Imaging genetic liability to schizophrenia: Systematic review of fMRI studies of patients' nonpsychotic relatives

Schizophrenia Bulletin

Volumn 35, Issue 6, 2009, Pages 1142-1162

  MacDonald III, Angus W ^a   Thermenos, Heidi W ^b,c,d   Barch, Deanna M ^e,f,g   Seidman, Larry J ^b,c,d  

^a UNIVERSITY OF MINNESOTA   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d MGH/MIT/HMS Athinoula A Martinos Center for Functional and Structural Biomedical Imaging   (United States)

^e WASHINGTON UNIVERSITY   (United States)

^f WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cognitive control; family study; fMRI; language; memory; neuroimaging; relatives; review; schizophrenia; working memory

Indexed keywords

BASAL GANGLION; CEREBELLUM; COGNITION; DIAGNOSTIC ACCURACY; DIAGNOSTIC IMAGING; FAMILY STUDY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENETIC ASSOCIATION; GENETIC RISK; HEMISPHERE; HUMAN; LANGUAGE; LANGUAGE PROCESSING; MEMORY; NEUROIMAGING; PARIETAL LOBE; PREFRONTAL CORTEX; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RELATIVE; REVIEW; SCHIZOPHRENIA; STATISTICAL SIGNIFICANCE; SYSTEMATIC REVIEW; TASK PERFORMANCE; TEMPORAL CORTEX; THALAMUS; WORKING MEMORY; ADULT; ATTENTION; BRAIN; COGNITIVE DEFECT; FEMALE; GENE EXPRESSION; GENETIC PREDISPOSITION; GENETICS; HEMISPHERIC DOMINANCE; IMAGE PROCESSING; LONG TERM MEMORY; MALE; NEUROPSYCHOLOGICAL TEST; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PHENOTYPE; PHYSIOLOGY; PROBLEM SOLVING; PSYCHOLOGICAL ASPECT; PSYCHOLOGY; REACTION TIME; SACCADIC EYE MOVEMENT; SHORT TERM MEMORY; VERBAL BEHAVIOR;

ADULT; ATTENTION; BRAIN; COGNITION DISORDERS; DOMINANCE, CEREBRAL; FEMALE; GENE EXPRESSION; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; MAGNETIC RESONANCE IMAGING; MALE; MEMORY, SHORT-TERM; NEUROPSYCHOLOGICAL TESTS; PHENOTYPE; PREFRONTAL CORTEX; PROBLEM SOLVING; REACTION TIME; RETENTION (PSYCHOLOGY); SACCADES; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY; VERBAL BEHAVIOR; YOUNG ADULT;

EID: 73949107517     PISSN: 05867614     EISSN: 17451701     Source Type: Journal    
DOI: 10.1093/schbul/sbn053     Document Type: Review

References (113)

1. Freedman R, Leonard S, Olincy A, et al. Evidence for the multigenic inheritance of schizophrenia. Am J Med Genet. 2001;105(8):794-800.
2. Tsuang MT, Stone WS, Faraone SV. Schizophrenia: a review of genetic studies. Harv Rev Psychiatry. 1999;7(4):185-207.
3. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003;160(4):636-645.
4. Tsuang MT, Faraone SV, Lyons MJ. Identification of the phenotype in psychiatric genetics. Eur Arch Psychiatry Neurol Sci. 1993;243:131-142.
5. Faraone SV, Tsuang MT, Tsuang D. Genetics of Mental Disorders: A Guide for Students, Clinicians, and Researchers. New York, NY: Guilford; 1999.
6. Braff DL, Freedman R. Endophenotypes in studies of the genetics of schizophrenia. In: Davis KI, Charney DS, Coyle JT, Nemeroff C, eds. Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia, PA: Lippincott Williams and Wilkins; 2002:703-716.
7. Gottesman II, Shields J. Schizophrenia and Genetics: A Twin Study Vantage Point. New York, NY: Academic Press; 1972: 703-716.
8. Tsuang MT. Genotypes, phenotypes, and the brain: a search for connections in schizophrenia. Br J Psychiatry. 1993;163: 299-307.
9. Faraone SV, Green AI, Seidman LJ, Tsuang MT. "Schizotaxia": clinical implications and new directions for research. Schizophr Bull. 2001;27(1):1-18.
10. Boos HB, Aleman A, Cahn W, Pol HH, Kahn RS. Brain volumes in relatives of patients with schizophrenia: a meta-analysis. Arch Gen Psychiatry. 2007;64(3):297-304.
11. Cirillo MA, Seidman LJ. Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms. Neuropsychol Rev. 2003; 13(2):43-77.
12. Cornblatt BA, Keilp JG. Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull. 1994;20:31-46.
13. Kremen WS, Seidman LJ, Pepple JR, Lyons MJ, Tsuang MT, Faraone SV. Neuropsychological risk indicators for schizophrenia: a review of family studies. Schizophr Bull. 1994;20:103-118.
14. Chen WJ, Faraone SV. Sustained attention deficits as markers of genetic susceptibility to schizophrenia. Am J Med Genet. 2000;97(1):52-57.
15. Sitskoorn MM, Aleman A, Ebisch SJ, Appels MC, Kahn RS. Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophr Res. 2004;71(1):285-295.
16. Snitz BE, MacDonald AW, III, Carter CS. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr Bull. 2006;32(1):179-194.
17. Trandafir A, Méary A, Schürhoff F, Leboyer M, Szöke A. Memory tests in first-degree adult relatives of schizophrenic patients: a meta-analysis. Schizophr Res. 2006;81(2-3):217-226.
18. Gur RC, Gur RE. Hypofrontality in schizophrenia: RIP. Lancet. 1995;345:1338-1340.
19. Roick C, Fritz-Wieacker A, Matschinger H, et al. Health habits of patients with schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 2007;42(4):268-276.
20. de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res. 2005;76(2-3): 135-157.
21. Thiel CM, Fink GR. Visual and auditory alertness: modality- specific and supramodal neural mechanisms and their modulation by nicotine. J Neurophysiol. 2007;97(4): 2758-2768.
22. Lyons MJ, Bar JL, Kremen WS, et al. Nicotine and familial vulnerability to schizophrenia: a discordant twin study. J Abnorm Psychol. 2002;111(4):687-693.
23. Habel U, Klein M, Shah NJ, et al. Genetic load on amygdala hypofunction during sadness in nonaffected brothers of schizophrenia patients. Am J Psychiatry. 2004;161: 1806-1813.
24. Bedwell JS, Miller LS, Brown JM, McDowell JE, Yanasak NE. Functional magnetic resonance imaging examination of the magnocellular visual pathway in nonpsychotic relatives of persons with schizophrenia. Schizophr Res. 2004;71:509-510.
25. Schneider F, Habel U, Reske M, Toni I, Falkai P, Shah NJ. Neural substrates of olfactory processing in schizophrenia patients and their healthy relatives. Psychiatry Res. 2007;155:103-112
26. Laird AR, Fox PM, Price BH, et al. ALE meta-analysis: controlling the false discovery rate and performing statistical contrasts. Hum Brain Mapp. 2005;25:155-164.
27. Raemaekers M, Ramsey NF, Vink M, van den Heuvel MP, Kahn RS. Brain activation during antisaccades in unaffected relatives of schizophrenia patients. Biol Psychiatry. 2006; 59:530-535.
28. Becker TM, Kerns JG, MacDonald AW, III, Carter CS. Prefrontal dysfunction in first-degree relatives of schizophrenia patients during a Stroop task. Neuropsychopharmacology. [Epub ahead of print] January 23, 2008; doi:10.1038/ sj.npp.1301673.
29. Thermenos HW, Seidman LJ, Breiter HC, et al. Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: a pilot study. Biol Psychiatry. 2004;55: 490-500.
30. Seidman LJ, Thermenos HW, Koch JK, et al. Auditory verbal working memory load and thalamic activation in nonpsychotic relatives of persons with schizophrenia: an fMRI replication. Neuropsychology. 2007;21(5):599-610.
31. Delawalla Z, Csernansky J, Barch DM. Prefrontal cortex function in non-psychotic siblings of individuals with schizophrenia. Biol Psychiatry. 2007;63(5):490-497.
32. MacDonald AW, III, Becker TM, Carter CS. Functional magnetic resonance imaging study of cognitive control in the healthy relatives of schizophrenia patients. Biol Psychiatry. 2006;60:1241-1249.
33. Vink M, Ramsey NF, Raemaekers M, Kahn RS. Striatal dysfunction in schizophrenia and unaffected relatives. Biol Psychiatry. 2006;60:32-39.
34. Miller EK, Cohen JD. Integrative theory of prefrontal cortex function. Annu Rev Neurosci. 2001;24(24):167-202.
35. Oltmanns TF, Neale JM. Schizophrenic performance when distractors are present: attentional deficit or differential task difficulty? J Abnorm Psychol. 1975;84:205-209.
36. Spring B, Lemon M, Weinstein L, Haskell A. Distractibility in schizophrenia: state and trait aspects. Br J Psychiatry. 1989;155(suppl 5):63-68.
37. MacDonald AW, III, Pogue-Geile MF, Johnson MK, Carter CS. A specific deficit in context processing in the unaffected siblings of patients with schizophrenia. Arch Gen Psychiatry. 2003;60:57-65.
38. Fukashima J, Fukashima K, Chiba T, Tanaka S, Tamashita I, Kato M. Disturbances of voluntary control of saccadic eye movements in schizophrenic patients. Biol Psychiatry. 1988;23:670-677.
39. Calkins ME, Curtis CE, Iacono WG, Grove WM. Antisaccade performance is impaired in medically and psychiatrically healthy biological relatives of schizophrenia patients. Schizophr Res. 2004;71:167-178.
40. Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol (Gen). 1935;18:643-662.
41. MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychol Bull. 1991;109(2):163-203.
42. Logan GD, Cowan WB. On the ability to inhibit thought and action: a theory of an act of control. Psychol Rev. 1984;91:295-327.
43. Wager TD, Smith EE. Neuroimaging studies of working memory: a meta-analysis. Cogn Affect Behav Neurosci. 2003;3:255-274.
44. Lee J, Park S. Working memory impairments in schizophrenia: a meta-analysis. J Abnorm Psychol. 2005;114:599-611.
45. Faraone SV, Seidman LJ, Kremen WS, Toomey R, Pepple JR, Tsuang MT. Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a 4-year follow-up study. J Abnorm Psychol. 1999;108(1): 176-181.
46. Nuechterlein KH, Dawson ME, Green MF. Informationprocessing abnormalities as neuropsychological vulnerability indicators for schizophrenia. Acta Psychiatr Scand Suppl. 1994;384:71-79.
47. Park S, Holzman P, Goldman-Rakic P. Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry. 1995;52(10):821-828.
48. Glahn DC, Ragland JD, Adramoff A, et al. Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Hum Brain Mapp. 2005;25:60-69.
49. Manoach DS, Gollub RL, Benson ES, et al. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry. 2000;48:99-109.
50. Thermenos HW, Goldstein JM, Buka SL, et al. The effect of working memory performance on functional MRI in schizophrenia. Schizophr Res. 2005;74:179-194.
51. Van Snellenberg JX, Torres IJ, Thornton AE. Functional neuroimaging of working memory in schizophrenia: task performance as a moderating variable. Neuropsychology. 2006;20:497-510.
52. Brahmbhatt SB, Haut K, Csernansky JG, Barch DM. Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings. Schizophr Res. 2006;87(1-3):191-204.
53. Seidman LJ, Thermenos HW, Poldrack RA, et al. Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: an fMRI study of working memory. Schizophr Res. 2006; 85(1-3):58-72.
54. Karlsgodt KH, Glahn DC, van Erp TG, et al. The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects. Schizophr Res. 2007;89(1-3):191-197.
55. Keshavan MS, Diwadkar VA, Spencer SM, Harenski KA, Luna B, Sweeney JA. A preliminary functional magnetic resonance imaging study in offspring of schizophrenic parents. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(6): 1143-1149.
56. Callicott JH, Egan MF, Mattay VS, et al. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry. 2003;160:709-719.
57. Gevins AS, Cutillo BC. Neuroelectric evidence for distributed processing in human working memory. Electroencephalogr Clin Neurophysiol. 1993;87:128-143.
58. Sternberg S. High-speed scanning in human memory. Science. 1966;153:652-654.
59. Squire LR. Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem. 2004;82(3): 171-177.
60. Schacter DL, Wagner AD, Buckner RL. Memory systems of 1999. In: Tulving E, Craik FIM, eds. The Oxford Handbook of Memory. New York, NY: Oxford University Press; 2000:627-644.
61. Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology. 1998;12(3):426-445.
62. Titone D, Ditman T, Holzman PS, Eichenbaum H, Levy DL. Transitive inference in schizophrenia: impairments in relational memory organization. Schizophr Res. 2004; 68(2-3):235-247.
63. Ongur D, Cullen TJ, Wolf DH, et al. The neural basis of relational memory deficits in schizophrenia. Arch Gen Psychiatry. 2006;63(4):356-365.
64. Heckers S, Rauch SL, Goff D, et al. Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nat Neurosci. 1998;1(4):318-323.
65. Weiss AP, Zalesak M, DeWitt I, Goff D, Kunkel L, Heckers S. Impaired hippocampal function during the detection of novel words in schizophrenia. Biol Psychiatry. 2004; 55(7):668-675.
66. Weiss AP, Schacter DL, Goff DC, et al. Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia. Biol Psychiatry. 2003;53:48-55.
67. Barch DM, Csernansky J, Conturo T, Snyder AZ, Ollinger J. Working and long-term memory deficits in schizophrenia. Is there a common underlying prefrontal mechanism? J Abnorm Psychol. 2002;111:478-494.
68. Ragland JD, Gur RC, Valdez JN, et al. Levels-of-processing effect on frontotemporal function in schizophrenia during word encoding and recognition. Am J Psychiatry. 2005;162(10):1840-1848.
69. Ragland JD, Gur RC, Valdez J, et al. Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia. Am J Psychiatry. 2004;161:1004-1015.
70. Toulopoulou T, Morris RG, Rabe-Hesketh S, Murray RM. Selectivity of verbal memory deficit in schizophrenic patients and their relatives. Am J Med Genet B Neuropsychiatr Genet. 2003;116(1):1-7.
71. Toulopoulou T, Rabe-Hesketh S, King H, Murray RM, Morris RG. Episodic memory in schizophrenic patients and their relatives. Schizophr Res. 2003;63(3):261-271.
72. Whyte MC, Whalley HC, Simonotto E, et al. Event-related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia. Psychol Med. 2006;36(10):1427-1439.
73. Bonner-Jackson A, Csernansky JG, Barch DM. Levels-ofprocessing effects in first-degree relatives of individuals with schizophrenia. Biol Psychiatry. 2007;61(10):1141-1147.
74. Thermenos HW, Seidman LJ, Poldrack RA, et al. Elaborative verbal encoding and altered anterior parahippocampal activation in adolescents and young adults at genetic risk for schizophrenia using FMRI. Biol Psychiatry. 2007; 61(4):564-574.
75. Woodward ND, Tibbo P, Purdon SE. An fMRI investigation of procedural learning in unaffected siblings of individuals with schizophrenia. Schizophr Res. 2007;94(1-3): 306-316.
76. Kumari V, Gray JA, Honey GD, et al. Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation. Schizophr Res. 2002;57(1):97-107.
77. Scherer H, Stip E, Paquet F, Bedard MA. Mild procedural learning disturbances in neuroleptic-naive patients with schizophrenia. J Neuropsychiatry Clin Neurosci. 2003;15(1): 58-63.
78. Zedkova L, Woodward ND, Harding I, Tibbo PG, Purdon SE. Procedural learning in schizophrenia investigated with functional magnetic resonance imaging. Schizophr Res. 2006;88(1-3):198-207.
79. Purdon SE, Woodward N, Lindborg SR, Stip E. Procedural learning in schizophrenia after 6 months of double-blind treatment with olanzapine, risperidone, and haloperidol. Psychopharmacology (Berl). 2003;169(3-4):390-397.
80. Paquet F, Soucy JP, Stip E, Levesque M, Elie A, Bedard MA. Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia. J Neuropsychiatry Clin Neurosci. 2004;16(1):47-56.
81. Scherer H, Bedard MA, Stip E, et al. Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments. Cogn Behav Neurol. 2004;17(1):32-40.
82. Exner C, Boucsein K, Degner D, Irle E. State-dependent implicit learning deficit in schizophrenia: evidence from 20- month follow-up. Psychiatry Res. 2006;142(1):39-52.
83. Reiss JP, Campbell DW, Leslie WD, et al. Deficit in schizophrenia to recruit the striatum in implicit learning: a functional magnetic resonance imaging investigation. Schizophr Res. 2006;87(1-3):127-137.
84. Seidman LJ, Faraone SV, Goldstein JM, et al. Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Arch Gen Psychiatry. 2002;59(9):839-849.
85. Andreasen NC. The Scale for the Assessment of Negative Symptoms (SANS). Iowa City, IA: University of Iowa; 1983.
86. Gourovitch ML, Goldberg TE, Weinberger DR. Verbal fluency deficits in patients with schizophrenia: semantic fluency is differentially impaired as compared to phonologic fluency. Neuropsychology. 1996;10:573-577.
87. Melinder MR, Barch DM, Heydebrand G, Csernansky JG. Easier tasks can have better discriminating power: the case of verbal fluency. J Abnorm Psychol. 2005;114(3):385-391.
88. Melinder MR, Barch DM. The influence of a working memory load manipulation on language production in schizophrenia. Schizophr Bull. 2003;29(3):473-485.
89. Sommer IE, Ramsey NF, Mandl RC, van Oel CJ, Kahn RS. Language activation in monozygotic twins discordant for schizophrenia. Br J Psychiatry. 2004;184:128-135.
90. Weiss EM, Hofer A, Golaszewski S, Siedentopf C, Felber S, Fleischhacker WW. Language lateralization in unmedicated patients during an acute episode of schizophrenia: a functional MRI study. Psychiatry Res. 2006;146(2):185-190.
91. Sommer IE, Ramsey NF, Kahn RS. Language lateralization in schizophrenia, an fMRI study. Schizophr Res. 2001; 52(1-2):57-67.
92. Sommer IE, Ramsey NF, Mandl RC, Kahn RS. Language lateralization in female patients with schizophrenia: an fMRI study. Schizophr Res. 2003;60(2-3):183-190.
93. Weiss EM, Hofer A, Golaszewski S, et al. Brain activation patterns during a verbal fluency test-a functional MRI study in healthy volunteers and patients with schizophrenia. Schizophr Res. 2004;70(2-3):287-291.
94. Dollfus S, Razafimandimby A, Delamillieure P, et al. Atypical hemispheric specialization for language in right-handed schizophrenia patients. Biol Psychiatry. 2005;57(9): 1020-1028.
95. Spence SA, Liddle PF, Stefan MD, et al. Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Br J Psychiatry. 2000;176:52-60.
96. Li X, Branch CA, Bertisch HC, et al. An fMRI study of language processing in people at high genetic risk for schizophrenia. Schizophr Bull. 2007;91:62-72.
97. Whalley HC, Simonotto E, Flett S, et al. fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia. Brain. 2004;127(pt 3):478-490.
98. Davidson LL, Heinrichs RW. Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis. Psychiatry Res. 2003;122:69-87.
99. Fusar-Poli P, Perez J, Broome M, et al. Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2007;31: 465-484.
100. Callicott JH, Bertolino A, Mattay V, et al. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex. 2000;11: 1078-1092.
101. Manoach DS. Prefrontal cortex dysfunction during working memory in schizophrenia: reconciling discrepant findings. Schizophr Res. 2003;60:285-298.
102. Iacono WG. Control groups in schizophrenia research: a neglected source of variability. In: Cicchetti D, Grove WM, eds. Thinking Clearly About Psychology: Essays in Honor of Paul Everett Meehl. Minneapolis, MN: University of Minnesota Press; Vol 2 (1991) 430-450.
103. Andrews J, Wang L, Csernansky JG, Gado MH, Barch DM. Abnormalities of thalamic activation and cognition in schizophrenia. Am J Psychiatry. 2006;163(3): 463-469.
104. Heinrichs RW. The primacy of cognition in schizophrenia. Am Psychol. 2005;60(3):229-242.
105. Poldrack RA, Fletcher PC, Henson RN, Worsley KJ, Brett M, Nichols TE. Guidelines for reporting an fMRI study. NeuroImage. 2008;40(2):409-414.
106. Gazzaniga MS, Van Horn JD, Bloom F, Shepherd GM, Raichle M, Jones E. Continuing progress in neuroinformatics. Science. 2006;311:176.
107. Whalley H, Simonotto E, Moorhead W, et al. Functional imaging as a predictor of schizophrenia. Biol Psychiatry. 2006;60:454-462.
108. Glatt SJ, Stone WS, Faraone SV, Seidman LJ, Tsuang MT. Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia. Br J Psychiatry. 2006;189:337-345.
109. Faraone SV, Seidman LJ, Kremen WS, Toomey R, Pepple JR, Tsuang MT. Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading. Biol Psychiatry. 2000;48:120-126.
110. Glahn DC, Thompson PM, Blangero J. Neuroimaging endophenotypes: strategies for finding genes influencing brain structure and function. Hum Brain Mapp. 2007;28:488-501.
111. Windemuth A, Calhoun VD, Pearlson GD, Kocherla M, Jagannathan K, Ruano G. Physiogenomic analysis of localized fMRI brain activity in schizophrenia. Ann Biomed Eng. 2008;36(6):877-888.
112. Tan H-Y, Chen Q, Sust S, et al. Epistasis between catechol- O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function. Proc Natl Acad Sci U S A. 2007;104(30):12536- 12541.
113. Meyer-Lindenberg A, Nicodemus KK, Egan MF, Callicott JH, Mattay V, Weinberger DR. False positives in imaging genetics. NeuroImage. 2008;40(2):655-661.