Longitudinal MR study of brain structure and hippocampus volume in major depressive disorder.

OBJECTIVE: To determine whether long-term course of treated major depression has an effect on the structure of the brain and the hippocampal volume. METHOD: An 11-year follow-up procedure was used with data collection at baseline and again at follow-up. Tensor-based morphometry (TBM) and automatic hippocampal volume measure was performed on different datasets. The baseline dataset consisted of T1-weighted magnetic resonance images (MRIs) of 24 in-patients suffering from major depression and 33 healthy controls. The second dataset consisted of T1-weighted MRIs of 31 remitted depressive patients and 36 healthy controls. The longitudinal dataset consisted of 19 patients and 19 matched healthy controls present at both the first and the second dataset. Brain segmentation and hippocampal segmentation were fully automated and were based on a spatial normalization to the International Consortium of Brain Mapping (ICBM) non-linear model. RESULTS: Depressed patients were found to have smaller temporal lobes bilaterally, medulla and right hippocampus at baseline. However, these changes were not found at follow-up 11 years later. Moreover, these changes did not significantly correlate with the illness outcome. CONCLUSION: Brain structure changes seem to be state dependent in major depression, only occurring in acute episode of major depression and normalizing after remission.

Regional brain atrophy in primary fatigued patients with multiple sclerosis.

OBJECTIVE: To examine the relationship between fatigue, regional brain atrophy and normal appearing white matter damage in patients with multiple sclerosis. METHODS: Primary fatigued (PF) (n, 17) and non-fatigued (NF) (n, 17) patients with relapsing remitting multiple sclerosis and moderate disability were grouped according to their subjective fatigue score. Also, they were examined with respect to processing speed and central motor activation during isometric contraction. Using 3 Tesla MRI quantitative analyses were performed on normal appearing brain tissue and of brain structure volumes with tensor based morphometry. RESULTS: Between the PF and NF patients there was no significant differences in brain parenchymal fraction (81.5% vs. 82.4%), lesion load (0.53% vs. 0.36%) and NAA/Cr ratio (1.29 vs. 1.32 respectively). Eleven clusters of atrophy in PF versus NF involved gray and nearby white matter, the majority being located in areas functionally related to attentional control. Central motor activation was associated with atrophy in five regions in PF patients, three clusters involving the premotor and primary motor cortex. Normal appearing white matter did not differ between groups. CONCLUSION: Primary fatigued patients with multiple sclerosis have extended regional atrophy of supratentorial brain parenchyma, involving the cerebral cortex, nearby white matter and the caudate head, areas which are functionally related to attentional control. We suggest that impaired central motor activation is due to interruption of the cortico-subcortical motor circuits involving the motor cortex.

Localization of white-matter lesions and effect of vascular risk factors in late-onset major depression.

BACKGROUND: Several studies suggest that patients with late-onset major depression (MD) have an increased load of cerebral white-matter lesions (WMLs) compared with age-matched controls. Vascular risk factors such as hypertension and smoking may confound such findings. Our aim was to investigate the association between the localization and load of WMLs in late-onset MD with respect to vascular risk factors. METHOD: We examined 22 consecutive patients with late-onset first-episode MD and 22 age- and gender-matched controls using whole-brain magnetic resonance imaging (MRI). The localization, number and volume of WMLs were compared between patients and controls, while testing the effect of vascular risk factors. RESULTS: Among subjects with one or more WMLs, patients displayed a significantly higher WML density in two white-matter tracts: the left superior longitudinal fasciculus and the right frontal projections of the corpus callosum. These tracts are part of circuitries essential for cognitive and emotional functions. Analyses revealed no significant difference in the total number and volume of WMLs between groups. Patients and controls showed no difference in vascular risk factors, except for smoking. Lesion load was highly correlated with smoking. CONCLUSIONS: Our results indicate that lesion localization rather than lesion load differs between patients with late-onset MD and controls. Increased lesion density in regions associated with cognitive and emotional functions may be crucial in late-onset MD, and vascular risk factors such as smoking may play an important role in the pathophysiology of late-onset MD, consistent with the vascular depression hypothesis.