井野 敬子

2026年9月15日早期公開版。巻・号・頁は未確認。

Importance Despite the rising prevalence of bulimia nervosa and the associated risks of chronicity and severe physical and psychological morbidity, access to effective treatment remains poor. The effectiveness and acceptability of internet-based cognitive behavior therapy (ICBT) for women with bulimia nervosa in clinical settings in East Asia remain unclear. Objective To determine the effectiveness and acceptability of a guided ICBT program to treat women with bulimia nervosa in Japan. Design, Setting, and Participants This randomized clinical trial was conducted at 7 university hospitals in Japan between August 2022 and October 2024. This study enrolled female participants aged 13 to 65 years whose symptoms met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for bulimia nervosa, had a body mass index (BMI) of 17.5 or greater, had internet access, and had no history of practicing CBT-related techniques within the past 2 years. Interventions Both the control and intervention groups received usual care. The intervention consisted of ICBT with additional guidance from a therapist. The therapy program was tailored to Japanese culture and grounded in a specific cognitive behavior model, and it was performed over a 12-week period. Main Outcomes and Measures Severity of bulimia nervosa, measured by the weekly combined frequency of episodes involving binge eating and compensatory behaviors, was assessed by a blinded, independent rating team at baseline and at the 12-week intervention end point. Intention-to-treat analyses were conducted using a linear mixed model with effect sizes calculated using Cohen d. Results A total of 61 women met the eligibility criteria and were randomized to the intervention group (n = 31) or the control group (n = 30). Participants were predominantly young (mean [SD] age, 27.8 [9.0] years), had normal weight (mean [SD] BMI, 21.1 [3.6]), and had a mean (SD) duration of illness of 9.3 (8.8) years; half (31 [50.8%]) were employed. Intent-to-treat analysis revealed that guided ICBT significantly reduced the weekly combined frequency of episodes involving binge eating and compensatory behaviors (by an adjusted mean difference of 9.84 episodes [95% CI, 2.49-17.18 episodes], P = .01; Cohen d = 0.73 [95% CI, 0.21-1.26]). Sensitivity analyses supported these findings. Conclusions and Relevance In this randomized clinical trial, the intervention group experienced a significant decrease in bulimia symptoms compared with the control group, supporting the effectiveness and acceptability of the therapist-guided ICBT program. These findings suggest that integration of therapist-guided ICBT in usual care has the potential to improve accessibility to efficacious treatment options for women with bulimia nervosa. Trial Registration UMIN Clinical Trials Registry Identifier: UMIN00048732

Abstract Background Subthreshold post‐traumatic stress disorder (PTSD) is associated with nearly the same impairment level as full PTSD. However, the standard treatment for subthreshold PTSD remains unclear. Furthermore, no consensus has been reached on the best way to address grief following the improvement of PTSD symptoms. Case Presentation A single Japanese woman in her 50s experienced sudden fear and insomnia after her only son committed suicide. She visited our hospital 6 months after the death and was diagnosed with depression and subthreshold PTSD. Pharmacotherapy slightly improved her depression and insomnia, but no improvement was observed in her PTSD symptoms, therefore she underwent 13 prolonged exposure (PE) sessions, including grief care in the final two sessions. Through imaginal exposure, she was able to feel her anger toward her deceased son and the feelings he had at the time of the suicide for the first time. Furthermore, as she processed her feelings about her son's suicide, her perception changed, which substantially alleviated her depressive and PTSD symptoms. After her PTSD symptoms improved, she felt sadness for his loss. Consequently, the grieving process was facilitated. Conclusion PE incorporating brief grief care may be effective for the bereaved with suicide‐related PTSD symptoms.

Background/objective: Posttraumatic stress disorder (PTSD) is known to be associated with deficits in working memory (WM). However, findings regarding the relationship of PTSD with non-emotional WM have not necessarily been uniform. This study aimed to clarify the relationship between PTSD and non-emotional WM using the N-back task, a well-established WM task.Method: A total of 111 women with PTSD and 120 healthy control women without trauma were enrolled. Most of the patients developed PTSD after experiencing interpersonal violence. Participants completed 0-back and 2-back tasks using non-emotional stimuli (number), as well as a standardised neuropsychological test battery and self-report questionnaires for PTSD and depression symptoms.Results: The PTSD group showed significantly less accuracy in the 2-back task than the control group, while no significant difference was observed in the accuracy of the 0-back task. The PTSD group showed significantly prolonged reaction time compared to controls in both the 0-back and 2-back tasks. The prolonged reaction time in the 2-back task was significantly correlated with more severe overall symptoms and avoidance symptoms in the PTSD group after controlling for age.Conclusion: Individuals with PTSD exhibited reduced WM capacity. Drawing on a relatively large civilian sample, this study contributes to the accumulating evidence of such deficits. Notably, the observed association between WM dysfunction and avoidance symptoms suggests a symptom-specific cognitive profile in PTSD.

Increasing evidence suggests that posttraumatic stress disorder (PTSD), a serious mental health condition, is associated with physical health problems. Lipid-related molecules are crucial for central nervous system functions associated with PTSD symptoms; however, case-control studies exploring the relationship between PTSD and lipid-related molecules are scarce. We examined 68 civilian PTSD patients and 97 healthy controls, evaluating PTSD symptoms, childhood maltreatment history, suicidality, and cognitive functions. Cholesterol, triglycerides, and inflammation-related marker levels were analyzed in serum, while fatty acid levels were measured in plasma. Compared to controls, patients exhibited significantly lower high-density lipoprotein cholesterol and n-6 linoleic acid levels, alongside higher saturated palmitic acid levels and the triene-to-tetraene (T/T) ratio. PTSD symptoms, particularly hyperarousal, were significantly positively correlated with n-6 γ-linolenic, n-6 dihomo-γ-linolenic, and n-9 mead acid levels, and the T/T ratio. Cognitive functions were significantly positively correlated with n-3 docosahexaenoic acid and total n-3 fatty acid levels, and negatively correlated with dihomo-γ-linolenic, palmitic, and total saturated fatty acid levels. Suicidality was significantly positively correlated with dihomo-γ-linolenic acid, mead acid levels, and the T/T ratio, and negatively correlated with polyunsaturated fatty acid (PUFA) levels. Inflammation-related marker levels were significantly correlated with higher palmitic, n-9 oleic, and total n-9 fatty acid levels, and lower linoleic acid and PUFA levels. Latent profile analysis (LPA) revealed distinct subgroups associated with unique fatty acid profiles. These lipid-related alterations may improve the understanding of PTSD pathophysiology. Distinct fatty acid profiles identified by LPA may help subtype PTSD patients and guide nutrition-based personalized treatment strategies.

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Accumulated evidence shows that psychological trauma and posttraumatic stress disorder (PTSD) are associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis. Besides the HPA axis hormones, recent evidence suggests that the renin-angiotensin-aldosterone (RAA) system and genetic factors may be involved in trauma/PTSD as well as in HPA axis regulation. This study attempted to better understand the HPA axis function in relation to PTSD and childhood maltreatment by simultaneously examining RAA system and genetic polymorphisms of candidate genes. Here we studied 69 civilian women with PTSD and 107 healthy control women without DSM-IV-based traumatic experience. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire. PTSD severity was assessed with the Posttraumatic Diagnostic Scale. Functional disability was assessed with the Sheehan Disability Scale. HPA axis was examined by measuring blood levels of cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone-sulphate (DHEA-S). RAA system was examined by measuring blood renin and aldosterone levels. The FKBP5 rs1360780 and CACNA1C rs1006737 polymorphisms were genotyped. No significant differences were seen between patients and controls in any of the five hormone levels. DHEA-S levels were significantly negatively correlated with overall PTSD severity (p = 0.003) and functional disability (p = 0.008). A two-way analysis of variance with diagnostic groups and genotypes as fixed factors revealed that patients with the rs1006737 A-allele had significantly lower DHEA-S levels than patients with the GG genotype (p = 0.002) and controls with the A-allele (p = 0.006). Childhood maltreatment history was not significantly correlated with any of the five hormone levels. These results were generally unchanged after controlling for the potentially confounding effect of age, depression, and anxiety. Our findings suggest that lower DHEA-S levels could indicate more severe subtype of PTSD, the association of which might be partly modified by the CACNA1C polymorphism.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with increased inflammation. C-reactive protein (CRP) is a marker of systemic inflammation, and recently, single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with increased blood CRP protein levels and illness severity in PTSD patients. However, the mechanism by which the CRP SNPs are involved in PTSD remains unclear. Here we investigated the association of CRP genetic variation with blood proinflammatory protein levels, symptomatology, and cognitive function, and further explored the moderating effect of childhood maltreatment history, in adult patients with PTSD. METHODS: Fifty-seven Japanese civilian women with PTSD and 73 healthy control women were enrolled. Three SNPs in the CRP gene, namely rs2794520, rs1130864, and rs3093059, were genotyped, and analyses focused on rs2794520 (T/C). Serum levels of high-sensitivity CRP (hsCRP), high-sensitivity tumor necrosis factor-α (hsTNF-α), and interleukin-6 were measured. PTSD symptoms were evaluated by the Posttraumatic Diagnostic Scale. Cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status. Childhood maltreatment history was assessed by the Childhood Trauma Questionnaire. RESULTS: Patients with the rs2794520 CC/CT genotype, compared to those with the TT genotype, showed significantly higher levels of hsCRP (p=0.009) and hsTNF-α (p=0.001), more severe PTSD symptoms (p=0.036), and poorer cognitive function (p=0.018). A two-way analysis of variance revealed a significant genotype-by-maltreatment interaction for more severe PTSD avoidance symptom (p=0.012). LIMITATIONS: The relatively small sample size limited our findings. CONCLUSIONS: These findings may provide an insight into the etiology of PTSD from the inflammatory perspective.

Accumulated evidence shows that individuals with posttraumatic stress disorder (PTSD) have compromised cognitive function. PTSD is associated with childhood maltreatment, which also can negatively affect cognitive function. It is therefore possible that cognitive dysfunction in adult patients with PTSD can be due at least partly to childhood maltreatment, although little is documented on this issue. Here we aimed to examine the possible effect of childhood maltreatment on cognitive function in adult patients with PTSD. A total of 50 women with DSM-IV PTSD and 94 healthy control women were enrolled. Most of the patients developed PTSD after experiencing interpersonal violence during adulthood. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Compared to controls, patients reported significantly more experiences of all types of childhood maltreatment as assessed by the CTQ and showed significantly poorer performance on immediate memory, language, attention, and the total score of RBANS. In patients, sexual abuse scores were significantly negatively correlated with RBANS language (p < 0.001) and total score (p = 0.005). Further analyses revealed that PTSD patients with childhood sexual abuse had even poorer cognitive function than those without the abuse. In controls, no significant correlation was found between CTQ and RBANS scores. These results suggest that childhood maltreatment, specifically sexual abuse, may lead to persistent cognitive impairment in individuals with PTSD. Our findings might underscore the importance of early detection and intervention of childhood maltreatment, which will be achieved by careful observation of, and listening to, maltreated children in education and welfare scenes as well as clinical settings.

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.

Etiology of posttraumatic stress disorder (PTSD) remains largely unknown. Studies have shown that a significant subset of patients with PTSD exhibit increased inflammation, suggesting that the understanding of this disorder could be facilitated by classifying these patients by inflammatory status. Here we performed a microarray-based blood transcriptome analysis on proinflammatory status-stratified Japanese civilian women with PTSD most of whom developed the disorder after experiencing interpersonal violence. By utilizing our previously identified cut-off serum interleukin-6 (IL-6) level that approximately corresponded to the median IL-6 level of our PTSD patients, we classified patients into those with high IL-6 levels and those with normal IL-6 levels (n = 16 for each). Transcriptome profiles of these 2 groups were compared with the profile of 16 age-matched healthy control women. Differentially expressed genes between high IL-6 patients and controls showed significant enrichment in a number of gene ontology terms and pathways primarily involved in immune/inflammatory responses, and their protein-protein interaction network was significantly enriched. In contrast, differentially expressed genes between normal IL-6 patients and controls showed significant enrichment in several gene ontology terms related to ion transport and neural function. The microarray data were confirmed by reverse transcription quantitative PCR. These findings illustrate the heterogeneous molecular mechanisms of PTSD within this relatively homogeneous sample in terms of sex, trauma type, and ethnicity, suggesting that peripheral proinflammatory status such as IL-6 levels could be a useful subtyping marker for this disorder. With further research, it is hoped that our findings will be translated into personalized medicine.

Individuals with posttraumatic stress disorder (PTSD) show low resilience and impaired quality of life (QOL). Accumulating evidence shows that PTSD is associated with increased inflammation. Studies suggest that inflammation can be a key mechanism underlying low resilience/QOL, but this relationship has been understudied in individuals with PTSD. Here, we investigated the association of blood proinflammatory markers with self-reported resilience and QOL in civilian women with PTSD. Fifty-six women with PTSD and 73 healthy control women participated in this study. Resilience was assessed using the Connor-Davidson Resilience Scale. QOL was assessed using the World Health Organization Quality of Life-BREF. Blood samples were collected for the measurement of three proinflammatory markers including interleukin-6 (IL-6), high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Compared to controls, patients showed significantly higher IL-6 levels and lower resilience and QOL. In patients, IL-6 levels were significantly negatively correlated with resilience, and hsCRP levels were significantly negatively correlated with psychological QOL. These results show that increased levels of proinflammatory markers including IL-6 and hsCRP are associated with lower psychological resilience and QOL in PTSD patients. Our findings suggest that interventions and treatments targeting inflammation may aid in the recovery from PTSD and lead to better prognosis.

BACKGROUND: Memory abnormalities are among a central feature of posttraumatic stress disorder (PTSD). It is suggested that individuals with PTSD exhibit memory bias; while evidence shows poor memory function in these individuals. We aimed to examine memory bias in PTSD patients relative to controls and to explore an association between memory bias and memory function. METHODS: Forty-six women with DSM-IV PTSD, most of whom developed the disorder after interpersonal violence, and 68 non-trauma-exposed healthy control women were studied. Memory bias was assessed by a recognition memory task using negative, neutral, and positive words. Memory function was assessed by a standardized neuropsychological test battery. Depression and anxiety symptoms were assessed by self-report measures. RESULTS: Compared to controls, patients showed significantly greater negative bias scores (i.e., correctly recognized rates for negative words minus those for neutral words) and poorer memory function. Negative bias scores were significantly correlated with worse memory function in patients. When patients were divided into those with lower vs. normal memory function, the former patients had significantly greater negative bias than the latter patients and controls. Memory bias scores in patients were not significantly correlated with depression or anxiety symptoms, nor were they significantly different between patients with comorbid major depressive disorder and those without. LIMITATIONS: The cross-sectional design and absence of the trauma-exposed non-PTSD group limited our findings. CONCLUSIONS: PTSD patients have greater negative memory bias, which can be associated with poorer memory function. Our findings may provide an insight into the nature of memory abnormalities in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with cognitive impairments, yet little is documented on the cognitive function of PTSD patients in Asian countries. It is shown that regular exercise can reduce PTSD symptoms, while no study has investigated the association between exercise and cognition in PTSD patients. This study aimed to examine cognitive functions of Japanese women with PTSD, and to explore the association between regular exercise and cognitive functions. METHODS: Forty-two women with DSM-IV PTSD and 66 demographically matched healthy control women participated in this study. Most of the patients developed PTSD after experiencing interpersonal violence. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regular exercise habit was assessed by a self-reported questionnaire. RESULTS: Compared to controls, PTSD patients performed significantly more poorly in all cognitive domains examined, including immediate memory, visuospatial construction, language, attention, delayed memory, as well as the total score of RBANS (all p < 0.001). Compared to PTSD patients without the habit of exercise, those who habitually exercised showed significantly better performance on delayed memory (p = 0.006), which survived after controlling for potentially confounding variables in a multiple regression model. LIMITATIONS: The cross-sectional design and relatively small sample size limited our findings. CONCLUSIONS: PTSD in Japanese women is associated with pervasively impaired cognitive functions, including notable impairments in verbal memory. Such memory deficits might be improved by regular exercise, although further studies are needed to investigate the causal relationship between exercise and cognition in PTSD.

Posttraumatic stress disorder (PTSD) has been associated with increased inflammation, albeit with some controversy. Another key feature of PTSD is compromised function in wide-ranging cognitive domains. Increased peripheral inflammation can contribute to cognitive dysfunction, although this relationship has not been studied in patients with PTSD. Here, we examined blood inflammatory markers in adult patients with PTSD compared to healthy controls taking account of potentially confounding effects of childhood maltreatment and comorbid major depressive disorder (MDD), and explored the association between inflammation and cognition. We enrolled 40 women with PTSD, most of whom developed the disorder after interpersonal violence during adulthood, and 65 healthy control women. Diagnoses were made based on DSM-IV. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Blood samples were collected for the measurement of 5 inflammatory markers including interleukin-6 (IL-6), soluble IL-6 receptor, interleukin-1β, high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein. Compared to controls, patients with PTSD showed significantly higher IL-6 levels (p = 0.009) and lower scores on all RBANS domains (all p < 0.01). IL-6 levels in patients were not significantly associated with the presence/absence of comorbid MDD or CTQ scores. IL-6 levels in patients were significantly negatively correlated with RBANS visuospatial construction (p = 0.046), language (p = 0.008), attention (p = 0.036) and total score (p = 0.008). These results suggest that elevated IL-6 is associated with PTSD and that the lower cognitive function in PTSD may be due at least partly to increased inflammation.

Background: Many patients with panic disorder meet criteria for at least one other diagnosis, most commonly other anxiety or mood disorders. Cognitive-behavioral therapy is the best empirically supported psychotherapy for panic disorder. There is now evidence indicating that cognitive-behavioral therapy for panic disorder yields positive benefits upon comorbid disorders. Objectives: The present study aimed to examine the predictors of broad dimensions of psychopathology in panic disorder after cognitive-behavioral therapy. Methods: Two hundred patients affected by panic disorder were treated with manualized group cognitive-behavioral therapy. We examined if the baseline personality dimensions of NEO Five Factor Index predicted the subscales of Symptom Checklist-90 Revised at endpoint using multiple regression analysis based on the intention-to-treat principle. Results: Conscientiousness score of NEO Five Factor Index at baseline was a predictor of four Symptom Checklist-90 Revised subscales including obsessive-compulsive (β = -0.15, P < 0.01), depression (β = -0.13, P < 0.05), phobic anxiety (β = -0.15, P < 0.05), and Global Severity Index (β = -0.13, P < 0.05). Conclusion: Conscientiousness at baseline may predict several dimensions of psychopathology in patients with panic disorder after cognitive-behavioral therapy. For the purpose of improving a wide range of psychiatric symptoms with patients affected by panic disorder, it may be useful to pay more attention to this personal trait at baseline.

BACKGROUND: Panic disorder (PD) is a common disease and presents with broad dimensions of psychopathology. Cognitive behavioral therapy (CBT) is known to improve these broad dimensions of psychopathology in addition to PD symptoms. However, little is known about the predictors of treatment response in comorbid psychiatric symptoms after CBT for PD. Recent studies suggest that anxiety sensitivity (AS) may be a key vulnerability for PD. This study aimed to examine AS as a predictor of broad dimensions of psychopathology after CBT for PD. MATERIALS AND METHODS: In total, 118 patients with PD were treated with manualized group CBT. We used multiple regression analysis to examine the associations between 3 Anxiety Sensitivity Index (ASI) factors (physical concerns, mental incapacitation concerns, and social concerns) at baseline and the subscales of the Symptom Checklist-90 Revised (SCL-90-R) at endpoint. RESULTS: Low levels of social concerns at baseline predicted low levels on 5 SCL-90-R subscales after CBT: interpersonal sensitivity, depression, hostility, paranoid ideation, and psychosis. High levels of mental incapacitation concerns significantly predicted low levels on 3 SCL-90-R subscales after treatment: interpersonal sensitivity, hostility, and paranoid ideation. Physical concerns at baseline did not predict broad dimensions of psychopathology. CONCLUSION: This study suggested that the social concerns and mental incapacitation concerns subscales of the ASI at baseline predicted several dimensions of psychopathology after CBT for PD. To improve comorbid psychopathology, it may be useful to direct more attention to these ASI subscales.

Epub 2016年8月1日。出版年月は巻号の2017年6月。