Clinical features of inherited neuropathy with BSCL2 mutations in Japan.

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene have been reported with different clinical phenotypes including Silver syndrome (SS)/spastic paraplegia 17 (SPG17), distal hereditary motor neuropathy type V (dHMN-V), and Charcot-Marie-Tooth (CMT) disease type 2. We screened 407 Japanese patients who were clinically suspected of having CMT by exome sequencing and searched mutations in BSCL2. As a result, we identified five patients with heterozygous mutations in BSCL2. We confirmed three cases of known mutations (p.N88S and p.S90L) and two cases of novel mutations (p.N88T and p.S141A). The clinical features of the cases with known mutations in Japan were similar to those previously reported in other countries. In particular, there were many cases with sensory disturbance. The case with p.N88T mutation showed severe phenotype such as early onset age and prominent vocal cord paresis. The case with p.S141A mutation showed characteristics of demyelinating neuropathy such as CMT disease type 1 by electrophysiological examination. In this article, we report the clinical features and spread of cases with BSCL2 mutation in a Japanese cohort.

Mutations in COA7 cause spinocerebellar ataxia with axonal neuropathy.

Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. We also found that all four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy, and some patients showed leukoencephalopathy or spinal cord atrophy on MRI scans. Validated mutations were located at highly conserved residues among different species and segregated with the disease in each family. Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration with a marked loss of large and medium myelinated fibres. An immunohistochemical assay with an anti-COA7 antibody in the sural nerve from the control patient showed the positive expression of COA7 in the cytoplasm of Schwann cells. We also observed mildly elevated serum creatine kinase levels in all patients and the presence of a few ragged-red fibres and some cytochrome c oxidase-negative fibres in a muscle biopsy obtained from one patient, which was suggestive of subclinical mitochondrial myopathy. Mitochondrial respiratory chain enzyme assay in skin fibroblasts from the three patients showed a definitive decrease in complex I or complex IV. Immunocytochemical analysis of subcellular localization in HeLa cells indicated that mutant COA7 proteins as well as wild-type COA7 were localized in mitochondria, which suggests that mutant COA7 does not affect the mitochondrial recruitment and may affect the stability or localization of COA7 interaction partners in the mitochondria. In addition, Drosophila COA7 (dCOA7) knockdown models showed rough eye phenotype, reduced lifespan, impaired locomotive ability and shortened synaptic branches of motor neurons. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3.

Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary motor neuropathy 2B in Japan.

Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1-related disorders.

Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2.

OBJECTIVE: The objective of this study was to identify new causes of Charcot-Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT. METHODS: To efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation. RESULTS: We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Aß)-degrading enzymes. All patients had a similar phenotype consistent with late-onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of-function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aß in Pittsburgh compound-B positron emission tomography imaging. INTERPRETATION: Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR-CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT.

Myopathy in a patient with systemic AA amyloidosis possibly induced by psoriasis vulgaris: An autopsy case.

INTRODUCTION: Amyloid myopathy is a rare manifestation of primary systemic amyloid light-chain (AL) amyloidosis, but it has not been reported to occur in secondary amyloid A (AA) amyloidosis. METHODS: We describe a 46-year-old man with psoriasis vulgaris who presented with idiopathic upper and lower limb weakness and was eventually diagnosed with hypertrophic cardiomyopathy. Muscle biopsy findings were compatible with mild inflammatory myopathy. He died of cardiopulmonary arrest, and an autopsy was performed. RESULTS: The autopsy revealed amyloid plaques immunopositive for AA (but not AL or transthyretin) in the perimysial, perivascular, and endomysial regions of the iliopsoas muscle. The final diagnosis was systemic AA amyloidosis with muscle amyloid angiopathy, possibly induced by psoriasis vulgaris. CONCLUSION: This is an extremely rare autopsy case of myopathy in a patient with systemic AA amyloidosis. The reason for the unusually large amount of amyloid deposition in muscle blood vessel walls remains unclear.

Direct and indirect influences of childhood abuse on depression symptoms in patients with major depressive disorder.

BACKGROUND: It is known that the onset, progression, and prognosis of major depressive disorder are affected by interactions between a number of factors. This study investigated how childhood abuse, personality, and stress of life events were associated with symptoms of depression in depressed people. METHODS: Patients with major depressive disorder (N = 113, 58 women and 55 men) completed the Beck Depression Inventory-II (BDI-II), the Neuroticism Extroversion Openness Five Factor Inventory (NEO-FFI), the Child Abuse and Trauma Scale (CATS), and the Life Experiences Survey (LES), which are self-report scales. Results were analyzed with correlation analysis and structural equation modeling (SEM), by using SPSS AMOS 21.0. RESULTS: Childhood abuse directly predicted the severity of depression and indirectly predicted the severity of depression through the mediation of personality. Negative life change score of the LES was affected by childhood abuse, however it did not predict the severity of depression. CONCLUSIONS: This study is the first to report a relationship between childhood abuse, personality, adulthood life stresses and the severity of depression in depressed patients. Childhood abuse directly and indirectly predicted the severity of depression. These results suggest the need for clinicians to be receptive to the possibility of childhood abuse in patients suffering from depression. SEM is a procedure used for hypothesis modeling and not for causal modeling. Therefore, the possibility of developing more appropriate models that include other variables cannot be excluded.

Effects of Subjective Social Status and Self-Esteem in the Association Between Childhood Abuse and Adulthood Anxiety.

Background: Subjective social status influences anxiety, but at present, the mechanism is not fully understood. It has been reported that negative childhood experiences, such as abuse, can influence depressive symptoms through subjective social status and personality traits, such as self-esteem. A similar mechanism is presumed to underlie anxiety symptoms in adulthood. Therefore, we hypothesized that subjective social status and self-esteem are intermediate factors in the indirect effects of childhood abuse on state anxiety in adulthood, and analyzed the indirect effects via these factors using a path analysis. Subjects and Methods: Child Abuse and Trauma Scale, Subjective Social Status, Rosenberg Self-Esteem Scale, and State-Trait Anxiety Inventory Form Y questionnaires were administered in a self-report format to 404 adult volunteers from January 2014 to August 2014. In addition, a path analysis was conducted to determine whether subjective social status and self-esteem are associated with the indirect effects of childhood abuse on anxiety symptoms in adulthood. Results: Childhood abuse did not directly affect state anxiety in adulthood, but affected state anxiety via subjective social status and self-esteem. Subjective social status affected state anxiety via self-esteem. This model explained 25.2% of the variation in state anxiety in adult volunteers. Conclusion: The present study demonstrated that childhood abuse affects anxiety in adulthood through subjective social status and self-esteem. Therefore, interventions that enhance subjective social status and self-esteem for adults who experienced childhood abuse may help reduce their anxiety.

Moderation by better sleep of the association among childhood maltreatment, neuroticism, and depressive symptoms in the adult volunteers: A moderated mediation model.

BACKGROUND: Previously, we demonstrated that childhood maltreatment could worsen depressive symptoms through neuroticism. On the one hand, some studies report that sleep disturbances are related to childhood maltreatment and neuroticism and worsens depressive symptoms. But, to our knowledge, no reports to date have shown the interrelatedness between childhood maltreatment, neuroticism, and depressive symptoms, and sleep disturbance in the one model. We hypothesized that sleep disturbance enhances the influence of maltreatment victimization in childhood or neuroticism on adulthood depressive symptoms and the mediation influence of neuroticism between maltreatment victimization in childhood and adulthood depressive symptoms. SUBJECTS AND METHODS: Total 584 Japanese volunteer adults recruited through convenience sampling from 4/2017 to 4/2018 were assessed regarding their characteristics of demographics, history of childhood maltreatment, sleep disturbance, neuroticism, and depressive symptoms with questionnaires self-administered. Survey data were analyzed using simple moderation models and a moderating mediation model. RESULTS: The interaction of sleep disturbance with childhood maltreatment or neuroticism on depressive symptoms was significantly positive. Furthermore, the moderating effect of sleep disturbance on the indirect effect of childhood maltreatment to depressive symptoms through neuroticism was significantly positive. LIMITATIONS: Because this was a cross-sectional study, a causal relationship could not be confirmed. CONCLUSIONS: Our findings indicate that individuals with milder sleep disturbance experience fewer depressive symptoms attributable to neuroticism and childhood maltreatment. Additionally, people with less sleep disturbance have fewer depressive symptoms arising from neuroticism owing to childhood maltreatment. Therefore, improvement of sleep disturbance will buffer the aggravating effect of childhood maltreatment, neuroticism caused by various factors, and neuroticism resulting from childhood maltreatment on depressive symptoms.

Neuroticism mediates the association between childhood abuse and the well-being of community dwelling adult volunteers.

BACKGROUND: Previous studies reported that the experience of maltreatment in childhood reduces subjective well-being in adulthood and that neuroticism is negatively associated with subjective well-being. However, the interrelationship between childhood maltreatment, adult life events, neuroticism, and subjective well-being has not been analyzed to date. METHODS: A total of 404 adult volunteers provided responses to the following questionnaires: 1) Childhood Abuse and Trauma Scale, 2) Life Experiences Survey, 3) Neuroticism Subscale of the Shortened Eysenck Personality Questionnaire-Revised, and 4) Subjective Well-Being Inventory. The path model was used to analyze possible interrelationships among these parameters. RESULTS: The effect of childhood abuse on subjective well-being was indirect and was mediated by neuroticism. The effect of neuroticism on the negative, but not positive, change score on the Life Experiences Survey was significant. The indirect effect of neuroticism on subjective well-being was not significant via either negative or positive change scores. CONCLUSIONS: This study demonstrated that age, subjective social status, neuroticism, and negative and positive life events were significantly associated with subjective well-being. Furthermore, using path analysis, we demonstrated the mediating role of neuroticism in the indirect effect of childhood abuse on subjective well-being.

Affective temperaments mediate the effect of childhood maltreatment on bipolar depression severity.

Aim: Bipolar disorder is a leading disorder contributing to global disease burden, and bipolar depression often becomes severe and refractory. Therefore, clarifying the pathophysiology of bipolar disorder is an urgent issue. Previous reports suggested that factors, such as affective temperaments and childhood maltreatment, aggravate bipolar depression severity. However, to our knowledge, no reports to date have clarified the interrelationship between the above factors and bipolar depression severity. We here hypothesized that childhood maltreatment worsens bipolar depression severity via increasing affective temperaments. To test this hypothesis, a covariance structural analysis was conducted. Methods: The following information was evaluated for a total of 75 people with bipolar disorder using self-administered questionnaires: demographic characteristics, depressive symptoms (Patient Health Questionnaire-9), history of childhood maltreatment (Child Abuse and Trauma Scale), and affective temperaments (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire). The results were analyzed using covariance structure analysis. Results: A significant indirect effect of childhood maltreatment on bipolar depression severity via increasing affective temperaments was identified, whereas the direct effect of childhood maltreatment was not significant. Conclusion: Our results reveal that affective temperaments can mediate the adverse effects of childhood maltreatment on the severity of bipolar depression.

Roles of childhood maltreatment, personality traits, and life stress in the prediction of severe premenstrual symptoms.

BACKGROUND: About 3% to 8% of women of fertile age are thought to have premenstrual dysphoric disorder (PMDD), which is regarded as a serious form of premenstrual syndrome (PMS), although the details of this common condition remain unclear. The aim of this study was to analyze the interrelations of childhood maltreatment, personality traits, and life stress in the etiology of PMS/PMDD. METHODS: A total of 240 adult female volunteers from a community in Japan were investigated, using the following 5 questionnaires: Patient Health Quesstionaire-9, Child Abuse and Trauma Scale, Temperament and Character Inventory (TCI), Life Experiences Survey, and premenstrual dysphoric disorder (PMDD) scale. The questionnaire data were subjected to path analyses to clarify the association between childhood maltreatment and the severity of premenstrual symptoms, mediated by personality traits and life stress. RESULTS: The 2 path analysis models showed that high harm avoidance (HA) on the TCI and low self-directedness (SD) on the TCI had significant direct effects on the severity of premenstrual symptoms. Moreover, childhood maltreatment was associated with the severity of premenstrual symptoms, both directly and indirectly through personality traits. CONCLUSION: Our findings suggest that HA on the TCI might be a risk factor for severe premenstrual symptoms among general women and furthermore that SD on the TCI may be a protective factor. In addition, childhood maltreatment is associated with severe premenstrual symptoms both directly and indirectly through personality traits.

Symptom Patterns of the Occurrence of Depression and Anxiety in a Japanese General Adult Population Sample: A Latent Class Analysis.

BACKGROUND: Given the high comorbidity and shared risk factors between depression and anxiety, whether they represent theoretically distinct disease entities or are just characteristics of a common negative affect dimension remains debated. Employing a data-driven and person-centered approach, the present study aims to identify meaningful and discrete symptom patterns of the occurrence of depression and anxiety. METHODS: Using data from an adult sample from the Japanese general population (n = 403, including 184 females, age = 42.28 ± 11.87 years), we applied latent class analysis to identify distinct symptom patterns of depression (PHQ-9) and anxiety (STAI Y1). To empirically validate the derived class memberships, we tested the association between the derived classes and personal profiles including childhood experiences, life events, and personality traits. RESULTS: The best-fitting solution had four distinct symptom patterns or classes. Whereas both Class 1 and 2 had high depression, Class 1 showed high anxiety due to high anxiety-present symptoms (e.g., "I feel nervous") while Class 2 showed moderate anxiety due to few anxiety-absent symptoms (e.g., "I feel calm"). Class 3 manifested mild anxiety symptoms due to lacking responses on anxiety-absent items. Class 4 manifested the least depressive and anxiety-present symptoms as well as the most anxiety-absent symptoms. Importantly, whereas both Class 1 and 2 had higher childhood neglect and reduced reward responsiveness, etc. compared to Class 4 (i.e., the most healthy class), only Class 1 had greater negative affect and reported more negative life events. CONCLUSIONS: To our knowledge, this is the first latent class analysis that examined the symptom patterns of depression and anxiety in Asian subjects. The classes we identified have distinct features that confirm their unique patterns of symptom endorsement. Our findings may provide insights into the etiology of depression, anxiety, and their comorbidity.

Childhood Victimization and Neuroticism Mediate the Effects of Childhood Abuse on Adulthood Depressive Symptoms in Volunteers.

BACKGROUND: When assessing patients with depressive and anxiety disorders in psychiatric clinical practice, it is common to encounter children and adolescents who have experienced abuse and victimization. To date, it has been clarified that experiences of "childhood abuse" and "childhood victimization" lead to "neuroticism", and that neuroticism leads to "adult depressive symptoms". In this study, we analyzed how these four factors are interrelated. SUBJECTS AND METHODS: The following self-administered questionnaire surveys were conducted in 576 adult volunteers: Patient Health Questionnaire-9, Eysenck Personality Questionnaire-revised shortened version, Child Abuse and Trauma Scale, and Childhood Victimization Rating Scale. For statistical analysis, Pearson correlation coefficient analysis, t-test, multiple regression analysis, and covariance structure analysis (path analysis) were performed. RESULTS: Path analysis showed that the indirect effects of childhood abuse and childhood victimization on depressive symptoms through neuroticism were statistically significant. In addition, the indirect effects of childhood abuse on neuroticism through childhood victimization were statistically significant. Finally, the indirect effects of childhood abuse on depressive symptoms through the combined paths of childhood victimization and neuroticism were statistically significant. CONCLUSION: Our results suggest that "childhood abuse (A)" induces changes in the personality trait of "neuroticism (C)" with "childhood victimization (B)" as a mediator, and that these adversities affect the expression of "depressive symptoms in adulthood (D)" through "neuroticism (C)" as a mediator. In other words, to our knowledge, this is the first study to clarify that these four factors are not only individually associated with each other but also cause a chain reaction of A to B to C to D.

Complex effects of childhood abuse, subjective social status, and trait anxiety on presenteeism in adult volunteers from the community.

Background: Presenteeism, which is reduced productivity levels owing to physical or mental problems, causes substantial economic loss. It is known to be associated with personal and working environment factors, but the mechanism has not been fully clarified to date. Therefore, we analyzed the effects of childhood abuse on presenteeism of general adult workers, and the mediating effects of subjective social status and trait anxiety. Methods: From 2017 to 2018, a cross-sectional survey was performed, and 469 adult workers provided written consent. Demographic information, and results from the Child Abuse and Trauma Scale, Subjective Social Status, State-Trait Anxiety Inventory form Y, and Work Limitations Questionnaire were investigated. Multiple linear regression and path analyzes were performed. Results: Childhood abuse indirectly affected current presenteeism via subjective social status and trait anxiety. Presenteeism was directly affected only by trait anxiety, childhood abuse directly affected subjective social status and trait anxiety, and subjective social status affected trait anxiety. Conclusion: This study clarified the long-term effects of childhood abuse on presenteeism in adulthood via trait anxiety. Therefore, assessing childhood abuse, subjective social status, and trait anxiety may help to elucidate the mechanism of workplace presenteeism and develop measures against it.

Interpersonal Sensitivity Mediates the Effects of Childhood Maltreatment on the Evaluation of Life Events and Anxiety States in Adult Community Volunteers.

BACKGROUND: Childhood maltreatment has long-lasting psychological effects, which often manifest in adulthood. Previous studies have suggested that the effects of childhood maltreatment are not only direct but also indirect, being mediated by other factors. In this study, we hypothesized that the effects of childhood maltreatment on state anxiety in adulthood are mediated by interpersonal sensitivity and the evaluation of life events, and investigated this possibility by covariance structure analysis. SUBJECTS AND METHODS: Self-administered questionnaires (Child Abuse and Trauma Scale, State-Trait Anxiety Inventory Form Y, Life Experiences Survey, and Interpersonal Sensitivity Measure) were distributed to adult community volunteers in Japan, and 404 eligible responses were collected. A structural equation model was constructed to analyze the direct and indirect effects of childhood maltreatment on state anxiety, with interpersonal sensitivity and the evaluation of life events as potential mediators. RESULTS: Our model showed that childhood maltreatment increases state anxiety in adulthood both directly and indirectly via interpersonal sensitivity. In addition, interpersonal sensitivity mediated the effects of childhood maltreatment on the negative evaluation of life events, and the negative evaluation of life events mediated the effects of interpersonal sensitivity on anxiety symptoms. LIMITATIONS: There may be possible recall bias owing to the self-administration of the questionnaire. In addition, this study had a cross-sectional design, and hence the results should be validated by a prospective study. CONCLUSION: The effects of childhood maltreatment on the state anxiety of adult volunteers are not only direct but are also mediated by interpersonal sensitivity. Our results suggest that assessing interpersonal sensitivity may help to determine optimal treatments for patients with anxiety who experienced maltreatment in childhood.

Rumination Mediates the Effects of Childhood Maltreatment and Trait Anxiety on Depression in Non-Clinical Adult Volunteers.

BACKGROUND: Several psychological studies have shown that depressive rumination is associated with the onset and severity of depression. However, it is unclear how rumination interacts with other predisposing factors to cause depression. In this study, we hypothesized that rumination mediates the association between depression and two predisposing factors of depression, ie, childhood maltreatment and trait anxiety. SUBJECTS AND METHODS: Between 2017 and 2018, 473 adult volunteers were surveyed using self-report questionnaires regarding the following: demographic information, rumination (Ruminative Responses Scale), trait anxiety (State-Trait Anxiety Inventory-Y), and the experience of childhood maltreatment (Child Abuse and Trauma Scale). The effects of these factors on depression (Patient Health Questionnaire-9) were analyzed by multiple regression and path analysis to analyze the mediating effects of rumination. This study was conducted with approval from the relevant ethics committee. RESULTS: Multiple regression analysis using depression as a dependent variable demonstrated that trait anxiety, rumination, childhood maltreatment, and living alone were significantly associated with depression. Path analysis showed that childhood maltreatment had a positive effect on trait anxiety, rumination, and depression; trait anxiety had a positive effect on rumination and depression; and rumination had a positive effect on depression. Regarding indirect effects, the experience of childhood maltreatment increased rumination and depression indirectly via trait anxiety. Furthermore, the experience of childhood maltreatment increased depression indirectly via rumination, and trait anxiety significantly increased depression via rumination. In other words, rumination mediated the indirect effects of abusive experiences and trait anxiety on depression. This model accounted for 50% of the variance in depression in adult volunteers. CONCLUSION: Our results suggest that rumination mediates the association between childhood maltreatment, trait anxiety, and depression in adulthood.

Structural equation modeling approach to explore the influence of childhood maltreatment in adults.

BACKGROUND: Childhood maltreatment affects social functioning in the general adult population. However, how child abuse affects functional disability in adulthood remains unknown. Thus, we investigated the correlation between child abuse, depressive symptoms, cognitive complaints, and functional disability in adult community volunteers. METHODS: Participants (N = 556) completed the Child Abuse and Trauma Scale, Patient Health Questionnaire-9, Cognitive Complaints in Bipolar Disorder Rating Assessment, and Sheehan Disability Scale. Multiple regression analyses and structural equation modeling were performed to evaluate scale correlations. RESULTS: Structural equation modeling showed that the direct effect of childhood maltreatment on depressive symptoms, the indirect effect of childhood maltreatment on cognitive function via depressive symptoms, and the indirect effects of childhood maltreatment on functional disability via depressive symptoms and via cognitive function were all significant. The direct effects of childhood maltreatment on cognitive function and functional disability were not significant. There was no significant association between variables. LIMITATIONS: Cross-sectional designs cannot identify causal relationships between parameters. Participants were adult volunteers from the community; therefore, results may not be generalizable to individuals with psychiatric disorders. Sociodemographic variability was a limitation because we used self-reported childhood maltreatment. CONCLUSIONS: Childhood maltreatment indirectly affects functional disability via depressive symptoms and via cognitive function through depressive symptoms. We suggest that depressive symptoms and cognitive function play crucial roles in the influence of childhood maltreatment on functional disability in adult community volunteers.

Influence of Childhood Maltreatment, Adulthood Stressful Life Events, and Affective Temperaments on Premenstrual Mental Symptoms of Nonclinical Adult Volunteers.

BACKGROUND: Previous studies have shown that childhood maltreatment is associated with premenstrual dysphoric disorder (PMDD). In this study we analyzed how multiple factors, such as childhood maltreatment, affective temperaments, and adult life events influence the severity of premenstrual mental (PMM) symptoms in nonclinical adult volunteers from the community. METHODS: A total of 204 participants were recruited and administered the following self-administered questionnaire surveys: PMDD scale, visual analogue scale, Patient Health Questionnaire-9, Life Experience Survey, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire version, and the Child Abuse and Trauma scale. In addition to single and multiple regression analyses, structural equation modeling was used for the statistical analyses. RESULTS: A history of neglect indirectly predicted PMM symptoms through affective temperaments in nonclinical adult volunteers. Three affective temperaments (irritable, cyclothymic, and anxious) directly predicted PMM symptoms. CONCLUSION: This study is the first to report that childhood maltreatment, particularly neglect, indirectly predicted PMM symptoms through affective temperaments. The results of our study suggest that affective temperament is a mediator of the influence of childhood maltreatment on PMM symptoms.

Complex effects of childhood abuse, affective temperament, and subjective social status on depressive symptoms of adult volunteers from the community.

BACKGROUND: How subjective social status is associated with childhood abuse and affective temperament in the mechanism of depressive symptom exacerbation remains unknown. In this study, we investigated how the complex effects of subjective social status, childhood abuse, and affective temperament influence depressive symptoms in adulthood. METHODS: Self-report questionnaires were distributed to 853 adult volunteers between January and August 2014. Of them, 404 people gave full consent and returned complete anonymous responses. The following five questionnaires were analyzed: demographic information, Patient Health Questionnaire-9, subjective social status, Child Abuse and Trauma Scale, and Temperament Evaluation of Memphis, Pisa, Paris and San Diego autoquestionnaire. The associations between the scores were analyzed by structural equation modeling. This study was conducted with approval from the ethics committees of Tokyo Medical University and Hokkaido University Hospital. RESULTS: Covariance structure analysis demonstrated that childhood abuse and subjective social status did not have a direct effect on adulthood depressive symptoms. Childhood abuse had direct effects on subjective social status and affective temperament and childhood abuse indirectly affected adulthood depressive symptoms through subjective social status and affective temperament. Subjective social status also affected depressive symptoms through an effect on affective temperament. This model explained 43% of the variability in depressive symptoms and the fitness of this model was good. CONCLUSION: Regarding childhood abuse and adulthood depressive symptoms, subjective social status as well as affective temperament may be mediators. The results of this study are expected to contribute to the elucidation of the mechanism of depression.

Relationship between the subtypes of child abuse and affective temperaments: Comparison of depression and bipolar disorder patients and healthy controls using the reclassified Child Abuse and Trauma Scale.

BACKGROUND: We previously reported that child abuse indirectly predicts the diagnosis of major depressive disorder (MDD) or bipolar disorder (BP) based on higher scores of affective temperaments; however, the subtypes of child abuse have not been examined sufficiently. Therefore, in the present study, we used the reclassified version of the Child Abuse and Trauma Scale (CATS) to determine how the subtypes of child abuse affect affective temperaments. METHODS: A total of 502 participants (212 healthy controls, 163 patients with MDD and 127 patients with BP) were administered the Japanese version of the CATS; the Japanese version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire; and the Japanese version of the Patient Health Questionnaire-9. Data were analyzed by exploratory and confirmatory factor analyses, as well as by univariate and multivariate analyses. RESULTS: A five-factor structure was appropriate for the CATS. The MDD group scored significantly higher on all subtypes of the reclassified CATS than did the control group. Among the subscales of the reclassified CATS, physical abuse and loneliness/psychological stress were significant predictors of affective temperaments, although all subscales were significantly associated with affective temperaments compared to the original CATS. LIMITATIONS: Since child abuse was assessed retrospectively, there might be recall bias. Furthermore, as the study was limited to Japanese individuals, particularly those with mood disorders, the findings might not be generalizable. CONCLUSIONS: This study revealed that the subtypes of child abuse (especially physical abuse and loneliness/psychological stress) might be associated with MDD and BP.