COMT as a drug target for cognitive functions and dysfunctions

CNS and Neurological Disorders - Drug Targets

Volumn 11, Issue 3, 2012, Pages 209-221

  Scheggia, Diego ^a   Sannino, Sara ^a   Scattoni, Maria Luisa ^b   Papaleo, Francesco ^a,c  

^a ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^b ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^c UNIVERSITY OF PADOVA   (Italy)

Author keywords

Attention; Development; Executive function; Pharmacological treatment; Prefrontal cortex; Psychiatric disorders; Working memory

Indexed keywords

CATECHOL METHYLTRANSFERASE;

ATTENTION; COGNITION; COGNITIVE DEFECT; DOPAMINERGIC SYSTEM; DRUG DOSE; DRUG EFFICACY; DRUG TARGETING; EXECUTIVE FUNCTION; GENETIC ANALYSIS; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; LONG TERM MEMORY; MENTAL DISEASE; NERVE CELL DIFFERENTIATION; NONHUMAN; PREDICTION; PREFRONTAL CORTEX; REVIEW; WORKING MEMORY;

EID: 84861723854     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/187152712800672481     Document Type: Review

References (169)

1. Davies, W. Using mouse models to investigate sex-linked genetic effects on brain, behaviour and vulnerability to neuropsychiatric disorders, Brain Res Bull, 2011.
2. Savitz, J.; Solms, M.; Ramesar, R. The molecular genetics of cognition: dopamine, COMT and BDNF. Genes Brain Behav., 2006, 5, 311-328.
3. Barnett, J.H.; Xu, K.; Heron, J.; Goldman, D.; Jones, P.B. Cognitive effects of genetic variation in monoamine neurotransmitter systems: A population-based study of COMT, MAOA, and 5HTTLPR. Am. J. Med. Genet. Part B Neuropsych. Genet., 2011, 156, 158-167.
4. Papaleo, F.; Lipska, B.K.; Weinberger, D.R. Mouse models of genetic effects on cognition: Relevance to schizophrenia. Neuropharmacology, 2012, 62(3), 1204-1220.
5. Davies, G.; Tenesa, A.; Payton, A.; Yang, J.; Harris, S.E.; Liewald, D.; Ke, X.; Le Hellard, S.; Christoforou, A.; Luciano, M.; McGhee, K.; Lopez, L.; Gow, A.J.; Corley, J.; Redmond, P.; Fox, H.C.; Haggarty, P.; Whalley, L.J.; McNeill, G.; Goddard, M.E.; Espeseth, T.; Lundervold, A.J.; Reinvang, I.; Pickles, A.; Steen, V.M.; Ollier, W.; Porteous, D.J.; Horan, M.; Starr, J.M.; Pendleton, N.; Visscher, P.M.; Deary, I.J. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol. Psychiatry, 2011, 16, 996-1005.
6. Axelrod, J.; Tomchick, R. Enzymatic O-Methylation of epinephrine and other catechols. J. Biol. Chem., 1958, 233, 702-705.
7. Männistö, P.T.; Kaakkola, S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol. Rev., 1999, 51, 593-628.
8. Chen, J.; Lipska, B.K.; Halim, N.; Ma, Q.D.; Matsumoto, M.; Melhem, S.; Kolachana, B.S.; Hyde, T.M.; Herman, M.M.; Apud, J.; Egan, M.F.; Kleinman, J.E.; Weinberger, D.R. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am. J. Hum. Genet., 2004, 75, 807-821.
9. Chen, J.; Song, J.; Yuan, P.; Tian, Q.; Ji, Y.; Ren-Patterson, R.; Liu, G.; Sei, Y.; Weinberger, D.R. Orientation and cellular distribution of membrane-bound Catechol-O-methyltransferase in cortical neurons. J. Biol. Chem., 2011, 286, 34752-34760.
10. Roth, J.A. Membrane-bound catechol-O-methyltransferase: a reevaluation of its role in the O-methylation of the catecholamine neurotransmitters. Rev. Physiol. Biochem. Pharmacol., 1992, 120, 1-29.
11. Yavich, L.; Forsberg, M.M.; Karayiorgou, M.; Gogos, J.A.; Mannisto, P.T. Site-specific role of catechol-O-methyltransferase in dopamine overflow within prefrontal cortex and dorsal striatum. J. Neurosci., 2007, 27, 10196-10209.
12. Gogos, J.A.; Morgan, M.; Luine, V.; Santha, M.; Ogawa, S.; Pfaff, D.; Karayiorgou, M. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc. Natl. Acad. Sci., 1998, 95, 9991-9996.
13. Matsumoto, M.; Weickert, C.S.; Akil, M.; Lipska, B.K.; Hyde, T.M.; Herman, M.M.; Kleinman, J.E.; Weinberger, D.R. Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience, 2003, 116, 127-137.
14. Karoum, F.; Chrapusta, S.J.; Egan, M.F. 3-methoxytyramine is the major metabolite of released dopamine in the rat frontal cortex: reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum by a simple two pool model. J. Neurochem., 1994, 63, 972-979.
15. Goldman-Rakic, P.S. The cortical dopamine system: role in memory and cognition. Adv. Pharmacol., 1998, 42, 707-711.
16. Verma, A.; Moghaddam, B. NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine. J. Neurosci., 1996, 16, 373-379.
17. Seamans, J.K.; Gorelova, N.; Durstewitz, D.; Yang, C.R. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J. Neurosci., 2001, 21, 3628-3638.
18. Williams, G.V.; Goldman-Rakic, P.S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature, 1995, 376, 572-575.
19. Arnsten, A.F.; Cai, J.X.; Murphy, B.L.; Goldman-Rakic, P.S. Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology, 1994, 116, 143-151.
20. Vijayraghavan, S.; Wang, M.; Birnbaum, S.G.; Williams, G.V.; Arnsten, A.F. Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat. Neurosci., 2007, 10, 376-384.
21. Lachman, H.M.; Papolos, D.F.; Saito, T.; Yu, Y.M.; Szumlanski, C.L.; Weinshilboum, R.M. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics, 1996, 6, 243-250.
22. Nackley, A.G.; Shabalina, S.A.; Tchivileva, I.E.; Satterfield, K.; Korchynskyi, O.; Makarov, S.S.; Maixner, W.; Diatchenko, L. Human catechol-o-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science, 2006, 314, 1930-1933.
23. Meyer-Lindenberg, A.; Nichols, T.; Callicott, J.H.; Ding, J.; Kolachana, B.; Buckholtz, J.; Mattay, V.S.; Egan, M.; Weinberger, D.R. Impact of complex genetic variation in COMT on human brain function. Mol. Psychiatry, 2006, 11, 867-877.
24. Bray, N.J.; Buckland, P.R.; Williams, N.M.; Williams, H.J.; Norton, N.; Owen, M.J.; O Donovan, M.C. A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain. Am. J Hum. Genet., 2003, 73, 152-161.
25. Bertocci, B.; Miggiano, V.; Da Prada, M.; Dembic, Z.; Lahm, H.W.; Malherbe, P. Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. Proc. Natl. Acad. Sci., 1991, 88, 1416-1420.
26. Lundstrom, K.; Salminen, M.; Jalanko, A.; Savolainen, R.; Ulmanen, I. Cloning and characterization of human placental catechol-O-methyltransferase cDNA. DNA Cell Biol., 1991, 10, 181-189.
27. Floderus, Y.; Ross, S.B.; Wetterberg, L. Erythrocyte catechol-O-methyltransferase activity in a Swedish population. Clin. Genet., 1981, 19, 389-392.
28. Robbins, T.W. Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications. Phil. Trans. R. Soc. B. Biol. Sci., 2007, 362, 917-932.
29. Robbins, T.W. Chemical neuromodulation of frontal-executive function in humans and other animals. Exp. Brain Res., 2000, 133, 130-138.
30. Eling, P.; Derckx, K.; Maes, R. On the historical and conceptual background of the Wisconsin Card Sorting Test. Brain Cogn., 2008, 67, 247-253.
31. Milner, B. Effects of different brain lesions on card-sorting: the role of the frontal lobes. Arch. Neurol., 1963, 9, 100-110.
32. Roberts, A.C.; Robbins, T.W.; Everitt, B.J. The effects of intradimensional and extradimensional shifts on visual discrimination learning in humans and non-human primates. Q. J. Exp. Psychol. B., 1988, 40, 321-341.
33. Barnett, J.H.; Robbins, T.W.; Leeson, V.C.; Sahakian, B.J.; Joyce, E.M.; Blackwell, A.D. Assessing cognitive function in clinical trials of schizophrenia. Neurosci Amp. Biobehav. Rev., 2010, 34, 1161-1177.
34. Birrell, J.M.; Brown, V.J. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J. Neurosci., 2000, 20, 4320-4324.
35. Garner, J.P.; Thogerson, C.M.; Würbel, H.; Murray, J.D.; Mench, J.A. Animal neuropsychology: Validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice. Behav. Brain Res., 2006, 173, 53-61.
36. Bissonette, G.B.; Martins, G.J.; Franz, T.M.; Harper, E.S.; Schoenbaum, G.; Powell, E.M. Double dissociation of the effects of medial and orbital prefrontal cortical lesions on attentional and affective shifts in mice. J Neurosci, 2008, 28, 11124-11130.
37. Papaleo, F.; Crawley, J.N.; Song, J.; Lipska, B.K.; Pickel, J.; Weinberger, D.R.; Chen, J. Genetic dissection of the role of catechol-O-methyltransferase in cognition and stress reactivity in mice. J. Neurosci., 2008, 28, 8709-8723.
38. Owen, A.M.; Roberts, A.C.; Polkey, C.E.; Sahakian, B.J.; Robbins, T.W. Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia, 1991, 29, 993-1006.
39. Rahman, S.; Sahakian, B.J.; Hodges, J.R.; Rogers, R.D.; Robbins, T.W. Specific cognitive deficits in mild frontal variant frontotemporal dementia. Brain, 1999, 122, 1469-1493.
40. Barch, D.M.; Braver, T.S.; Carter, C.S.; Poldrack, R.A.; Robbins, T.W. CNTRICS final task selection: executive control. Schizophr. Bull., 2009, 35, 115-135.
41. Egerton, A.; Reid, L.; McKerchar, C.E.; Morris, B.J.; Pratt, J.A. Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia. Psychopharmacology, 2005, 179, 77-84.
42. Goetghebeur, P.; Dias, R. Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat-a back translational study. Psychopharmacology, 2009, 202, 287-293.
43. Weinberger, D.R.; Berman, K.F.; Zec, R.F. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia: I. Regional cerebral blood flow evidence. Arch. Gen. Psychiatry, 1986, 43, 114-124.
44. Hampshire, A.; Owen, A.M. Fractionating attentional control using event-related fMRI. Cereb. Cortex, 2006, 16, 1679-1689.
45. Dias, R.; Robbins, T.W.; Roberts, A.C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature, 1996, 380, 69-72.
46. Roberts, A.; De Salvia, M.; Wilkinson, L.; Collins, P.; Muir, J.; Everitt, B.; Robbins, T. 6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine. J. Neurosci, 1994, 14, 2531-2544.
47. Brown, V.J.; Bowman, E.M. Rodent models of prefrontal cortical function. Trends Neurosci., 2002, 25, 340-343.
48. Berman, K.F.; Ostrem, J.L.; Randolph, C.; Gold, J.; Goldberg, T.E.; Coppola, R.; Carson, R.E.; Herscovitch, P.; Weinberger, D.R. Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: A positron emission tomography study. Neuropsychologia, 1995, 33, 1027-1046.
49. Barnett, J.H.; Jones, P.B.; Robbins, T.W.; Muller, U. Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls. Mol. Psychiatry, 2007, 12, 502-509.
50. Malhotra, A.K.; Kestler, L.J.; Mazzanti, C.; Bates, J.A.; Goldberg, T.; Goldman, D.A. Functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am. J. Psychiatry, 2002, 159, 652-654.
51. Joober, R.; Gauthier, J.; Lal, S.; Bloom, D.; Lalonde, P.; Rouleau, G.; Benkelfat, C.; Labelle, A. Catechol-O-Methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting Test. Arch. Gen. Psychiatry, 2002, 59, 662-663.
52. Egan, M.F.; Goldberg, T.E.; Kolachana, B.S.; Callicott, J.H.; Mazzanti, C.M.; Straub, R.E.; Goldman, D.; Weinberger, D.R. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci USA, 2001, 98, 6917-6922.
53. Mattay, V.S.; Goldberg, T.E.; Fera, F.; Hariri, A.R.; Tessitore, A.; Egan, M.F.; Kolachana, B.; Callicott, J.H.; Weinberger, D.R. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc. Natl. Acad. Sci., 2003, 100, 6186-6191.
54. Rosa, A.; Peralta, V.; Cuesta, M.J.; Zarzuela, A.; Serrano, F.; Martinez-Larrea, A.; Fananas, L. New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis. Am. J. Psychiatry, 2004, 161, 1110-1112.
55. Diaz-Asper, C.M.; Weinberger, D.R.; Goldberg, T.E. Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics. NeuroRx, 2006, 3, 97-105.
56. Tsai, S.-J.; Yu, Y.W.Y.; Chen, T.-J.; Chen, J.-Y.; Liou, Y.-J.; Chen, M.-C.; Hong, C.-J. Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females. Neurosci. Lett., 2003, 338, 123-126.
57. Ho, B.C.; Wassink, T.H.; O'Leary, D.S.; Sheffield, V.C.; Andreasen, N.C. Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow. Mol. Psychiatry, 2005, 10, 287-298.
58. Harrison, P.J.; Tunbridge, E.M. Catechol-O-Methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders. Neuropsychopharmacology, 2007, 33, 3037-3045.
59. Robbins, T.; Roberts, A. Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cereb. Cortex, 2007, 17, i151-i160.
60. Williams-Gray, C.H.; Hampshire, A.; Barker, R.A.; Owen, A.M. Attentional control in Parkinson's disease is dependent on COMT val158met genotype. Brain, 2008, 131, 397-408.
61. Williams-Gray, C.H.; Hampshire, A.; Robbins, T.W.; Owen, A.M.; Barker, R.A. Catechol O-Methyltransferase val158met genotype influences frontoparietal activity during planning in patients with parkinson's disease. J. Neurosci., 2007, 27, 4832-4838.
62. Foltynie, T.; Goldberg, T.E.; Lewis, S.G.J.; Blackwell, A.D.; Kolachana, B.S.; Weinberger, D.R.; Robbins, T.W.; Barker, R.A. Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism. Movem. Disord., 2004, 19, 885-891.
63. Williams-Gray, C.H.; Evans, J.R.; Goris, A.; Foltynie, T.; Ban, M.; Robbins, T.W.; Brayne, C.; Kolachana, B.S.; Weinberger, D.R.; Sawcer, S.J.; Barker, R.A. The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort, Brain, 2009, 132, 2958-2969.
64. Rakshi, J.S.; Uema, T.; Ito, K.; Bailey, D.L.; Morrish, P.K.; Ashburner, J.; Dagher, A.; Jenkins, I.H.; Friston, K.J.; Brooks, D.J. Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [18F]dopa-PET study. Brain, 1999, 122, 1637-1650.
65. Kaasinen, V.; Nurmi, E.; Brück, A.; Eskola, O.; Bergman, J.; Solin, O.; Rinne, J.O. Increased frontal [18F] fluorodopa uptake in early Parkinson's disease: sex differences in the prefrontal cortex. Brain, 2001, 124, 1125-1130.
66. Tunbridge, E.M.; Bannerman, D.M.; Sharp, T.; Harrison, P.J. Catechol-O-Methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J. Neurosci, 2004, 24, 5331-5335.
67. Apud, J.A.; Mattay, V.; Chen, J.; Kolachana, B.S.; Callicott, J.H.; Rasetti, R.; Alce, G.; Iudicello, J.E.; Akbar, N.; Egan, M.F.; Goldberg, T.E.; Weinberger, D.R. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology, 2006, 32, 1011-1020.
68. Green, M.F.; Nuechterlein, K.H. Should schizophrenia be treated as a neurocognitive disorder? Schizophr. Bull., 1999, 25, 309-319.
69. Bosia, M.; Bechi, M.; Marino, E.; Anselmetti, S.; Poletti, S.; Cocchi, F.; Smeraldi, E.; Cavallaro, R. Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia. Neurosci. Lett., 2007, 417, 271-274.
70. Baddeley, A. Working memory. Curr. Biol., 2010, 20, R136-R140.
71. Chudasama, Y.; Robbins, T.W. Functions of frontostriatal systems in cognition: Comparative neuropsychopharmacological studies in rats, monkeys and humans. Biol. Psychology, 2006, 73, 19-38.
72. Brozoski, T.; Brown, R.; Rosvold, H.; Goldman, P. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science, 1979, 205, 929-932.
73. Weickert, T.W.; Goldberg, T.E.; Mishara, A.; Apud, J.A.; Kolachana, B.S.; Egan, M.F.; Weinberger, D.R. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications, Biol. Psychiatry, 2004, 56, 677-682.
74. Pomarol-Clotet, E.; Fatjó-Vilas, M.; McKenna, P.J.; Monté, G.C.; Sarró, S.; Ortiz-Gil, J.; Aguirre, C.; Gomar, J.J.; Guerrero, A.; Landin, R.; Capdevila, A.; Fañanás, L.; Salvador, R. COMT Val158Met polymorphism in relation to activation and deactivation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects. NeuroImage, 2010, 53, 899-907.
75. Callicott, J.H.; Bertolino, A.; Mattay, V.S.; Langheim, F.J.P.; Duyn, J.; Coppola, R.; Goldberg, T.E.; Weinberger, D.R. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb. Cortex, 2000, 10, 1078-1092.
76. Goldberg, T.E.; Egan, M.F.; Gscheidle, T.; Coppola, R.; Weickert, T.; Kolachana, B.S.; Goldman, D.; Weinberger, D.R. Executive Subprocesses in Working Memory: Relationship to Catechol-O-methyltransferase Val158Met Genotype and Schizophrenia. Arch. Gen. Psychiatry, 2003, 60, 889-896.
77. Tunbridge, E.M.; Harrison, P.J.; Weinberger, D.R. Catechol-o-Methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol. Psychiatry, 2006, 60, 141-151.
78. Stefanis, N.C.; Os, J.V.; Avramopoulos, D.; Smyrnis, N.; Evdokimidis, I.; Hantoumi, I.; Stefanis, C.N. Variation in catechol-o-methyltransferase val158met genotype associated with schizotypy but not cognition: A population study in 543 young men. Biol. Psychiatry, 2004, 56, 510-515.
79. 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, 31, 6692-6698.
80. Farrell, S.M.; Tunbridge, E.M.; Braeutigam, S.; Harrison, P.J. COMT Val158Met genotype determines the direction of cognitive effects produced by catechol-o-methyltransferase inhibition. Biol. Psychiatry, 2012, 71(6), 538-544.
81. Giakoumaki, S.G.; Roussos, P.; Bitsios, P. Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism. Neuropsychopharmacology, 2008, 33, 3058-3068.
82. Bertolino, A.; Caforio, G.; Blasi, G.; De Candia, M.; Latorre, V.; Petruzzella, V.; Altamura, M.; Nappi, G.; Papa, S.; Callicott, J.H.; Mattay, V.S.; Bellomo, A.; Scarabino, T.; Weinberger, D.R.; Nardini, M. 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.
83. Manoach, D.S. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr. Res., 2003, 60, 285-298.
84. Jogia, J.; Dima, D.; Kumari, V.; Frangou, S. Frontopolar cortical inefficiency may underpin reward and working memory dysfunction in bipolar disorder. World J. Biol. Psychiatry, 2011, in press.
85. Murrough, J.W.; Iacoviello, B.; Neumeister, A.; Charney, D.S.; Iosifescu, D.V. Cognitive dysfunction in depression: Neurocircuitry and new therapeutic strategies. Neurobiol. Learn. Mem., 2011, 96(4), 553-563.
86. Martinussen, R.; Hayden, J.; Hogg-Johnson, S.; Tannock, R.A. Meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adoles. Psychiatry, 2005, 44, 377-384.
87. Chudasama, Y.; Passetti, F.; Rhodes, S.E.; Lopian, D.; Desai, A.; Robbins, T.W. Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav. Brain Res., 2003, 146, 105-119.
88. Hamidovic, A.; Dlugos, A.; Palmer, A.A.; de Wit, H. Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine. Psychiatric Genet., 2010, 20, 85-92.
89. Goldberg, T.E.; Egan, M.F.; Gscheidle, T.; Coppola, R.; Weickert, T.; Kolachana, B.S.; Goldman, D.; Weinberger, D.R. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch. Gen. Psychiatry, 2003, 60, 889-896.
90. Stefanis, N.C.; Van Os, J.; Avramopoulos, D.; Smyrnis, N.; Evdokimidis, I.; Hantoumi, I.; Stefanis, C.N. Variation in catechol-o-methyltransferase val158met genotype associated with schizotypy but not cognition: a population study in 543 young men. Biol. Psychiatry, 2004, 56, 510-515.
91. Muir, J.L.; Everitt, B.J.; Robbins, T.W. The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task. Cereb. Cortex, 1996, 6, 470-481.
92. Bilder, R.M.; Volavka, J.; Czobor, P.á.; Malhotra, A.K.; Kennedy, J.L.; Ni, X.; Goldman, R.S.; Hoptman, M.J.; Sheitman, B.; Lindenmayer, J.-P.; Citrome, L.; McEvoy, J.P.; Kunz, M.; Chakos, M.; Cooper, T.B.; Lieberman, J.A. Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia. Biol. Psychiatry, 2002, 52, 701-707.
93. Rosa, E.; Dickinson, D.; Apud, J.; Weinberger, D.; Elvevag, B. COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination. Behav. Brain Func., 2010, 6, 53.
94. Takarae, Y.; Schmidt, L.; Tassone, F.; Simon, T.J. Catechol-O-methyltransferase polymorphism modulates cognitive control in children with chromosome 22q11.2 deletion syndrome. Cogn. Affect. Behav. Neurosci., 2009, 9, 83-90.
95. Kereszturi, E.; Tarnok, Z.; Bognar, E.; Lakatos, K.; Farkas, L.; Gadoros, J.; Sasvari-Szekely, M.; Nemoda, Z. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am. J. Med. Genet. Part B. Neuropsychiatric Genet., 2008, 147B, 1431-1435.
96. Quinn, J.J.; Ma, Q.D.; Tinsley, M.R.; Koch, C.; Fanselow, M.S. Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories. Learn. Mem., 2008, 15, 368-372.
97. Restivo, L.; Vetere, G.; Bontempi, B.; Ammassari-Teule, M. The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulate cortex. J. Neurosci., 2009, 29, 8206-8214.
98. Fanselow, M.S.; Gale, G.D. The amygdala, fear, and memory. Ann. NY Acad. Sci., 2003, 985, 125-134.
99. Feenstra, M.G.P.; Botterblom, M.H. A. Rapid sampling of extracellular dopamine in the rat prefrontal cortex during food consumption, handling and exposure to novelty. Brain Res., 1996, 742, 17-24.
100. Arnsten, A.F. Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine alpha-1 receptor mechanisms. Prog. Brain Res., 2000, 126, 183-192.
101. Lonsdorf, T.B.; Weike, A.I.; Nikamo, P.; Schalling, M.; Hamm, A.O.; Öhman, A. Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder. Psychol. Sci., 2009, 20, 198-206.
102. Enoch, M.A.; Waheed, J.F.; Harris, C.R.; Albaugh, B.; Goldman, D. COMT Val158Met and cognition: main effects and interaction with educational attainment. Genes Brain Behav., 2009, 8, 36-42.
103. de Frias, C.M.; Annerbrink, K.; Westberg, L.; Eriksson, E.; Adolfsson, R.; Nilsson, L.G. COMT gene polymorphism is associated with declarative memory in adulthood and old age. Behav. Genet., 2004, 34, 533-539.
104. Bertolino, A.; Rubino, V.; Sambataro, F.; Blasi, G.; Latorre, V.; Fazio, L.; Caforio, G.; Petruzzella, V.; Kolachana, B.; Hariri, A.; Meyer-Lindenberg, A.; Nardini, M.; Weinberger, D.R.; Scarabino, T. Prefrontal-hippocampal coupling during memory processing is modulated by COMT Val158Met genotype. Biol. Psychiatry, 2006, 60, 1250-1258.
105. Schott, B.H.; Seidenbecher, C.I.; Fenker, D.B.; Lauer, C.J.; Bunzeck, N.; Bernstein, H.G.; Tischmeyer, W.; Gundelfinger, E.D.; Heinze, H.J.; Duzel, E. The dopaminergic midbrain participates in human episodic memory formation: evidence from genetic imaging. J. Neurosci., 2006, 26, 1407-1417.
106. Quirk, G.J.; Garcia, R.; González-Lima, F. Prefrontal Mechanisms in Extinction of Conditioned Fear. Biol. Psychiatry, 2006, 60, 337-343.
107. Kolassa, I.-T.; Kolassa, S.; Ertl, V.; Papassotiropoulos, A.; De Quervain, D.J.F. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the Catechol-O-Methyltransferase Val158Met polymorphism. Biol. Psychiatry, 2010, 67, 304-308.
108. Tau, G.Z.; Peterson, B.S. Normal development of brain circuits. Neuropsychopharmacology, 2010, 35, 147-168.
109. Wahlstrom, D.; White, T.; Luciana, M. Neurobehavioral evidence for changes in dopamine system activity during adolescence. Neurosci. Biobehav. Rev., 2010, 34, 631-648.
110. Rosenberg, D.R.; Lewis, D.A. Postnatal maturation of the dopaminergic innervation of monkey prefrontal and motor cortices: a tyrosine hydroxylase immunohistochemical analysis. J. Comp. Neurol., 1995, 358, 383-400.
111. Lambe, E.K.; Krimer, L.S.; Goldman-Rakic, P.S. Differential postnatal development of catecholamine and serotonin inputs to identified neurons in prefrontal cortex of rhesus monkey. J. Neurosci., 2000, 20, 8780-8787.
112. Kalsbeek, A.; Voorn, P.; Buijs, R.M.; Pool, C.W.; Uylings, H.B. Development of the dopaminergic innervation in the prefrontal cortex of the rat. J. Comp. Neurol., 1988, 269, 58-72.
113. Lewis, D.A. Development of the prefrontal cortex during adolescence: insights into vulnerable neural circuits in schizophrenia. Neuropsychopharmacology, 1997, 16, 385-398.
114. Luna, B.; Garver, K.E.; Urban, T.A.; Lazar, N.A.; Sweeney, J.A. Maturation of cognitive processes from late childhood to adulthood. Child Dev., 2004, 75, 1357-1372.
115. Casey, B.J.; Galvan, A.; Hare, T.A. Changes in cerebral functional organization during cognitive development. Curr. Opin. Neurobiol., 2005, 15, 239-244.
116. Cannon, T.D.; van Erp, T.G.; Bearden, C.E.; Loewy, R.; Thompson, P.; Toga, A.W.; Huttunen, M.O.; Keshavan, M.S.; Seidman, L.J.; Tsuang, M.T. Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. Schizophr. Bull., 2003, 29, 653-669.
117. Woodin, M.; Wang, P.P.; Aleman, D.; McDonald-McGinn, D.; Zackai, E.; Moss, E.Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion. Genet. Med., 2001, 3, 34-39.
118. Sergeant, J.A.; Geurts, H.; Oosterlaan, J.How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder? Behav. Brain Res., 2002, 130, 3-28.
119. Shaw, P.; Eckstrand, K.; Sharp, W.; Blumenthal, J.; Lerch, J.P.; Greenstein, D.; Clasen, L.; Evans, A.; Giedd, J.; Rapoport, J.L. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc. Natl. Acad. Sci. USA, 2007, 104, 19649-19654.
120. Maia, T.V.; Cooney, R.E.; Peterson, B.S. The neural bases of obsessive-compulsive disorder in children and adults. Develop. Psychopathol., 2008, 20, 1251-1283.
121. Huyser, C.; Veltman, D.J.; de Haan, E.; Boer, F. Paediatric obsessive-compulsive disorder, a neurodevelopmental disorder? Evidence from neuroimaging. Neurosci. Amp. Biobehav. Rev., 2009, 33, 818-830.
122. Watkins, L.H.; Sahakian, B.J.; Robertson, M.M.; Veale, D.M.; Rogers, R.D.; Pickard, K.M.; Aitken, M.R.; Robbins, T.W. Executive function in Tourette's syndrome and obsessive-compulsive disorder. Psychol. Med., 2005, 35, 571-582.
123. Welsh, M.C.; Pennington, B.F.; Ozonoff, S.; Rouse, B.; McCabe, E.R. Neuropsychology of early-treated phenylketonuria: specific executive function deficits. Child. Dev., 1990, 61, 1697-1713.
124. Diamond, A. Consequences of Variations in genes that affect dopamine in prefrontal cortex. Cereb. Cortex, 2007, 17, i161-i170.
125. Cullen, A.E.; Dickson, H.; West, S.A.; Morris, R.G.; Mould, G.L.; Hodgins, S.; Murray, R.M.; Laurens, K.R. Neurocognitive performance in children aged 9-12years who present putative antecedents of schizophrenia. Schizophr. Res., 2010, 121, 15-23.
126. Messias, E.L.; Chen, C.-Y.; Eaton, W.W. Epidemiology of schizophrenia: review of findings and myths. Psychiatric Clin. North Am., 2007, 30, 323-338.
127. Lewandowski, K.E.; Shashi, V.; Berry, P.M.; Kwapil, T.R. Schizophrenic-like neurocognitive deficits in children and adolescents with 22q11 deletion syndrome. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2007, 144B, 27-36.
128. Maynard, T.M.; Haskell, G.T.; Peters, A.Z.; Sikich, L.; Lieberman, J.A.; LaMantia, A.S. A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Proc. Natl. Acad. Sci. USA, 2003, 100, 14433-14438.
129. Tunbridge, E.M.; Weickert, C.S.; Kleinman, J.E.; Herman, M.M.; Chen, J.; Kolachana, B.S.; Harrison, P.J.; Weinberger, D.R. Catechol-o-methyltransferase enzyme activity and protein expression in human prefrontal cortex across the postnatal lifespan. Cereb. Cortex, 2007, 17, 1206-1212.
130. Liu, B.; Song, M.; Li, J.; Liu, Y.; Li, K.; Yu, C.; Jiang, T. Prefrontal-related functional connectivities within the default network are modulated by COMT val158met in healthy young adults. J. Neurosci., 2010, 30, 64-69.
131. Shaw, P.; Wallace, G.L.; Addington, A.; Evans, A.; Rapoport, J.; Giedd, J.N. Effects of the Val158Met catechol-O-methyltransferase polymorphism on cortical structure in children and adolescents, Mol Psychiatry, 2009, 14, 348-349.
132. Diamond, A.; Briand, L.; Fossella, J.; Gehlbach, L. Genetic and Neurochemical Modulation of Prefrontal Cognitive Functions in Children. Am. J. Psychiatry, 2004, 161, 125-132.
133. Davidson, M.C.; Amso, D.; Anderson, L.C.; Diamond, A. Development of cognitive control and executive functions from 4 to 13 years: evidence from manipulations of memory, inhibition, and task switching. Neuropsychologia, 2006, 44, 2037-2078.
134. Barnett, J.H.; Heron, J.; Goldman, D.; Jones, P.B.; Xu, K. Effects of catechol-O-methyltransferase on normal variation in the cognitive function of children. Am. J. Psychiatry, 2009, 166, 909-916.
135. Wahlstrom, D.; White, T.; Hooper, C.J.; Vrshek-Schallhorn, S.; Oetting, W.S.; Brott, M.J.; Luciana, M. Variations in the Catechol O-methyltransferase polymorphism and prefrontally guided behaviors in adolescents. Biol. Psychiatry, 2007, 61, 626-632.
136. Weickert, C.S.; Webster, M.J.; Gondipalli, P.; Rothmond, D.; Fatula, R.J.; Herman, M.M.; Kleinman, J.E.; Akil, M. Postnatal alterations in dopaminergic markers in the human prefrontal cortex. Neuroscience, 2007, 144, 1109-1119.
137. Staiti, A.M.; Morgane, P.J.; Galler, J.R.; Grivetti, J.Y.; Bass, D.C.; Mokler, D.J. A microdialysis study of the medial prefrontal cortex of adolescent and adult rats, Neuropharmacology, 2011, 61, 544-549.
138. Jacobs, E.; D'Esposito, M. Estrogen shapes dopamine-dependent cognitive processes: implications for women's health. J. Neurosci., 2011, 31, 5286-5293.
139. Dumontheil, I.; Roggeman, C.; Ziermans, T.; Peyrard-Janvid, M.; Matsson, H.; Kere, J.; Klingberg, T. Influence of the COMT genotype on working memory and brain activity changes during development. Biol. Psychiatry, 2011, 70, 222-229.
140. Voelker, P.; Sheese, B.E.; Rothbart, M.K.; Posner, M.I. Variations in catechol-O-methyltransferase gene interact with parenting to influence attention in early development. Neuroscience, 2009, 164, 121-130.
141. Kent, K.; Pelham, W.; Molina, B.; Sibley, M.; Waschbusch, D.; Yu, J.; Gnagy, E.; Biswas, A.; Babinski, D.; Karch, K. The academic experience of male high school students with ADHD. J. Abnormal Child. Psychol., 2011, 39, 451-462.
142. Diamond, A. Biological and social influences on cognitive control processes dependent on prefrontal cortex. Prog. Brain Res., 2011, 189, 319-339.
143. Diamond, A.; Lee, K. Interventions shown to aid executive function development in children 4 to 12 years old. Science, 2011, 333, 959-964.
144. Bosia, M.; Bechi, M.; Marino, E.; Anselmetti, S.; Poletti, S.; Cocchi, F.; Smeraldi, E.; Cavallaro, R. Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia. Neurosci. Lett., 2007, 417, 271-274.
145. Gothelf, D.; Hoeft, F.; Ueno, T.; Sugiura, L.; Lee, A.D.; Thompson, P.; Reiss, A.L. Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome. J. Psychiatr. Res., 2011, 45, 322-331.
146. Campbell, L.E.; Azuma, R.; Ambery, F.; Stevens, A.; Smith, A.; Morris, R.G.; Murphy, D.G.M.; Murphy, K.C. Executive functions and memory abilities in children with 22q11.2 deletion syndrome. Aust. NZ J. Psychiatry, 2010, 44, 364-371.
147. Schaer, M.; Debbané, M.; Bach Cuadra, M.; Ottet, M.-C.; Glaser, B.; Thiran, J.-P.; Eliez, S. Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): A cross-sectional and longitudinal study. Schizophr Res., 2009, 115, 182-190.
148. Simon, T.J.; Bish, J.P.; Bearden, C.E.; Ding, L.; Ferrante, S.; Nguyen, V.; Gee, J.C.; McDonald-McGinn, D.M.; Zackai, E.H.; Emanuel, B.S. A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children. Dev. Psychopathol., 2005, 17, 753-784.
149. Gothelf, D.; Eliez, S.; Thompson, T.; Hinard, C.; Penniman, L.; Feinstein, C.; Kwon, H.; Jin, S.; Jo, B.; Antonarakis, S.E.; Morris, M.A.; Reiss, A.L. COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nat. Neurosci., 2005, 8, 1500-1502.
150. Bearden, C.E.; Jawad, A.F.; Lynch, D.R.; Sokol, S.; Kanes, S.J.; McDonald-McGinn, D.M.; Saitta, S.C.; Harris, S.E.; Moss, E.; Wang, P.P.; Zackai, E.; Emanuel, B.S.; Simon, T.J. Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome. Am. J. Psychiatry, 2004, 161, 1700-1702.
151. Diamond, A.; Prevor, M.B.; Callender, G.; Druin, D.P. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monogr. Soc. Res. Child. Dev., 1997, 62, 1-208.
152. Diamond, A.; Ciaramitaro, V.; Donner, E.; Djali, S.; Robinson, M.B. An animal model of early-treated PKU. J. Neurosci., 1994, 14, 3072-3082.
153. Enns, G.M.; Koch, R.; Brumm, V.; Blakely, E.; Suter, R.; Jurecki, E. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence, Mol. Genet. Metab., 2010, 101, 99-109.
154. Leuzzi, V.; Pansini, M.; Sechi, E.; Chiarotti, F.; Carducci, C.; Levi, G.; Antonozzi, I. Executive function impairment in early-treated PKU subjects with normal mental development. J. Inherit. Metab. Dis., 2004, 27, 115-125.
155. MacDonald, A.; Gokmen-Ozel, H.; van Rijn, M.; Burgard, P. The reality of dietary compliance in the management of phenylketonuria. J. Inherit. Metab. Dis., 2010, 33, 665-670.
156. Sengupta, S.; Grizenko, N.; Schmitz, N.; Schwartz, G.; Bellingham, J.; Polotskaia, A.; Stepanian, M.T.; Goto, Y.; Grace, A.A.; Joober, R. COMT Val108/158Met Polymorphism and the Modulation of Task-Oriented Behavior in Children with ADHD. Neuropsychopharmacology, 2008, 33, 3069-3077.
157. Eisenberg, J.; Mei-Tal, G.; Steinberg, A.; Tartakovsky, E.; Zohar, A.; Gritsenko, I.; Nemanov, L.; Ebstein, R.P. Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): Association of the highenzyme activity val allele with adhd impulsive-hyperactive phenotype. Am. J. Med. Genet., 1999, 88, 497-502.
158. Bellgrove, M.A.; Domschke, K.; Hawi, Z.; Kirley, A.; Mullins, C.; Robertson, I.H.; Gill, M. The methionine allele of the COMT polymorphism impairs prefrontal cognition in children and adolescents with ADHD. Exp. Brain Res., 2005, 163, 352-360.
159. Viggiano, D.; Vallone, D.; Ruocco, L.A.; Sadile, A.G. Behavioural, pharmacological, morpho-functional molecular studies reveal a hyperfunctioning mesocortical dopamine system in an animal model of attention deficit and hyperactivity disorder. Neurosci. Biobehav. Rev., 2003, 27, 683-689.
160. Pliszka, S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J. Am. Acad. Child. Adolesc. Psychiatry, 2007, 46, 894-921.
161. Agster, K.L.; Clark, B.D.; Gao, W.J.; Shumsky, J.S.; Wang, H.X.; Berridge, C.W.; Waterhouse, B.D. Experimental strategies for investigating psychostimulant drug actions and prefrontal cortical function in ADHD and related attention disorders. Anat. Rec. (Hoboken), 2011, 294, 1698-1712.
162. Wilens, T.E. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J. Clin. Psychopharmacol., 2008, 28, S46-S53.
163. Kereszturi, E.; Tarnok, Z.; Bognar, E.; Lakatos, K.; Farkas, L.; Gadoros, J.; Sasvari-Szekely, M.; Nemoda, Z. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2008, 147B, 1431-1435.
164. Tunbridge, E.M.; Harrison, P.J. Importance of the COMT Gene for Sex Differences in Brain Function and Predisposition to Psychiatric Disorders Biological Basis of Sex Differences in Psychopharmacology; Neill, J.C.; Kulkarni, J.; Eds.; Springer Berlin, Heidelberg, 2011, pp. 119-140.
165. Shifman, S.; Bronstein, M.; Sternfeld, M.; Pisanté-Shalom, A.; Lev-Lehman, E.; Weizman, A.; Reznik, I.; Spivak, B.; Grisaru, N.; Karp, L.; Schiffer, R.; Kotler, M.; Strous, R.D.; Swartz-Vanetik, M.; Knobler, H.Y.; Shinar, E.; Beckmann, J.S.; Yakir, B.; Risch, N.; Zak, N.B.; Darvasi, A. A highly significant association between a COMT haplotype and schizophrenia. Am J. Hum. Genet., 2002, 71, 1296-1302.
166. Talkowski, M.E.; Kirov, G.; Bamne, M.; Georgieva, L.; Torres, G.; Mansour, H.; Chowdari, K.V.; Milanova, V.; Wood, J.; McClain, L.; Prasad, K.; Shirts, B.; Zhang, J.; O'Donovan, M.C.; Owen, M.J.; Devlin, B.; Nimgaonkar, V.L. A network of dopaminergic gene variations implicated as risk factors for schizophrenia. Hum. Mol. Genet., 2008, 17, 747-758.
167. Karayiorgou, M.; Altemus, M.; Galke, B.L.; Goldman, D.; Murphy, D.L.; Ott, J.; Gogos, J.A. Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc. Natl. Acad. Sci., 1997, 94, 4572-4575.
168. Pooley, E.C.; Fineberg, N.; Harrison, P.J. The met158 allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol. Psychiatry, 2007, 12, 556-561.
169. Biederman, J.; Kim, J.W.; Doyle, A.E.; Mick, E.; Fagerness, J.; Smoller, J.W.; Faraone, S.V. Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2008, 147B, 1511-1518.