Yuko Hakamata

Attention Bias Modification Treatment: A Meta-Analysis Toward the Establishment of Novel Treatment for Anxiety

BACKGROUND Attention Bias Modification Treatment (ABMT) is a newly emerging, promising treatment for anxiety disorders. Although recent randomized control trials (RCTs) suggest that ABMT reduces anxiety, therapeutic effects have not been summarized quantitatively. METHODS Standard meta-analytic procedures were used to summarize the effect of ABMT on anxiety. With MEDLINE, January 1995 to February 2010, we identified RCTs comparing the effects on anxiety of ABMT and quantified effect sizes with Hedges d. RESULTS Twelve studies met inclusion criteria, including 467 participants from 10 publications. Attention Bias Modification Treatment produced significantly greater reductions in anxiety than control training, with a medium effect (d = .51 [corrected] (p < .001). Age and gender did not moderate the effect of ABMT on anxiety, whereas several characteristics of the ABMT training did. CONCLUSIONS Attention Bias Modification Treatment shows promise as a novel treatment for anxiety. Additional RCTs are needed to fully evaluate the degree to which these findings replicate and apply to patients. Future work should consider the precise role for ABMT in the broader anxiety-disorder therapeutic armamentarium.

Gene–gene interaction analysis of personality traits in a Japanese population using an electrochemical DNA array chip analysis

It has been suggested that genes involved in the central dopaminergic pathway may contribute to personality traits. However, the results of association studies for these genes have not been consistent. The present study investigated the relationship between the specific polymorphisms of MAO-A, COMT, DRD2, DRD3 and personality traits in Japanese women using a novel genotyping method involving electrochemical DNA array (ECA) chip analysis. Single marker association analysis for each mutation revealed no significant association between scores for Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) items. Gene-gene interaction analysis showed that a MAO-A 30-bp repeatxCOMT (Val158Met)xDRD3 (Ser9Gly) had a marginally significant association with Agreeableness (P=0.0547). The present results suggest that a combination of polymorphisms of MAO-A, COMT, and DRD3 might affect personality traits in Japanese women.

Regional brain cerebral glucose metabolism and temperament : A positron emission tomography study

Personality, and in particular temperament, is thought to have a biological basis. In the present study, the relationships between regional brain glucose metabolism and temperament have been investigated. Regional brain glucose metabolism was measured using [18F] fluorodeoxyglucose positron emission tomography in 31 healthy subjects. Temperament was assessed using the Temperament and Character Inventory. Temperament dimensions were observed to be significantly correlated with specific brain regions. In particular, novelty seeking was significantly correlated with the superior temporal gyrus, inferior parietal lobule, and the precuneus, which have been reported to be related with impulsiveness, while reward dependence was significantly correlated with the caudate head, which has been shown to be associated with reward processing. The various aspects of temperament may have biological bases in the specific brain regions. The accumulation of results from studies of this kind should provide further evidence connecting personality traits with their biological bases.

Gender difference in relationship between anxiety-related personality traits and cerebral brain glucose metabolism.

Recent functional neuroimaging studies have suggested that specific brain regions might be associated with the formation of anxiety-related personality traits, which are well known to be influenced by gender. Such anxiety-related personality traits are one of the representative predisposing factors for mood and anxiety disorders, whose incidence is also known to be much influenced by gender. However, little is known about the gender differences in brain function related to anxiety-related personality traits. The aim of the present study was to examine gender-related differences in the pattern of the relationships between an anxiety-related personality trait and cerebral brain glucose metabolism. Regional brain glucose metabolism was measured using [(18)F]fluorodeoxyglucose positron emission tomography in 102 healthy subjects (65 males and 37 females). An anxiety-related trait was assessed using the Temperament and Character Inventory dimension Harm Avoidance (HA). HA was negatively correlated with glucose metabolism in the anterior portion of the ventromedial prefrontal cortex (vmPFC) in females but not in males. The anterior vmPFC may be a possible neural target for the prevention or therapy of emotional disorders, especially in females.

Hippocampal and Amygdalar Volumes in Breast Cancer Survivors with Posttraumatic Stress Disorder

Although smaller hippocampi and amygdalae were found in cancer survivors with intrusions, associations between cancer-related posttraumatic stress disorder (PTSD) and these volumes are unknown. The authors performed MRI volumetric analyses of these regions in 15 cancer survivors with PTSD, 15 cancer survivors without PTSD, and 15 healthy comparison subjects. The authors also examined the correlation between PTSD symptom scores of the Impact of Event Scale and these volumes in the PTSD group. These volumes were not significantly different among the groups, but the intrusion score was inversely associated with the hippocampal volume. Results suggest intrusions, not PTSD diagnosis, might be associated with hippocampal volume.

No association between monoamine oxidase A promoter polymorphism and personality traits in Japanese females

Monoamine oxidase A (MAO-A) is an enzyme involved in the metabolism of monoamine neurotransmitters such as dopamine, serotonin, and noradrenaline in the brain. Previous studies have demonstrated a significant association between MAO-A gene polymorphism and personality traits in males. The purpose of the present study was to examine this association in females. The subjects were 219 healthy Japanese females. We genotyped a variable number of tandem repeats located upstream of the MAO-A gene. Personality traits were assessed using the Temperament and Character Inventory (TCI). There was no association between any personality trait and MAO-A genotype. The present results do not support the hypothesis that MAO-A gene polymorphism is related to certain personality traits in females.

The neural correlates of mindful awareness: a possible buffering effect on anxiety-related reduction in subgenual anterior cingulate cortex activity.

Background 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). Methods 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. Results 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 β = −0.248, p = 0.003; ST: β = 0.250, p = 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, k = 423, Z = 4.41, corrected p FDR = 0.030). Conclusion 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.

Amygdala-centred functional connectivity affects daily cortisol concentrations: a putative link with anxiety

The amygdala plays a critical role in emotion. Its functional coupling with the hippocampus and ventromedial prefrontal cortex extending to a portion of the anterior cingulate cortex (ACC) is implicated in anxiogenesis and hypothalamic-pituitary-adrenal (HPA) system regulation. However, it remains unclear how amygdala-centred functional connectivity (FC) affects anxiety and cortisol concentrations in everyday life. Here, we investigate the relationship between daily cortisol concentrations (dCOR) and amygdala-centred FC during emotional processing in forty-one healthy humans. FC analyses revealed that higher dCOR predicted strengthened amygdala-centred FC with the hippocampus and cerebellum, but inhibited FC with the supramarginal gyrus and a perigenual part of the ACC (pgACC) when processing fearful faces (vs. neutral faces). Notably, the strength of amygdala-hippocampus FC mediated the positive relationship between cortisol and anxiety, specifically when the effect of amygdala-pgACC FC, a presumptive neural indicator of emotional control, was taken into account. Individuals with diminished connectivity between the amygdala and pgACC during fear-related processing might be more vulnerable to anxiogenesis as it pertains to greater circulating cortisol levels in everyday life. Individual functional patterns of amygdala-hippocampal-pgACC connectivity might provide a key to understand the complicate link between cortisol and anxiety-related behaviors.

Does neurocognitive function affect cognitive bias toward an emotional stimulus? Association between general attentional ability and attentional bias toward threat

Background: Although poorer cognitive performance has been found to be associated with anxiety, it remains unclear whether neurocognitive function affects biased cognitive processing toward emotional information. We investigated whether general cognitive function evaluated with a standard neuropsychological test predicts biased cognition, focusing on attentional bias toward threat. Methods: One hundred and five healthy young adults completed a dot-probe task measuring attentional bias and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measuring general cognitive function, which consists of five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Stepwise multiple regression analysis was performed to examine the relationship between attentional bias and cognitive function. Results: The attentional domain was the best predictor of attentional bias toward threat (β = −0.26, p = 0.006). Within the attentional domain, digit symbol coding was negatively correlated with attentional bias (r = −0.28, p = 0.005). Conclusions: The present study provides the first evidence that general attentional ability, which was assessed with a standard neuropsychological test, affects attentional bias toward threatening information. Individual cognitive profiles might be important for the measurement and modification of cognitive biases.

Higher cortisol levels at diurnal trough predict greater attentional bias towards threat in healthy young adults

BACKGROUND Attentional bias (AB), selective information processing towards threat, can exacerbate anxiety and depression. Despite growing interest, physiological determinants of AB are yet to be understood. We examined whether stress hormone cortisol and its diurnal variation pattern contribute to AB. METHODS Eighty-seven healthy young adults underwent assessments for AB, anxious personality traits, depressive symptoms, and attentional function. Salivary cortisol was collected at three time points daily (at awakening, 30 min after awakening, and bedtime) for 2 consecutive days. We performed: (1) multiple regression analysis to examine the relationships between AB and the other measures and (2) analysis of variance (ANOVA) between groups with different cortisol variation patterns for the other measures. RESULTS Multiple regression analysis revealed that higher cortisol levels at bedtime (p<0.001), an anxious personality trait (p=0.011), and years of education (p=0.036) were included in the optimal model to predict AB (adjusted R(2)=0.234, p<0.001). ANOVA further demonstrated significant mean differences in AB and depressive symptoms; individuals with blunted cortisol variation exhibited significantly greater AB and depression than those with moderate variation (p=0.037 and p=0.009, respectively). LIMITATIONS Neuropsychological assessment focused on attention and cortisol measurement at three time points daily. CONCLUSIONS We showed that higher cortisol levels at bedtime and blunted cortisol variation are associated with greater AB. Individuals who have higher cortisol levels at diurnal trough might be at risk of clinical anxiety or depression but could also derive more benefits from the attentional-bias-modification program.