Elsevier

Biological Psychiatry

Volume 69, Issue 4, 15 February 2011, Pages 318-325
Biological Psychiatry

Archival Report
Cross-Sectional and Longitudinal Assessment of Structural Brain Alterations in Melancholic Depression

https://doi.org/10.1016/j.biopsych.2010.07.029Get rights and content

Background

Whole-brain imaging approaches may contribute to the characterization of neuroanatomic alterations in major depression, especially in clinically homogenous patient groups such as those with melancholic features. We assessed brain anatomic alterations, both cross-sectionally and longitudinally, in patients with melancholic depression using a whole-brain voxel-wise approach.

Methods

Whole-brain magnetic resonance images were collected from a relatively aged sample of 70 consecutively recruited major depressive disorder inpatients with melancholic features and from a group of 40 healthy control subjects. All patients were clinically followed for at least 2 years, and a subset of 30 depressive patients and 20 control subjects were rescanned after a 7-year period. Imaging data were analyzed with voxel- and tensor-based morphometry techniques.

Results

Melancholic patients showed gray matter reductions in the left insula and white matter increases in the upper brainstem tegmentum. Male patients showed gray matter decreases in the right thalamus, and periventricular white matter reductions were specifically observed in older patients. Volume decreases in the left insula, hippocampus, and lateral parietal cortex predicted a slower recovery after treatment initiation. In longitudinal assessment, white matter of the upper brainstem tegmentum showed a different temporal evolution between groups. Additionally, bilateral gray matter reductions in the insulae were associated with the number of relapses during follow-up.

Conclusions

Structural alterations were identified in regions potentially related to relevant aspects of melancholia pathophysiology. Longitudinal analyses indicated region-specific interactions of baseline alterations with age as well as a significant association of clinical severity with focal changes occurring over time.

Section snippets

Subjects

We assessed 70 MDD patients (41 female) consecutively recruited from the Mood Disorders Unit of the Bellvitge University Hospital. All but three patients were right-handed according to the Edinburgh Inventory (21). The group comprised patients with a current depression episode fulfilling DMS-IV criteria for MDD with melancholic features and who required hospital admission for treatment. Patient diagnosis was independently confirmed by two senior psychiatrists (MU and NC) using the Structured

Global Volume Measurements

There were no significant differences in global gray and white matter volumes between patients and controls (see Supplement1, Table S2).

Cross-Sectional Analyses

Patients showed a significant gray matter volume reduction in left posterior insula (Figure 1A) and a white matter volume increase in the upper brainstem tegmentum, at the level of midbrain and rostral pons (Figure 1B; see also Supplement 1, note 1). These findings did not interact with gender or age.

Gender-Specific and Age-Related Effects

Male MDD patients exhibited a gray matter reduction in the

Discussion

We used a whole-brain imaging approach to characterize structural brain alterations in a large series of melancholic patients and identified regional volumetric alterations in gray and white matter. The most significant alterations were identified in regions not commonly assessed in studies of general MDD samples (i.e., insula and brainstem). Nevertheless, as discussed subsequently, such changes may relate to the clinical and neurobiological features of melancholia. We also described gender-

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