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Increased cerebrospinal fluid fibrinogen in major depressive disorder.

Hattori K, Ota M, Sasayama D, Yoshida S, Matsumura R, Miyakawa T, Yokota Y, Yamaguchi S, Noda T, Teraishi T, Hori H, Higuchi T, Kohsaka S, Goto Y, Kunugi H - Sci Rep (2015)

Bottom Line: Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77).In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%).Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan [2] Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan.

ABSTRACT
Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9-39.1, p = 0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.

No MeSH data available.


Related in: MedlinePlus

Diffusion tensor imaging analysis for patients with a high cerebrospinal (CSF) fibrinogen level.(a–c) The difference of fractional anisotropy (FA) values in patients with MDD and high fibrinogen levels compared with controls. Significant decreases of FA were detected diffusely. (d, e) The difference of FA values in patients with high fibrinogen levels compared with patients with normal fibrinogen levels. Significant decreases of FA were detected in the left inferior temporal region (d) and left superior temporal region (e). L, left; R, right. Green voxels, FA white matter skeleton; Red-yellow voxels, threshold-free cluster enhancement (p < 0.05, family wise error). The background image is the standard Montreal Neurological Institute (MNI152) brain template.
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f3: Diffusion tensor imaging analysis for patients with a high cerebrospinal (CSF) fibrinogen level.(a–c) The difference of fractional anisotropy (FA) values in patients with MDD and high fibrinogen levels compared with controls. Significant decreases of FA were detected diffusely. (d, e) The difference of FA values in patients with high fibrinogen levels compared with patients with normal fibrinogen levels. Significant decreases of FA were detected in the left inferior temporal region (d) and left superior temporal region (e). L, left; R, right. Green voxels, FA white matter skeleton; Red-yellow voxels, threshold-free cluster enhancement (p < 0.05, family wise error). The background image is the standard Montreal Neurological Institute (MNI152) brain template.

Mentions: The brain MRI scan was examined for nine patients with a high CSF fibrinogen level, 20 patients with a normal fibrinogen level matched for age, sex, education, and depression severity, and 26 controls matched for age, sex, and education (Supplemental Table S2). There were significant decreases of FA value in the patients with a high fibrinogen level compared with controls (Fig. 3a–c). Among patients with a high fibrinogen level, there were significant decreases in the FA value in the left inferior temporal (Fig. 3d) and left superior temporal regions (Fig. 3e) compared with patients with a normal fibrinogen level. When we compared the FA value between patients with a normal fibrinogen level and controls, no significant difference was found in any region. In T2-weighted images, no obvious periventricular or deep white-matter hyperintensity was detected in 8 of 9 patients with a high fibrinogen level (grade 0). Only one patient with a high fibrinogen level (69 years old) had a modest hyperintensity in periventricular area (grade 2) but not in deep white matter (grade 0). We also evaluated the gray matter volume differences by performing a DARTEL analysis. However, no significant difference was detected between patients with a high fibrinogen level and patients with a normal fibrinogen level, or between patients with a high fibrinogen level and controls.


Increased cerebrospinal fluid fibrinogen in major depressive disorder.

Hattori K, Ota M, Sasayama D, Yoshida S, Matsumura R, Miyakawa T, Yokota Y, Yamaguchi S, Noda T, Teraishi T, Hori H, Higuchi T, Kohsaka S, Goto Y, Kunugi H - Sci Rep (2015)

Diffusion tensor imaging analysis for patients with a high cerebrospinal (CSF) fibrinogen level.(a–c) The difference of fractional anisotropy (FA) values in patients with MDD and high fibrinogen levels compared with controls. Significant decreases of FA were detected diffusely. (d, e) The difference of FA values in patients with high fibrinogen levels compared with patients with normal fibrinogen levels. Significant decreases of FA were detected in the left inferior temporal region (d) and left superior temporal region (e). L, left; R, right. Green voxels, FA white matter skeleton; Red-yellow voxels, threshold-free cluster enhancement (p < 0.05, family wise error). The background image is the standard Montreal Neurological Institute (MNI152) brain template.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4469953&req=5

f3: Diffusion tensor imaging analysis for patients with a high cerebrospinal (CSF) fibrinogen level.(a–c) The difference of fractional anisotropy (FA) values in patients with MDD and high fibrinogen levels compared with controls. Significant decreases of FA were detected diffusely. (d, e) The difference of FA values in patients with high fibrinogen levels compared with patients with normal fibrinogen levels. Significant decreases of FA were detected in the left inferior temporal region (d) and left superior temporal region (e). L, left; R, right. Green voxels, FA white matter skeleton; Red-yellow voxels, threshold-free cluster enhancement (p < 0.05, family wise error). The background image is the standard Montreal Neurological Institute (MNI152) brain template.
Mentions: The brain MRI scan was examined for nine patients with a high CSF fibrinogen level, 20 patients with a normal fibrinogen level matched for age, sex, education, and depression severity, and 26 controls matched for age, sex, and education (Supplemental Table S2). There were significant decreases of FA value in the patients with a high fibrinogen level compared with controls (Fig. 3a–c). Among patients with a high fibrinogen level, there were significant decreases in the FA value in the left inferior temporal (Fig. 3d) and left superior temporal regions (Fig. 3e) compared with patients with a normal fibrinogen level. When we compared the FA value between patients with a normal fibrinogen level and controls, no significant difference was found in any region. In T2-weighted images, no obvious periventricular or deep white-matter hyperintensity was detected in 8 of 9 patients with a high fibrinogen level (grade 0). Only one patient with a high fibrinogen level (69 years old) had a modest hyperintensity in periventricular area (grade 2) but not in deep white matter (grade 0). We also evaluated the gray matter volume differences by performing a DARTEL analysis. However, no significant difference was detected between patients with a high fibrinogen level and patients with a normal fibrinogen level, or between patients with a high fibrinogen level and controls.

Bottom Line: Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77).In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%).Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan [2] Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan.

ABSTRACT
Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9-39.1, p = 0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.

No MeSH data available.


Related in: MedlinePlus