Journal of the American Academy of Child & Adolescent Psychiatry
Volume 47, Issue 11 , Pages 1262-1272 , November 2008

Brain Imaging in Pediatric Obsessive-Compulsive Disorder

,Accepted 15 May 2008.

References 

  1. Pauls DL, Alsobrook JP, Goodman W, Rasmussen S, Leckman JF. A family study of obsessive-compulsive disorder. Am J Psychiatry. 1995;152(1):76–84
  2. Rosenberg DR, Keshavan MSAE. Bennett Research Award. Toward a neurodevelopmental model of obsessive-compulsive disorder. Biol Psychiatry. 1998;43(9):623–640
  3. Rosenberg DR, MacMaster FP, Mirza Y, Easter PC, Buhagiar CJ. Neurobiology, neuropsychology and neuroimaging of child and adolescent obsessive-compulsive disorder. In:  Storch E,  Geffken G,  Murphy T editor. Handbook of Child and Adolescent Obsessive-Compulsive Disorder. Mahwah, NJ: Lawrence Erlbaum Associates; 2007;p. 131–161
  4. Rosenberg DR, Dick EL, O'Hearn KM, Sweeney JA. Response-inhibition deficits in obsessive-compulsive disorder: an indicator of dysfunction in frontostriatal circuits. J Psychiatry Neurosci. 1997;22(1):29–38
  5. Beers SR, Rosenberg DR, Dick EL, et al. Neuropsychological study of frontal lobe function in psychotropic-naive children with obsessive-compulsive disorder. Am J Psychiatry. 1999;156(5):777–779
  6. Chang SW, McCracken JT, Piacentini JC. Neurocognitive correlates of child obsessive compulsive disorder and Tourette syndrome. J Clin Exp Neuropsychol. 2007;29(7):724–733
  7. Rosenberg DR, Averbach DH, O'Hearn KM, Seymour AB, Birmaher B, Sweeney JA. Oculomotor response inhibition abnormalities in pediatric obsessive-compulsive disorder. Arch Gen Psychiatry. 1997;54(9):831–838
  8. Woolley J, Heyman I, Brammer M, Frampton I, McGuire PK, Rubia K. Brain activation in paediatric obsessive compulsive disorder during tasks of inhibitory control. Br J Psychiatry. 2008;192(1):25–31
  9. Szeszko P, Christian C, MacMaster FP, et al. Gray matter structural alterations in psychotropic drug-naïve pediatric obsessive-compulsive disorder: an optimized voxel based morphometry study. Am J Psychiatry. Published online ahead of print April 15, 2008.
  10. Swedo SE, Schapiro MB, Grady CL, et al. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 1989;46(6):518–523
  11. Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32(3):525–549
  12. Szeszko PR, MacMillan S, McMeniman M, et al. Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder. Am J Psychiatry. 2004;161(6):1049–1056
  13. Carmona S, Bassas N, Rovira M, et al. Pediatric OCD structural brain deficits in conflict monitoring circuits: a voxel-based morphometry study. Neurosci Lett. 2007;421(3):218–223
  14. Thacker NA. Tutorial: A Critical Analysis of Voxel Based Morphometry (VBM). Manchester: University of Manchester; 2005;
  15. Rosenberg DR, Mirza Y, Russell A, et al. Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry. 2004;43(9):1146–1153
  16. Yucel M, Wood SJ, Wellard RM, et al. Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-compulsive disorder. Aust N Z J Psychiatry. 2008;42(6):467–477
  17. Russell A, Cortese B, Lorch E, et al. Localized functional neurochemical marker abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2003;13(suppl 1):S31–S38
  18. Rosenberg DR, Keshavan MS, O'Hearn KM, et al. Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder. Arch Gen Psychiatry. 1997;54(9):824–830
  19. Rosenberg DR, Keshavan MS, Dick EL, Bagwell WW, MacMaster FP, Birmaher B. Corpus callosal morphology in treatment-naive pediatric obsessive compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 1997;21(8):1269–1283
  20. MacMaster FP, Keshavan MS, Dick EL, Rosenberg DR. Corpus callosal signal intensity in treatment-naive pediatric obsessive compulsive disorders. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23(4):601–612
  21. Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000;39(9):1096–1103
  22. Benazon NR, Moore GJ, Rosenberg DR. Neurochemical analyses in pediatric obsessive-compulsive disorder in patients treated with cognitive-behavioral therapy. J Am Acad Child Adolesc Psychiatry. 2003;42(11):1279–1285
  23. Gilbert AR, Moore GJ, Keshavan MS, et al. Decrease in thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine. Arch Gen Psychiatry. 2000;57(5):449–456
  24. Rosenberg DR, Benazon NR, Gilbert A, Sullivan A, Moore GJ. Thalamic volume in pediatric obsessive-compulsive disorder patients before and after cognitive behavioral therapy. Biol Psychiatry. 2000;48(4):294–300
  25. Fitzgerald KD, Moore GJ, Paulson LA, Stewart CM, Rosenberg DR. Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive-compulsive disorder. Biol Psychiatry. 2000;47(3):174–182
  26. Rosenberg DR, Amponsah A, Sullivan A, MacMillan S, Moore GJ. Increased medial thalamic choline in pediatric obsessive-compulsive disorder as detected by quantitative in vivo spectroscopic imaging. J Child Neurol. 2001;16(9):636–641
  27. Smith EA, Russell A, Lorch E, et al. Increased medial thalamic choline found in pediatric patients with obsessive-compulsive disorder versus major depression or healthy control subjects: a magnetic resonance spectroscopy study. Biol Psychiatry. 2003;54(12):1399–1405
  28. Mirza Y, O'Neill J, Smith EA, et al. Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls. J Child Neurol. 2006;21(2):106–111
  29. Szeszko PR, MacMillan S, McMeniman M, et al. Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings. Neuropsychopharmacology. 2004;29(4):826–832
  30. MacMaster FP, Russell A, Mirza Y, et al. Pituitary volume in pediatric obsessive-compulsive disorder. Biol Psychiatry. 2006;59(3):252–257
  31. Gilbert AR, Keshavan M, Diwadkar VA, et al. Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: a preliminary voxel-based morphometry study. Neurosci Lett. 2008;435:45–50
  32. Bloch MH, Leckman JF, Zhu H, Peterson BS. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology. 2005;65(8):1253–1258
  33. Moore GJ, MacMaster FP, Stewart C, Rosenberg DR. Case study: caudate glutamatergic changes with paroxetine therapy for pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1998;37(6):663–667
  34. Bolton J, Moore GJ, MacMillan S, Stewart CM, Rosenberg DR. Case study: caudate glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD. J Am Acad Child Adolesc Psychiatry. 2001;40(8):903–906
  35. Amat JA, Bronen RA, Saluja S, et al. Increased number of subcortical hyperintensities on MRI in children and adolescents with Tourette's syndrome, obsessive-compulsive disorder, and attention deficit hyper-activity disorder. Am J Psychiatry. 2006;163(6):1106–1108
  36. Altemus M, Cizza G, Gold PW. Chronic fluoxetine treatment reduces hypothalamic vasopressin secretion in vitro. Brain Res. 1992;593(2):311–313
  37. Monteleone P, Catapano F, Tortorella A, Maj M. Cortisol response to d-fenfluramine in patients with obsessive-compulsive disorder and in healthy subjects: evidence for a gender-related effect. Neuropsychobiology. 1997;36(1):8–12
  38. Monteleone P, Catapano F, Tortorella A, Di Martino S, Maj M. Plasma melatonin and cortisol circadian patterns in patients with obsessive-compulsive disorder before and after fluoxetine treatment. Psychoneuroendocrinology. 1995;20(7):763–770
  39. Catapano F, Monteleone P, Fuschino A, Maj M, Kemali D. Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Psychiatry Res. 1992;44(3):217–225
  40. MacMaster FP, Kusumakar V. Pituitary gland volume in adolescent depression. J Psychiatr Res. 2004;
  41. MacMaster FP, Russell A, Mirza Y, et al. Pituitary volume in treatment-naive pediatric major depressive disorder. Biol Psychiatry. 2006;60(8):862–866
  42. MacMaster FP, Leslie R, Rosenberg DR, Kusumakar V. Pituitary gland volume in adolescent and young adult bipolar and unipolar depression. Bipolar Disord. 2008;10(1):101–104
  43. MacMaster FP, Easter PC, Rix C, Kmiecik L, Buhagiar CJ, Rosenberg DR. Regional Volumetric Changes With Treatment in Pediatric Major Depression. Washington, DC: Society for Biological Psychiatry; 2008;
  44. MacMaster FP, El-Sheikh R, Upadhyaya AR, Nutche J, Rosenberg DR, Keshavan M. Effect of antipsychotics on pituitary gland volume in treatment-naive first-episode schizophrenia: a pilot study. Schizophr Res. 2007;92(1–3):207–210
  45. Eichstedt JA, Arnold SL. Childhood-onset obsessive-compulsive disorder: a tic-related subtype of OCD?. Clin Psychol Rev. 2001;21(1):137–157
  46. Giedd JN, Rapoport JL, Leonard HL, Richter D, Swedo SE. Case study: acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy. J Am Acad Child Adolesc Psychiatry. 1996;35(7):913–915
  47. Giedd JN, Rapoport JL, Garvey MA, Perlmutter S, Swedo SE. MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection. Am J Psychiatry. 2000;157(2):281–283
  48. van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet. 2005;8(5):450–458
  49. Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63(7):769–776
  50. Dickel DE, Veenstra-VanderWeele J, Cox NJ, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 2006;63(7):778–785
  51. Stewart SE, Fagerness JA, Platko J, et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144(8):1027–1033
  52. Aoyama K, Suh SW, Hamby AM, et al. Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci. 2006;9(1):119–126
  53. Franklin RB, Zou J, Yu Z, Costello LC. EAAC1 is expressed in rat and human prostate epithelial cells; functions as a high-affinity l-aspartate transporter; and is regulated by prolactin and testosterone. BMC Biochem. 2006;7:10
  54. Guillet BA, Velly LJ, Canolle B, Masmejean FM, Nieoullon AL, Pisano P. Differential regulation by protein kinases of activity and cell surface expression of glutamate transporters in neuron-enriched cultures. Neurochem Int. 2005;46(4):337–346
  55. Zerangue N, Kavanaugh MP. Interaction of l-cysteine with a human excitatory amino acid transporter. J Physiol. 1996;493(pt 2):419–423
  56. Rothstein JD, Martin L, Levey AI, et al. Localization of neuronal and glial glutamate transporters. Neuron. 1994;13(3):713–725
  57. Kanai Y, Smith CP, Hediger MA. A new family of neurotransmitter transporters: the high-affinity glutamate transporters. FASEB J. 1993;7(15):1450–1459
  58. Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S. The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?. J Neurochem. 2006;98(4):1007–1018
  59. Peghini P, Janzen J, Stoffel W. Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration. EMBO J. 1997;16(13):3822–3832
  60. O'Neill J, Gorbis E, Feusner J, et al. 1H MRSI study of effects of cognitive-behavioral therapy on obsessive-compulsive disorder. Paper presented at ISMRM 15th Scientific Meeting and Exhibition, May 19–25, 2007, Berlin.
  61. O'Neill J, Gorbis E, Feusner J, et al. 1H MRSI study of effects of cognitive-behavioral therapy on obsessive-compulsive disorder. Paper presented at Organization for Human Brain Mapping, June 12, 2007, Chicago.
  62. O'Neill J, Gorbis E, Feusner J, et al. Effects of cognitive-behavioral therapy on regional neurometabolism in obsessive-compulsive disorder. Paper presented at ISNR 15th Annual Conference; September 6–9, 2007; San Diego.
  63. Zurowski B, Fahr WW, Freyer T, et al. Neurochemical abnormalities in patients with obsessive-compulsive disorder diminish in the course of behavior therapy. Paper presented at Society for Neuroscience 37th Annual Meeting, November 3–7, 2007, San Diego.
  64. Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA. Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a preliminary study. Psychopharmacology (Berl). 2004;174(4):530–538
  65. Loftis JM, Janowsky A. The N-methyl-d-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther. 2003;97(1):55–85
  66. Li D, He L. Association study between the NMDA receptor 2B subunit gene (GRIN2B) and schizophrenia: a HuGE review and meta-analysis. Genet Med. 2007;9(1):4–8
  67. Dorval KM, Wigg KG, Crosbie J, et al. Association of the glutamate receptor subunit gene GRIN2B with attention-deficit/hyperactivity disorder. Genes Brain Behav. 2007;6(5):444–452
  68. Martucci L, Wong AH, De Luca V, et al. N-methyl-d-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: polymorphisms and mRNA levels. Schizophr Res. 2006;84(2–3):214–221
  69. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature. 1994;368(6467):144–147
  70. Beas-Zarate C, Rivera-Huizar SV, Martinez-Contreras A, Feria-Velasco A, Armendariz-Borunda J. Changes in NMDA-receptor gene expression are associated with neurotoxicity induced neonatally by glutamate in the rat brain. Neurochem Int. 2001;39(1):1–10
  71. Ueda Y, Doi T, Tsuru N, Tokumaru J, Mitsuyama Y. Expression of glutamate transporters and ionotropic glutamate receptors in GLAST knockout mice. Brain Res Mol Brain Res. 2002;104(2):120–126
  72. Jenike MA. Clinical practice. Obsessive-compulsive disorder. N Engl J Med. 2004;350(3):259–265
  73. Whiteside SP, Port JD, Deacon BJ, Abramowitz JS. A magnetic resonance spectroscopy investigation of obsessive-compulsive disorder and anxiety. Psychiatry Res. 2006;146(2):137–147
  74. Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutama-tergic dysfunction in OCD. Neuropsychopharmacology. 2005;30(9):1735–1740
  75. Delorme R, Krebs MO, Chabane N, et al. Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder. Neuroreport. 2004;15(4):699–702
  76. Nordstrom EJ, Burton FH. A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry. 2002;7(6):617–625524.
  77. Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006;3(1):69–Y81
  78. Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH. Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major depressive disorder. Psychopharmacology (Berl). 2003;167(2):219–220
  79. Coric V, Taskiran S, Pittenger C, et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005;58(5):424–428
  80. Zarate CA, Payne JL, Quiroz J, et al. An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004;161(1):171–174
  81. Zarate CA, Quiroz JA, Singh JB, et al. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry. 2005;57(4):430–432
  82. Sanacora G, Kendell SF, Fenton L, Coric V, Krystal JH. Riluzole augmentation for treatment-resistant depression. Am J Psychiatry. 2004;161(11):2132
  83. Sanacora G, Kendell SF, Levin Y, et al. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry. 2007;61(6):822–825
  84. Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994;330(9):585–591
  85. Lacomblez L, Bensimon G, Leigh PN, et al. A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II. Neurology. 1996;47(6 suppl 4):S242–S250
  86. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet. 1996;347(9013):1425–1431
  87. Stefani A, Spadoni F, Bernardi G. Differential inhibition by riluzole, lamotrigine, and phenytoin of sodium and calcium currents in cortical neurons: implications for neuroprotective strategies. Exp Neurol. 1997;147(1):115–122
  88. Jehle T, Bauer J, Blauth E, et al. Effects of riluzole on electrically evoked neurotransmitter release. Br J Pharmacol. 2000;130(6):1227–1234
  89. Urbani A, Belluzzi O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci. 2000;12(10):3567–3574
  90. Grant P, Lougee L, Hirschtritt M, Swedo SE. An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2007;17(6):761–767
  91. Insel TR, Scolnick EM. Cure therapeutics and strategic prevention: raising the bar for mental health research. Mol Psychiatry. 2006;11(1):11–17
  92. Insel TR, Quirion R. Psychiatry as a clinical neuroscience discipline. JAMA. 2005;294(17):2221–2224
  93. Wong DF, Grunder G, Brasic JR. Brain imaging research: does the science serve clinical practice?. Int Rev Psychiatry. 2007;19(5):541–558
  94. Cerna M. Genetics of autoimmune diabetes mellitus. Wien Med Wochenschr. 2008;158(1–2):2–12
  95. Ridderstrale M, Parikh H, Groop L. Calpain 10 and type 2 diabetes: are we getting closer to an explanation?. Curr Opin Clin Nutr Metab Care. 2005;8(4):361–366
  96. Love-Gregory L, Permutt MA. HNF4A genetic variants: role in diabetes. Curr Opin Clin Nutr Metab Care. 2007;10(4):397–402
  97. American Psychiatric Association . Diagnostic and Statistical Manual of Psychiatric Disorders. 4th ed.. Washington, DC: American Psychiatric Association; 1994;
  98. Rosenberg DR, MacMaster FP, Mirza Y, et al. Reduced anterior cingulate glutamate in pediatric major depression: a magnetic resonance spectroscopy study. Biol Psychiatry. 2005;58(9):700–704
  99. Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14(4):260–264
  100. Kanowski M, Kaufmann J, Braun J, Bernarding J, Tempelmann C. Quantitation of simulated short echo time 1H human brain spectra by LCModel and AMARES. Magn Reson Med. 2004;51(5):904–912
  101. Barker PB, Hearshen DO, Boska MD. Single-voxel proton MRS of the human brain at 1.5T and 3.0T. Magn Reson Med. 2001;45(5):765–769
  102. Hariri AR, Weinberger DR. Imaging genomics. Br Med Bull. 2003;65:259–270
  103. Schiffer HH. Glutamate receptor genes: susceptibility factors in schizophrenia and depressive disorders?. Mol Neurobiol. 2002;25(2):191–212
  104. Martinez-Hernandez A, Bell KP, Norenberg MD. Glutamine synthetase: glial localization in brain. Science. 1977;195(4284):1356–1358
  105. Chaudhry FA, Reimer RJ, Krizaj D, et al. Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission. Cell. 1999;99(7):769–780
  106. Varoqui H, Zhu H, Yao D, Ming H, Erickson JD. Cloning and functional identification of a neuronal glutamine transporter. J Biol Chem. 2000;275(6):4049–4054
  107. Kvamme E, Torgner IA, Svenneby G. Glutaminase from mammalian tissues. Methods Enzymol. 1985;113:241–256
  108. Petroff OA, Mattson RH, Rothman DL. Proton MRS: GABA and glutamate. Adv Neurol. 2000;83:261–271

 This research was supported in part by the State of Michigan Joe F. Young Sr. Psychiatric Research and Training Program, the Miriam L. Hamburger Endowed Chair of Child Psychiatry at Children's Hospital of Michigan, and Wayne State University, and grants from the National Institute of Mental Health (R01MH59299, R01MH65122, K24MH02037) and the Mental Illness Research Association.Portions of this article were presented at the 2007 research forum The Future of Neuroimaging: Relevance for Child Psychiatry, American Academy of Child and Adolescent Psychiatry, Boston, MA, October 2007.This article is the subject of an editorial by Dr. Ellen Leibenluft in this issue.

PII: S0890-8567(08)60118-5

doi: 10.1097/CHI.0b013e318185d2be

Journal of the American Academy of Child & Adolescent Psychiatry
Volume 47, Issue 11 , Pages 1262-1272 , November 2008

Article Tools

* Image Usage & Resolution