How Acute and Chronic Alcohol Consumption Affects Brain Networks: Insights from Multimodal Neuroimaging

Alcoholism: Clinical and Experimental Research

Volumn 36, Issue 12, 2012, Pages 2017-2027

  Schulte, Tilman ^a   Oberlin, Brandon G ^b   Kareken, David A ^b   Marinkovic, Ksenija ^c   Müller Oehring, Eva M ^a,d   Meyerhoff, Dieter J ^e,f   Tapert, Susan ^g  

^a SRI INTERNATIONAL   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f VETERANS AFFAIRS MEDICAL CENTER   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Acute and Chronic Alcohol; Multimodal Neuroimaging

Indexed keywords

ALCOHOL; COCAINE; DOPAMINE; DOPAMINE 3 RECEPTOR; NICOTINE; RACLOPRIDE C 11;

ALCOHOL BLOOD LEVEL; ALCOHOL CONSUMPTION; ALCOHOLISM; ANTERIOR CINGULATE; ARTICLE; AUTOREGULATION; BOLD SIGNAL; BRAIN SIZE; COGNITION; CORONA RADIATA (BRAIN); CORPUS STRIATUM; DIFFUSION TENSOR IMAGING; DOPAMINE RELEASE; DOPAMINERGIC TRANSMISSION; DRINKING BEHAVIOR; EMOTION; EXECUTIVE FUNCTION; FUNCTIONAL MAGNETIC RESONANCE IMAGING; FUNCTIONAL NEUROIMAGING; GRAY MATTER; HUMAN; INSULA; LEARNING; LIMBIC SYSTEM; MAGNETOENCEPHALOGRAPHY; MESENCEPHALON; MOTOR CORTEX; NEOCORTEX; NERVE CELL NETWORK; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; ORBITAL CORTEX; POSITRON EMISSION TOMOGRAPHY; PREFRONTAL CORTEX; PRIORITY JOURNAL; REWARD; SCINTIGRAPHY; SELF REPORT; SPINAL CORD; SPORTS DRINK; TOBACCO DEPENDENCE; TRANSCRANIAL MAGNETIC STIMULATION; WHITE MATTER;

ALCOHOLISM; BRAIN; DIFFUSION TENSOR IMAGING; ETHANOL; HUMANS; MAGNETIC RESONANCE IMAGING; MAGNETIC RESONANCE SPECTROSCOPY; MAGNETOENCEPHALOGRAPHY; NEUROIMAGING; POSITRON-EMISSION TOMOGRAPHY;

EID: 84870904242     PISSN: 01456008     EISSN: 15300277     Source Type: Journal    
DOI: 10.1111/j.1530-0277.2012.01831.x     Document Type: Article

References (92)

1. Andrew C, Fein G (2010) Event-related oscillations versus event-related potentials in a P300 task as biomarkers for alcoholism. Alcohol Clin Exp Res 34:669-680.
2. Andrews-Hanna JR, Reidler JS, Sepulcre J, Poulin R, Buckner RL (2010) Functional-anatomic fractionation of the brain's default network. Neuron 25:550-562.
3. Anton RF, Litten RZ, Falk DE, Palumbo JM, Bartus RT, Robinson RL, Kranzler HR, Kosten TR, Meyer RE, O'Brien CP, Mann K, Meulien D (2012) The Alcohol Clinical Trials Initiative (ACTIVE): purpose and goals for assessing important and salient issues for medications development in alcohol use disorders. Neuropsychopharmacology 37:402-411.
4. Bédard P, Sanes JN (2009) On a basal ganglia role in learning and rehearsing visual-motor associations. Neuroimage 47:1701-1710.
5. Berridge KC (2007) The debate over dopamine's role in reward: the case for incentive salience [review]. Psychopharmacology 191:391-431.
6. Bickel WK, Yi R, Landes RD, Hill PF, Baxter C (2011) Remember the future: working memory training decreases delay discounting among stimulant addicts. Biol Psychiatry 69:260-265.
7. Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, Tremblay RE, Dagher A (2003) Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49:226-231.
8. Botvinick MM (2007) Conflict monitoring and decision making: reconciling two perspectives on anterior cingulate function. Cogn Affect Behav Neurosci 7:356-366.
9. Bowirrat A, Oscar-Berman M (2005) Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome. Am J Med Genet B Neuropsychiatr Genet 132B:29-37.
10. Bragulat V, Dzemidzic M, Talavage T, Davidson D, O'Connor SJ, Kareken DA (2008) Alcohol sensitizes cerebral responses to the odors of alcoholic drinks: an fMRI study. Alcohol Clin Exp Res 32:1124-1134.
11. Buckholtz JW, Treadway MT, Cowan RL, Woodward ND, Benning SD, Li R, Ansari MS, Baldwin RM, Schwartzman AN, Shelby ES, Smith CE, Cole D, Kessler RM, Zald DH (2010) Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci 13:419-421.
12. Bühler M, Mann K (2011) Alcohol and the human brain: a systematic review of different neuroimaging methods. Alcohol Clin Exp Res 35:1771-1793.
13. Buxton RB (2002) Introduction to Functional Magnetic Resonance Imaging. Cambridge University Press, New York, NY.
14. Cardenas VA, Durazzo TC, Gazdzinski S, Mon A, Studholme C, Meyerhoff DJ (2011) Brain morphology at entry into treatment for alcohol dependence is related to relapse propensity. Biol Psychiatry 70:561-567.
15. Chanraud S, Pitel AL, Pfefferbaum A, Sullivan EV (2011) Disruption of functional connectivity of the default-mode network in alcoholism. Cereb Cortex 21:2272-2281.
16. Chanraud S, Reynaud M, Wessa M, Penttilä J, Kostogianni N, Cachia A, Artiges E, Delain F, Perrin M, Aubin HJ, Cointepas Y, Martelli C, Martinot JL (2009) Diffusion tensor tractography in mesencephalic bundles: relation to mental flexibility in detoxified alcohol-dependent subjects. Neuropsychopharmacology 34:1223-1232.
17. Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis: segmentation and surface reconstruction. Neuroimage 9:179-194.
18. Dale AM, Liu AK, Fischl BR, Buckner RL, Belliveau JW, Lewine JD, Halgren E (2000) Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity. Neuron 26:55-67.
19. Damoiseaux JS, Greicius MD (2009) Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity. Brain Struct Funct. 213:525-533.
20. De Ridder D, Vanneste S, Kovacs S, Sunaert S, Dom G (2011) Transient alcohol craving suppression by rTMS of dorsal anterior cingulate: an fMRI and LORETA EEG study. Neurosci Lett 496:5-10.
21. Devinsky O, Morrell MJ, Vogt BA (1995) Contributions of anterior cingulate cortex to behaviour. Brain 118:279-306.
22. Doyon WM, Anders SK, Ramachandra VS, Czachowski CL, Gonzales RA (2005) Effect of operant self-administration of 10% ethanol plus 10% sucrose on dopamine and ethanol concentrations in the nucleus accumbens. J Neurochem 93:1469-1481.
23. Durazzo TC, Fryer SL, Rothlind JC, Vertinski M, Gazdzinski S, Mon A, Meyerhoff DJ (2010) Measures of learning, memory and processing speed accurately predict smoking status in short-term abstinent treatment-seeking alcohol-dependent individuals. Alcohol Alcohol 45:507-513.
24. Durazzo TC, Mon A, Gazdzinski S, Meyerhoff DJ (in press) Chronic cigarette smoking in alcohol dependence: associations with cortical thickness and N-acetylaspartate levels in the extended brain reward system. Addict Biol doi: 10.1111/j.1369-1600.2011.00407.x [Epub ahead of print].
25. Durazzo TC, Rothlind JC, Gazdzinski S, Meyerhoff DJ (2008) The relationships of sociodemographic factors, medical, psychiatric, and substance-misuse co-morbidities to neurocognition in short-term abstinent alcohol-dependent individuals. Alcohol 42:439-449.
26. Durazzo TC, Tosun D, Buckley S, Gazdzinski S, Mon A, Fryer SL, Meyerhoff DJ (2011) Cortical thickness, surface area, and volume of the brain reward system in alcohol dependence: relationships to relapse and extended abstinence. Alcohol Clin Exp Res 35:1187-1200.
27. Düzel E, Bunzeck N, Guitart-Masip M, Wittmann B, Schott BH, Tobler PN (2009) Functional imaging of the human dopaminergic midbrain. Trends Neurosci 32:321-328.
28. Dypvik A, Bland B (2004) Functional connectivity between the red nucleus and the hippocampus supports the role of the hippocampal formation in sensorimotor integration. J Neuropsychol 92:2040-2050.
29. Esposito F, Pignataro G, Di Renzo G, Spinali A, Paccone A, Tedeschi G, Annunziato L (2010) Alcohol increases spontaneous BOLD signal fluctuations in the visual network. Neuroimage 53:534-543.
30. Field M, Wiers RW, Christiansen P, Fillmore MT, Verster JC (2010) Acute alcohol effects on inhibitory control and implicit cognition: implications for loss of control over drinking. Alcohol Clin Exp Res 34:1346-1352.
31. Filbey FM, Claus E, Audette AR, Niculescu M, Banich MT, Tanabe J, Du YP, Hutchison KE (2008) Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry. Neuropsychopharmacology 33:1391-1401.
32. Galvan A, Hare TA, Davidson M, Spicer J, Glover G, Casey BJ (2005) The role of ventral frontostriatal circuitry in reward-based learning in humans. J Neurosci 25:8650-8656.
33. Glimcher PW (2011) Understanding dopamine and reinforcement learning: the dopamine reward prediction error hypothesis. Proc Natl Acad Sci USA 108:15647-15654.
34. Greicius MD, Supekar K, Menon V, Dougherty RF (2009) Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex 19:72-78.
35. Gundersen H, Gruner R, Specht K, Hugdahl K (2008) The effects of alcohol intoxication on neuronal activation at different levels of cognitive load. Open Neuroimag J 2:65-72.
36. Haber SN, Kim KS, Mailly P, Calzavara R (2006) Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci 26:8368-8376.
37. Haber SN, Knutson B (2010) The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35:4-26.
38. Hämäläinen M, Hari R, Ilmoniemi RJ, Knuutila J, Lounasmaa OV (1993) Magnetoencephalography-theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev Mod Phys 65:413-497.
39. Harris GJ, Jaffin SK, Hodge SM, Kennedy D, Caviness VS, Marinkovic K, Papadimitriou GM, Makris N, Oscar-Berman M (2008) Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism. Alcohol Clin Exp Res 32:1001-1013.
40. Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Grusser SM, Flor H, Braus DF, Buchholz HG, Grunder G, Schreckenberger M, Smolka MN, Rosch F, Mann K, Bartenstein P (2004) Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 161:1783-1789.
41. Ihssen N, Cox WM, Wiggett A, Fadardi JS, Linden DE (2011) Differentiating heavy from light drinkers by neural responses to visual alcohol cues and other motivational stimuli. Cereb Cortex 21:1408-1415.
42. Kahkonen S (2005) MEG and TMS combined with EEG for mapping alcohol effects. Alcohol 37:129-133.
43. Karch S, Jager L, Karamatskos E, Graz C, Stammel A, Flatz W, Lutz J, Holtschmidt-Taschner B, Genius J, Leicht G, Pogarell O, Born C, Moller HJ, Hegerl U, Reiser M, Soyka M, Mulert C (2008) Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses. J Psychiatr Res 42:734-745.
44. Kareken DA, Bragulat V, Dzemidzic M, Cox C, Talavage T, Davidson D, O'Connor SJ (2010a) Family history of alcoholism mediates the frontal response to alcoholic drink odors and alcohol in at-risk drinkers. Neuroimage 50:267-276.
45. Kareken DA, Claus ED, Sabri M, Dzemidzic M, Kosobud AE, Radnovich AJ, Hector D, Ramchandani VA, O'Connor SJ, Lowe M, Li TK (2004) Alcohol-related olfactory cues activate the nucleus accumbens and ventral tegmental area in high-risk drinkers: preliminary findings. Alcohol Clin Exp Res 28:550-557.
46. Kareken DA, Grahame N, Dzemidzic M, Walker MJ, Lehigh CA, O'Connor SJ (2012) fMRI of the brain's response to stimuli experimentally paired with alcohol intoxication. Psychopharmacology 220:787-797.
47. Kareken DA, Liang T, Wetherill L, Dzemidzic M, Bragulat V, Cox C, Talavage T, O'Connor SJ, Foroud T (2010b) A polymorphism in GABRA2 is associated with the medial frontal response to alcohol cues in an fMRI study. Alcohol Clin Exp Res 34:2169-2178.
48. Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35:217-238.
49. Kovacevic S, Azma S, Sherfey J, Sheldon S, Irimia A, Halgren E, Marinkovic K (2011) Alcohol modulates oscillatory activity during cognitive control: anatomically-constrained magnetoencephalography. Society for Neuroscience Annual Meeting Program: Nov 16, Scientific Sessions Listings 735-946, p.87:855.13.
50. Makris N, Gasic GP, Kennedy DN, Hodge SM, Kaiser JR, Lee MJ, Kim BW, Blood AJ, Evins AE, Seidman LJ, Iosifescu DV, Lee S, Baxter C, Perlis RH, Smoller JW, Fava M, Breiter HC (2008) Cortical thickness abnormalities in cocaine addiction-a reflection of both drug use and a pre-existing disposition to drug abuse? Neuron 60:174-188.
51. Marinkovic K, Halgren E, Maltzman I (2001) Arousal-related P3a to novel auditory stimuli is abolished by moderately low alcohol dose. Alcohol Alcohol 36:529-539.
52. Marinkovic K, Rickenbacher E, Azma S, Artsy E (2011) Acute alcohol intoxication impairs top-down regulation of Stroop incongruity as revealed by blood oxygen level-dependent functional magnetic resonance imaging. Hum Brain Mapp 33:319-333.
53. Millan EZ, Furlong TM, McNally GP (2010) Accumbens shell-hypothalamus interactions mediate extinction of alcohol seeking. J Neurosci 31:4626-4635.
54. Myrick H, Anton RF, Li X, Henderson S, Randall PK, Voronin K (2008) Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people. Arch Gen Psychiatry 65:466-475.
55. Naqvi NH, Rudrauf D, Damasio H, Bechara A (2007) Damage to the insula disrupts addiction to cigarette smoking. Science 315:531-534.
56. Norman AL, Pulido C, Squeglia LM, Spadoni AD, Paulus MP, Tapert SF (2011) Neural activation during inhibition predicts initiation of substance use in adolescence. Drug Alcohol Depend 119:216-223.
57. Oberlin BG, Dzemidzic M, Albrecht DS, Yoder KK, Kareken DA (2011) What combined fMRI and PET imaging of dopamine reveals about ventral striatal responses to tasting a favorite beer. Alcohol Clin Exp Res 35:282A.
58. Oscar-Berman M, Marinković K (2007) Alcohol: effects on neurobehavioral functions and the brain [review]. Neuropsychol Rev 17:239-257.
59. Paulus MP, Tapert SF, Pulido C, Schuckit MA (2006) Alcohol attenuates load-related activation during a working memory task: relation to level of response to alcohol. Alcohol Clin Exp Res 30:1363-1371.
60. Pfefferbaum A, Rosenbloom M, Rohlfing T, Sullivan EV (2009) Degradation of association and projection white matter systems in alcoholism detected with quantitative fiber tracking. Biol Psychiatry 65:680-690.
61. Pfefferbaum A, Rosenbloom MJ, Fama R, Sassoon SA, Sullivan EV (2010) Transcallosal white matter degradation detected with quantitative fiber tracking in alcoholic men and women: selective relations to dissociable functions. Alcohol Clin Exp Res 34:1201-1211.
62. Pfefferbaum A, Sullivan EV, Rosenbloom MJ, Mathalon DH, Lim KO (1998) A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval. Arch Gen Psychiatry 55:905-912.
63. Porjesz B, Rangaswamy M, Kamarajan C, Jones KA, Padmanabhapillai A, Begleiter H (2005) The utility of neurophysiological markers in the study of alcoholism. Clin Neurophysiol 116:993-1018.
64. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci U S A 98:676-682.
65. Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M (2011) A genetic determinant of the striatal dopamine response to alcohol in men. Mol Psychiatry 16:809-817.
66. Rangaswamy M, Jones KA, Porjesz B, Chorlian DB, Padmanabhapillai A, Kamarajan C, Kuperman S, Rohrbaugh J, O'Connor SJ, Bauer LO, Schuckit MA, Begleiter H (2007) Delta and theta oscillations as risk markers in adolescent offspring of alcoholics. Int J Psychophysiol 63:3-15.
67. Rickenbacher E, Greve D, Azma S, Pfeuffer J, Marinkovic K (2011) Effects of alcohol intoxication and gender on cerebral perfusion: an Arterial Spin Labeling (ASL) study. Alcohol 45:725-737.
68. Ridderinkhof KR, de Vlugt Y, Bramlage A, Spaan M, Elton M, Snel J, Band GP (2002) Alcohol consumption impairs detection of performance errors in mediofrontal cortex. Science 298:2209-2211.
69. Rushworth MF, Behrens TE, Rudebeck PH, Walton ME (2007) Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour. Trends Cogn Sci 11:168-176.
70. Salloum JB, Ramchandani VA, Bodurka J, Rawlings R, Momenan R, George D, Hommer DW (2007) Blunted rostral anterior cingulate response during a simplified decoding task of negative emotional facial expressions in alcoholic patients. Alcohol Clin Exp Res 31:1490-1504.
71. Schulte T, Müller-Oehring EM, Rohlfing T, Pfefferbaum A, Sullivan EV (2010) White matter fiber degradation attenuates hemispheric asymmetry when integrating visuomotor information. J Neurosci 30:12168-12178.
72. Schulte T, Müller-Oehring EM, Sullivan EV, Pfefferbaum A (2012) Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men. Biol Psychiatry 71:269-278.
73. Schulte T, Müller-Oehring EM, Vinco S, Hoeft F, Pfefferbaum A, Sullivan EV (2009) Double dissociation between action-driven and perception-driven conflict resolution invoking anterior versus posterior brain systems. Neuroimage 48:381-390.
74. Schultz W, Apicella P, Ljungberg T (1993) Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J Neurosci 13:900-913.
75. Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593-1599.
76. Tapert SF, Brown GG, Baratta MV, Brown SA (2004) fMRI BOLD response to alcohol stimuli in alcohol dependent young women. Addict Behav 29:33-50.
77. Twamley EW, Burton CZ, Vella L (2011) Compensatory cognitive training for psychosis: who benefits? Who stays in treatment? Schizophr Bull 37:S55-S62.
78. 11C]raclopride. Biol Psychiatry 68:689-696.
79. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y, Wong C (2006) Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26:6583-6588.
80. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y, Wong C (2008) Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues. Neuroimage 39:1266-1273.
81. Vollstadt-Klein S, Loeber S, Kirsch M, Bach P, Richter A, Buhler M, von der Goltz C, Hermann D, Mann K, Kiefer F (2011) Effects of cue-exposure treatment on neural cue reactivity in alcohol dependence: a randomized trial. Biol Psychiatry 69:1060-1066.
82. Wang C, Ulbert I, Schomer DL, Marinkovic K, Halgren E (2005) Responses of human anterior cingulate cortex microdomains to error detection, conflict monitoring, stimulus-response mapping, familiarity, and orienting. J Neurosci 25:604-613.
83. Wang JJ, Durazzo TC, Gazdzinski S, Yeh PH, Mon A, Meyerhoff DJ (2009) MRSI and DTI: a multimodal approach for improved detection of white matter abnormalities in alcohol and nicotine dependence. NMR Biomed 22:516-522.
84. Wardell JD, Read JP, Curtin JJ, Merrill JE (2012) Mood and implicit alcohol expectancy processes: predicting alcohol consumption in the laboratory. Alcohol Clin Exp Res 36:119-129.
85. Wiers RW, Eberl C, Rinck M, Becker ES, Lindenmeyer J (2011) Retraining automatic action tendencies changes alcoholic patients' approach bias for alcohol and improves treatment outcome. Psychol Sci 22:490-497.
86. Wise RA (1978) Catecholamine theories of reward: a critical review. Brain Res 152:215-247.
87. Wise RA (2009) Roles for nigrostriatal-not just mesocorticolimbic-dopamine in reward and addiction. Trends Neurosci 32:517-524.
88. Yoder KK, Constantinescu CC, Kareken DA, Normandin MD, Cheng TE, O'Connor SJ, Morris ED (2007) Heterogeneous effects of alcohol on dopamine release in the striatum: a PET study. Alcohol Clin Exp Res 31:965-973.
89. Yoder KK, Kareken DA, Morris ED (2011) Assessing dopaminergic neurotransmission with PET: basic theory and applications in alcohol research. Curr Med Imaging Rev 7:118-124.
90. Yoder KK, Kareken DA, Seyoum RA, O'connor SJ, Wang C, Zheng QH, Mock B, Morris ED (2005) Dopamine D(2) receptor availability is associated with subjective responses to alcohol. Alcohol Clin Exp Res 29:965-970.
91. Yoder KK, Morris ED, Constantinescu CC, Cheng TE, Normandin MD, O'Connor SJ, Kareken DA (2009) When what you see isn't what you get: alcohol cues, alcohol administration, prediction error, and human striatal dopamine. Alcohol Clin Exp Res 33:139-149.
92. Zahr NM, Mayer D, Rohlfing T, Hasak MP, Hsu O, Vinco S, Orduna J, Luong R, Sullivan EV, Pfefferbaum A (2010) Brain injury and recovery following binge ethanol: evidence from in vivo magnetic resonance spectroscopy. Biol Psychiatry 67:846-854.