Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions.

Background: The immune system has major roles in the brain and related psychopathology. Disrupted interleukin-6 secretion and aberrant amygdala emotional reactivity are well-documented in stress-related mental disorders. The amygdala regulates psychosocial stress-related interleukin-6 affected by related genes. These led us to comprehensively examine the relationship between interleukin-6, amygdala activity, and stress-related mental symptoms under gene-stressor interactions. Methods: One hundred eight nonclinical participants with various levels of anxiety/depression underwent magnetic resonance imaging scans during an emotional face task for amygdala activity and saliva collection (at 10-time points across 2 days) for the total output and diurnal patterns of interleukin-6. Gene-stressor interactions between rs1800796 (C/G) and rs2228145 (C/A) and stressful life events for the biobehavioral measures were explored. Results: The blunting of interleukin-6 diurnal pattern was associated with hypoactivation of the basolateral amygdala in response to fearful (vs. neutral) faces (t = 3.67, FWE-corrected p = 0.003), and was predominantly observed in individuals with rs1800796 C-allele homozygotes and negative life changes in the past year (F = 19.71, p < 0.001). When considered in a comprehensive model, the diminished diurnal pattern predicted greater depressive symptoms (ß = -0.40), modulated by the amygdala hypoactivity (ß = 0.36) and rs1800796-stressor interactions (ß = -0.41; all p < 0.001). Conclusion: Here we show that the blunted interleukin-6 diurnal rhythm predicts depressive symptoms, modulated by amygdala emotional hyporeactivity and gene-stressor interactions. These findings indicate a potential mechanism underlying vulnerability to depressive disorders, suggesting their early detection, prevention, and treatment through the understanding of immune system dysregulation.

Neurobiology of early life adversity: A systematic review of meta-analyses towards an integrative account of its neurobiological trajectories to mental disorders.

Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review has comprehensively integrated existing evidence across the fields: hypothalamic-pituitary-adrenal axis, immune/inflammatory system, neuroimaging, and genetics/epigenetics. We thus systematically reviewed previous meta-analyses towards an integrative account of ACE-related neurobiological alterations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a total of 27 meta-analyses until October 2021 were identified. This review found that individuals with ACEs possess blunted cortisol response to psychosocial stressors, low-grade inflammation evinced by increased C-reactive protein levels, exaggerated amygdalar response to emotionally negative information, and diminished hippocampal gray matter volume. Importantly, these alterations were consistently observed in those with and without psychiatric diagnosis. These findings were integrated and discussed in a schematic model of ACE-related neurobiological alterations. Future longitudinal research based on multidisciplinary approach is imperative for ACE-related mental disorders' prevention and treatment.

Association of childhood maltreatment history with salivary interleukin-6 diurnal patterns and C-reactive protein in healthy adults.

Childhood maltreatment has been associated with increased inflammation, as indicated by elevated levels of proinflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Studies in humans show that secretion of IL-6 follows a clear circadian rhythm, implying that its disturbed rhythm represents an important aspect of dysregulated inflammatory system. However, possible alterations in diurnal secretion patterns of IL-6 associated with childhood maltreatment have not been studied. Here we investigated this association in 116 healthy adults. Diurnal levels of IL-6 were examined using saliva samples collected at 5 times a day across 2 consecutive days. Salivary CRP levels were also determined by averaging measurements at 2 times a day for 2 days. Different types of childhood maltreatment were assessed with the Childhood Trauma Questionnaire (CTQ). CTQ total and emotional abuse scores were significantly correlated with smaller IL-6 diurnal variation as indexed by lower standard deviation across the measurement times (p = 0.024 and p = 0.008, respectively). Individuals with emotional abuse, as defined by a cut-off score of CTQ, showed flatter IL-6 rhythm than those without (p = 0.031). These results, both correlation and group comparison, remained significant after controlling for age, sex, and body mass index. Childhood maltreatment was not associated with total output of IL-6 or CRP. Our findings indicate that childhood trauma can have a long-term negative effect on the circadian rhythm of inflammatory system. The findings are consistent with those of previous studies on adulthood trauma, suggesting that the disrupted IL-6 rhythmicity may be associated with a broad range of trauma-related conditions.

Implicit and explicit emotional memory recall in anxiety and depression: Role of basolateral amygdala and cortisol-norepinephrine interaction.

Anxiety and depression are linked to both explicit and implicit memory biases, which are defined as the tendency to preferentially recall emotionally negative information at conscious and subconscious levels, respectively. Functional connectivity (FC) of the basolateral amygdala (BLA) and related stress hormones (i.e., cortisol and norepinephrine) are purportedly implicated in these biases. However, previous findings on memory biases in anxiety and depression have been inconsistent, likely due to their symptomatic complications. Therefore, the underlying neurobiological mechanism remains unclear. We thus investigated whether anxiety and depression as premorbid predispositions are related to the memory biases, and whether FC of BLA, cortisol, and 3-methoxy-4-hydroxyphenylglycol (MHPG: a major metabolite of norepinephrine) would affect the anxiety/depression-related biased memory recall in 100 participants without psychiatric symptomatology. Psycho-behavioral assessment, resting-state fMRI scans, and saliva collection at 10-points-in-time across two days were conducted. Correlations of memory biases with anxiety/depression and neurobiological markers were explored. As a result, neither anxiety nor depression were correlated with explicit memory bias to negative (vs. positive) information, although depression was associated with better recall of the negative stimuli only when they were perceived as self-relevant. In contrast, both anxiety and depression were correlated with implicit memory bias; however, the effects were solely explained by anxiety. Furthermore, FC of the BLA with subgenual anterior cingulate cortex (sgACC) and the synergetic effect of cortisol and MHPG uniquely affected the implicit memory bias. These findings suggest that anxiety facilitates an initial snapshot of negative information and can be accompanied by depression when the information creates negative semantic associations with the self. The BLA-sgACC neural connectivity and cortisol-norepinephrine interaction that are associated with the implicit memory bias might be one of the important neurobiological targets in the prevention and treatment for comorbid anxiety and depressive disorders.

Childhood trauma affects autobiographical memory deficits through basal cortisol and prefrontal-extrastriate functional connectivity.

BACKGROUND: Psychological trauma can damage the brain, especially in areas where glucocorticoid receptors are expressed, via perturbed secretion of cortisol. Childhood trauma is associated with blunted basal cortisol secretion, brain alterations, and autobiographical memory deficits referred to as overgeneral autobiographical memory (OGM). However, it remains unknown whether childhood trauma affects OGM through altered cortisol and brain alterations. METHODS: Using resting-state fMRI in 100 healthy humans, we examined whether childhood trauma affects OGM through its related basal cortisol and brain functional connectivity (FC). Trauma and OGM were assessed using the Childhood Trauma Questionnaire (CTQ) and Autobiographical Memory Test (AMT), respectively. Basal cortisol levels were measured by 10 points-in-time across two days. Multiple mediation analysis was employed. RESULTS: CTQ was associated with greater semantic-associate memory of OGM, a retrieval tendency toward semantic content with no specific contextual details of an experienced event, as well as blunted basal cortisol levels. While CTQ was correlated with decreased FC between the hippocampus and medial prefrontal cortex (PFC), it showed a more predominant correlation with increased FC between the lateral and anteromedial PFC and extrastriate cortex. Importantly, the increased prefrontal-extrastriate FC completely mediated the relationship between CTQ and semantic-associate memory, affected by hyposecretion of cortisol. CONCLUSION: Childhood trauma may lead to the lack of visuoperceptual contextual details in autobiographical memory by altering basal cortisol secretion and connectivity of the prefrontal-hippocampal-extrastriate regions. The intensified prefrontal-extrastriate connectivity may contribute to OGM formation by strengthening the semantic content in memory retrieval. Understanding the mechanisms underlying the trauma-cortisol-brain-memory link will provide important clinical implications for trauma-related mental disorders.

Childhood maltreatment history and attention bias variability in healthy adult women: role of inflammation and the BDNF Val66Met genotype.

Childhood maltreatment has been associated with greater attention bias to emotional information, but the findings are controversial. Recently, a novel index of attention bias, i.e., attention bias variability (ABV), has been developed to better capture trauma-related attentional dysfunction. However, ABV in relation to childhood trauma has not been studied. Here, we examined the association of childhood maltreatment history with attention bias/ABV in 128 healthy adult women. Different types of childhood maltreatment were assessed with the Childhood Trauma Questionnaire. Attention bias/ABV was measured by the dot-probe task. Possible mechanisms whereby childhood maltreatment affects attention bias/ABV were also explored, focusing on blood proinflammatory markers and the BDNF Val66Met polymorphism. We observed a significant positive correlation between childhood emotional abuse and ABV (P = 0.002). Serum high-sensitivity tumor necrosis factor-α levels were significantly positively correlated with ABV (P < 0.001), but not with childhood maltreatment. Jonckheere-Terpstra trend test showed a significant tendency toward greater ABV with increasing numbers of the BDNF Met alleles (P = 0.021). A two-way analysis of variance further revealed that the genotype-by-emotional abuse interaction for ABV was significant (P = 0.022); individuals with the Val/Met and Met/Met genotypes exhibited even greater ABV when childhood emotional abuse was present. These results indicate that childhood emotional abuse can have a long-term negative impact on emotional attention control. Increased inflammation may be involved in the mechanism of ABV, possibly independently of childhood maltreatment. The BDNF Met allele may dose-dependently increase ABV by interacting with childhood emotional abuse.

The BDNF Val66Met polymorphism affects negative memory bias in civilian women with PTSD.

Memory abnormalities are considered a core feature of posttraumatic stress disorder (PTSD). Studies attempting to quantify such memory dysfunction in PTSD have reported that individuals with this disorder exhibit selective memory bias toward negative material. The low expression Met allele of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with the aetiology of PTSD and with memory abnormalities. It is therefore possible that the BDNF Val66Met polymorphism can moderate the relationship between PTSD and memory bias. Here we examined this association in 50 civilian women with PTSD and 70 non-trauma-exposed healthy control women. All subjects were genotyped for the BDNF Val66Met (rs6265) polymorphism. Negative memory bias was assessed using a recognition memory task. Patients showed significantly greater negative memory bias compared to controls. In patients, negative memory bias significantly increased with increasing numbers of Met alleles; while no significant relationship was seen in controls. Further pairwise analyses revealed that patients with the Met allele had significantly greater negative memory bias than controls. These results suggest that the relationship between PTSD and negative memory bias can be moderated by the BDNF Val66Met polymorphism. More studies are needed to further clarify the relationship between this polymorphism and memory abnormalities in PTSD.

Basolateral Amygdala Connectivity With Subgenual Anterior Cingulate Cortex Represents Enhanced Fear-Related Memory Encoding in Anxious Humans.

BACKGROUND: The amygdala can enhance emotional memory encoding as well as anxiogenesis via corticotropin-releasing factor neurons. However, the amygdala's explicit role in emotional encoding remains unclarified in humans. We examined how functional connectivity (FC) of amygdala subnuclei affects emotional encoding, considering its mechanism in which anxiety, attention, and cortisol conceivably participate. METHODS: A total of 65 healthy humans underwent resting-state functional magnetic resonance imaging scans and saliva collection at 10 points in time over 2 days. FC analysis was performed for basolateral amygdala subnucleus (BLA) and centromedial amygdala subnucleus. We assessed attentional control via an emotional Stroop task and assessed emotional encoding via a facial identification task that examines how strongly a neutral face is memorized when accompanied by an emotional face (fearful, sad, or happy). FC and task performance were compared between high-anxious and non-high-anxious groups classified by anxious personality scores. RESULTS: BLA connected with subgenual anterior cingulate cortex (sgACC) in proportion to the strength of fear-related encoding, whereas centromedial subnucleus connected with caudate nucleus for happy-related encoding. The high-anxious group showed more enhanced fear-related encoding but impaired happy-related encoding compared with the non-high-anxious group. BLA-sgACC FC was more intensified in the high-anxious group than in the non-high-anxious group; however, centromedial-caudate FC did not differ between them. Although emotional encoding was uncorrelated with either attentional control or cortisol, BLA-sgACC was positively correlated with cortisol increase after awakening. CONCLUSIONS: The study revealed that neural interactions of BLA, specifically with sgACC, might play a critical role in fear-related memory encoding, depending on the individual's level of anxiety. These findings aid in understanding the complicated mechanisms of emotional memory in anxiety disorders.

Cortisol-related hippocampal-extrastriate functional connectivity explains the adverse effect of cortisol on visuospatial retrieval.

Cortisol is known to affect visuospatial memory through its major binding site in the brain, the hippocampus. The synchronization of neural activity between the hippocampus, prefrontal cortex (PFC), and visual cortex is presumed to be essential for the formation of visuospatial memory because of their visuospatial learning-dependent neuroplasticity. However, it remains unclear how hippocampal connectivity with the PFC and visual cortex is involved in the relationship between cortisol and visuospatial memory in humans. We thus investigated whether functional connectivity (FC) of the hippocampus, specifically its rostral and caudal subdivisions, mediates the relationship between visuospatial memory and endogenous cortisol. One-hundred sixty-six healthy young adults underwent standard neuropsychological tests to assess visuospatial construction (a complex figure copying test) and retrieval (the corresponding recall test) and collected their saliva at 6-time points across 2 consecutive days for measurement of daily cortisol concentrations (dCOR). Ninety of them received resting-state fMRI scans. Greater dCOR was significantly associated with better figure copying performance, but contrastingly with poorer figure recall. In proportion to dCOR, the rostral hippocampus (rHC) showed significantly increased FC with the PFC (including its dorsolateral and medial parts) and the inferior lateral occipital cortex (iLOC), while the caudal hippocampus had increased FC with the anterior middle temporal cortex. Of the cortisol-related hippocampal connectivity, the rHC-iLOC FC was specifically correlated with figure recall and showed complete mediation for the negative relationship of dCOR with figure recall. These results suggest that cortisol might have enhancing effects on visuospatial encoding as well as impairing effects on visuospatial retrieval, possibly due to its occupancy patterns of corticosteroid receptors. Cortisol's adverse effects on visuospatial retrieval might be explained through cortisol-related rostral hippocampal connectivity with the iLOC, which is a part of the extrastriate cortex implicated in visuospatial perception. Thorough dissection of hippocampal-prefrontal-extrastriate connectivity might facilitate the understanding of neural mechanisms underlying cortisol's contrasting effects on encoding (or consolidation) and retrieval of visuospatial information.

Effects of zolpidem/triazolam on cognitive performance 12 hours after acute administration.

OBJECTIVE: Most previous studies have concluded that decreased cognitive function and performance due to ultra-short acting hypnotics do not persist after 6-9 h post-administration. This study examined the effects of ultra-short acting hypnotics on cognitive function and performance 12 h after administration, ie, a time considered sufficient for the effects of hypnotics to disappear. METHODS: Thirteen healthy young male volunteers (mean age, 23.4 ± 3.2 years) participated in this study. Participants attended three sessions of polysomnography (PSG) recording preceded by oral administration of placebo for the first session, and 5 mg zolpidem or 0.25 mg triazolam for the second and third sessions, in a double-blinded, randomized manner at intervals of at least five days. A cognitive test battery was administered following each session, consisting of a psychomotor vigilance task (PVT), which reflects alertness and sleepiness, digit symbol substitution test (DSST), which reflects attention and working memory function, and assessment of subjective sleepiness and mental condition using a visual analog scale (VAS). RESULTS AND CONCLUSIONS: The administration of hypnotics significantly increased total sleep time, sleep efficiency, and sleep stages 2 and 4, and significantly decreased wake after sleep onset and sleep stage 1. PVT parameters were not affected by the administration of hypnotics, but DSST score was significantly lower, and "subjective alertness," "vigor," and "sadness" significantly deteriorated, after administration. In conclusion, while objective sleepiness disappeared 12 h after the administration of ultra-short acting hypnotics, their effects to decrease cognitive function persisted even after 12 h post-administration.

Attentional bias modification alters intrinsic functional network of attentional control: A randomized controlled trial.

INTRODUCTION: Attentional bias modification (ABM) alleviates anxiety by moderating biased attentional processing toward threat; however, its neural mechanisms remain unclear. We examined how ABM changes functional connectivity (FC) and functional network measures, leading to anxiety reduction. METHODS: Fifty-four healthy anxious individuals received either ABM or sham training for 1 month in a double-blind randomized controlled trial. Anxious traits, attentional control, and attentional bias were assessed. Thirty-five participants completed resting-state functional magnetic resonance imaging (MRI) scans before and after training. RESULTS: ABM significantly mitigated an anxious traits regarding physical stress vulnerability (η2 = 0.12, p = 0.009). As compared to sham training, ABM significantly strengthened FC between the pulvinar and transverse temporal gyrus along the temporoparietal junction (T = 3.90, FDR-correctedp = 0.010), whereas it decreased FC between the postCG and ventral fronto-parietal network (vFPN) regions such as the anterior insula and ventrolateral prefrontal cortex (all T ≤ - 3.19, FDR-correctedp ≤ 0.034). Although ABM diminished network measures of the postcentral gyrus (postCG) (all T ≤ - 4.30, FDR-correctedp ≤ 0.006), only the pulvinar-related FC increase was specifically correlated with anxiety reduction (r = - 0.46, p = 0.007). LIMITATIONS: Per-protocol analysis and reduced sample size in MRI analysis. CONCLUSIONS: ABM might augment the pulvinar's control over vFPN to maintain endogenous attention to a behavioral goal, while diminishing the information exchanges of the postCG with vFPN to inhibit the capture of exogenous attention by potential threats. The pulvinar might play a critical role in ABM anxiolytic efficacy.

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.

The functional activity and effective connectivity of pulvinar are modulated by individual differences in threat-related attentional bias.

The pulvinar is important in selective attention, particularly to visual stimuli under the focus of attention. However, the pulvinar is assumed to process emotional stimuli even outside the focus of attention, because of its tight connection with the amygdala. We therefore investigated how unattended emotional stimuli affect the pulvinar and its effective connectivity (EC) while considering individual differences in selective attention. fMRI in 41 healthy human subjects revealed that the amygdala, but not the pulvinar, more strongly responded to unattended fearful faces than to unattended neutral faces (UF > UN), although we observed greater EC from the pulvinar to the amygdala. Interestingly, individuals with biased attention toward threat (i.e., attentional bias) showed significantly increased activity (UF > UN) and reduced grey matter volume in the pulvinar. These individuals also exhibited stronger EC from the pulvinar to the attention-related frontoparietal network (FPN), whereas individuals with greater attentional control showed more enhanced EC from the pulvinar to the amygdala, but not the FPN (UF > UN). The pulvinar may filter unattended emotional stimuli whose sensitivity depends on individual threat-related attentional bias. The connectivity patterns of the pulvinar may thus be determined based on individual differences in threat-related attentional bias and attentional control.

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 (ß = -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.

[Sleep disorders].

Some sleep disorders and sleep problems are reported as risk of dementia. It is reported that 50-80% of idiopathic REM sleep behavior had a later conversion to a synucleinopathy, thus this parasomnia is regarded as early marker of Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Obstructive sleep apnea syndrome causes reversible decline of cognitive functions in children and adults, and it increases the risk of dementia and mild cognitive impairment in elderly women. A decrease of amplitude of circadian activity rhythm and habitual long sleep duration (> or = 9 hours) are reported to increase the risk of dementia in elderly people. Some reports indicate that hypnotic use may be a risk factor of dementia. However, it is not cleared whether insomnia itself related with dementia or not, since no study evaluated the risk of insomnia without hypnotic treatment.

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 [(18)F] 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 ß = -0.248, p = 0.003; ST: ß = 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.

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.

[Definitions and clinical classifications of sleep disorders].

Sleep disorders are defined as disorders which symptoms or pathophysiology are related with sleep regardless of comorbid physical and/or mental disorders. Sleep disorders are classified into 6 major categories: sleep related breathing disorders which exhibit abnormal breathing during sleep, sleep related movement disorders which show involuntary movements and/or abnormal sensations during sleep and/or nighttime, hypersomnia of central origin not due to other sleep disorders, circadian rhythm sleep disorders due to desynchronization between sleep-wake pattern and required social schedule, parasomnia which exhibit abnormal behavior during sleep and/or around sleep, and insomnia not due to other sleep disorders.

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 Hedge's 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.

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.