Depressive symptoms related to low fractional anisotropy of white matter underlying the right ventral anterior cingulate in older adults with atherosclerotic vascular disease.

Kelly R Bijanki, Joy T Matsui, Helen S Mayberg, Vincent A Magnotta, Stephan Arndt, Hans J Johnson, Peg Nopoulos, Sergio Paradiso, Laurie M McCormick, Jess G Fiedorowicz, Eric A Epping, David J Moser
Author Information
  1. Kelly R Bijanki: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Department of Psychiatry, Emory University School of Medicine, Atlanta, GA USA.
  2. Joy T Matsui: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, IA USA.
  3. Helen S Mayberg: Department of Psychiatry, Emory University School of Medicine, Atlanta, GA USA ; Department of Neurology, Emory University School of Medicine, Atlanta, GA USA.
  4. Vincent A Magnotta: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, IA USA ; Department of Radiology, The University of Iowa Carver College of Medicine, Iowa City, IA USA.
  5. Stephan Arndt: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA USA.
  6. Hans J Johnson: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, IA USA.
  7. Peg Nopoulos: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA.
  8. Sergio Paradiso: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Núcleo UDP-Fundación INECO para las Neurociencias, Facultad de Psicología, Universidad Diego Portales, Santiago Chile.
  9. Laurie M McCormick: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA.
  10. Jess G Fiedorowicz: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA ; Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA USA.
  11. Eric A Epping: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA.
  12. David J Moser: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA USA.

Abstract

We sought to characterize the relationship between integrity of the white matter underlying the ventral anterior cingulate (vAC) and depressive symptoms in older adults with atherosclerotic vascular disease (AVD), a condition associated with preferential degeneration of the white matter. The vAC was defined as including white matter underlying ventral Brodmann Area 24 and Brodmann Area 25, corresponding with the "subcallosal" and "subgenual" cingulate respectively. This region of interest was chosen based on the preponderance of evidence that the white matter in the region plays a critical role in the manifestation of depressive symptoms. Participants had current unequivocal diagnoses of AVD and were between 55 and 90 years-old. Fractional anisotropy (FA) was used as an index of white matter integrity and organization. Whole-brain mean diffusivity (MD) was used as an index of global white matter lesion burden. Depressive symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R) Depression Scale. Depressive symptoms were significantly related to low FA in the right vAC (r = -0.356, df = 30, p = 0.045) but not the left vAC (r = 0.024, df = 30, p = 0.896) after controlling for total brain MD (a statistical control for global white matter lesion burden). Further, depressive symptoms were significantly related to low FA in the right vAC (r = -0.361, df = 31, p = 0.039), but not the left vAC (r = 0.259, df = 31, p = 0.145) when controlled for the contralateral vAC FA. The correlation coefficients for this follow-up analysis were found to be significantly different between left and right vAC (Z = 2.310, p = 0.021). Poor white matter health in the vAC may be a biological mechanism for depressive symptoms in older adults with vascular disease. Further studies may corroborate that the right vAC plays a unique role in depressive symptom manifestation in cases where the white matter is preferentially affected, as is the case in AVD. This could lead to future targeting of the region for somatic antidepressant treatment, as well as the development of a precise approach for patients with white matter damage, which could produce significant improvement in quality of life, medical morbidity, and mortality.

Keywords

References

  1. AJR Am J Roentgenol. 2003 Aug;181(2):571-6 [PMID: 12876050]
  2. CNS Neurol Disord Drug Targets. 2007 Jun;6(3):219-33 [PMID: 17511618]
  3. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2450-4 [PMID: 11842195]
  4. Am J Psychiatry. 1999 May;156(5):675-82 [PMID: 10327898]
  5. J Mol Neurosci. 2008;34(1):51-61 [PMID: 18157658]
  6. J Neurosurg. 2003 Dec;99(6):1010-7 [PMID: 14705729]
  7. Brain. 2005 Oct;128(Pt 10):2224-39 [PMID: 16141282]
  8. J Pers Assess. 1994 Jun;62(3):525-36 [PMID: 8027915]
  9. Biol Psychiatry. 2007 Sep 1;62(5):429-37 [PMID: 17210143]
  10. Neuroimage. 2006 Sep;32(3):1167-75 [PMID: 16859929]
  11. Neuron. 2005 Mar 3;45(5):651-60 [PMID: 15748841]
  12. Comput Med Imaging Graph. 2002 Jul-Aug;26(4):251-64 [PMID: 12074920]
  13. Stroke. 1996 Sep;27(9):1641-6; discussion 1647 [PMID: 8784142]
  14. J Magn Reson B. 1996 Jun;111(3):209-19 [PMID: 8661285]
  15. PLoS One. 2014 Oct 22;9(10):e110770 [PMID: 25338068]
  16. Am J Psychiatry. 2007 Jul;164(7):1005 [PMID: 17606649]
  17. Br J Psychiatry. 2012 Jul;201(1):40-5 [PMID: 22626634]
  18. Am J Psychiatry. 2002 May;159(5):728-37 [PMID: 11986125]
  19. Neuroimage. 2005 Jul 1;26(3):891-9 [PMID: 15955499]
  20. Brain. 1965 Jun;88(2):237-94 [PMID: 5318481]
  21. Stroke. 1982 Sep-Oct;13(5):635-41 [PMID: 7123596]
  22. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5391-6 [PMID: 24706828]
  23. Arch Gen Psychiatry. 1997 Oct;54(10):915-22 [PMID: 9337771]
  24. Biol Psychiatry. 2009 Aug 1;66(3):245-52 [PMID: 19375071]
  25. Cereb Cortex. 2008 Jun;18(6):1374-83 [PMID: 17928332]
  26. Mol Psychiatry. 2013 Sep;18(9):963-74 [PMID: 23439482]
  27. Biol Psychiatry. 2014 Dec 15;76(12):963-9 [PMID: 24832866]
  28. J Comput Assist Tomogr. 1999 Jan-Feb;23(1):144-54 [PMID: 10050826]
  29. Am J Psychiatry. 2004 Jul;161(7):1293-6 [PMID: 15229065]
  30. Am J Psychiatry. 2001 Feb;158(2):305-8 [PMID: 11156816]
  31. Arch Gen Psychiatry. 1998 Jul;55(7):580-92 [PMID: 9672048]
  32. Neuropsychologia. 2011 Nov;49(13):3599-604 [PMID: 21939675]
  33. Biol Psychiatry. 2006 Dec 15;60(12):1356-63 [PMID: 16876144]
  34. Neuropsychopharmacology. 2015 Dec;40(13):3027-35 [PMID: 26058663]
  35. Am J Psychiatry. 1997 Apr;154(4):497-501 [PMID: 9090336]
  36. J Clin Invest. 2009 Apr;119(4):717-25 [PMID: 19339763]
  37. Biol Psychiatry. 2013 Jan 15;73(2):169-76 [PMID: 23079234]
  38. Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):141-6 [PMID: 17068287]
  39. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13290-5 [PMID: 9789081]
  40. Am J Psychiatry. 2007 May;164(5):778-88 [PMID: 17475737]
  41. Psychiatry Res. 2013 Dec 30;214(3):389-94 [PMID: 24144509]
  42. Nature. 1997 Apr 24;386(6627):824-7 [PMID: 9126739]
  43. AMA Arch Neurol Psychiatry. 1959 Apr;81(4):409-18 [PMID: 13636509]
  44. Neuroimage. 2006 Jul 1;31(3):1075-85 [PMID: 16631385]
  45. Psychol Med. 1983 Aug;13(3):595-605 [PMID: 6622612]
  46. Int J Geriatr Psychiatry. 2013 Oct;28(10):1069-76 [PMID: 23348834]

Grants

  1. R01 AG030417/NIA NIH HHS
  2. U54 EB005149/NIBIB NIH HHS
  3. K23 AG020649/NIA NIH HHS
  4. S10 RR023392/NCRR NIH HHS
  5. UL1 RR024979/NCRR NIH HHS

Word Cloud

Created with Highcharts 10.0.0=whitemattervACsymptoms0cingulatedepressiverightpFArdfunderlyingventralolderadultsvasculardiseaseAVDregionanisotropyDepressivesignificantlyrelatedlowleftintegrityanterioratheroscleroticBrodmannAreaplaysrolemanifestationusedindexmeandiffusivityMDgloballesionburden-03031mayfractionalsoughtcharacterizerelationshipconditionassociatedpreferentialdegenerationdefinedincluding2425corresponding"subcallosal""subgenual"respectivelyinterestchosenbasedpreponderanceevidencecriticalParticipantscurrentunequivocaldiagnoses5590years-oldFractionalorganizationWhole-brainmeasuredusingSymptomChecklist-90-RevisedSCL-90-RDepressionScale356045024896controllingtotalbrainstatisticalcontrol361039259145controlledcontralateralcorrelationcoefficientsfollow-upanalysisfounddifferentZ2310021Poorhealthbiologicalmechanismstudiescorroborateuniquesymptomcasespreferentiallyaffectedcaseleadfuturetargetingsomaticantidepressanttreatmentwelldevelopmentpreciseapproachpatientsdamageproducesignificantimprovementqualitylifemedicalmorbiditymortalityagingatherosclerosisdepressiondiffusiontensorimagingsubcallosalsubgenual

Similar Articles

Cited By