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Glial fibrillary acidic protein in late life major depressive disorder: an immunocytochemical study
1Wolfson Research Centre, Institute for Aging and Health, Newcastle General Hospital, Newcastle upon Tyne, UK. s.m.davis@ncl.ac.uk
Insights
In elderly patients with major depressive disorder (MDD), glial fibrillary acidic protein (GFAP) levels were elevated in layer I of the dorsolateral prefrontal cortex (DLPFC). This finding supports the vascular depression hypothesis and implicates DLPFC abnormalities in late-life depression.
Area of Science:
- Neuroscience
- Psychiatry
- Pathology
Background:
- Late-life depression is common, with the vascular depression hypothesis suggesting cerebrovascular disease as a key factor.
- Inflammatory markers like ICAM-1 have been observed in the dorsolateral prefrontal cortex (DLPFC) of elderly depressed individuals, potentially indicating ischemia.
- Ischemia is known to cause astrogliosis, a process involving astrocytes.
Purpose of the Study:
- To investigate the "vascular depression hypothesis" by examining glial fibrillary acidic protein (GFAP) distribution in the DLPFC and anterior cingulate cortex (ACC).
- To assess GFAP as a marker for astrogliosis in elderly patients with major depressive disorder (MDD).
Main Methods:
- Postmortem brain tissue from 20 elderly MDD patients and 20 controls was analyzed.
- Standard immunocytochemistry was used to stain tissue sections for GFAP.
- Image analysis quantified GFAP percentage area in different cortical layers and white matter of the DLPFC and ACC.
Main Results:
- GFAP immunoreactivity was generally low in grey matter but higher in white matter.
- A significant increase in GFAP was found in layer I of the DLPFC in MDD subjects compared to controls (p=0.04).
- No significant differences in GFAP levels were detected in other brain regions examined.
Conclusions:
- Elevated GFAP in elderly MDD patients appears confined to layer I of the DLPFC.
- These findings offer support for the vascular depression hypothesis.
- The results further suggest abnormalities in the DLPFC are implicated in late-life depression.
Objectives:
Depression is a common psychiatric disorder in late life. Cerebrovascular disease has been postulated as an important aetiological factor in many cases (the "vascular depression" hypothesis). Consistent with this, an inflammatory response, most probably representing ischaemia, has been reported with increases in intercellular adhesion molecule 1 (ICAM-1), in the dorsolateral prefrontal cortex (DLPFC) in postmortem tissue from elderly depressed subjects. As ischaemia is known to cause astrogliosis, this study has further tested the "vascular depression hypothesis" by investigating the distribution of the astrocytic marker glial fibrillary acidic protein (GFAP) in the DLPFC and in the anterior cingulate cortex (ACC).
Methods:
Postmortem tissue was obtained from 20 elderly patients with a history of major depressive disorder (MDD) and 20 control subjects. Sections were stained for GFAP using standard immunocytochemistry. Sets of images were obtained from all cortical layers in the DLPFC and ACC with the exception of layer IV in the ACC, and from gyral and deep white matter in both regions. The percentage of the area of each image occupied by GFAP was calculated using true colour image analysis, and mean values obtained for each region examined.
Results:
Immunoreactivity for GFAP was low in grey matter (for example, Mean (SEM) 0.76 (0.2)% in DLPFC layer V in depressed subjects), but higher in white matter (for example, 12.02 (2.2)% in DLPFC deep white matter in depressed subjects). Pronounced gliosis was observed within grey matter in a few cases only. GFAP immunoreactivity was significantly higher in layer I of the DLPFC in depressed subjects 15.8 (2.6)% than in controls 9.7 (1.3)% (t=2.2; df=27.5, p=0.04). No difference was detected in any other region.
Conclusions:
The data suggest any increase in GFAP in elderly MDD patients is limited to layer 1 of the DLPFC. These results provide some support for the vascular depression hypothesis and further implicate DLPFC abnormalities in depression.
