Rare CRHR2 and GRM8 variants identified as candidate factors associated with eating disorders in Japanese patients by whole exome sequencing.

Eating disorders (EDs) are a type of psychiatric disorder characterized by pathological eating and related behavior and considered to be highly heritable. The purpose of this study was to explore rare variants expected to display biological functions associated with the etiology of EDs. We performed whole exome sequencing (WES) of affected sib-pairs corresponding to disease subtype through their lifetime and their parents. From those results, rare single nucleotide variants (SNVs) concordant with sib-pairs were extracted and estimated to be most deleterious in the examined families. Two non-synonymous SNVs located on corticotropin-releasing hormone receptor 2 (CRHR2) and glutamate metabotropic receptor 8 (GRM8) were identified as candidate disease susceptibility factors. The SNV of CRHR2 was included within the cholesterol binding motif of the transmembrane helix region, while the SNV of GRM8 was found to contribute to hydrogen bonds for an α-helix structure. CRHR2 plays important roles in the serotoninergic system of dorsal raphe nuclei, which is involved with feeding and stress-coping behavior, whereas GRM8 modulates glutamatergic neurotransmission. Moreover, GRM8 modulates glutamatergic neurotransmission, and is also considered to have effects on dopaminergic and adrenergic neurotransmission. Thus, identification of rare and deleterious variants in this study is expected to increase understanding and treatment of affected individuals. Further investigation regarding the biological function of these variants may provide an opportunity to elucidate the pathogenesis of EDs.

Factors associated with the improvement of body image dissatisfaction of female patients with overweight and obesity during cognitive behavioral therapy.

Background: Cognitive behavioral therapy (CBT) has become one of the most commonly used psychotherapeutic treatments for obesity. It stems from CBT for bulimia nervosa and binge eating disorder, which focuses on amelioration of the eating behavior and body image dissatisfaction (BID), but usually does not focus on weight loss. In contrast, CBT for obesity focuses on weight loss, as well as eating behavior and BID. It is at present unclear whether the improvement of BID during CBT for obesity is associated with improvement of factors other than weight loss. Objective: The purpose of this study was to determine whether improvement of BID during CBT for obesity was associated with improvement of factors other than weight loss. Methods: One hundred and sixty-five women (BMI 31.8 ± 5.2 kg/m2, age 49.3 ± 10.5 years) with overweight or obesity completed a 7-month CBT-based weight loss intervention. BID, depression, anxiety, binge eating, and perfectionism were assessed at both baseline and the end of the intervention through the use of psychological questionnaires. Results: Percent total weight loss, baseline BID, baseline binge eating disorder (BED), change in depression (Δdepression), Δstate anxiety, Δtrait anxiety, Δbinge eating, and Δperfectionism were significantly correlated with ΔBID. Multiple regression analysis showed that baseline BID, baseline BED, percent total weight loss, Δbinge eating, and Δdepression were independently associated with ΔBID. Conclusion: Improvement of binge eating, and improvement of depression, as well as weight loss, were independently associated with amelioration of BID. Clinical trial registration: [https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008052], identifier [UMIN000006803] and [https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R0000 55850], identifier [UMIN000049041].

Psychometric properties of the Eating Disorder Examination-Questionnaire and psychopathology in Japanese patients with eating disorders.

OBJECTIVE: The Eating Disorder Examination-Questionnaire (EDE-Q) is one of the most widely used tools to assess the core psychopathology of eating disorders (ED). However, recent empirical findings did not support the original four-factor structure. The aims of the present study were to investigate the factor structure of the EDE-Q in Japanese ED patients, to test the reliability and convergent validity of the EDE-Q, to examine group differences between various ED groups and healthy participants, and to explore the main behavioral features of Japanese ED patients using the newly developed Japanese version of EDE-Q. METHOD: A total of 148 ED patients and 469 healthy participants completed the EDE-Q, Eating Attitudes Test-26 (EAT-26), and Eating Disorder Inventory-2 (EDI-2). The factor structure, reliability, and validity of the EDE-Q were assessed in ED patients. Group differences were assessed using the new Japanese version of the EDE-Q (EDE-Q-J). RESULTS: The EDE-Q-J had three factors. Cronbach's alphas ranged from 0.83 to 0.93. Total score and subscale scores of "Dieting" and "Bulimia and Food Preoccupation" of EAT-26 and of "Drive for Thinness," "Body Dissatisfaction," and "Bulimia" of EDI-2 correlated with the global score and three subscale scores of the EDE-Q-J. DISCUSSION: For Japanese female ED patients, the EDE-Q-J had three subscales that were not consistent with the original subscales, but were interpretable. It demonstrated sufficient reliability and validity. Japanese female patients with restricting-type anorexia nervosa (AN-R) displayed less dissatisfaction with shape and weight than healthy participants. AN-R patients in Japan might present with a non-fat-phobic symptom profile.

Reliability and validity of the Japanese translation of the Eating Disorders Quality of Life (ED-QOL) scale for Japanese healthy female university undergraduate students and patients with eating disorders.

BACKGROUND: The Eating Disorder Quality of Life (ED-QOL) scale is a 25-item self-report measure that assesses health-related quality of life (HRQoL) of eating-disorder patients. Although the ED-QOL is one of the most widely used questionnaires in many countries, no prior research has addressed the psychometric properties of the Japanese translation of the ED-QOL. Therefore, the aim of the present study was to assess its reliability and validity. METHODS: A total of 99 Japanese female eating disorder patients and 469 female healthy university undergraduate students completed the Japanese translation of the ED-QOL in addition to the Eating Attitudes Test-26 (EAT-26) and Eating Disorder Inventory-2 (EDI-2). The patient group consisted of 37 patients with anorexia nervosa restricting type (AN-R), 35 patients with binge-eating/purge type (AN-BP), and 27 patients with bulimia nervosa (BN). We performed confirmatory factor analyses on the ED-QOL subscales both for Japanese eating disorder patients and for healthy university undergraduate students. Reliability was assessed using internal consistency indicated by Cronbach alpha coefficients and convergent validity was assessed using Pearson's correlation coefficients. To assess group differences between the eating disorder patients and healthy university undergraduate students, Student's t-tests were conducted. RESULTS: The CFA showed that the CFI was .90 and RMSEA was .084 (90% confidence interval = .079-.088). The internal consistency of the ED-QOL varied from good to excellent. The EAT-26 total score and three subscales and the EDI-2 subscales had significant correlations with the ED-QOL global QOL score and four subscales. There were no significant correlations between the EDI-2 subscale "Body Dissatisfaction" and the ED-QOL subscales "Physical/Cognitive" and "Work/School". Eating disorder patients scored significantly higher than healthy university undergraduate students on all ED-QOL subscales and the global QOL score. CONCLUSIONS: Based on this study, the Japanese translation of the ED-QOL can be regarded as reliable, valid, and functional for female eating-disorder patients and female healthy university undergraduate students.

Urocortin 1: A putative excitatory neurotransmitter in the enteric nervous system.

BACKGROUND: Urocortin 1 (Ucn1), a stress-related peptide, is a member of the corticotropin-releasing factor (CRF) family and acts as a CRF1 receptor agonist. Ucn1 and CRF1 receptor immunoreactivity are present in the enteric nervous system (ENS), and Ucn1 elicits contraction of colonic muscle strips. Considering these findings, we have hypothesized that Ucn1 acts as an excitatory neurotransmitter in the ENS. The present study was conducted to determine whether exogenously applied Ucn1 causes contractions, whether it participates in neurally mediated contraction, and whether it is released from the ENS of the rat colon. METHODS: Isometric tension of the rat colonic muscle strips (middle to distal colon) in a longitudinal direction was measured. The effects of Ucn1 on phasic contractions were examined in the absence and presence of antalarmin (CRF1 receptor antagonist), tetrodotoxin (TTX), and atropine. The effects of antalarmin on electrical field stimulation (EFS)-induced contractions were examined in the absence and presence of atropine. Ucn1 peptide in the bath solution was measured after EFS using an EIA kit. KEY RESULTS: Ucn1 caused a significant and dose-dependent increase in phasic contractions. These effects were completely inhibited by antalarmin, TTX, and atropine. EFS-induced contractions were inhibited by antalarmin. Atropine markedly reduced EFS-induced contractions, and antalarmin did not decrease these contractions further. EFS elicited a significant increase in the concentration of Ucn1 in the bath solution, and this increase was completely inhibited by TTX. CONCLUSIONS AND INFERENCES: These results suggest that Ucn1 acts as an excitatory neurotransmitter in the ENS enhancing the cholinergic neurotransmission.

Effects of Weight Loss on Sweet Taste Preference and Palatability following Cognitive Behavioral Therapy for Women with Obesity.

OBJECTIVE: Current evidence suggests that obesity is associated with alteration of sweet taste perception. The purpose of this study was to determine if nonsurgical cognitive behavioral therapy (CBT)-based weight loss can cause a change in sweet taste perception. METHODS: This case-control study consisted of 51 women aged 21-64 years. Twenty-seven with obesity or overweight were assigned to an obesity (OB) group (BMI: 29.8 ± 0.5 kg/m2) and 24 to a normal control (NC) group (BMI: 20.9 ± 0.3 kg/m2). The OB group underwent a 30-week weight loss intervention using CBT-based group therapy. The results of measurement of detection threshold, suprathreshold perceived intensity, preference, and palatability, elements of sweet taste perception, were compared before and after the intervention. Psychological variables and appetite-related hormonal levels were measured. RESULTS: Twenty-three patients and 22 controls completed the study. The OB group showed a 14.6% weight loss after the intervention. At baseline, the OB group preferred significantly higher sucrose concentrations than did the NC group; however, this difference was no longer significant after intervention. In the OB group, persistent pleasure and reduced desire for other taste, measured by repeated exposure to sweetness, normalized after weight loss to levels comparable to those seen in the NC group. No significant difference in discriminative perception of the threshold concentration or the suprathreshold sensory value was found between the two groups before or after intervention. A significant correlation was found between the basal preferred sucrose concentration and the serum leptin level of the OB group after adjusting for confounding factors, such as BMI, depressive symptom score, and trait-anxiety scores. CONCLUSIONS: Weight loss induced by CBT-based nonsurgical intervention resulted in the normalization of the sucrose preference and palatability of women with obesity. Leptin activity may be associated with the altered sweet taste preference of people with obesity.

Neural correlates of body comparison and weight estimation in weight-recovered anorexia nervosa: a functional magnetic resonance imaging study.

BACKGROUND: The neural mechanisms underlying body dissatisfaction and emotional problems evoked by social comparisons in patients with anorexia nervosa (AN) are currently unclear. Here, we elucidate patterns of brain activation among recovered patients with AN (recAN) during body comparison and weight estimation with functional magnetic resonance imaging (fMRI). METHODS: We used fMRI to examine 12 patients with recAN and 13 healthy controls while they performed body comparison and weight estimation tasks with images of underweight, healthy weight, and overweight female bodies. In the body comparison task, participants rated their anxiety levels while comparing their own body with the presented image. In the weight estimation task, participants estimated the weight of the body in the presented image. We used between-group region of interest (ROI) analyses of the blood oxygen level dependent (BOLD) signal to analyze differences in brain activation patterns between the groups. In addition, to investigate activation outside predetermined ROIs, we performed an exploratory whole-brain analysis to identify group differences. RESULTS: We found that, compared to healthy controls, patients with recAN exhibited significantly greater activation in the pregenual anterior cingulate cortex (pgACC) when comparing their own bodies with images of underweight female bodies. In addition, we found that, compared with healthy controls, patients with recAN exhibited significantly smaller activation in the middle temporal gyrus corresponding to the extrastriate body area (EBA) when comparing their own bodies, irrespective of weight, during self-other comparisons of body shape. CONCLUSIONS: Our findings from a group of patients with recAN suggest that the pathology of AN may lie in an inability to regulate negative affect in response to body images via pgACC activation during body comparisons. The findings also suggest that altered body image processing in the brain persists even after recovery from AN.

Predictors of successful long-term weight loss maintenance: a two-year follow-up.

BACKGROUND: Weight regain is a common problem following weight loss intervention, with most people who seek treatment for obesity able to lose weight, but few able to sustain the changes in behavior required to prevent subsequent weight regain. The identification of factors that predict which patients will successfully maintain weight loss or who are at risk of weight regain after weight loss intervention is necessary to improve the current weight maintenance strategies. The aim of the present study is identify factors associated with successful weight loss maintenance by women with overweight or obesity who completed group cognitive behavioral treatment (CBT) for weight loss. METHODS: Ninety women with overweight or obesity completed a 7-month weight loss intervention. The data of 86 who completed follow-up surveys 12 and 24 months after the end of the treatment was analyzed. Depression, anxiety, binge eating, food addiction, and eating behaviors were assessed before and after the weight loss intervention. Participants who lost at least 10% of their initial weight during the weight loss intervention and had maintained the loss at the month 24 follow-up were defined as successful. RESULTS: The intervention was successful for 27 participants (31.3%) and unsuccessful for 59 (68.6%). Multiple logistic regression analysis extracted larger weight reduction during the weight loss intervention, a lower disinhibition score, and a low food addiction score at the end of the weight loss intervention as associated with successful weight loss maintenance. CONCLUSION: The results suggest that larger weight reduction during the weight loss intervention and lower levels of disinhibition and food addiction at the end of the weight loss intervention predicted successful weight loss maintenance. TRIAL REGISTRATION: Trial registry name: Development and validation of effective treatments of weight loss and weight-loss maintenance using cognitive behavioral therapy for obese patients. Registration ID: UMIN000006803 Registered 1 January 2012. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000008052.

Psychometric properties of the eating disorder examination-questionnaire in Japanese adolescents.

BACKGROUND: Although the Eating Disorder Examination Questionnaire version 6.0 (EDE-Q) is one of the most widely used questionnaires for eating disorders in Western countries, no research has addressed the psychometric properties of the EDE-Q in a Japanese sample. METHODS: We explored the factor structure of the EDE-Q and examined the internal consistency of the derived scales for Japanese participants (Study I), the convergent validity with other eating disorder-related psychological measures (Study II) and the distinction between the derived two body image-related factors with psychological measures (StudyIII). The EDE-Q was administered to 1,430 undergraduate students in Study I and in Study II was subsequently assessed by two self-report measures of eating pathology, the Eating Attitudes Test (EAT-26) for 558 undergraduate students and the Eating Disorders Inventory-II (EDI-II) 111. In StudyIII, another 225 undergraduate students participated in an examination of the relationships of the derived body image-related subscales of the EDE-Q with the psychological measures of the Rosenberg Self-Esteem Scale, Beck Depression Inventory, Public Self-Consciousness Scale, and Multidimensional Perfectionism Scale. RESULTS: Exploratory factor analysis of the EDE-Q identified four meaningful factors. Of the original four EDE-Q factors, "Restriction" and "Eating Concern" were retained. However, the other two factors, "Shape" and "Weight" Concerns, were combined into two different factors: "Fear of Obesity" and "Self-Esteem Based on Shape and Weight". Internal consistency of the derived four factors was adequate, and the relationships with EDI-II and EAT-26 measures demonstrated convergent validity. Analysis of the distinction between "Fear of Obesity" and "Self-Esteem Based on Shape and Weight" revealed that only "Self-Esteem Based on Shape and Weight" was significantly associated with the measures assessing psychopathology related to eating disorders. CONCLUSIONS: This study describes restructured factors of the EDE-Q that were tested with undergraduate students. The distinction between two factors, "Fear of Obesity" and "Self-Esteem Based on Shape and Weight", may further the understanding of the psychopathology of the eating disorders of adolescent Japanese subjects to facilitate future developments in research and treatment.

Factors associated with caregiving burden and mental health conditions in caregivers of patients with anorexia nervosa in Japan.

BACKGROUND: There are no studies about the caregiving burdens in families of patients with eating disorders in Japan, and only limited studies on the role of caregivers' stress coping, social support, and mental health. This study examines caregiving burdens, mental health conditions, and associated factors in caregivers of anorexia nervosa (AN) patients in Japan. METHODS: Seventy-nine principal caregivers (70 mothers, 5 fathers, 3 spouses and 1 grandmother; mean age 56.0 ± 8.0 years) for outpatients with AN (all female; mean age 26.6 ± 7.9 years; BMI 14.6 ± 3.2 kg/m(2)) were evaluated using self-report questionnaires in a cross-sectional study. The questionnaires included caregiving burden (J-ZBI_8), mental health conditions (GHQ28), stress coping styles (CISS), social support (SNQ), severity of the patient's symptoms from the family's perspective (ABOS), and family functioning (GF-FAD). Clinical information about the patients was also obtained. RESULTS: Mean caregiving burden assessed by J-ZBI_8 score was 12.4 ± 7.0 (SD). The total GHQ score was 31.6 ± 13.7 (Likert scoring) and 9.2 ± 7.0 (GHQ scoring). Of the respondents, 48 (60.7 %) indicated a high risk for mental health problems that exceeded the cutoff point of the GHQ. Significantly higher caregiving burden and poor mental health conditions were shown in the group who had contact with patients > 6 h a day compared to the group with daily patient contact < 3 h (F (2, 76) = 3.19, p = 0.047 and F (2, 76) = 9.39, p < 0.001, respectively). Stepwise multiple regression analysis indicated that the factors that significantly predicted the caregiving burden were severity of the patient's symptoms from the family's perspective (ß = 0.47, p < 0.001) and Emotion-Oriented Coping (ß = 0.38, p = 0.002) (R(2) = 0.401), while predictors of mental health conditions were Emotion-Oriented Coping (ß = 0.522, p < 0.001), Affective Support (ß = -0.419, p < 0.001), and contact time with patient (ß = 0.201, p = 0.042) (R(2) = 0.602). CONCLUSION: Caregivers of AN patients experienced heavy burdens and manifested poor mental health conditions. The severity of the patient's symptoms from the family's perspective and the greater use of emotion-oriented coping were associated with higher burdens. Greater use of emotion-oriented coping, less affective support and longer contact with patients were related to worse mental health conditions. Interventions to promote caregivers' adaptive coping styles may help reduce their caregiving burden and improve their mental health.

Predictors of Dropout by Female Obese Patients Treated with a Group Cognitive Behavioral Therapy to Promote Weight Loss.

OBJECTIVE: To investigate predictors of dropout from a group cognitive behavioral therapy (CBT) intervention for overweight or obese women. METHODS: 119 overweight and obese Japanese women aged 25-65 years who attended an outpatient weight loss intervention were followed throughout the 7-month weight loss phase. Somatic characteristics, socioeconomic status, obesity-related diseases, diet and exercise habits, and psychological variables (depression, anxiety, self-esteem, alexithymia, parenting style, perfectionism, and eating attitude) were assessed at baseline. Significant variables, extracted by univariate statistical analysis, were then used as independent variables in a stepwise multiple logistic regression analysis with dropout as the dependent variable. RESULTS: 90 participants completed the weight loss phase, giving a dropout rate of 24.4%. The multiple logistic regression analysis demonstrated that compared to completers the dropouts had significantly stronger body shape concern, tended to not have jobs, perceived their mothers to be less caring, and were more disorganized in temperament. Of all these factors, the best predictor of dropout was shape concern. CONCLUSION: Shape concern, job condition, parenting care, and organization predicted dropout from the group CBT weight loss intervention for overweight or obese Japanese women.

The outcome of treatment for anorexia nervosa inpatients who required urgent hospitalization.

BACKGROUND: This study was done to determine which psychosocial factors are related to the urgent hospitalization of anorexia nervosa patients (AN) due to extremely poor physical condition and to evaluate their outcome after inpatient treatment. METHODS: 133 hospitalized AN patients were classified into an urgent hospitalization (n = 24) or a planned hospitalization (n = 109) group. Multiple regression analysis was done of clinical features, body mass index (BMI), psychological tests [The Minnesota Multiphasic Personality Inventory (MMPI), alexithymia, relationship with parents, and the Eating Disorder Inventory (EDI)]. The effectiveness of treatment was prospectively determined two years after discharge by the Global Clinical Score (GCS). The hospitalized weight gain and the frequency of outpatient visits were evaluated. RESULTS: Of the factors assessed, only BMI at admission was related to the necessity of urgent hospitalization (ß = - 1.063, P = 0.00). The urgent group had significantly more weight loss after discharge and poorer social adaptation on the GCS, even when the patient had a sufficient increase in body weight during inpatient treatment and an equivalent number of outpatient consultations. CONCLUSION: None of the parameters of the psychosocial tests studied were significantly different between the groups. The outcome of the urgent group was poor. Two years after discharge they had difficulty maintaining weight and continued to have poor social adaptation.

Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population.

The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653-0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557-0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

Neuroimaging studies of alexithymia: physical, affective, and social perspectives.

Alexithymia refers to difficulty in identifying and expressing one's emotions, and it is related to disturbed emotional regulation. It was originally proposed as a personality trait that plays a central role in psychosomatic diseases. This review of neuroimaging studies on alexithymia suggests that alexithymia is associated with reduced neural responses to emotional stimuli from the external environment, as well as with reduced activity during imagery, in the limbic and paralimbic areas (i.e., amygdala, insula, anterior/posterior cingulate cortex). In contrast, alexithymia is also known to be associated with enhanced neural activity in somatosensory and sensorimotor regions, including the insula. Moreover, neural activity in the medial, prefrontal, and insula cortex was lowered when people with alexithymia were involved in social tasks. Because most neuroimaging studies have been based on sampling by self-reported questionnaires, the contrasted features of neural activities in response to internal and external emotional stimuli need to be elucidated. The social and emotional responses of people with alexithymia are discussed and recommendations for future research are presented.

Diurnal variation of tension-type headache intensity and exacerbation: An investigation using computerized ecological momentary assessment.

BACKGROUNDS: Tension-type headache is a common psychosomatic disease. However, diurnal variation of headache is yet to be clarified, perhaps due to the lack of an appropriate method to investigate it. Like other painful diseases, it would be helpful to know if there is diurnal variation in tension-type headaches, both for managing headaches and understanding their pathophysiology. The aim of this study was to determine if there is diurnal variation in the intensity and exacerbation of tension-type headache. METHODS: Patients (N = 31) with tension-type headache recorded for one week their momentary headache intensity several times a day and their acute headache exacerbations using a watch-type computer as an electronic diary (computerized ecological momentary assessment). Multilevel modeling was used to test the effects of time of day on momentary headache intensity and on the occurrence of acute exacerbations. RESULTS: A significant diurnal variation in momentary headache intensity was shown (P = 0.0005), with the weakest headaches in the morning and a peak in the late afternoon. A between-individual difference in the diurnal pattern was suggested. On-demand medication use was associated with a different diurnal pattern (P = 0.025), suggesting that headache intensity decreases earlier in the evening in subjects who used on-demand medication, while headache subtype, prophylactic medication use, and sex were not associated with the difference. The occurrence of acute headache exacerbation also showed a significant diurnal variation, with a peak after noon (P = 0.0015). CONCLUSIONS: Tension-type headache was shown to have a significant diurnal variation. The relation to pathophysiology and psychosocial aspects needs to be further explored.

Daily physical complaints and hippocampal function: an fMRI study of pain modulation by anxiety.

Pain is a popular physical complaint in human. It is known that experimental anxiety modulates pain processing through hippocampal amplification, whereas it is not known whether a similar experimental reaction is related to daily physical complaints known as 'somatization'. The purpose of this study is to investigate the neural correlates of pain modulation induced by anxiety, particularly in the hippocampus, and how individual differences in this neural reaction relate to somatization. We measured neural response to noxious electrical stimulations, as well as the response to the preceding visual anticipatory cues (which induced low anxiety or high anxiety), by functional magnetic resonance imaging (fMRI). Individual daily physical symptoms were assessed by using the somatization subscale of the Symptom Checklist 90 revised (SCL-90-R). Correlation coefficients between the neural activations and the somatization scores were calculated. We found that manifestation of daily physical symptoms was related to smaller differences in hippocampus activation between high and low anxiety states, suggesting that the ability of the hippocampus to distinguish anxiety states was weakened by the chronic condition that caused the daily physical symptoms. The proper inhibition of neural activation in low anxiety states in the hippocampus and the anterior insula was observed to occur in companionship with lower daily physical complaints. These findings indicate that anxiety's alteration of the network that includes the hippocampus and that is associated with pain modulation underlies the manifestation of somatization.

No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese.

The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785-1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.

Does sleep aggravate tension-type headache?: An investigation using computerized ecological momentary assessment and actigraphy.

BACKGROUND: Both insufficient sleep and oversleeping have been reported as precipitating and aggravating factors of tension-type headache (TTH). However, previous studies relied on recalled self-reports, and the relationship has not been confirmed prospectively and objectively in a daily life situation. Recently, ecological momentary assessment (EMA) using electronic diaries, i.e., computerized EMA, is used to record subjective symptoms with the advantages of avoiding recall bias and faked compliance in daily settings. In addition, actigraphy has become an established method to assess sleep outside laboratories. Therefore, the aim of this study was to investigate the within-individual effect of sleep on the following momentary headache intensity in TTH patients during their daily lives utilizing EMA and actigraphy. METHODS: Twenty-seven patients with TTH wore watch-type computers as electronic diaries for seven consecutive days and recorded their momentary headache intensity using a visual analog scale of 0-100 approximately every six hours, on waking up, when going to bed, and at the time of headache exacerbations. They also recorded their self-report of sleep quality, hours of sleep and number of awakenings with the computers when they woke up. Physical activity was continuously recorded by an actigraph inside the watch-type computers. Activity data were analyzed by Cole's algorithm to obtain total sleep time, sleep efficiency, sleep latency, wake time after sleep onset and number of awakenings for each night. Multilevel modeling was used to test the effect of each subjective and objective sleep-related variable on momentary headache intensity on the following day. RESULTS: Objectively measured total sleep time was significantly positively associated with momentary headache intensity on the following day, while self-reported sleep quality was significantly negatively associated with momentary headache intensity on the following day. CONCLUSIONS: Using computerized EMA and actigraphy, longer sleep and worse sleep quality were shown to be related to more intense headache intensity on within-individual basis and they may be precipitating or aggravating factors of TTH.