Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I)

Dan V. Iosifescu, George I. Papakostas, In Kyoon Lyoo, Ho Kyu Lee, Perry F. Renshaw, Jonathan E. Alpert, Andrew Nierenberg, Maurizio Fava

Research output: Contribution to journalArticle

25 Scopus citations


The objective of the present work was to study the interrelationship between white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle including serum folate, vitamin B12, and homocysteine levels in a relatively young sample of outpatients with major depressive disorder (MDD), and to compare the severity of white matter hyperintensities in MDD patients and healthy volunteers. Fifty MDD outpatients (34% women, age 40.6 ± 10.3 years), free of psychotropic medications for at least 2 weeks before enrollment, underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs and also had (1) serum folate, vitamin B12, homocysteine and cholesterol levels measured, and (2) cardiovascular risk factors assessed during the same study visit. Thirty-five healthy comparison subjects (40% women, age 39.2 ± 9.8 years) also underwent brain MRI scans. Hypofolatemia, hypertension and age independently predicted a greater severity of total brain WMHs. Separately, the same factors also predicted a greater severity of subcortical WMHs. Hypofolatemic and hypertensive patients had more severe WMHs than normal controls. In light of the adverse impact of WMHs on a number of health-related outcomes later in life, hypofolatemia and hypertension may represent modifiable risk factors to prevent the occurrence of such adverse outcomes.

Original languageEnglish (US)
Pages (from-to)291-299
Number of pages9
JournalPsychiatry Research - Neuroimaging
Issue number3
Publication statusPublished - Dec 30 2005
Externally publishedYes



  • Cardiovascular
  • Depression
  • Folate
  • Hyperintensities
  • White matter

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Psychiatry and Mental health

Cite this