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Altered Brain Activation during Emotional Face Processing in Relation to Both Diagnosis and Polygenic Risk of Bipolar Disorder.

Tesli M, Kauppi K, Bettella F, Brandt CL, Kaufmann T, Espeseth T, Mattingsdal M, Agartz I, Melle I, Djurovic S, Westlye LT, Andreassen OA - PLoS ONE (2015)

Bottom Line: The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing.These findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD.While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one.

View Article: PubMed Central - PubMed

Affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

ABSTRACT

Objectives: Bipolar disorder (BD) is a highly heritable disorder with polygenic inheritance. Among the most consistent findings from functional magnetic imaging (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, the relation between reported brain functional abnormalities and underlying genetic risk remains elusive. This is the first cross-sectional study applying a whole-brain explorative approach to investigate potential influence of BD case-control status and polygenic risk on brain activation.

Methods: A BD polygenic risk score (PGRS) was estimated from the Psychiatric Genomics Consortium BD case-control study, and assigned to each individual in our independent sample (N=85 BD cases and 121 healthy controls (HC)), all of whom participated in an fMRI emotional faces matching paradigm. Potential differences in BOLD response across diagnostic groups were explored at whole-brain level in addition to amygdala as a region of interest. Putative effects of BD PGRS on brain activation were also investigated.

Results: At whole-brain level, BD cases presented with significantly lower cuneus/precuneus activation than HC during negative face processing (Z-threshold=2.3 as cluster-level correction). The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing. For amygdala activation, there were no correlations with diagnostic status or PGRS.

Conclusions: These findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD. While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one.

No MeSH data available.


Related in: MedlinePlus

Bipolar disorder polygenic risk score is positively correlated with BOLD activation in the right inferior frontal gyrus in the entire sample (N = 206) including bipolar disorder cases and healthy controls for the Negative Faces > Shapes contrast.Color bar indicates z values. Coordinates are given in MNI space. Y = 18 (coronal view), Z = 12 (transversal view). Abbreviations: R, right; A, anterior.
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pone.0134202.g002: Bipolar disorder polygenic risk score is positively correlated with BOLD activation in the right inferior frontal gyrus in the entire sample (N = 206) including bipolar disorder cases and healthy controls for the Negative Faces > Shapes contrast.Color bar indicates z values. Coordinates are given in MNI space. Y = 18 (coronal view), Z = 12 (transversal view). Abbreviations: R, right; A, anterior.

Mentions: PGRS was positively correlated with brain activation in the right inferior frontal gyrus (rIFG) (Table 2) (Fig 2). This effect remained significant also when WASI (IQ) and education level were used as covariates, but did not reach the Bonferroni corrected significance threshold. No significant associations between amygdala activation and PGRS were observed (S1 Table).


Altered Brain Activation during Emotional Face Processing in Relation to Both Diagnosis and Polygenic Risk of Bipolar Disorder.

Tesli M, Kauppi K, Bettella F, Brandt CL, Kaufmann T, Espeseth T, Mattingsdal M, Agartz I, Melle I, Djurovic S, Westlye LT, Andreassen OA - PLoS ONE (2015)

Bipolar disorder polygenic risk score is positively correlated with BOLD activation in the right inferior frontal gyrus in the entire sample (N = 206) including bipolar disorder cases and healthy controls for the Negative Faces > Shapes contrast.Color bar indicates z values. Coordinates are given in MNI space. Y = 18 (coronal view), Z = 12 (transversal view). Abbreviations: R, right; A, anterior.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519303&req=5

pone.0134202.g002: Bipolar disorder polygenic risk score is positively correlated with BOLD activation in the right inferior frontal gyrus in the entire sample (N = 206) including bipolar disorder cases and healthy controls for the Negative Faces > Shapes contrast.Color bar indicates z values. Coordinates are given in MNI space. Y = 18 (coronal view), Z = 12 (transversal view). Abbreviations: R, right; A, anterior.
Mentions: PGRS was positively correlated with brain activation in the right inferior frontal gyrus (rIFG) (Table 2) (Fig 2). This effect remained significant also when WASI (IQ) and education level were used as covariates, but did not reach the Bonferroni corrected significance threshold. No significant associations between amygdala activation and PGRS were observed (S1 Table).

Bottom Line: The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing.These findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD.While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one.

View Article: PubMed Central - PubMed

Affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

ABSTRACT

Objectives: Bipolar disorder (BD) is a highly heritable disorder with polygenic inheritance. Among the most consistent findings from functional magnetic imaging (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, the relation between reported brain functional abnormalities and underlying genetic risk remains elusive. This is the first cross-sectional study applying a whole-brain explorative approach to investigate potential influence of BD case-control status and polygenic risk on brain activation.

Methods: A BD polygenic risk score (PGRS) was estimated from the Psychiatric Genomics Consortium BD case-control study, and assigned to each individual in our independent sample (N=85 BD cases and 121 healthy controls (HC)), all of whom participated in an fMRI emotional faces matching paradigm. Potential differences in BOLD response across diagnostic groups were explored at whole-brain level in addition to amygdala as a region of interest. Putative effects of BD PGRS on brain activation were also investigated.

Results: At whole-brain level, BD cases presented with significantly lower cuneus/precuneus activation than HC during negative face processing (Z-threshold=2.3 as cluster-level correction). The PGRS was associated positively with increased right inferior frontal gyrus (rIFG) activation during negative face processing. For amygdala activation, there were no correlations with diagnostic status or PGRS.

Conclusions: These findings are in line with previous reports of reduced precuneus and altered rIFG activation in BD. While these results demonstrate the ability of PGRS to reveal underlying genetic risk of altered brain activation in BD, the lack of convergence of effects at diagnostic and PGRS level suggests that this relation is a complex one.

No MeSH data available.


Related in: MedlinePlus