Soshiro Ogata

Chronic widespread pain : clinical comorbidities and psychological correlates

Abstract Recent studies have provided consistent evidence for a genetic influence on chronic widespread pain (CWP). The aim of this study was to investigate (1) the etiological structure underlying CWP by examining the covariation between CWP and psychological comorbidities and psychoaffective correlates and (2) the decomposition of the covariation into genetic and environmental components. A total of 3266 female twins (mean age 56.6 years) were subject to multivariate analyses. Using validated questionnaires to classify twins as having CWP, the prevalence of CWP was 20.8%. In the multivariate analysis, the most suitable model was the common pathway model. This model revealed 2 underlying latent variables, one common to anxiety, emotional intelligence, and emotional instability (f1) and the other common to depression and CWP (f2), the latter being highly heritable (86%). Both latent variables (f1 and f2) shared an additive genetic and a nonshared environmental factor. In addition, a second additive genetic factor loading only on f2 was found. This study reveals the structure of genetic and environmental influences of CWP and its psychoaffective correlates. The results show that the clustering of CWP and depression is due to a common, highly heritable, underlying latent trait. In addition, we found evidence that CWP, anxiety, emotional instability, and emotional intelligence are influenced by different underlying latent traits sharing the same genetic and nonshared environmental factors. This is the first study to reveal the structure and relative importance of genetic and environmental influences on complex etiological mechanisms of CWP and its correlates.

Common Genetic Factors Influence Hand Strength, Processing Speed, and Working Memory

Background It is important to detect cognitive decline at an early stage, especially before onset of mild cognitive impairment and dementia. Processing speed and working memory are aspects of cognitive function that are associated with cognitive decline. Hand strength is an inexpensive, easily measurable indicator of cognitive decline. However, associations between hand strength, processing speed, and working memory have not been studied. In addition, the genetic and environmental structure of the association between hand strength and cognitive decline is unclear. We investigated phenotypic associations between hand strength, processing speed, and working memory and examined the genetic and environmental structure of the associations between phenotypes. Methods Hand strength, processing speed (digit symbol performance), and working memory (digit span performance) were examined in monozygotic and dizygotic twin pairs. Generalized estimating equations were used to identify phenotypic associations, and structural equation modeling was used to investigate the genetic and environmental structure of the association. Results Generalized estimating equations showed that hand strength was phenotypically associated with digit symbol performance but not with digit span performance. Structural equation modeling showed that common genetic factors influenced hand strength and digit symbol and digit span performance. Conclusions There was a phenotypic association between hand strength and processing speed. In addition, some genetic factors were common to hand strength, processing speed, and working memory.

Association between subjective memory complaints and impaired higher-level functional capacity in people aged 60 years or older

OBJECTIVE We aimed to investigate the association between subjective memory complaints and higher-level functional capacity in either people with long-term care needs or those who require help to maintain functional capacity. METHODS We conducted a cross-sectional study among participants aged 60 years or older. We measured subjective memory complaints, higher-level functional capacity, and depressive symptoms, and then estimated odds ratios (ORs) by multiple logistic analysis. Subjective memory complaints were used as the predictor variable, higher-level functional capacity as the outcome variable, and age, depressive symptoms, medical history of diabetes and hypertension, frequency of going out, falling within a year, and body mass index as possible confounders. We assessed higher-level functional capacity using the Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence score ≤5 as a cut-off (which is associated with higher one-year mortality rates). RESULTS We conducted analyses using 501 people aged 60 years or older. Among women, subjective memory complaints were associated with impaired higher-level functional capacity after adjustment for age and depressive symptoms (OR=3.36; 95% confidence interval [CI], 1.59-7.08). Among the men, subjective memory complaints were not significantly associated with impaired higher-level functional capacity after adjustment for age and depressive symptoms (OR=1.91; 95% CI, 0.88-4.12). CONCLUSIONS Subjective memory complaints among women can indicate impaired higher-level functional capacity and may suggest higher one-year mortality rates.

The Association between Chronic Widespread Musculoskeletal Pain, Depression and Fatigue Is Genetically Mediated.

Background Chronic widespread muscoloskeletal pain (CWP) is prevalent in the general population and associated with high health care costs, so understanding the risk factors for chronic pain is important for both those affected and for society. In the present study we investigated the underlying etiological structure of CWP to understand better the association between the major clinical features of fatigue, depression and dihydroepiandrosterone sulphate (DHEAS) using a multivariate twin design. Methodology/Principle Findings Data were available in 463 UK female twin pairs including CWP status and information on depression, chronic fatigue and serum DHEAS levels. High to moderate heritabilities for all phenotypes were obtained (42.58% to 74.24%). The highest phenotypic correlation was observed between fatigue and CWP (r = 0.45), and the highest genetic correlation between CWP and fatigue (rg = 0.78). Structural equation modeling revealed the AE Cholesky model to provide the best model of the observed data. In this model, two additive genetic factors could be detected loading heavily on CWP—A2 explaining 40% of the variance and A3 20%. The factor loading heaviest on DHEAS showed only a small loading on the other phenotypes and none on fatigue at all. Furthermore, one distinct non-shared environmental factor loading specifically on CWP—but not on any of the other phenotypes—could be detected suggesting that the association between CWP and the other phenotypes is due only to genetic factors. Conclusions/Significance Our results suggest that CWP and its associated features share a genetic predisposition but that they are relatively distinct in their environmental determinants.

Influence of genetic and environmental factors on oral diseases and function in aged twins

This study was conducted to quantify the genetic and environmental contributions to oral disease and function in twins. Participants were middle-aged and old twins, 116 monozygotic and 16 dizygotic pairs whose mean age was 66·1 ± 10·3 (SD) years. Number of teeth, percentage of decayed, filled and missing teeth and periodontal status were recorded as indicators of oral disease. The widths of upper and lower dental arch served as indicators of morphological figures. Furthermore, stimulated salivary flow rate, occlusal force and masticatory performance were measured as indicators of oral function. Univariate genetic analysis with monozygotic and dizygotic twin pairs was conducted to detect the fittest structural equation model of each outcome. Both number of teeth and periodontal status fitted the model composed of common environmental factor and unique environmental factor. Decayed, filled and missing teeth, morphological figures and measurements of oral function fitted the model composed of additive genetic factor and unique environmental factor. The model fitting of each measurement suggested that periodontal disease was mainly affected by environmental factors, while morphological figures and oral functions were influenced by both genetic and environmental factors.

Language-related cerebral oscillatory changes are influenced equally by genetic and environmental factors

Twin studies have suggested that there are genetic influences on inter-individual variation in terms of verbal abilities, and candidate genes have been identified by genome-wide association studies. However, the brain activities under genetic influence during linguistic processing remain unclear. In this study, we investigated neuromagnetic activities during a language task in a group of 28 monozygotic (MZ) and 12 dizygotic (DZ) adult twin pairs. We examined the spatio-temporal distribution of the event-related desynchronizations (ERDs) in the low gamma band (25-50Hz) using beamformer analyses and time-frequency analyses. Heritability was evaluated by comparing the respective MZ and DZ correlations. The genetic and environmental contributions were then estimated by structural equation modeling (SEM). We found that the peaks of the low gamma ERDs were localized to the left frontal area. The power of low gamma ERDs in this area exhibited higher similarity between MZ twins than that between DZ twins. SEM estimated the genetic contribution as approximately 50%. In addition, these powers were negatively correlated with the behavioral verbal scores. These results improve our understanding of how genetic and environmental factors influence cerebral activities during linguistic processes.

Female sexual pain: Epidemiology and genetic overlap with chronic widespread pain

Increased tender spots and lowered general pain thresholds have been observed in patients with dyspareunia. Based on this, the aim of the study was to compare the co‐occurrence of female sexual pain across various pain populations and to further explore the aetiological structure underlying sexual pain by dissecting the genetic and environmental covariation among sexual pain, chronic widespread pain (CWP) and the previously reported psychological correlates of anxiety sensitivity and depression.

Stability of Genetic and Environmental Influences on Female Sexual Functioning

BACKGROUND Genetic factors have been implicated in the etiology of female sexual dysfunction. Yet, how much the dynamic nature of sexual functioning is influenced by changes in genetic and/or environmental factors remains unknown. AIM To explore temporal stability of genetic and environmental influences on female sexual functioning over a 4-year period. METHODS Data on desire, arousal, lubrication, orgasm, satisfaction, and pain were collected in 2009 and 2013 using the Female Sexual Function Index and were available for 1,209 British twin women. OUTCOMES To track the stability of genetic influences the Female Sexual Function Index sub-domain and total scores were subject to multivariate twin analyses for repeated measures. RESULTS Desire showed a lower heritability at follow-up (37% vs 14%) whereas for arousal and sexual pain the heritability at follow-up was higher compared to baseline (28% vs 34% and 30% vs 45%, respectively). The heritability of lubrication remained stable at 27%. According to the best-fitting additive environmental (AE) Cholesky model for all domains except for sexual pain there were no new genetic factors expressing themselves over the 4-year period, but an addition of new, unique environmental determinants could be observed. For sexual pain an additional genetic factor could be observed at follow-up, explaining 39% of the phenotypic variance. CLINICAL TRANSLATION The biological pre-disposition to sexual problems seems to remain relatively stable over time. CONCLUSIONS This is the first study to investigate the genetic stability of female sexual functioning in a large population sample of women. White ethnicity and the relatively high mean age of women asks for caution in extrapolating the findings to other ethnic and age groups. The findings highlight the value of more in-depth exploration of the non-shared environmental influences that could provide clues to the mechanisms behind remittance and/or persistence of sexual problems. Integration of these findings may provide a useful conceptual framework for the treatment and prevention of certain types of sexual problems. Burri A, Ogata S. Stability of Genetic and Environmental Influences on Female Sexual Functioning. J Sex Med 2018;15:550-557.

Pain catastrophizing, neuroticism, fear of pain, and anxiety: Defining the genetic and environmental factors in a sample of female twins

The objective of the present study was to establish the heritability of pain catastrophizing and its subdomains of helplessness, magnification, and rumination and to further explore the genetic and environmental sources that may contribute to pain catastrophizing as well as to its commonly reported psycho-affective correlates, including neuroticism, anxiety sensitivity, and fear of pain. N = 2,401 female twin individuals from the TwinsUK registry were subject to univariate and multivariate twin analyses. Well validated questionnaires including the Pain Catastrophizing Scale, the Pain Anxiety Symptom Scale, the Ten Item Personality Index, and the Anxiety Sensitivity Index were used to assess the study variables. Moderate estimates of heritability for pain catastrophizing (36%) and the three subdomains of helplessness (35%), rumination (27%), and magnification (36%) were detected. The high correlations observed between the three subdomains were explained mainly by overlapping genetic factors, with a single factor loading on all three phenotypes. High genetic correlations between pain catastrophizing and its psycho-affective correlates of fear of pain and anxiety sensitivity were found, while the genetic overlap between neuroticism and pain catastrophizing was low. Each measure of negative affect demonstrated relatively distinct environmental contributing factors, with very little overlap. This is the first study to show shared genetic factors in the observed association between pain catastrophizing and other measures of negative affect. Our findings provide deeper insight into the aetiology of pain catastrophizing and confirm that it is at least partially distinct from other measures of negative affect and personality that may influence the development and treatment of chronic pain conditions. Further research in males is warranted to check the comparability of the findings.

Twelve-year follow-up of chronic pain in twins: Changes in environmental and genetic influence over time

While genetic influences on chronic pain have been repeatedly demonstrated, we do not know whether these effects are stable or dynamic over time.