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Altered activation of innate immunity associates with white matter volume and diffusion in first-episode psychosis.

Mäntylä T, Mantere O, Raij TT, Kieseppä T, Laitinen H, Leiviskä J, Torniainen M, Tuominen L, Vaarala O, Suvisaari J - PLoS ONE (2015)

Bottom Line: CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls.We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment.Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology.

View Article: PubMed Central - PubMed

Affiliation: Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Brain Research Unit, O.V. Lounasmaa Laboratory and Advanced Magnetic Imaging Centre, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.

ABSTRACT
First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFα, CXCL1, CCL7, IFN-α2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.

No MeSH data available.


Related in: MedlinePlus

The associations of serum CCL22 levels with white matter volume (WMV) and diffusion measures within the patient group.(A) CCL22 level correlated negatively with WMV within the frontal regions of interest (ROIs) (see main text for ROI definitions) bilaterally. Voxels with p < 0.005 (uncorrected, for visualization only; see corrected p-values in Table 4) within frontal ROIs are shown in hot colors on an SPM’s canonical single subject T1 image. Color bar for the t-values depicted in (A) is shown on the right. In (B–C), the FMRIB58 FA mean skeleton is shown in green on a T1 template image. (B) Mean diffusivity and (C) radial diffusivity were positively correlated with CCL22 levels; clusters with p < 0.05 TFCE-corrected for family-wise error rate within unilateral ROIs are shown. On the right of (B) and (C), a color bar shows the corrected p-level for these images. Crosshair in all the images is at x = -12, y = 34, z = 10. In the images, left hemisphere is on the left.
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pone.0125112.g001: The associations of serum CCL22 levels with white matter volume (WMV) and diffusion measures within the patient group.(A) CCL22 level correlated negatively with WMV within the frontal regions of interest (ROIs) (see main text for ROI definitions) bilaterally. Voxels with p < 0.005 (uncorrected, for visualization only; see corrected p-values in Table 4) within frontal ROIs are shown in hot colors on an SPM’s canonical single subject T1 image. Color bar for the t-values depicted in (A) is shown on the right. In (B–C), the FMRIB58 FA mean skeleton is shown in green on a T1 template image. (B) Mean diffusivity and (C) radial diffusivity were positively correlated with CCL22 levels; clusters with p < 0.05 TFCE-corrected for family-wise error rate within unilateral ROIs are shown. On the right of (B) and (C), a color bar shows the corrected p-level for these images. Crosshair in all the images is at x = -12, y = 34, z = 10. In the images, left hemisphere is on the left.

Mentions: We then investigated whether the serum levels of markers CCL22, CXCL1, and ApoA-I correlated with brain volume and diffusion measures in FEP patients. The results of these analyses are presented in Table 4. In the ROI analyses of volumetric measures, CCL22 was negatively correlated with WM volume in the left and right frontal lobes (Fig 1A). Decreased serum levels of ApoA-I in patients associated with smaller volume of the medial temporal WM (Fig 2). No statistically significant associations were found between any of these measures and GM volume.


Altered activation of innate immunity associates with white matter volume and diffusion in first-episode psychosis.

Mäntylä T, Mantere O, Raij TT, Kieseppä T, Laitinen H, Leiviskä J, Torniainen M, Tuominen L, Vaarala O, Suvisaari J - PLoS ONE (2015)

The associations of serum CCL22 levels with white matter volume (WMV) and diffusion measures within the patient group.(A) CCL22 level correlated negatively with WMV within the frontal regions of interest (ROIs) (see main text for ROI definitions) bilaterally. Voxels with p < 0.005 (uncorrected, for visualization only; see corrected p-values in Table 4) within frontal ROIs are shown in hot colors on an SPM’s canonical single subject T1 image. Color bar for the t-values depicted in (A) is shown on the right. In (B–C), the FMRIB58 FA mean skeleton is shown in green on a T1 template image. (B) Mean diffusivity and (C) radial diffusivity were positively correlated with CCL22 levels; clusters with p < 0.05 TFCE-corrected for family-wise error rate within unilateral ROIs are shown. On the right of (B) and (C), a color bar shows the corrected p-level for these images. Crosshair in all the images is at x = -12, y = 34, z = 10. In the images, left hemisphere is on the left.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430522&req=5

pone.0125112.g001: The associations of serum CCL22 levels with white matter volume (WMV) and diffusion measures within the patient group.(A) CCL22 level correlated negatively with WMV within the frontal regions of interest (ROIs) (see main text for ROI definitions) bilaterally. Voxels with p < 0.005 (uncorrected, for visualization only; see corrected p-values in Table 4) within frontal ROIs are shown in hot colors on an SPM’s canonical single subject T1 image. Color bar for the t-values depicted in (A) is shown on the right. In (B–C), the FMRIB58 FA mean skeleton is shown in green on a T1 template image. (B) Mean diffusivity and (C) radial diffusivity were positively correlated with CCL22 levels; clusters with p < 0.05 TFCE-corrected for family-wise error rate within unilateral ROIs are shown. On the right of (B) and (C), a color bar shows the corrected p-level for these images. Crosshair in all the images is at x = -12, y = 34, z = 10. In the images, left hemisphere is on the left.
Mentions: We then investigated whether the serum levels of markers CCL22, CXCL1, and ApoA-I correlated with brain volume and diffusion measures in FEP patients. The results of these analyses are presented in Table 4. In the ROI analyses of volumetric measures, CCL22 was negatively correlated with WM volume in the left and right frontal lobes (Fig 1A). Decreased serum levels of ApoA-I in patients associated with smaller volume of the medial temporal WM (Fig 2). No statistically significant associations were found between any of these measures and GM volume.

Bottom Line: CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls.We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment.Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology.

View Article: PubMed Central - PubMed

Affiliation: Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Brain Research Unit, O.V. Lounasmaa Laboratory and Advanced Magnetic Imaging Centre, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.

ABSTRACT
First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFα, CXCL1, CCL7, IFN-α2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.

No MeSH data available.


Related in: MedlinePlus