Biology: a brief overview.  Science. 2002a;  295 1662-1664
    CrossrefPubMedGoogle Scholar
  • 50 Kitano H. Computational Systems Biology.  Nature. 2002b;  420 206-210
    CrossrefPubMedGoogle Scholar
  • 51 Kitano H. (Ed) Foundations of Systems Biology. Cambridge, MA: MIT Press 2001
  • 52 Klipp E, Herwig R, Kowald A, Wielring C, Lehrach H. Systems Biology in Practice. Weinheim: Wiley-VCH 2005
  • 53 Koch M. Animal Models of Neuropsychiatric Diseases. London: Imperial College Press 2006
  • 54 Koob G, Le Moal M. Drug addiction, dysregulation of reward and allostasis.  Neuropsychopharmacology. 2001;  24 97-129
    CrossrefPubMedGoogle Scholar
  • 55 Koob G, Le Moal M. Neurobiology of addiction. New York: Academic Press 2006
  • 56 Koshkina E. Extracellular Dopamine Concentration Control: Computational Model of Feedback Control.  Diss Drexel Univ. 2006; 
    PubMedGoogle Scholar
  • 57 Koza JR. Genetic programming: On the programming of computers by means of natural selection. Cambridge, MA: MIT Press 1992
  • 58 Le Novere N. The long journey to a Systems Biology of neuronal function.  BMC Systems Biology. 2007;  1 28
    CrossrefPubMedGoogle Scholar
  • 59 Lindskog M, Kim MS, Wikstrom MA, Blackwell KT, Kotaleski JH. Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation.  PloS Comput Biol. 2006;  2 ((9)) e119
    CrossrefPubMedGoogle Scholar
  • 60 Lorenz EN. Deterministic Nonperiodic Flow.  Journal of the Atmospheric Sciences. 1963;  20 ((2)) 130-141
    CrossrefPubMedGoogle Scholar
  • 61 Lotka A. J Elements of Physical Biology. Baltimore: Williams and Wilkins 1925
  • 62 Mackey MC, Heiden U Van der. The dynamics of recurrent inhibition.  J Math Biol. 1984;  19 ((2)) 211-225
    CrossrefPubMedGoogle Scholar
  • 63 Mandelbrot BB. Fractals and Chaos. Berlin: Springer 2004
  • 64 MacGuffin P, Owen MJ, Gottesman II. (Ed). Psychiatric Genetics and Genomics. New York: Oxford University Press 2004
  • 65 Meadows DH, Meadows DL, Randers J, Behrens III WW. The Limits to Growth. New York: Universe Books 1972
  • 66 Meinhardt H. Models of Biological Pattern Formation. London: Academic Press 1982
  • 67 Meyer-Lindenberg A, Weinberger DR. Intermediate phenotypes. and genetic mechanisms of psychiatric disorders.  Nat Rev Neurosci. 2006;  10 818-827
    PubMedGoogle Scholar
  • 68 Miyano S, Matsuno H. , How to model and simulate biological pathways with Petri nets – a new challenge for systems biology – 25th Int. Conf. Appl. Theory Petri Nets, Bologna, Italy, 22 June 2004
  • 69 Murray JD. An introduction to Mathematical Biology. An Introductory Course. New York: Springer 2004
  • 70 Murray JD. Mathematical Biology. Spatial models and biomedical applications. New York: Springer 2003
  • 71 Nestler E. Historical review: molecular and cellular mechanisms of opiate and cocaine addiction.  Trends in Pharmacological Science. 2004;  25 ((4)) 210-219
    CrossrefPubMedGoogle Scholar
  • 72 Nestler EJ. Is there a common molecular pathway for addiction?.  Nat Neurosci. 2005;  8 ((11)) 1445-1449
    CrossrefPubMedGoogle Scholar
  • 73 Neve KA, Semans JK, Trantham-Davidson H. Dopamine receptor signalling.  J Recept Signal Transduct Res. 2004;  24 ((3)) 165-205
    CrossrefPubMedGoogle Scholar
  • 74 Newton RG. From clockwork to crapshoot: a history of physics. Cambridge, MA: Pelknap Press of Harvard University Press 2007
  • 75 NIH . Systems Biology. http://www.nigms.nih.gov/Initiatives/SysBio/ 2007; 
    PubMed
  • 76 Noble D. Multilevel modelling in Systems Biology: From Cells to Whole Organs. In: Szallasi Z, Periwal V, Stelling J (Ed). System, modelling in Cellular Biology. Cambridge, MA: MIT Press 2006: 297-312
    Google Scholar
  • 77 Noble D. The Music of Life: Biology Beyond the Genome. New York: Oxford Univ Press 2006
  • 78 Odum HT. Environment, power and society. New York: Wiley 1971
  • 79 Palsson BO. Systems Biology. Cambridge: Cambridge Univ Press 2006
  • 80 Paulsson J, Elf J. Modeling molecular of intracellular kinetics. In: Szallasi Z, Periwal V, Stelling J (Ed). System, modelling in Cellular Biology. Cambridge, MA: MIT Press 2006: 149-176
    Google Scholar
  • 81 Peper A. A theory of drug tolerance and dependence I: a conceptual analysis.  J Theor Biol. 2004;  229 477-490
    CrossrefPubMedGoogle Scholar
  • 82 Peper A. A theory of drug tolerance and dependence II: the mathematical model.  J Theor Biol. 2004;  229 491-500
    CrossrefPubMedGoogle Scholar
  • 83 Periwal V, Szallasi Z, Stelling J. System modeling – why and how?. In: Szallasi Z, Periwal V, Stelling J (Ed). System modelling in Cellular Biology. Cambridge, MA: MIT Press 2005: vii-xiv
    Google Scholar
  • 84 Pevzner P. Computational molecular biology. Cambridge, MA: MIT Press 2000
  • 85 Pietschmann H. Phänomenologie der Naturwissenschaft: Wissenschaftstheoretische und philosophische Probleme der Physik. Wien: Ibera 2007
  • 86 Prigogine I. Thermodynamics of Irreversible Processes Second Edition. New York: Wiley 1961
  • 87 Quarteroni A, Formaggia L, Veneziani A. (Eds). Complex Systems in Biomedicine. Berlin: Springer 2006
  • 88 Redish AD, Johnson A. A computational model of craving and obsession.  Ann N Y Acad Sci. 2007;  1104 324-339
    CrossrefPubMedGoogle Scholar
  • 89 Rohlff C, Hollis K. Modern proteomic strategies in the study of complex neuropsychiatric disorders.  Biolog Psychiatry. 2003;  53 ((10)) 847-853
    PubMedGoogle Scholar
  • 90 Savageau M. Biochemical Systems Analysis: A Study of Function and Design in Molecular Biology. Reading, MA: Addison-Wesley 1976
  • 91 Schlösser RGM, Koch C, Wagner G. Assessing the state space of the brain with fMRI: An integrateive view of Current Methods.  Pharamcopsychiatry. 2007;  40 ((Suppl.1)) S85-S92
    Article in Thieme ConnectPubMedGoogle Scholar
  • 92 Schmitz Y, Schmauss C, Sulzer D. Altered dopamine release and uptake kinetics in mice lacking D2 receptors.  J Neurosci. 2002;  22 ((18)) 8002-8009
    PubMedGoogle Scholar
  • 93 Searle JR. Mind. A Brief Introduction. New York: Oxford Univ Press 2005
  • 94 Sel’kov EE. Self-oscillations in glycolysis.  Europ J Biochem. 1968;  4 79
    CrossrefPubMedGoogle Scholar
  • 95 Seeman P. Atypical antipsychotics: mechanism of action.  Can J Psychiatry. 2002;  47 ((1)) 27-38
    PubMedGoogle Scholar
  • 96 Shepherd G. The synaptic organization of the brain. New York: Oxford Univ Press 2004
  • 97 Shepherd G. Neurobiology. New York: Oxford Univ Press 1994
  • 98 Shiflet AB, Shiflet GW. Introduction to Computational Science. Princeton: Princeton University Press 2006
  • 99 Singer W. Neuronal synchrony: a versatile code for the definition of relations?.  Neuron. 1999;  24 49-65
    CrossrefPubMedGoogle Scholar
  • 100 Sober E. Philosophy of biology. Bolder: Westview Press 2000
  • 101 Sterling Sauer UJ, Doyle F. J Doyle Complexity and robustness of cellular systems. In: Szallasi Z, Stelling J, Periwal V (Ed). System modeling in cellular biology. Cambridge, MA: MIT Press 2006: 19-39
    Google Scholar
  • 102 Sterman J. Business dynamics. New York: McGraw-Hill 2000
  • 103 Strogatz StH. Nonlinear Dynamics and Chaos. With Applications to Physics, Biology, Chemistry and Engineering. New York: The Perseus Books Group 2001
  • 104 Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC, Greengard P. DARPP-32: an integrator of neurotransmission.  Annu Rev Pharmacol Toxicol. 2004;  44 269-296
    CrossrefPubMedGoogle Scholar
  • 105 Svenningsson P, Nairn AC, Greengard P. DARPP-32 mediates the actions of multiple drugs of abuse.  AAPS J. 2005;  7 ((2)) E353-E360
    CrossrefPubMedGoogle Scholar
  • 106 Szallasi Z, Stelling J, Periwal V. (Ed). System modeling in cellular biology. Cambridge, MA: MIT Press 2006
  • 107 Tabachnick BG, Fidell LS. Using Multivariate Statistics Allyn & Bacon Instock. 2007; 
    PubMed
  • 108 Thompson JL, Pogue-Geile MF, Grace AA. Developmental pathology, dopamine and stress: a model for the age of onset of schizophrenia symptoms.  Schizophr Bulletin. 2004;  30 ((4)) 875-900
    PubMedGoogle Scholar
  • 109 Thome J. Molekulare Psychiatrie. Bern: Huber 2004
  • 110 Tretter F. Systemwissenschaft in der Medizin.  Deutsches Ärzteblatt. 1989;  43 3198-3209
    PubMedGoogle Scholar
  • 111 Tretter F. Systemtheorie im klinischen Kontext. Lengerich: Pabst Science Publisher 2005
  • 112 Tretter F. Die Gehirn-Geist-Debatte – Wissenschaftstheoretische Probleme in Hinblick auf die Psychiatrie 1.  Nervenarzt. 2007;  78 ((5)) 498 , 501–504
    CrossrefPubMedGoogle Scholar
  • 113 Tretter F, Scherer J. Schizophrenia, neurobiology and the methodology of systemic modeling.  Pharmacopsychiatry. 2006;  39 ((Suppl.1)) S26-S42
    Article in Thieme ConnectPubMedGoogle Scholar
  • 114 Tretter F, Müller W. , (Eds) Computational neuropsychiatry vol 2: The functional architecture of working memory networks in schizophrenia – data and models.  Pharmacopsychiatry. 2007;  40 ((Suppl.1))
    PubMedGoogle Scholar
  • 115 Tretter F, Albus M. “Computational neuropsychiatry” of working memory disorders in schizophrenia: The network connectivity in prefrontal cortex – data and models.  Pharmacopsychiatry. 2007;  40 ((Suppl.1)) S2-S16
    Article in Thieme ConnectPubMedGoogle Scholar
  • 116 Tretter F, Müller W, Carlsson A. , (Eds) Systems Science, Computational Science and Neurobiology of Schizophrenia.  Pharmacopsychiatry. 2006;  39 ((Suppl.1))
    PubMedGoogle Scholar
  • 117 Tyson JJ. Bringing cartoons to life.  Nature. 2007;  445 823
    CrossrefPubMedGoogle Scholar
  • 118 Venter JC, Adams MD, Myers EW, Li PW, Mural RJ. et al . The sequence of the human genome.  Science. 2001;  291 1304-1351
    CrossrefPubMedGoogle Scholar
  • 119 Virchow R. Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre. Berlin: August Hirschwald 1858/CellularPathology. Translated by Frank Chance. New York: Dover 1971
  • 120 Voit E. Computational Analysis of Biochemical Systems. Cambridge: Cambridge Univ Press 2000
  • 121 Wang X-J. Toward a microcircuit model for cognitive deficits in schizophrenia.  Pharmacopsychiatry. 2006;  39 ((Suppl.1)) S80-S87
    PubMedGoogle Scholar
  • 122 Wassef A, Baker J, Kochan LD. GABA and schizophrenia: a review of basic science and clinical studies.  J Clin Psychopharmacol. 2003;  23 ((6)) 601-640
    CrossrefPubMedGoogle Scholar
  • 123 Watts DJ, Strogatz S. Collective dynamics of ‘Small world’ networks.  Nature. 1998;  393 440-442
    CrossrefPubMedGoogle Scholar
  • 124 Wiener N. Cybernetics. Cambridge, MA: MIT Press 1948
  • 125 Wightman RM, Amatore C, Engstrom C, Hale PD, Kristensen EW, Kuhr WG, May LJ. Real-time characterization of dopamine overflow and uptake in the rat striatum.  Neuroscience. 1988;  25 ((2)) 513-523
    CrossrefPubMedGoogle Scholar
  • 126 Wolfram St A. New Kind of Science. Champaign, IL: Wolfram Media 2002
  • 127 Zaccalo M, Pozzon T. cAMP and Ca2+interplay: a matter of oscillation patterns.  TRENDS in Neuroscience. 2003;  26 ((2)) 53-55
    CrossrefPubMedGoogle Scholar

Correspondence

Dr. F. Tretter

Department of Addictions Isar Amper Clincis

Clinic Munich East

85529 Haar/Munich

Germany

Phone: +49/89/4562 37 08

Fax: +49/89/4562 37 08

Email: Felix.Tretter@IAK-KMO.de