The endophenotype concept in psychiatry: Etymology and strategic intentions

American Journal of Psychiatry

Volumn 160, Issue 4, 2003, Pages 636-645

  Gottesman, Irving I ^a   Gould, Todd D ^b  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

COGNITION; DISEASE ASSOCIATION; EYE; GENETIC ANALYSIS; GENOTYPE; HEALTH HAZARD; HUMAN; MEDICAL RESEARCH; MENTAL DISEASE; NEUROANATOMY; NEUROLOGIC DISEASE; NEUROPHYSIOLOGY; NEUROPSYCHIATRY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PSYCHIATRIC DIAGNOSIS; REVIEW; SELF REPORT; BIOLOGICAL MODEL; DISEASE MODEL; FAMILY; GENETIC PREDISPOSITION; GENETICS; MEMORY DISORDER; METHODOLOGY; NOMENCLATURE; PATHOPHYSIOLOGY; PHYSIOLOGY; PREFRONTAL CORTEX; PSYCHIATRY; PSYCHOLOGY; RISK; SACCADIC EYE MOVEMENT; SCHIZOPHRENIA; SMOOTH PURSUIT EYE MOVEMENT;

DISEASE MODELS, ANIMAL; FAMILY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MEMORY DISORDERS; MENTAL DISORDERS; MODELS, BIOLOGICAL; MODELS, GENETIC; PHENOTYPE; PREFRONTAL CORTEX; PSYCHIATRY; PURSUIT, SMOOTH; RESEARCH DESIGN; RISK; SACCADES; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY; TERMINOLOGY;

EID: 0038823525     PISSN: 0002953X     EISSN: None     Source Type: Journal    
DOI: 10.1176/appi.ajp.160.4.636     Document Type: Review

References (141)

1. Sturtevant AH: A History of Genetics. New York, Cold Spring Harbor Laboratory Press, 1965 (reprinted 2001) (full text available online at http://www.esp.org/books/sturt/history)
2. Zerba KE, Ferrell RE, Sing CF: Complex adaptive systems and human health: the influence of common genotypes of the apolipoprotein E (ApoE) gene polymorphism and age on the relational order within a field of lipid metabolism traits. Hum Genet 2000; 107:466-475
3. Sing CF, Zerba KE, Reilly SL: Traversing the biological complexity in the hierarchy between genome and CAD endpoints in the population at large. Clin Genet 1994; 46(1 special number):6-14
4. Province MA, Shannon WD, Rao DC: Classification methods for confronting heterogeneity. Adv Genet 2001; 42:273-286
5. Gottesman II: Psychopathology through a life span-genetic prism. Am Psychol 2001; 56:867-878
6. Merikangas KR, Swendsen JD: Genetic epidemiology of psychiatric disorders. Epidemiol Rev 1997; 19:144-155
7. Petronis A, Gottesman, II, Crow TJ, DeLisi LE, Klar AJ, Macciardi F, McInnis MG, McMahon FJ, Paterson AD, Skuse D, Sutherland GR: Psychiatric epigenetics: a new focus for the new century. Mol Psychiatry 2000; 5:342-346
8. Rakyan VK, Preis J, Morgan HD, Whitelaw E: The marks, mechanisms and memory of epigenetic states in mammals. Biochem J 2001; 356(part 1):1-10
9. McGuffin P, Owen MJ, Gottesman II: Psychiatric Genetics and Genomics. Oxford, UK, Oxford University Press, 2002
10. Lewis DA, Levitt P: Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 2002; 25:409-432
11. Petronis A: Human morbid genetics revisited: relevance of epigenetics. Trends Genet 2001; 17:142-146
12. Glazier AM, Nadeau JH, Aitman TJ: Finding genes that underlie complex traits. Science 2002; 298:2345-2349
13. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, et al: The sequence of the human genome. Science 2001; 291:1304-1305; correction, 2001; 292:1838
14. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, et al: Initial sequencing and analysis of the human genome. Nature 2001; 409:860-921
15. Cowan WM, Kopnisky KL, Hyman SE: The human genome project and its impact on psychiatry. Annu Rev Neurosci 2002; 25:1-50
16. Sklar P: Linkage analysis in psychiatric disorders: the emerging picture. Annu Rev Genomics Hum Genet 2002; 3:371-413
17. Gottesman II, Moldin SO: Schizophrenia genetics at the millennium: cautious optimism. Clin Genet 1997; 52:404-407
18. Cloninger CR: The discovery of susceptibility genes for mental disorders. Proc Natl Acad Sci USA 2002; 99:13365-13367
19. Andreasen NC: Understanding the causes of schizophrenia (letter). N Engl J Med 1999; 340:645-647
20. Lewis DA: In pursuit of the pathogenesis and pathophysiology of schizophrenia: where do we stand? (editorial). Am J Psychiatry 2002; 159:1467-1469
21. Chakravarti A, Little P: Nature, nurture and human disease. Nature 2003; 421:412-414
22. Andreasen NC: Schizophrenia: the fundamental questions. Brain Res Brain Res Rev 2000; 31:106-112
23. Kandel ER: A new intellectual framework for psychiatry. Am J Psychiatry 1998; 155:457-469
24. Gottesman, II, Shields J: A polygenic theory of schizophrenia. Proc Natl Acad Sci USA 1967; 58:199-205
25. Gottesman II, Shields J: Schizophrenia and Genetics: A Twin Study Vantage Point. New York, Academic Press, 1972
26. Gottesman II, Shields J: Genetic theorizing and schizophrenia. Br J Psychiatry 1973; 122:15-30
27. John B, Lewis KR: Chromosome variability and geographical distribution in insects: chromosome rather than gene variation provide the key to differences among populations. Science 1966; 152:711-721
28. Lenox RH, Gould TD, Manji HK: Endophenotypes in bipolar disorder. Am J Med Genet 2002; 114:391-406
29. Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J: Psychiatric genetics: search for phenotypes. Trends Neurosci 1998; 21:102-105
30. Callicott JH, Weinberger DR: Brain imaging as an approach to phenotype characterization for genetic studies of schizophrenia. Methods Mol Med 2003; 77:227-247
31. Weinberger DR, Egan MF, Bertolino A, Callicott JH, Mattay VS, Lipska BK, Berman KF, Goldberg TE: Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry 2001; 50:825-844
32. Egan MF, Goldberg TE: Intermediate cognitive phenotypes associated with schizophrenia. Methods Mol Med 2003; 77:163-197
33. Braff DL, Freedman R: Endophenotypes in studies of the genetics of schizophrenia, in Neuropsychopharmacology: The Fifth Generation of Progress. Edited by Davis KL, Charney DS, Coyle JT, Nemeroff C. Philadelphia, Lippincott Williams & Wilkins, 2002, pp 703-716
34. Leboyer M: Searching for alternative phenotypes in psychiatric genetics. Methods Mol Med 2003; 77:145-161
35. MacCorquodale K, Meehl PE: On a distinction between hypothetical constructs and intervening variables. Psychol Rev 1948; 55:95-107
36. Turkheimer E, Goldsmith HH, Gottesman II: Commentary: some conceptual deficiencies in "developmental" behavior genetics. Hum Dev 1995; 38:142-153
37. Faraone SV, Tsuang D, Tsuang MT: Genetics of Mental Disorders: A Guide for Students, Clinicians, and Researchers. New York, Guilford, 1999
38. Heinrichs RW: In Search of Madness: Schizophrenia and Neuroscience. New York, Oxford University Press, 2001
39. Braff DL, Geyer MA, Swerdlow NR: Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl) 2001; 156:234-258
40. Freedman R: Electrophysiological phenotypes. Methods Mol Med 2003; 77:215-225
41. Holzman PS: Less is truly more: psychopathology research in the 21st century, in Principles of Psychopathology: Essays in Honor of Brendan A. Maher. Edited by Lenzenweger MF, Hooley JM. Washington, American Psychological Association, 2003, pp 175-194
42. Calkins ME, Iacono WG: Eye movement dysfunction in schizophrenia: a heritable characteristic for enhancing phenotype definition. Am J Med Genet 2000; 97:72-76
43. Lee KH, Williams LM: Eye movement dysfunction as a biological marker of risk for schizophrenia. Aust N Z J Psychiatry 2000; 34(Suppl):S91-S100
44. Goldberg TE, Green MF: Neurocognitive functioning in patients with schizophrenia: an overview, in Neuropsychopharmacology: The Fifth Generation of Progress. Edited by Davis KL, Charney DS, Coyle JT, Nemeroff C. Philadelphia, Lippincott Williams & Wilkins, 2002, pp 657-669
45. Goldman-Rakic PS: The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry 1999; 46:650-661
46. Erlenmeyer-Kimling L, Rock D, Roberts SA, Janal M, Kestenbaum C, Cornblait B, Adamo UH, Gottesman II: Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project. Am J Psychiatry 2000; 157:1416-1422
47. Moises HW, Zoega T, Gottesman II: The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia. BMC Psychiatry 2002; 2:8, http://www.biomedcentral.com/1471-244X/2/8/
48. Wise LH, Lanchbury JS, Lewis CM: Meta-analysis of genome searches. Ann Hum Genet 1999; 63(part 3):263-272
49. Owen MJ, O'Donovan MC, Gottesman II: Schizophrenia, in Psychiatric Genetics and Genomics. Edited by McGuffin P, Owens MJ, Gottesman II. Oxford, UK, Oxford University Press, 2002, pp 247-266
50. Pulver AE, Pearlson G, McGrath J, Lasseter VK, Swarts K, Papadimitriou G: Schizophrenia, in The Genetic Basis of Common Diseases. Edited by King RA, Rotter JI, Motulsky AG. New York, Oxford University Press, 2002
51. Trumbetta SL, Gottesman II: Endophenotypes for marital status in the NAS-NRC Twin Registry, in Genetic Influences on Human Fertility and Sexuality. Edited by Rodgers JL, Rowe DC, Miller WB. Boston, Kluwer Academic, 2000, pp 253-269
52. Skuse DH: Endophenotypes and child psychiatry. Br J Psychiatry 2001; 178:395-396
53. Gasperoni TL, Ekelund J, Huttunen M, Palmer CG, Tuulio-Henriksson A, Lonnqvist J, Kaprio J, Peltonen L, Cannon TD: Genetic linkage and association between chromosome 1q and working memory function in schizophrenia. Am J Med Genet 2003; 116(1 suppl):8-16
54. Castellanos FX, Tannock R: Neuroscience of attention-deficit/ hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 2002; 3:617-628
55. Ahearn EP, Speer MC, Chen YT, Steffens DC, Cassidy F, Van Meter S, Provenzale JM, Weisler RH, Krishnan KR: Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype. Am J Med Genet 2002; 114:652-658
56. Cadenhead KS, Light GA, Geyer MA, McDowell JE, Braff DL: Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype? Am J Psychiatry 2002; 159:869-871
57. Cornblatt BA, Malhotra AK: Impaired attention as an endophenotype for molecular genetic studies of schizophrenia. Am J Med Genet 2001; 105:11-15
58. Merikangas KR, Chakravarti A, Moldin SO, Araj H, Blangero JC, Burmeister M, Crabbe J Jr, Depaulo JR Jr, Foulks E, Freimer NB, Koretz DS, Lichtenstein W, Mignot E, Reiss AL, Risch NJ, Takahashi JS: Future of genetics of mood disorders research. Biol Psychiatry 2002; 52:457-477
59. Seibyl JP, Scanley E, Krystal JH, Innis RB: Neuroimaging methodologies, in Neurobiology of Mental Illness. Edited by Charney DS, Nester EJ, Bunney BS. New York, Oxford University Press, 1999, pp 170-189
60. Diwadkar VA, Keshavan MS: Newer techniques in magnetic resonance imaging and their potential for neuropsychiatric research. J Psychosom Res 2002; 53:677-685
61. Martinez D, Broft A, Laruelle M: Imaging neurochemical endophenotypes: promises and pitfalls. Pharmacogenomics 2001; 2:223-237
62. Gershon ES, Goldin LR: Clinical methods in psychiatric genetics, I: robustness of genetic marker investigative strategies. Acta Psychiatr Scand 1986; 74:113-118
63. Keating MT, Sanguinetti MC: Molecular and cellular mechanisms of cardiac arrhythmias. Cell 2001; 104:569-580
64. Keating M, Atkinson D, Dunn C, Timothy K, Vincent GM, Leppert M: Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene. Science 1991; 252:704-706
65. Vincent GM, Timothy KW, Leppert M, Keating M: The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med 1992; 327:846-852
66. Casimiro MC, Knollmann BC, Ebert SN, Vary JC Jr, Greene AE, Franz MR, Grinberg A, Huang SP, Pfeifer K: Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen syndrome. Proc Natl Acad Sci USA 2001; 98:2526-2531
67. Lalouel JM, Le Mignon L, Simon M, Fauchet R, Bourel M, Rao DC, Morton NE: Genetic analysis of idiopathic hemochromatosis using both qualitative (disease status) and quantitative (serum iron) information. Am J Hum Genet 1985; 37:700-718
68. Greenberg DA, Delgado-Escueta AV, Widelitz H, Sparkes RS, Treiman L, Maldonado HM, Park MS, Terasaki PI: Juvenile myoclonic epilepsy (JME) may be linked to the BF and HLA loci on human chromosome 6. Am J Med Genet 1988; 31:185-192
69. Leppert M, Burt R, Hughes JP, Samowitz W, Nakamura Y, Woodward S, Gardner E, Lalouel JM, White R: Genetic analysis of an inherited predisposition to colon cancer in a family with a variable number of adenomatous polyps. N Engl J Med 1990; 322:904-908
70. Gottesman II, Erlenmeyer-Kimling L: Family and twin strategies as a head start in defining prodromes and endophenotypes for hypothetical early-interventions in schizophrenia. Schizophr Res 2001; 51:93-102
71. Lenzenweger MF: Schizophrenia: refining the phenotype, resolving endophenotypes. Behav Res Ther 1999; 37:281-295
72. Andreasen NC, O'Leary DS, Cizadlo T, Arndt S, Rezai K, Ponto LL, Watkins GL, Hichwa RD: Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci U S A 1996; 93:9985-9990
73. Andreasen NC, Nopoulos P, O'Leary DS, Miller DD, Wassink T, Flaum M: Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biol Psychiatry 1999; 46:908-920
74. Berman RM, Narasimhan M, Miller HL, Anand A, Cappiello A, Oren DA, Heninger GR, Charney DS: Transient depressive relapse induced by catecholamine depletion: potential phenotypic vulnerability marker? Arch Gen Psychiatry 1999; 56:395-403
75. Niculescu AB III, Akiskal HS: Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic considerations. Mol Psychiatry 2001; 6:363-366
76. Neugroschl J, Davis KL: Biological markers in Alzheimer disease. Am J Geriatr Psychiatry 2002; 10:660-677
77. Kurz A, Riemenschneider M, Drzezga A, Lautenschlager N: The role of biological markers in the early and differential diagnosis of Alzheimer's disease. J Neural Transm Suppl 2002:127-133
78. Gould TD, Bastain TM, Israel ME, Hommer DW, Castellanos FX: Altered performance on an ocular fixation task in attention-deficit/hyperactivity disorder. Biol Psychiatry 2001; 50:633-635
79. Seidman LJ, Biederman J, Monuteaux MC, Weber W, Faraone SV: Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder. J Abnorm Psychol 2000; 109:252-265
80. New AS, Siever LJ: Biochemical endophenotypes in personality disorders. Methods Mol Med 2003; 77:199-213
81. Braff DL, Geyer MA: Sensorimotor gating and schizophrenia: human and animal model studies. Arch Gen Psychiatry 1990; 47:181-188
82. Grillon C, Courchesne E, Ameli R, Geyer MA, Braff DL: Increased distractibility in schizophrenic patients: electrophysiologic and behavioral evidence. Arch Gen Psychiatry 1990; 47:171-179
83. McGhie A, Chapman J: Disorders of attention and perception in early schizophrenia. Br J Med Psychol 1961; 34:103-116
84. Braff DL: Psychophysiological and information-processing approaches to schizophrenia, in Neurobiology of Mental Illness. Edited by Charney DS, Nester EJ, Bunney BS. New York, Oxford University Press, 1999, pp 258-271
85. Braff DL, Grillon C, Geyer MA: Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 1992; 49:206-215
86. Geyer MA, McIlwain KL, Paylor R: Mouse genetic models for prepulse inhibition: an early review. Mol Psychiatry 2002; 7:1039-1053
87. Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL: Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry 2000; 157:1660-1668; correction, 157:1904
88. Ellenbroek BA, Cools AR: Early maternal deprivation and prepulse inhibition: the role of the postdeprivation environment. Pharmacol Biochem Behav 2002; 73:177-184
89. Weiss IC, Feldon J: Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review. Psychopharmacology (Berl) 2001; 156:305-326
90. Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL: A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry 1993; 33:298-301
91. Swerdlow NR, Paulsen J, Braff DL, Butters N, Geyer MA, Swenson MR: Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease. J Neurol Neurosurg Psychiatry 1995; 58:192-200
92. Adler LE, Pachtman E, Franks RD, Pecevich M, Waldo MC, Freedman R: Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 1982; 17:639-654
93. Freedman R, Adler LE, Waldo MC, Pachtman E, Franks RD: Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. Biol Psychiatry 1983; 18:537-551
94. Freedman R, Adler LE, Gerhardt GA, Waldo M, Baker N, Rose GM, Drebing C, Nagamoto H, Bickford-Wimer P, Franks R: Neurobiological studies of sensory gating in schizophrenia. Schizophr Bull 1987; 13:669-678
95. Siegel C, Waldo M, Mizner G, Adler LE, Freedman R: Deficits in sensory gating in schizophrenic patients and their relatives: evidence obtained with auditory evoked responses. Arch Gen Psychiatry 1984; 41:607-612
96. Myles-Worsley M: P50 sensory gating in multiplex schizophrenia families from a Pacific Island isolate. Am J Psychiatry 2002; 159:2007-2012
97. Clementz BA, Geyer MA, Braff DL: Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Am J Psychiatry 1998; 155:1691-1694
98. Waldo MC, Carey G, Myles-Worsley M, Cawthra E, Adler LE, Nagamoto HT, Wender P, Byerley W, Plaetke R, Freedman R: Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. Psychiatry Res 1991; 39:257-268
99. Waldo M, Myles-Worsley M, Madison A, Byerley W, Freedman R: Sensory gating deficits in parents of schizophrenics. Am J Med Genet 1995; 60:506-511
100. Myles-Worsley M, Coon H, Byerley W, Waldo M, Young D, Freedman R: Developmental and genetic influences on the P50 sensory gating phenotype. Biol Psychiatry 1996; 39:289-295
101. Young DA, Waldo M, Rutledge JH III, Freedman R: Heritability of inhibitory gating of the P50 auditory-evoked potential in monozygotic and dizygotic twins. Neuropsychobiology 1996; 33:113-117
102. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams C, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W: Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997; 94:587-592
103. Freedman R, Leonard S, Gault JM, Hopkins J, Cloninger CR, Kaufmann CA, Tsuang MT, Faraone SV, Malaspina D, Svrakic DM, Sanders A, Gejman P: Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the α7-nicotinic acetylcholine receptor subunit gene (CHRNA7). Am J Med Genet 2001; 105:20-22
104. Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M, Drebing C, Berger R, Venn D, Sirota P, Zerbe G, Olincy A, Ross RG, Adler LE, Freedman R: Association of promoter variants in the α7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry 2002; 59:1085-1096
105. Diefendorf AR, Dodge R: An experimental study of the ocular reactions of the insane from photographic records. Brain 1908; 31:451-489
106. Holzman PS, Proctor LR, Hughes DW: Eye-tracking patterns in schizophrenia. Science 1973; 181:179-181
107. Holzman PS, Proctor LR, Levy DL, Yasillo NJ, Meltzer HY, Hurt SW: Eye-tracking dysfunctions in schizophrenic patients and their relatives. Arch Gen Psychiatry 1974; 31:143-151
108. Munoz DP: Commentary: saccadic eye movements: overview of neural circuitry. Prog Brain Res 2002; 140:89-96
109. Arolt V, Lencer R, Nolte A, Muller-Myhsok B, Purmann S, Schurmann M, Leutelt J, Pinnow M, Schwinger E: Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease. Am J Med Genet 1996; 67(6):564-579
110. O'Driscoll GA, Benkelfat C, Florencio PS, Wolff AL, Joober R, Lal S, Evans AC: Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients: a positron emission tomography study. Arch Gen Psychiatry 1999; 56:1127-1134
111. Park S, Lee J: Spatial working memory function in schizophrenia, in Principles of Psychopathology: Essays in Honor of Brendan A. Maher. Edited by Lenzenweger MF, Hooley JM. Washington, American Psychological Association, 2003, pp 83-106
112. Snitz BE, Curtis CE, Zald DH, Katsanis J, Iacono WG: Neuropsychological and oculomotor correlates of spatial working memory performance in schizophrenia patients and controls. Schizophr Res 1999; 38(1):37-50
113. Levy R, Goldman-Rakic PS: Segregation of working memory functions within the dorsolateral prefrontal cortex. Exp Brain Res 2000; 133:23-32
114. Harrison PJ: The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 1999; 122(part 4):593-624
115. Park S, Holzman PS, Goldman-Rakic PS: Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry 1995; 52:821-828
116. Conklin HM, Curtis CE, Katsanis J, Iacono WG: Verbal working memory impairment in schizophrenia patients and their first-degree relatives: evidence from the Digit Span Task. Am J Psychiatry 2000; 157:275-277
117. Cannon TD, Huttunen MO, Lonnqvist J, Tuulio-Henriksson A, Pirkola T, Glahn D, Finkelstein J, Hietanen M, Kaprio J, Koskenvuo M: The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. Am J Hum Genet 2000; 67:369-382
118. Goldberg TE, Kelsoe JR, Weinberger DR, Pliskin NH, Kirwin PD, Berman KF: Performance of schizophrenic patients on putative neuropsychological tests of frontal lobe function. Int J Neurosci 1988; 42:51-58
119. Hovatta I, Varilo T, Suvisaari J, Terwilliger JD, Ollikainen V, Arajarvi R, Juvonen H, Kokko-Sahin ML, Vaisanen L, Mannila H, Lonnqvist J, Peltonen L: A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci. Am J Hum Genet 1999; 65:1114-1124
120. Ekelund J, Lichtermann D, Hovatta I, Ellonen P, Suvisaari J, Terwilliger JD, Juvonen H, Varilo T, Arajarvi R, Kokko-Sahin ML, Lonnqvist J, Peltonen L: Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22. Hum Mol Genet 2000; 9:1049-1057
121. St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G, Gosden C, Evans HJ: Association within a family of a balanced autosomal translocation with major mental illness. Lancet 1990; 336:13-16
122. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, Clair DM, Muir WJ, Blackwood DH, Porteous DJ: Disruption of two novel genes by a translocation cosegregating with schizophrenia. Hum Mol Genet 2000; 9:1415-1423
123. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR: Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98:6917-6922
124. Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E, Saper CB, Rauch SL: Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry 2000; 48:99-109
125. Manoach DS, Press DZ, Thangaraj V, Searl MM, Goff DC, Halpern E, Saper CB, Warach S: Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry 1999; 45:1128-1137
126. 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; 10:1078-1092
127. Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B, Weinberger DR: Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry 2003; 160:709-719
128. Duffy A, Grof P: Psychiatric diagnoses in the context of genetic studies of bipolar disorder. Bipolar Disord 2001; 3:270-275
129. Crawley JN: What's Wrong With My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. New York, Wiley-Liss, 2000
130. Einat H, Belmaker RH, Manji HK: New approaches to modeling bipolar disorder. Psychopharmacol Bull (in press)
131. Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Greshenfeld HK, Hen R, Koester S, Lederhendler I, Meaney M, Robbins T, Winsky L, Zalcman S: Preclinical models: status of basic research in depression. Biol Psychiatry 2002; 52:503-528
132. Einat H, Kofman O, Belmaker RH: Animal models of bipolar disorder: from a single episode to progressive cycling models, in Contemporary Issues in Modeling Psychopharmacology. Edited by Weiner I. Boston, Kluwer Academic, 2000, pp 165-180
133. Gould TD, Gray NA, Manji HK: The cellular neurobiology of severe mood and anxiety disorders: implications for the development of novel therapeutics, in Molecular Neurobiology for the Clinician. Edited by Charney DS. Washington, American Psychiatric Publishing (in press)
134. Crawley JN: Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res 1999; 835:18-26
135. Geller B, Cook EH Jr: Ultradian rapid cycling in prepubertal and early adolescent bipolarity is not in transmission disequilibrium with val/met COMT alleles. Biol Psychiatry 2000; 47:605-609
136. Cardno AG, Holmans PA, Rees MI, Jones LA, McCarthy GM, Hamshere ML, Williams NM, Norton N, Williams HJ, Fenton I, Murphy KC, Sanders RD, Gray MY, O'Donovan MC, McGuffin P, Owen MJ: A genomewide linkage study of age at onset in schizophrenia. Am J Med Genet 2001; 105:439-445
137. Zubenko GS, Hughes HB, Stiffler JS, Zubenko WN, Kaplan BB: Genome survey for susceptibility loci for recurrent, early-onset major depression: results at 10cM resolution. Am J Med Genet 2002; 114:413-422
138. Wall TL, Carr LG, Ehlers CL: Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians. Am J Psychiatry 2003; 160:41-46
139. Saccone NL, Kwon JM, Corbett J, Goate A, Rochberg N, Edenberg HJ, Foroud T, Li TK, Begleiter H, Reich T, Rice JP: A genome screen of maximum number of drinks as an alcoholism phenotype. Am J Med Genet 2000; 96:632-637
140. Mansour HA, Alda M, Nimgaonkar VL: Pharmacogenetics of bipolar disorder. Curr Psychiatry Rep 2002; 4:117-123
141. Detera-Wadleigh SD: Lithium-related genetics of bipolar disorder. Ann Med 2001; 33:272-285