title: In vivo imaging of oxidative stress and fronto-limbic white matter integrity in young adults with mood disorders.
abstract: Fronto-limbic connectivity is compromised in mood disorders, as reflected by impairments in white matter (WM) integrity revealed by diffusion tensor imaging. Although the underlying mechanisms remain unclear, disruption to normal myelination due to oxidative stress is thought to play a key role. We aimed to determine whether fronto-limbic WM integrity is compromised, and associated with in vivo antioxidant levels (indexed by glutathione; GSH), in young adults with unipolar depression (DEP) and bipolar (BD) disorders. Ninety-four patients with DEP, 76 with BD and 59 healthy controls (18-30 years) underwent diffusion tensor and proton magnetic resonance spectroscopy imaging. Fractional anisotropy (FA) was calculated from the cingulum bundle (cingulate, hippocampus), fornix, stria terminalis (ST) and uncinate fasciculus tracts. GSH concentration was measured in anterior cingulate cortex (ACC) and hippocampus (HIPP). Compared to controls, DEP showed significantly reduced FA in ST, whereas BD did not significantly differ in FA across the five tracts. There were significant positive correlations between ST-FA and HIPP-GSH across groups. Regression analysis revealed that having DEP or BD and reduced HIPP-GSH were significantly associated with reduced ST-FA. Similarly, decreased ST-FA was associated with poorer neuropsychological performance in conjunction with having DEP. Our findings suggest a structural disconnectivity specific to the limbic region of young adults with DEP. Decreased WM integrity was associated with depleted levels of hippocampal GSH suggesting that this particular disruption may be linked to oxidative stress at early stages of illness. Young adults with BD do not have the same degree of impairment.
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia. daniel.hermens@sydney.edu.au.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hermens
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.|Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Sean N
authors.initials: SN
authors.lastname: Hatton
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.
authors.forename: Rico S C
authors.initials: RSC
authors.lastname: Lee
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, NSW, Australia.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Naismith
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, NSW, Australia.
authors.forename: Shantel L
authors.initials: SL
authors.lastname: Duffy
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Paul Amminger
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.|Monash Alfred Psychiatry Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Manreena
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.|School of Medicine, University of Notre Dame, Sydney, NSW, Australia.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Scott
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.|Sunshine Coast Mind and Neuroscience - Thompson Institute, University of the Sunshine Coast, Maroochydore, QLD, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
authors.affiliation: Brain and Mind Centre, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D056344:Executive Function; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007858:Learning; D008032:Limbic System / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019964:Mood Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D009434:Neural Pathways / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000502:physiology*; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: Bipolar disorder; Depression; Diffusion tensor imaging; Glutathione; Hippocampus; Magnetic resonance spectroscopy