Strain-specific response to fluoxetine in mouse FST.

<p>Immobility time in the FST of B6 (1a), BALB (1b), FVB (1c), DBA (1d) and C3H (1e) mice after administration of different doses of fluoxetine. The FST was conducted 30 minutes after fluoxetine or saline injection (i.p.). “*” denotes a p-value lower than 0.05 compared with the saline group in the post hoc analysis. FST: forced swim test.</p

LOD scores for linkage for FST_FLX.

<p>The solid red line at LOD  = 3.33 and the blue dashed line at LOD  = 4.68 denote the genome-wide significance threshold for FST_FLX (SIM) and FST_FLX (CIM), respectively. The gray zone indicates the 2-LOD confidence interval. FST: forced swim test; FST_FLX: immobility in the mouse FST with fluoxetine treatment; LOD: logarithm of odds; SIM: simple interval mapping; CIM: composite interval mapping.</p

Mouse single nucleotide polymorphisms (SNPs) that were associated with immobility time in the FST after fluoxetine treatment (FST_FLX).

<p>SD: standard deviation; cM: centi-morgan; LOD: logarithm (base 10) of odds; LOD_(SIM): the LOD scores derived from simple interval mapping; LOD_(CIM): LOD scores derived from composite interval mapping;</p>a<p>The proportion of contribution the genetic polymorphism on the overall variation of the immobility time in FST after fluoxetine treatment.</p>b<p>P-value for one way analysis of variance.</p>c<p>The allele that shows significantly shorter immobility time in FST after fluoxetine treatment than the other allele.</p>d<p>The list of the gene located in 1 mega-bases from the SNP.</p

The association of mouse <i>Zfp326</i> function SNP with FST response to fluoxetine treatment.

<p>Genetic variations in <i>Zfp326</i>, rs33550587 (Asp494Gly) (4a) and rs13473815 (4b), are associated with the mouse response to fluoxetine in the FST. The B6×FVB-F2 mice were grouped according to genotype. * p<0.05; ^#p<0.0001. The digits in the bars represent the number of animals in each group. <i>Zfp326</i>: zinc finger protein 326 gene; SNP: single nucleotide polymorphism; FST: forced swim test.</p

Genotype and allele distribution of <i>ZNF326</i> polymorphisms in the controls, and in the patients with major depressive disorder and their responses to 8-weeks’ antidepressant treatment.

*<p>The P-value in boldface indicates the significance survived after correction for multiple comparisons (adjusted significant threshold with Bonferroni’s procedure: P<0.0125). “#” denotes the p-value obtained from Fisher exact test.</p

Interaction of <i>Bcl-2</i> genotype and age on regional gray matter volume.

<p>Interaction of Bcl-2 genotype and age on (<b>A</b>) right cerebellum, (<b>B</b>) right lingual gyrus (BA17), (<b>C</b>) left lingual gyrus (BA18), (<b>D</b>) right middle temporal gyrus (BA19), and (<b>E</b>) right parahippocampal gyrus (hippocampus). (<b>F</b>) Showing the interaction results of voxel-wised covariate analysis using Bcl-2 genotype as a condition and age as covariates, controlling sex and education level as nuisance variables (uncorrected p<0.001, cluster size larger than 50). Abbreviations: MTG, middle temporal gyrus; BA, Brodmann Area.</p

Catechol-O-Methyltransferase Val158Met Polymorphism on the Relationship between White Matter Hyperintensity and Cognition in Healthy People

<div><p>Background</p><p>White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear.</p><p>Methods</p><p>We recruited 315 ethnic Chinese adults with a mean age of 54.9±21.8 years (range: 21–89 y) to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant.</p><p>Results</p><p>Negative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r = −.123, <i>P = </i>.032, uncorrected) were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (<i>P = </i>.016, uncorrected), whole brain (<i>P = </i>.047, uncorrected), and a trend over the frontal region (<i>P = </i>.050, uncorrected) were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen’s f) revealed a small effect.</p><p>Conclusions</p><p>The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.</p></div

Demographic characteristics and cognitive assessments between COMT genotypic groups in healthy participants.

<p>Abbreviation: TIV: total intracranial volume.</p><p>Data are expressed as Mean (SE).</p><p>*Bonferroni-corrected <i>P</i><.05.</p

Correlation between WMH volumes and Digit Span Forward score according to COMT Val158Met genotyping.

<p>Abbreviation: WMH: white matter hyperintensities.</p><p>Partial correlation analysis was performed controlling age, sex, years of education, and total intracranial volume as nuisance variable. All of the p-values showed in this table were unadjusted p-values.</p><p>*Bonferroni-corrected <i>P</i><.05.</p

Regional WMH volume differences between COMT genotypic groups.

<p>Abbreviation: WMH: white matter hyperintensities.</p><p>The P values obtained by ANCOVA using age, sex, years of education, and total intracranial volume as covariates.</p><p>Data are expressed as mean (SE).</p>#<p>A trend toward greater WMH volumes than the Val/Val group, uncorrected P<.05.</p