Elsevier

Biological Psychiatry

Volume 73, Issue 5, 1 March 2013, Pages 482-491
Biological Psychiatry

Archival Report
Testing the Hypothesis of Accelerated Cerebral White Matter Aging in Schizophrenia and Major Depression

https://doi.org/10.1016/j.biopsych.2012.10.002Get rights and content

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.

Section snippets

Methods and Materials

Testing of the study’s hypotheses was performed in two distinct cohorts, each with its own normal control group.

Diagnosis and Diagnosis-by-Age Effects for Whole-Brain FA Values

SCZ Cohort. Beta coefficients and their significance for age and gender effects for the whole-brain average FA values are shown in Table 3. The quadratic and linear age models were significant for the whole-brain FA values (p = 6.9×10−5 and 9.2×10−5, respectively). There were no significant main effects on diagnosis. Instead, quadratic effects of the diagnosis-by-age interaction were significant (β2age⁎SCZ =−6.9±3.4·10−6; p = .04) and linear effects of the diagnosis-by-age interaction

Discussion

We aimed to test whether the rates of age-related decline in the integrity of cerebral WM were higher in patients affected with SCZ or MDD than in normal control subjects. In SCZ patients, age-related decline in the whole-brain FA values were more than twice that of control subjects, which was significant under the quadratic model. In contrast, the effects of accelerated aging in the whole-brain FA values were not statistically significant in the MDD patients. Exploration of regional

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