Enlargement of Brain Cerebrospinal Fluid Spaces as a Predictor of Poor Clinical Outcome in Melancholia
J Clin Psychiatry 2003;64(6):691-697
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Background: A number of recent
neuroimaging findings in depression have provided new insight
into the biological substratum of depressive illness. The
question now is what particular relevance the structural brain
alteration described may have within the clinical context of
depressive patients. We investigated a possible relationship
between brain cerebrospinal fluid (CSF) space changes and patient
prognosis in melancholic depression.
Method: Fifty-five patients who met
DSM-IV criteria for major depressive disorder with melancholic
features were examined with 3-dimensional magnetic resonance
imaging, and CSF volumes were measured for global brain CSF and
for lateral ventricles and left and right sylvian fissure
regions. Clinical outcome was prospectively assessed during a
6-month standardized antidepressive treatment period (Phase I)
and in a 2-year follow-up (Phase II) of recovered patients. The
outcome measurements were total days to symptom remission (Phase
I) and to eventual symptom relapse or recurrence (Phase II). The
study took place from July 1998 to Dec. 2001.
Results: Phase I: Enlargement of CSF spaces in
the left sylvian fissure region predicted poor treatment
response. Volume measurements from this region accounted for 35%
of remission time variance. Median time to full clinical
remission was 82 days in patients with severe changes, 51 days in
the case of mild-to-moderate CSF enlargement, and 35 days in
patients with no left sylvian fissure region alterations. Phase
II: Severe enlargement of global cortical CSF spaces was
associated with increased risk of depression relapse or
recurrence. Patients with severe cortical CSF changes showed a
7.8-fold excess risk of depression relapse/recurrence compared
with patients with no cortical CSF space alteration.
Conclusion: Our data suggest that MRI-detected
CSF space enlargement may be an important neuroimaging marker for
poor prognosis in melancholic depression.