Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

Authors

Peter Kochunov
David C. Glahn
Laura M. Rowland
Rene L. Olvera
Anderson M. Winkler, The University of Texas Rio Grande ValleyFollow
Hemalatha Sampath
Ravi Duggirala, The University of Texas Rio Grande Valley
Joanne E. Curran, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
L. Elliot Hong

Document Type

Article

Publication Date

3-1-2013

Abstract

Background

Elevated rate of aging-related biological and functional decline, termed “accelerated aging,” is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD.

Methods

The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20–60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20–79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts.

Results

Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =−.61 and−.80, p<.05, respectively). No such trends existed for MDD cohort.

Conclusions

Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort.

Comments

Original published version available at https://doi.org/10.1016/j.biopsych.2012.10.002

Recommended Citation

Kochunov, P., Glahn, D. C., Rowland, L. M., Olvera, R. L., Winkler, A., Yang, Y. H., Sampath, H., Carpenter, W. T., Duggirala, R., Curran, J., Blangero, J., & Hong, L. E. (2013). Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression. Biological psychiatry, 73(5), 482–491. https://doi.org/10.1016/j.biopsych.2012.10.002

First Page

482

Last Page

91

Publication Title

Biological psychiatry

DOI

10.1016/j.biopsych.2012.10.002

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics