Our results add to previously published data which suggest that regional gray matter volume should be investigated further as a clinical diagnostic tool to predict BD before the appearance of a manic or hypomanic episode.
White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n=16) and healthy volunteers (HV, n=12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p<0.001, peak t-score=8.10, p=0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t=−1.874, df=13.56, p=0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p<0.001, peak t-score=5.04, p=0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.
Background
Major depressive disorder (MDD) is associated with impaired attention control and alterations in frontal-subcortical connectivity. We hypothesized that attention control as assessed by Stroop task interference depends on white matter integrity in fronto-cingulate regions and assessed this relationship using diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV).
Methods
DTI images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs, aged 18–65 years. The relationship between Stroop interference and fractional anisotropy (FA) was examined using region-of-interest (ROI) and tract-based spatial statistics (TBSS) analyses.
Results
ROI analysis revealed that Stroop interference correlated positively with FA in left caudal anterior cingulate cortex (cACC) in HVs (r= 0.62, p= 0.01), but not in MDD (r= −0.05, p= 0.79) even after controlling for depression severity. The left cACC was among 4 ROIs in fronto-cingulate network where FA was lower in MDD relative to HVs (F(1,41)= 8.87, p= 0.005). Additionally, TBSS showed the same group interaction of differences and correlations, although only at a statistical trend level.
Limitations
The modest sample size limits the generalizability of the findings.
Conclusions
Structural connectivity of white matter network of cACC correlated with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal network, sub-serving attention control, may be disrupted in MDD. Less cognitive control may include enhanced effects of salience in HVs, or less effective response inhibition in MDD. Further studies of salience and inhibition components of executive function may better elucidate the relationship between brain white matter changes and executive dysfunction in MDD.
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