The Neural Correlates of Mindful Awareness: A Possible Buffering Effect on Anxiety-Related Reduction in Subgenual Anterior Cingulate Cortex Activity

<div><p>Background</p><p>Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC).</p><p>Methods</p><p>Resting brain glucose metabolism (GM) was measured using [¹⁸F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively.</p><p>Results</p><p>Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA <i>β</i> = −0.248, <i>p</i> = 0.003; ST: <i>β</i> = 0.250, <i>p</i> = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = −8, y = 32, z = −8, <i>k</i> = 423, <i>Z</i> = 4.41, corrected <i>p</i>^FDR = 0.030).</p><p>Conclusion</p><p>The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders.</p></div

Stepwise multiple regression analysis for glucose metabolism in the right anterior cingulate cortex and ventromedial prefrontal cortex (<i>N</i> = 140).

<p>Controlled for age, sex, and the temperament dimensions. Degrees of freedom (7,132).</p><p>Dependent variable was the average glucose metabolism level of the right subgenual anterior cingulate cortex and ventromedial prefrontal cortex.</p><p>ROI definitions: the right anterior cingulate cortex: box center at x = 7, y = 26, z = −6, volume = 10×10×10 mm; right vmPFC: box center at x = 7, y = 40, z = −18, volume = 14×14×14 mm.</p><p>These definitions were based on the previous studies (32, 33).</p

Partial correlations between harm avoidance and glucose metabolism in the subgenual anterior cingulate cortex and ventromedial prefrontal cortex (<i>N</i> = 140).

<p>Controlled for age and sex. Degrees of freedom = 136.</p>*<p><i>p</i><0.05,</p>**<p><i>p</i><0.01,</p>***<p><i>p</i><0.001.</p><p><b><i>Bold italic values</i></b>: Coefficients survived Bonferroni correction (<i>p</i><0.013).</p><p>HA, harm avoidance; sgACC, subgenual anterior cingulate cortex; vmPFC, ventromedial prefrontal cortex; R, right; L, left.</p><p>ROI definitions: sgACC: box center at x = 7/−8, y = 26, z = −6, volume = 10×10×10 mm; vmPFC: box center at x = 7/−8, y = 40, z = −18, volume = 14×14×14 mm.</p><p>The definitions were based on the previous studies (32, 33).</p

Scatter plot of the positive correlation between self-transcendence and glucose metabolism in the sgACC/vmPFC (<i>N</i> = 140).

<p>sgACC, subgenual anterior cingulate cortex; vmPFC, ventromedial prefrontal cortex. Peak voxel at x = −8, y = 32, z = −8, <i>k</i> = 423, <i>Z</i> = 4.41, corrected <i>p</i>^FDR = 0.030.</p

The subgenual anterior cingulate cortex encompassing a ventromedial portion of the prefrontal cortex that showed a significant positive correlation with self-transcendence (<i>N</i> = 140).

<p>Peak voxel at x = −8, y = 32, z = −8, <i>k</i> = 423, <i>Z</i> = 4.41, corrected <i>p</i>^FDR = 0.030.</p

Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (<i>SP8</i>) as Susceptibility Loci for Psychotic Disorders: A Genetic Association Study

<div><p>Background</p><p>Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population.</p><p>Methods</p><p>Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis.</p><p>Results</p><p>Eight SNPs revealed nominal association signals for all comparisons (P_uncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: P_corrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: P_corrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (<i>PBRM1</i>) was significant on genome-wide association level (P = 5×10⁻⁸) only for BD (P = 9.4×10⁻⁹) and psychosis (P = 2.0×10⁻¹⁰). Although the association of rs2709722 in Sp8 transcription factor (<i>SP8</i>) was suggestive in the Asian population (P = 2.1×10⁻⁷ for psychosis), this signal weakened when the samples size was increased by including data from a Caucasian population (P = 4.3×10⁻³).</p><p>Conclusions</p><p>We found 3p21.1 (including <i>PBRM1</i>, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and <i>SP8</i> as risk loci for BD, SCZ and psychosis. Further replication studies will be required for conclusive results.</p></div

Association analysis in the first-set screening samples (SNPs with nominal significant association).

<p>a: BP: base position based upon hg19.</p><p>b: A1: minor allele based upon whole sample.</p><p>c: A2: major allele.</p><p>d: BD: bipolar disorder, SCZ: schizophrenia.</p><p>e: F_A: Frequency of A1 in affected subjects.</p><p>f: F_U: Frequency of A1 in unaffected subjects.</p><p>g: P values based upon one-tailed test.</p><p>h: OR: Odds ratio for A1 (i.e. A2 is reference).</p><p>i: SE: standard error.</p><p>j: direction: direction of the effect size based upon the original studies. +: same direction. −: opposite direction.</p

meta analysis of the two SNPs detected in the first-set screening analysis.

<p>a: A1: first allele code.</p><p>b: A2: second allele code.</p><p>c: Lee et al. reported the P values based upon dominant model. To conduct meta-analysis of allelic model, we re-caluculated P values based upon their results.</p><p>d: BD: bipolar disorder, SCZ: schizophrenia.</p><p>e: the effect is with respect to the A1 allele.</p

Behavioral effects of CB2-R activation and blockade.

<p><i>A</i>, Mouse spontaneous locomotor activity following acute treatment with CB2 agonist JWH015 (1–20 mg/kg), in mouse strain, C57Bl/6 (a and b); BALBc, (c and d) and DBA/2 (e and f). <i>B</i>, Effect of JWH015 in C57Bl/6 mice in the two compartment black and white box, showing time spent in the black and white chamber. <i>C</i>, Acute effects of SR144528 – a CB2-R antagonist on DBA/2 mouse spontaneous locomotor activity and stereotype behavior. <i>D</i>, Acute effects of SR144528, in DBA/2 male and female mice in the two chamber black and white test box, showing time spent in the black and white chamber.</p

CB2-R gene targeting modifies behavior.

<p><i>A</i>, Behavioral effects of CB2 intracerebral gene targeting by antisense oligonucleotide microinjected into the mouse brain and performance of mice in plus-maze test was assessed before and after 3 days of twice daily microinjection. AS1 and AS2 were before and after CB2 antisense oligo microinjection. V1 and V2 are controls. <i>B</i>, performance in plus-maze test following CMS or mice exposed prenatally to capsaicin and the effect of JWH015 (20 mg/kg).</p