AMI  Vol.3 No.4 , October 2013
Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory*
ABSTRACT

Background: There is emerging evidence that the increased susceptibility to developing alcohol and substance use dis- orders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Methods: Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results: High-risk subjects showed poorer Working Memory functioning. Caudate volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Conclusions: Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.


Cite this paper
S. Y. Hill, S. Lichenstein, S. Wang, H. Carter and M. McDermott, "Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory*," Advances in Molecular Imaging, Vol. 3 No. 4, 2013, pp. 43-54. doi: 10.4236/ami.2013.34007.
References
[1]   P. A. Woicik, C. Urban, N. Alla-Klein, A. Henry, T. Maloney, et al., “A Pattern of Perseveration in Cocaine Ad- diction May Reveal Neurocognitive Processes Implicit in the Wisconsin Card Sorting Test,” Neuropsychologia, Vol. 49, No. 7, 2011, pp. 1660-1669. http://dx.doi.org/10.1016/j.neuropsychologia.2011.02.037

[2]   M. Haruno, T. Kuorda, K. Doya, K. Toyama, M. Kimura, et al., “A Neural Correlate of Reward-Based Behavioral Learning in Caudate Nucleus: A Functional Magnetic Resonance Imaging Study of Stochastic Decision Task,” The Journal of Neuroscience, Vol. 24, No. 7, 2004, pp. 1660-1665. http://dx.doi.org/10.1523/JNEUROSCI.3417-03.2004

[3]   C. A. Seger, and C. M. Cincotta, “The Roles of the Caudate Nucleus in Human Classification Learning,” The Journal of Neuroscience, Vol. 25, No. 11, 2005, pp. 2941- 2951. http://dx.doi.org/10.1523/JNEUROSCI.3401-04.2005

[4]   N. Carrey, D. Bernier, M. Emms, E. Gunde, S. Sparkes, et al., “Smaller Volumes of Caudate Nuclei in Prepubertal Children with ADHD: Impact of Age,” Journal of Psy- chiatric Research, Vol. 46, No. 8, 2012, pp. 1066-1072. http://dx.doi.org/10.1016/j.jpsychires.2012.04.025

[5]   E. M. Valera, S. V. Faraone, K. E. Murray, L. J. Seidman, “Meta-Analysis of Structural Imaging Findings in Attention-Deficit/Hyperactivity Disorder,” Biological Psychia- try, Vol. 61, No.12, 2007, pp. 1361-1369. http://dx.doi.org/10.1016/j.biopsych.2006.06.011

[6]   A. Qiu, D. Crocetti, M. Adler, E. M. Mahone, M. B. Den- ckla, et al., “Basal Ganglia Volume and Shape in Children with Attention Deficit Hyperactivity Disorder,” The American Journal of Psychiatry, Vol. 166, No. 1, 2009, pp. 74-82. http://dx.doi.org/10.1176/appi.ajp.2008.08030426

[7]   E. C. Finger, A. A. Marsh, D. G. Mitchell, M. E. Reid, C. Sims, et al., “Abnormal Ventromedial Prefrontal Cortex Function in Children with Psychopathic Traits During Re- versal Learning,” Archives of General Psychiatry, Vol. 65, No. 5, 2008, pp. 586-594. http://dx.doi.org/10.1001/archpsyc.65.5.586

[8]   K. Rubia, R. Halari, A. B. Smith, M. Mohammed, S. Scott, et al., “Dissociated Functional Brain Abnormalities of Inhibition in Boys with Pure Conduct Disorder and Boys with Pure Attention Deficit Hyperactivity Disorder,” The American Journal of Psychiatry, Vol. 165, No. 7, 2008, pp. 889-897. http://dx.doi.org/10.1176/appi.ajp.2008.07071084

[9]   S. Y. Hill, S. Shen, L. Lowers, J. Locke-Wellman, A. G. Matthews and M. McDermott, “Psychopathology in Offspring from Multiplex Alcohol Dependence Families With and Without Parental Alcohol Dependence: A Prospective Study During Childhood and Adolescence,” Psy- chiatry Research, Vol. 160, No. 2, 2008, pp. 155-166. http://dx.doi.org/10.1016/j.psychres.2008.04.017

[10]   S. Y. Hill, K. D. Tessner and M. D. McDermott, “Psy- chopathology in Offspring from Families of Alcohol Dependent Female Probands: A Prospective Study,” Journal of Psychiatric Research, Vol. 45, No. 3, 2011, pp. 285-294. http://dx.doi.org/10.1016/j.jpsychires.2010.08.005

[11]   W. S. Slutske, A. C. Heath, S. H. Dinwiddie, P. A. F. Ma- dden, K. K. Bucholz, et al., “Common Genetic Risk Factors for Conduct Disorder and Alcohol Dependence,” Journal of Abnormal Psychology, Vol. 107, No. 3, 1998, pp. 363-374. http://dx.doi.org/10.1037/0021-843X.107.3.363

[12]   R. M. Kessler, W. O. Whetsell, S. Ansari, J. R. Votaw, T. de Paulis, et al., “Identification of Extrastriatal Dopamine D2 Receptors in Post Mortem Human Brain with [125] Epidepride,” Brain Research, Vol. 609, No. 1-2, 1993, pp. 237-243. http://dx.doi.org/10.1016/0006-8993(93)90878-Q

[13]   J.-C. Dreher, P. Kohn, B. Kolachana, D. R. Weinberger and K. F. Berman, “Variation in Dopamine Genes Influence Responsivity of the Human Reward System,” Pro- ceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 2, 2009. pp. 617- 622. http://dx.doi.org/10.1073/pnas.0805517106

[14]   G. D. Chiara and V. Bassareo, “Reward Systems and Addiction: What Dopamine Does and Doesn’t Do,” Current Opinion in Pharmacology, Vol. 7, No. 1, 2007, pp. 69-76. http://dx.doi.org/10.1016/j.coph.2006.11.003

[15]   N. D. Volkow, J. S. Fowler, G. J. Wang, R. Hitzemann, J. Logan, et al., “Decreased Dopamine D2 Receptor Availability is Associated with Reduced Frontal Metabolism in Cocaine Abusers,” Synapse, Vol. 14 No. 2, 1993, pp. 169-177. http://dx.doi.org/10.1002/syn.890140210

[16]   N. D. Volkow, G. J. Wang, J. S. Fowler, J. Logan, S. J. Gatley, et al., “Decreased Striatal Dopaminergic Respon- siveness in Detoxified Cocaine-Dependent Subjects,” Nature, Vol. 386, No. 6627, 1997, pp. 830-833. http://dx.doi.org/10.1038/386830a0

[17]   N. D. Volkow, G. J. Wang, L. Maynard, J. S. Fowler, B. Jayne, et al., “Effects of Alcohol Detoxification on Dopamine D2 Receptors in Alcoholics: A Preliminary Study,” Psychiatry Research: Neuroimaging, Vol. 116, No. 3, 2002, pp. 163-172. http://dx.doi.org/10.1016/S0925-4927(02)00087-2

[18]   N. D. Volkow, G. J. Wang, H. Begleiter, B. Porjesz, J. S. Fowler, et al., “High Levels of Dopamine D2 Receptors in Unaffected Members of Alcoholic Families: Possible Protective Factors,” Archives of General Psychiatry, Vol. 63, No. 9, 2006, pp. 999-1008. http://dx.doi.org/10.1001/archpsyc.63.9.999

[19]   E. Tupala, H. Hall, K. Bergstrom, T. Mantere, P. Rasanen, et al., “Dopamine D2 Receptors and Transporters in Type 1 and 2 Alcoholics Measured with Human Whole Hemi- sphere Autoradiography,” Human Brain Mapping, Vol. 20, No. 2, 2003, pp. 91-102. http://dx.doi.org/10.1002/hbm.10129?

[20]   E. Tupala, H. Hall, K. Bergstrom, T. Mantere, P. Rasanen, et al., “Different Effect of Age on Dopamine Transporters in the Dorsal and Ventral Striatum of Controls and Alco- holics,” Synapse, Vol. 48, No. 4, 2003, pp. 205-211. http://dx.doi.org/10.1002/syn.10206?

[21]   R. M. Weinshilboum, D. M. Otterness, C. L. Szumlanski, “Methylation Pharmacogenetics: Catechol O-Methyltransferase, Thiopurine Methyltransferase, and Histamine N- Methyltransferase,” Annual Review of Pharmacology and Toxicology, Vol. 39, 1999, pp. 19-52. http://dx.doi.org/10.1146/annurev.pharmtox.39.1.19

[22]   J. Chen, B. K. Lipska, N. Halim, Q. D. Ma, M. Matsu- moto, et al., “Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme Activity in Postmortem Human Brain,” American Journal of Human Genetics, Vol. 75, No. 5, 2004, pp. 807-821. http://dx.doi.org/10.1086/425589

[23]   X. Caldu, P. Vandrell, D. Bartres-Faz, I. Clemente, N. Bargallo, et al., “Impact of the COMT Val 108/158 Met and DAT Genotypes on Prefrontal Function in Healthy Subjects,” NeuroImage, Vol. 37, No. 4, 2007, pp. 1437- 1444. http://dx.doi.org/10.1016/j.neuroimage.2007.06.021

[24]   A. Diamond, “Consequences of Variation in Genes That Affect Dopamine in Prefrontal Cortex,” Cerebral Cortex, Vol. 17, No.1, 2007, pp. i161-i170. http://dx.doi.org/10.1093/cercor/bhm082

[25]   M. J. Kreek, D. A. Nielsen, K. S. LaForge, “Genes Associated with Addiction: Alcoholism, Opiate, and Cocaine Addiction,” Neuromolecular Medicine, Vol. 5, No. 1, 2004, pp. 85-108. http://dx.doi.org/10.1385/NMM:5:1:085

[26]   D. J. Vandenbergh, L. A. Rodriguez, I. T. Miller, G. R. Uhl and H. M. Lachman, “High-Activity Catechol-O- Methyltransferase Allele Is More Prevalent in Polysubstance Abusers,” American Journal of Medical Genetics, Vol. 74, No. 4, 1997, pp. 439-442. http://dx.doi.org/10.1002/(SICI)1096-8628(19970725)74:4<439::AID-AJMG16>3.0.CO;2-J

[27]   R. Horowitz, M. Kotler, E. Shufman, S. Aharoni, I. Kremer, et al., “Confirmation of an Excess of the High Enzyme Activity COMT val Allele in Heroin Addicts in a Family-Based Haplotype Relative Risk Study,” American Journal of Medical Genetics, Vol. 96, No. 5, 2000, pp. 599-603. http://dx.doi.org/10.1002/1096-8628(20001009)96:5<599::AID-AJMG4>3.0.CO;2-O

[28]   M. J. Kreek, G. Bart, C. Lilly, K. S. LaForge and D. A. Nielsen, “Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments,” Pharmacological Reviews, Vol. 57, No. 1, 2005, pp. 1-26. http://dx.doi.org/10.1124/pr.57.1.1

[29]   M. J. Kreek, D. A. Nielsen, E. R. Butelman and K. S. LaForge, “Genetic Influences on Impulsivity, Risk Taking, Stress Responsivity and Vulnerability to Drug Abuse and Addiction,” Nature Neuroscience, Vol. 8, No. 11, 2005, pp. 1450-1457. http://dx.doi.org/10.1038/nn1583

[30]   S. Y. Hill, E. K. Hoffman, N. Zezza, A. Thalamuthu, D. E. Weeks, et al., “Dopaminergic Mutations: Within-Family Association and Linkage in Multiplex Alcohol Dependence Families” American Journal of Medical Genetics Part B Neuropsychiatry Genetics, Vol. 147, No. 4, 2008. pp. 517-526. http://dx.doi.org/10.1002/ajmg.b.30630

[31]   M. D. Lezak, D. B. Howieson, E. D. Bigler and D. Tranel, “Neuropsychological Assessment,” 5th Edition, Oxford University Press, New York, 2012.

[32]   S. A. Brown, S. F. Tapert, E. Granholm and D. C. Delis, “Neurocognitive Functioning of Adolescents: Effects of Protracted Alcohol Use,” Alcohol: Clinical and Experimental Research, Vol. 24, No. 2, 2000, pp. 164-171. http://dx.doi.org/10.1111/j.1530-0277.2000.tb04586.x

[33]   P. R. Giancola and H. B. Moss, “Executive Cognitive Functioning in Alcohol Use Disorders,” In: M. Galanter Ed., Recent Developments in Alcoholism, Vol. 14: The Consequences of Alcoholism, Plenum Press, New York, 1998, pp. 227-251. http://dx.doi.org/10.1007/0-306-47148-5_10

[34]   S. F. Tapert and S. A. Brown, “Substance Dependence, Family History of Alcohol Dependence and Neuropsy- chological Functioning in Adolescence,” Addiction, Vol. 95, No. 7, 2000, pp. 1043-1053. http://dx.doi.org/10.1046/j.1360-0443.2000.95710436.x

[35]   J. T. Nigg, E. Poon, H. E. Fitzgerald, J. M. Glass, M. M. Wong, et al., “Neuropsychological Executive Functioning in Children at Elevated Risk for Alcoholism: Findings in Early Adolescence,” Journal of Abnormal Psychology, Vol. 113, No. 2, 2004, pp. 302-314. http://dx.doi.org/10.1037/0021-843X.113.2.302

[36]   K. D. Tessner and S. Y. Hill, “Neural Circuitry Associated with Risk for Alcohol Use Disorders,” Neuro- psychology Review, Vol. 20, No. 1, 2010, pp. 1-20. http://dx.doi.org/10.1007/s11065-009-9111-4

[37]   H. A. Wishart, R. M. Roth, A. J. Saykin, C. H. Rhodes, G. J. Tsongalis, et al., “COMT Val158Met Genotype and Individual Difference in Executive Function in Healthy Adults,” Journal of the International Neuropsychological Society, Vol. 17, No. 1, 2011, pp. 174-180. http://dx.doi.org/10.1017/S1355617710001402

[38]   H. Xu, C. B. Kellendonk, E. H. Simpson, J. G. Keilp, G. E. Bruder, et al., “DRD2 C957T Polymorphism Interacts with the COMT Val158Met Polymorphism in Human Working Memory,” Schizophrenia Research, Vol. 90, No. 1-3, 2007, pp. 104-107. http://dx.doi.org/10.1016/j.schres.2006.10.001

[39]   M. F. Gosso, E. J. C. deGeus, T. J. C. Polderman, D. I. Boomsma, P. Heutink and D. Posthuma, “Catechol O-Methyl Transferase and Dopamine D2 Receptor Gene Polymorphisms: Evidence of Positive Heterosis and Gene-Gene Interaction on Working Memory Functioning,” European Journal of Human Genetics, Vol. 16, No. 9, 2008, pp. 1075-1082. http://dx.doi.org/10.1038/ejhg.2008.57

[40]   C. Stelzel, U. Basten, C. Montag, M. Reuter and C. J. Fiebach, “Effects of Dopamine-Related Gene-Gene Interactions on Working Memory Component Processes,” The European Journal of Neuroscience, Vol. 29, No. 5, 2009 pp. 1056-1063. http://dx.doi.org/10.1111/j.1460-9568.2009.06647.x

[41]   J. Zinkstok, N. Schmitz, T. van Amelsvoort, M. de Win, W. van den Brink, et al., “The COMT Val158 Met Polymorphism and Brain Morphometry in Healthy Young Adults,” Neuroscience Letters, Vol. 405, No. 1-2, 2006, pp. 34-39. http://dx.doi.org/10.1016/j.neulet.2006.06.034

[42]   W. D. Taylor, S. Züchner, M. E. Payne, D. F. Messer, T. J. Doty, et al., “The COMT Val158Met Polymorphism and Temporal Lobe Morphometry in Healthy Adults,” Psy- chiatry Research Neuroimaging, Vol. 155, No. 2, 2007, pp. 173-177. http://dx.doi.org/10.1016/j.pscychresns.2007.01.005

[43]   D. Bartres-Faz, C. Junque, J. M. Serra-Grabulosa, A. Lopez-Alomar, A. Moya, et al., “Dopamine DRD2 Taq1 Polymorphism Associates with Caudate Nucleus Volume and Cognitive Performance in Memory Impaired Subjects,” Neuroreport, Vol. 13, No. 9, 2002, pp. 1121-1125. http://dx.doi.org/10.1097/00001756-200207020-00010

[44]   G. T. Voelbel, M. E. Bates, J. F. Buckman, G. Pandina and R. L. Hendren, “Caudate Nucleus Volume and Cognitive Performance: Are They Related to Childhood Psychopathology? Biological Psychiatry, Vol. 60, No. 9, 2006, pp. 942-950. http://dx.doi.org/10.1016/j.biopsych.2006.03.071

[45]   W. J. Chambers, J. Puig-Antich, M. Hirsch, P. Paez, P. Ambrosini, et al., “The Assessment of Affective Disorders in Children and Adolescents by Semi-Structured In- terview,” Archives of General Psychiatry, Vol. 42, No. 7, 1985, pp. 696-702. http://dx.doi.org/10.1001/archpsyc.1985.01790300064008

[46]   S. Y. Hill, J. Locke, L. Lowers and J. Connolly, “Psychopathology and Achievement in Children at High Risk for Developing Alcoholism,” Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 38, No. 7, 1999, pp. 883-891. http://dx.doi.org/10.1097/00004583-199907000-00019

[47]   L. N. Robins, J. Wing, H. U. Wittchen, J. E. Helzer, T. F. Babor, et al., “The Composite International Diagnostic Interview. An Epidemiological Instrument Suitable for use in Conjunction with Different Diagnostic Systems and in Different Cultures,” Archives of General Psychiatry, Vol. 45, No. 12, 1988, pp. 1069-1077. http://dx.doi.org/10.1001/archpsyc.1988.01800360017003

[48]   L. B. Cottler, L. E. Robins and J. E. Helzer, “The Reliability of the CIDI-SAM: A Comprehensive Substance Abuse Interview,” British Journal of Addiction, Vol. 84, No. 7, 1989, pp. 801-814. http://dx.doi.org/10.1111/j.1360-0443.1989.tb03060.x

[49]   V. A. Magnotta, G. Harris, N. C. Andreason, D. S. O’Leary, W. T. C. Yuh and D. Heckel, “Structural MR Image Processing Using BRAINS2 Toolbox,” Compute- rized Medical Imaging and Graphics, Vol. 26, No. 4, 2002, pp. 251-264. http://dx.doi.org/10.1016/S0895-6111(02)00011-3

[50]   W. S. Tae, S. S. Kim, K. U. Lee, E. C. Nam and K. W. Kim, “Validation of Hippocampal Volumes Measures Using a Manual Method and Two Automated Methods (FreeSurfer and IBASPM) in Chronic Major Depressive Disorder,” Neuroradiology, Vol. 50, No. 7, 2008, pp. 569-581. http://dx.doi.org/10.1007/s00234-008-0383-9

[51]   J. C. Looi, O. Lindberg, B. Liberg, V. Tatham, R. Kumar, et al., “Volumetrics of the Caudate Nucleus: Reliability and Validity of a New Manual Tracing Protocol,” Psychiatry Research, Vol. 163, No. 3, 2008, pp. 279-288. http://dx.doi.org/10.1016/j.pscychresns.2007.07.005

[52]   R. M. Reitan and D. Wolfson, “The Halstead-Reitan Neuropsychological Test Battery: Theory and Clinical Interpretation,” Neuropsychology Press, Tucson, 1985.

[53]   R. M. Reitan and D. Wolfson, “Neuropsychological Evaluation of Young Children. Manual for the Administration and Scoring of the Reitan-Indiana Neuropsychological Test Battery,” Neuropsychology Press, Tucson, 1990.

[54]   R. M. Reitan, “Trail Making Test Results for Normal and Brain-Damaged Children,” Perceptual and Motor Skills, Vol. 33, No. 2, 1971, pp. 575-581. http://dx.doi.org/10.2466/pms.1971.33.2.575

[55]   T. N. Tombaugh, “Trail Making Test A and B: Normative Data Stratified by Age and Education,” Archives of Clinical Neuropsychology, Vol. 19 No. 2, 2004, pp. 203-214. http://dx.doi.org/10.1016/S0887-6177(03)00039-8

[56]   I. Sánchez-Cubillo, J. A. Periá?ez, D. Adrover-Roig, J. M. Rodríguez-Sánchez, M. Ríos-Lago, et al., “Construct Validity of the Trail Making Test: Role of Task-Switching, Working Memory, Inhibition/Interference Control, and Visuomotor Abilities,” Journal of the International Neuro- psychological Society, Vol. 15 No. 3, 2009, pp. 438-450. http://dx.doi.org/10.1017/S1355617709090626

[57]   C. J. Golden, “Stroop Color and Word Test: A Manual for Clinical and Experimental Uses,” Stoelting Co., Chicago, 1978.

[58]   The Psychological Corporation, “WAIS-III/WMS-III Updated Technical Manual,” San Antonio, 2002.

[59]   L. K. Jacobsen, K. R. Pugh, W. E. Menel and J. Gelernter, “C957T Polymorphism of the Dopamine D2 Receptor Gene Modulates the Effect of Nicotine on Working Memory Performance and Cortical Processing Efficiency,” Psychopharmacology, Vol. 188, No. 4, 2006, pp. 530-540. http://dx.doi.org/10.1007/s00213-006-0469-1

[60]   E. V. Sullivan, A. Deshmukh, E. De Rosa, M. J. Rosenbloom and A. Pfefferbaum, “Striatal and Forebrain Nuclei Volumes: Contribution to Motor Function and Working Memory Deficits in Alcoholism,” Biological Psychiatry, Vol. 57, No. 7, 2005, pp. 768-776. http://dx.doi.org/10.1016/j.biopsych.2004.12.012

[61]   F. X. Castellanos, J. N. Giedd, P. Eckburg, W. L. Marsh, A. C. Vaituzis, et al., “Quantitative Morphology of the Caudate Nucleus in Attention Deficit Hyperactivity Dis- order,” American Journal of Psychiatry, Vol. 151, No. 12, 1994, pp. 1791-1796.

[62]   F. X. Castellanos, P. P. Lee, W. Sharp, N. O. Jeffries, D. K. Greenstein, et al., “Developmental Trajectories of Brain Volume Abnormalities in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder,” The Journal of the American Medical Association, Vol. 288, No. 14, 2001, pp. 1740-1748. http://dx.doi.org/10.1001/jama.288.14.1740

[63]   A. Cubillo, R. Halari, A. Smith, E. Taylor and K. Rubia, “A Review of Fronto-Striatal and Fronto-Cortical Brain Abnormalities in Children and Adults with Attention Deficit Hyperactivity Disorder (ADHD) and New Evidence for Dysfunction in Adults with ADHD During Motivation and Attention,” Cortex, Vol. 48, No. 2, 2012, pp. 194- 215. http://dx.doi.org/10.1016/j.cortex.2011.04.007

[64]   J. H. Barnett, P. B. Jones, T. W. Robbins and U. Miller, “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,” Molecular Psychiatry, Vol. 12, No. 5, 2007, pp. 502-509. http://dx.doi.org/10.1038/sj.mp.4001973

[65]   M. M. Hirvonen, L. Ville, J. Hirvonen, U. Personen, K. Nagren, et al., “C957T Polymorphism of the Human Dopamine D2 Receptor Gene Predicts Extrastriatal Dopamine Receptor Availability in Vivo,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 33, No. 4, 2009, pp. 630-636. http://dx.doi.org/10.1016/j.pnpbp.2009.02.021

[66]   C. D. Swagell, B. R. Lawford, I. P. Hughes, J. Voisey, G. F. Feeney, et al., “DRD2 C957T and Taq1A Genotyping Reveals Gender Effects and Unique Low-Risk and High-Risk Genotypes in Alcohol Dependence,” Alcohol and Alcoholism, Vol. 47, No. 4, 2012, pp. 397-403. http://dx.doi.org/10.1093/alcalc/ags047

[67]   H. A. Flynn, S. Marcus, K. L. Barry and F. C. Blow, “Rates and Correlates of Alcohol Use among Pregnant Women in Obstetrics Clinics,” Alcohol: Clinical and Experimental Research, Vol. 27, No. 1, 2003, pp. 81-87. http://dx.doi.org/10.1111/j.1530-0277.2003.tb02725.x

[68]   A. B. Hollingshead, “Four Factor Index of Social Status,” Yale University, New Haven, 1975.

[69]   L. M. Dunn and L. M. Dunn, “Peabody Picture Vocabulary Test,” 3rd Edition, American Guidance Service, Circle Pines, 1997.

 
 
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