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The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

  • G. Lelli-Chiesa (a1) (a2), M. J. Kempton (a1), J. Jogia (a1), R. Tatarelli (a2), P. Girardi (a2), J. Powell (a3), D. A. Collier (a4) and S. Frangou (a1)
  • DOI: http://dx.doi.org/10.1017/S0033291710001431
  • Published online: 29 July 2010
Abstract
Background

The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.

Method

We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.

Results

Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.

Conclusions

Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

Copyright
Corresponding author
*Address for correspondence: Dr S. Frangou, Section of Neurobiology of Psychosis (PO66), Department of Psychosis Studies, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email: sophia.frangou@kcl.ac.uk)
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

R Adolphs (2002). Recognizing emotion from facial expressions: psychological and neurological mechanisms. Behavioral and Cognitive Neuroscience Reviews 1, 2162.

LL Altshuler , SY Bookheimer , J Townsend , MA Proenza , N Eisenberger , F Sabb , J Mintz , MS Cohen (2005). Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study. Biological Psychiatry 58, 763769.

DG Amaral , JL Price (1984). Amygdalo-cortical projections in the monkey (Macaca fascicularis). Journal of Comparative Neurology 230, 465496.

A Bertolino , G Blasi , V Latorre , V Rubino , A Rampino , L Sinibaldi , G Caforio , V Petruzzella , A Pizzuti , T Scarabino , M Nardini , DR Weinberger , B Dallapiccola (2006 a). Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain. Journal of Neuroscience 26, 39183922.

A Bertolino , V Rubino , F Sambataro , G Blasi , V Latorre , L Fazio , G Caforio , V Petruzzella , B Kolachana , A Hariri , A Meyer-Lindenberg , M Nardini , DR Weinberger , T Scarabino (2006 b). Prefrontal–hippocampal coupling during memory processing is modulated by COMT Val158Met genotype. Biological Psychiatry 60, 12501258.

RM Bilder , J Volavka , HM Lachman , AA Grace (2004). The catechol-O-methyltransferase polymorphism: relations to the tonic–phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology 29, 19431961.

G Blasi , VS Mattay , A Bertolino , B Elvevag , JH Callicott , S Das , BS Kolachana , MF Egan , TE Goldberg , DR Weinberger (2005). Effect of catechol-O-methyltransferase Val158Met genotype on attentional control. Journal of Neuroscience 25, 50385045.

HP Blumberg , HC Leung , P Skudlarski , CM Lacadie , CA Fredericks , BC Harris , DS Charney , JC Gore , JH Krystal , BS Peterson (2003). A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Archives of General Psychiatry 60, 601609.

M Bosia , M Bechi , E Marino , S Anselmetti , S Poletti , F Cocchi , E Smeraldi , R Cavallaro (2007). Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia. Neuroscience Letters 417, 271274.

AJ Calder , AW Young , D Rowland , DI Perrett (1997). Computer-enhanced emotion in facial expressions. Proceedings of the Royal Society of London, Series B: Biological Sciences 264, 919925.

N Craddock , MJ Owen , MC O'Donovan (2006). The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Molecular Psychiatry 11, 446458.

AR Damasio , TJ Grabowski , A Bechara , H Damasio , LL Ponto , J Parvizi , RD Hichwa (2000). Subcortical and cortical brain activity during the feeling of self-generated emotions. Nature Neuroscience 3, 10491056.

RJ Dolan (2007). The human amygdala and orbital prefrontal cortex in behavioural regulation. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 362, 787799.

K Domschke , P Ohrmann , M Braun , T Suslow , J Bauer , C Hohoff , A Kersting , A Engelien , V Arolt , W Heindel , J Deckert , H Kugel (2008). Influence of the catechol-O-methyltransferase Val158Met genotype on amygdala and prefrontal cortex emotional processing in panic disorder. Psychiatry Research: Neuroimaging 163, 1320.

EM Drabant , AR Hariri , A Meyer-Lindenberg , KE Munoz , VS Mattay , BS Kolachana , MF Egan , DR Weinberger (2006). Catechol O-methyltransferase Val158Met genotype and neural mechanisms related to affective arousal and regulation. Archives of General Psychiatry 63, 13961406.


MF Egan , TE Goldberg , BS Kolachana , JH Callicott , CM Mazzanti , RE Straub , D Goldman , DR Weinberger (2001). Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proceedings of the National Academy of Sciences USA 98, 69176922.

SL Fairhall , A Ishai (2007). Effective connectivity within the distributed cortical network for face perception. Cerebral Cortex 17, 24002406.

LC Foland , LL Altshuler , SY Bookheimer , N Eisenberger , J Townsend , PM Thompson (2008). Evidence for deficient modulation of amygdala response by prefrontal cortex in bipolar mania. Psychiatry Research 162, 2737.

B Freeman , N Smith , C Curtis , L Huckett , J Mill , IW Craig (2003). DNA from buccal swabs recruited by mail: evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behavioral Genetics 33, 6772.

S Frangou (2009). Risk and resilience in bipolar disorder: rationale and design of the Vulnerability to Bipolar Disorders Study (VIBES). Biochemical Society Transactions 37, 10851089.

SJ Glatt , SV Faraone , MT Tsuang (2003). Association between a functional catechol-O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case–control and family-based studies. American Journal of Psychiatry 160, 469476.

JA Gogos , M Morgan , V Luine , M Santha , S Ogawa , D Pfaff , M Karayiorgou (1998). Catechol-O-methyltransferase deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proceedings of the National Academy of Sciences USA 95, 99919996.


M Hamilton (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.

SP Hamilton , SL Slager , GA Heiman , Z Deng , F Haghighi , DF Klein , SE Hodge , MM Weissman , AJ Fyer , JA Knowles (2002). Evidence for a susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22. Biological Psychiatry 51, 591601.

AR Hariri , SY Bookheimer , JC Mazziotta (2000). Modulating emotional responses: effects of a neocortical network on the limbic system. Neuroreport 11, 4348.

R Honea , BA Verchinski , L Pezawas , BS Kolachana , JH Callicott , VS Mattay , DR Weinberger , A Meyer-Lindenberg (2009). Impact of interacting functional variants in COMT on regional gray matter volume in human brain. Neuroimage 45, 4451.

J Hong , H Shu-Leong , X Tao , Y Lap-Ping (1998). Distribution of catechol-O-methyltransferase expression in human central nervous system. Neuroreport 9, 28612864.

R Joober , J Gauthier , S Lal , D Bloom , P Lalonde , G Rouleau , C Benkelfat , A Labelle (2002). Catechol-O-methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting Test. Archives of General Psychiatry 59, 662663.

F Karoum , SJ Chrapusta , R Brinjak , A Hitri , RJ Wyatt (1994). Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain. British Journal of Pharmacology 113, 13911399.

P Keedwell , D Drapier , S Surguladze , V Giampietro , M Brammer , M Phillips (2009). Neural markers of symptomatic improvement during antidepressant therapy in severe depression: subgenual cingulate and visual cortical responses to sad, but not happy, facial stimuli are correlated with changes in symptom score. Journal of Psychopharmacology 23, 775788.

WM Kelley , CN Macrae , CL Wyland , S Caglar , S Inati , TF Heatherton (2002). Finding the self? An event-related fMRI study. Journal of Cognitive Neuroscience 14, 785794.

MJ Kempton , M Haldane , J Jogia , T Christodoulou , J Powell , D Collier , SC Williams , S Frangou (2009). The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study. International Journal of Neuropsychopharmacology 12, 371381.

TT Kircher , C Senior , ML Phillips , PJ Benson , ET Bullmore , M Brammer , A Simmons , SC Williams , M Bartels , AS David (2000). Towards a functional neuroanatomy of self processing: effects of faces and words. Cognitive Brain Research 10, 133144.

HM Lachman , DF Papolos , T Saito , YM Yu , CL Szumlanski , RM Weinshilboum (1996). Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6, 243250.

JE LeDoux (2000). Emotion circuits in the brain. Annual Review of Neuroscience 23, 155184.

BT Lee , JH Seok , BC Lee , SW Cho , BJ Yoon , KU Lee , JH Chae , IG Choi , BJ Ham (2008). Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder. Progress in Neuro-psychopharmacology and Biological Psychiatry 32, 778785.

T Lotta , J Vidgren , C Tilgmann , I Ulmanen , K Melen , I Julkunen , J Taskinen (1995). Kinetics of human soluble and membrane-bound catechol-O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34, 42024210.

JA Maldjian , PJ Laurienti , RA Kraft , JH Burdette (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19, 12331239.

I Massat , D Souery , J Del-Favero , M Nothen , D Blackwood , W Muir , R Kaneva , A Serretti , C Lorenzi , M Rietschel , V Milanova , GN Papadimitriou , D Dikeos , C Van Broekhoven , J Mendlewicz (2005). Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Molecular Psychiatry 10, 598605.

VS Mattay , TE Goldberg , F Fera , AR Hariri , A Tessitore , MF Egan , B Kolachana , JH Callicott , DR Weinberger (2003). Catechol-O-methyltransferase Val158-Met genotype and individual variation in the brain response to amphetamine. Proceedings of the National Academy of Sciences USA 100, 61866191.

EB McClure , CS Monk , EE Nelson , JM Parrish , A Adler , RJ Blair , S Fromm , DS Charney , E Leibenluft , M Ernst , DS Pine (2007). Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Archives of General Psychiatry 64, 97–106.

FC Murphy , I Nimmo-Smith , AD Lawrence (2003). Functional neuroanatomy of emotions: a meta-analysis. Cognitive, Affective and Behavioral Neuroscience 3, 207233.

K Ohara , M Nagai , Y Suzuki , K Ohara (1998). Low activity allele of catechol-O-methyltransferase gene and Japanese unipolar depression. NeuroReport 9, 13051308.

JE Overall , DR Gorham (1962). The Brief Psychiatric Rating Scale. Psychological Reports 10, 799812.

KL Phan , T Wager , SF Taylor , I Liberzon (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 16, 331348.

ML Phillips (2003). Understanding the neurobiology of emotion perception: implications for psychiatry. British Journal of Psychiatry 182, 190192.

ML Phillips , AW Young , C Senior , M Brammer , C Andrew , AJ Calder , ET Bullmore , DI Perrett , D Rowland , SC Williams , JA Gray , AS David (1997). A specific neural substrate for perceiving facial expressions of disgust. Nature 389, 495498.

GJ Quirk , JS Beer (2006). Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Current Opinion in Neurobiology 16, 723727.

N Ramnani , AM Owen (2004). Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nature Reviews Neuroscience 5, 184194.

R Revay , R Vaughan , S Grant , MJ Kuhar (1996). Dopamine transporter immunohistochemistry in median eminence, amygdala, and other areas of the rat brain. Synapse 22, 9399.

BH Schott , CI Seidenbecher , DB Fenker , CJ Lauer , N Bunzeck , HG Bernstein , W Tischmeyer , ED Gundelfinger , HJ Heinze , E Duzel (2006). The dopaminergic midbrain participates in human episodic memory formation: evidence from genetic imaging. Journal of Neuroscience 26, 14071417.

MN Smolka , G Schumann , J Wrase , SM Grusser , H Flor , K Mann , DF Braus , D Goldman , C Buchel , A Heinz (2005). Catechol-O-methyltransferase Val158Met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. Journal of Neuroscience 25, 836842.

M Walterfang , AG Wood , S Barton , D Velakoulis , J Chen , C Pantelis , DC Reutens , M Kempton , M Haldane , S Frangou (2009). Corpus callosum size and shape alterations in individuals with bipolar disorder and their first degree relatives. Progress in Neuro-psychopharmacology and Biological Psychiatry 33, 10501057.

G Winterer , F Musso , G Vucurevic , P Stoeter , A Konrad , B Seker , J Gallinat , N Dahmen , DR Weinberger (2006). COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits. Neuroimage 32, 17221732.

JM Woo , KS Yoon , BH Yu (2002). Catechol-O-methyltransferase genetic polymorphism in panic disorder. American Journal of Psychiatry 159, 17851787.

R Young , J Biggs , V Zieglar , D Meyer (1978). A rating scale for mania: reliability, validity, sensitivity. British Journal of Psychiatry 133, 429435.

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