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We used the community-based University of Washington Twin Registry to investigate the genetic association between circadian type and sleep duration. Habitual sleep duration was obtained by self-report and circadian type was measured using a reduced 5-item Horne-Östberg Morningness-Eveningness questionnaire. Univariate and bivariate genetic analyses were fit using structural equation models. We used multinomial logistic regression to examine the overall and within-pair effects of circadian type on sleep duration in total and monozygotic (MZ) restricted twin samples. We surveyed 1620 twins, mostly female (70%), from same-sex pairs (1098 monozygotic, 522 dizygotic) with a mean age of 36 years (SD = 15). Among all twins, 23% were habitual short (<7 h/night), 68% normal (7-8 h/night), and 9% long (≥9 h/night) sleepers. Overall, 33% were morning-type, 52% neither-type, and 15% evening-type. The heritability of sleep duration was 31% and 40% for circadian type (both P < 0.05). The bivariate analysis did not reveal shared genetic influences on circadian type and sleep duration. When analyzing twins as individuals, eveningness was associated with short and long sleep duration in the total ( P < 0.001) and MZ restricted ( P < 0.05) twin samples. These findings were attenuated in the within-pair analysis in both samples suggesting that familial factors, namely genetics and shared environment, are in the pathway of interest or confound the association between circadian type and sleep duration. Because both short and long sleep is associated with adverse health outcomes, our findings suggest circadian evening-type may represent an endophenotype for poor health. [ABSTRACT FROM AUTHOR]

: PurposeChronic fatigue syndrome (CFS) is characterized by profound fatigue accompanied by disturbances of sleep, cognition, mood, and other symptoms. Our objective was to describe sleep architecture in CFS-discordant twin pairs.: MethodsWe conducted a co-twin control study of 22 pairs of monozygotic twins where one twin met criteria for CFS and the co-twin was healthy. Twins underwent two nights of polysomnography.: ResultsThe percentage of Stage 3 and REM sleep was greater among the CFS twins than their healthy co-twins (P≤.05 for both), but no other differences in sleep architecture including sleep latency, REM latency, and total sleep time were observed. Compared to their co-twins, CFS twins had higher values for the apnea–hypopnea index and apnea–hypopnea arousal index (P≤.05 for both).: ConclusionThese results do not provide strong evidence for a major role for abnormalities in sleep architecture in CFS. Respiration appears impaired in CFS, but these clinical abnormalities cannot alone account for the prominence of sleep complaints in this illness. The co-twin control methodology highlights the importance of selecting well-matched control subjects. [Copyright &y& Elsevier]

Diurnal preference changes across the lifespan. However, the mechanisms underlying this age-related shift are poorly understood. The aim of this twin study was to determine the extent to which genetic and environmental influences on diurnal preference are moderated by age. Seven hundred and sixty-eight monozygotic and 674 dizygotic adult twin pairs participating in the University of Washington Twin Registry completed the reduced Morningness-Eveningness Questionnaire as a measure of diurnal preference. Participants ranged in age from 19 to 93 years (mean = 36.23, SD = 15.54) and were categorized on the basis of age into three groups: younger adulthood (19-35 years, n = 1715 individuals), middle adulthood (36-64 years, n = 1003 individuals) and older adulthood (65+ years, n = 168 individuals). Increasing age was associated with an increasing tendency towards morningness ( r = 0.42, p < 0.001). Structural equation modeling techniques parsed the variance in diurnal preference into genetic and environmental influences for the total sample as well as for each age group separately. Additive genetic influences accounted for 52%[46-57%], and non-shared environmental influences 48%[43-54%], of the total variance in diurnal preference. In comparing univariate genetic models between age groups, the best-fitting model was one in which the parameter estimates for younger adults and older adults were equated, in comparison with middle adulthood. For younger and older adulthood, additive genetic influences accounted for 44%[31-49%] and non-shared environmental influences 56%[49-64%] of variance in diurnal preference, whereas for middle adulthood these estimates were 34%[21-45%] and 66%[55-79%], respectively. Therefore, genetic influences on diurnal preference are attenuated in middle adulthood. Attenuation is likely driven by the increased importance of work and family responsibilities during this life stage, in comparison with younger and older adulthood when these factors may be less influential in determining sleep-wake timing. These findings have implications for studies aimed at identifying specific non-shared environmental influences, as well as molecular genetic studies aimed at identifying specific polymorphisms associated with diurnal preference. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies of the association between posttraumatic stress disorder (PTSD) and chronic widespread pain (CWP) or fibromyalgia have not examined the role of familial or genetic factors. The goals of this study were to determine if symptoms of PTSD are related to CWP in a genetically informative community-based sample of twin pairs, and if so, to ascertain if the association is due to familial or genetic factors. Data were obtained from the University of Washington Twin Registry, which contains 1042 monozygotic and 828 dizygotic twin pairs. To assess the symptoms of PTSD, we used questions from the Impact of Events Scale (IES). IES scores were partitioned into terciles. CWP was defined as pain located in 3 body regions lasting at least 1 week during the past 3 months. Random-effects regression models, adjusted for demographic features and depression, examined the relationship between IES and CWP. IES scores were strongly associated with CWP (P <0.0001). Compared to those in the lowest IES tercile, twins in the highest tercile were 3.5 times more likely to report CWP. Although IES scores were associated with CWP more strongly among dizygotic than among monozygotic twins, this difference was not significant. Our findings suggest that PTSD symptoms, as measured by IES, are strongly linked to CWP, but this association is not explained by a common familial or genetic vulnerability to both conditions. Future research is needed to understand the temporal association of PTSD and CWP, as well as the physiological underpinnings of this relationship. [Copyright &y& Elsevier]

Posttraumatic stress disorder (PTSD) and eating disorders (ED) frequently co-occur, but the mechanisms underlying this association remain unclear. EDs are characterized by features of maladaptive eating behaviors including disinhibited eating and cognitive dietary restraint. Identifying the genetic overlap between PTSD symptoms and maladaptive eating behaviors may elucidate biological mechanisms and potential treatment targets. A community sample of 400 same-sex twins (102 monozygotic and 98 dizygotic pairs) completed the PTSD Checklist-Civilian (PCL-C) for PTSD symptoms and the Three-Factor Eating Questionnaire-Reduced (TFEQ-R18) for eating behaviors (uncontrolled eating, emotional eating, and cognitive dietary restraint). We used biometric modeling to examine the genetic and environmental relationships between PCL-C and TFEQ-R18 total and subscales scores. Heritability was estimated at 48% for PTSD symptoms and 45% for eating behavior overall. Bivariate models revealed a significant genetic correlation between PTSD symptoms and eating behavior overall (rg =.34; CI:.07,.58) and Uncontrolled Eating (rg =.53; CI:.24,.84), and a significant environmental correlation between PTSD symptoms and Emotional Eating (re =.30; CI:.12,.45). These findings suggest the influence of common etiology. Future research and clinical efforts should focus on developing integrated treatments. [ABSTRACT FROM AUTHOR]

In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide. [ABSTRACT FROM AUTHOR]

Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs.Methods: Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations.Results: There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome.Conclusions: CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities. [ABSTRACT FROM AUTHOR]

Background: There is a dearth of knowledge about the link between cortisol and pain sensitivity. Purpose: We examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding. Methods: Three-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations. Results: Lower diurnal variation of cortisol was associated with higher pain ratings at threshold ( p = 0.02) and tolerance ( p < 0.01). The relationship of diurnal variation with pain ratings at threshold and tolerance was minimally influenced by familial factors (i.e., genetics and common environment). Conclusions: Understanding the genetic and non-genetic mechanisms underlying the link between HPA axis dysregulation and pain sensitivity may help to prevent chronic pain development and maintenance. [ABSTRACT FROM AUTHOR]

Background: Informal caregiving can be deleterious to mental health, but research results are inconsistent and may reflect an interaction between caregiving and vulnerability to stress. Methods: We examined psychological distress among 1,228 female caregiving and non-caregiving twins. By examining monozygotic and dizygotic twin pairs discordant for caregiving, we assessed the extent to which distress is directly related to caregiving or confounded by common genes and environmental exposures. Results: Caregiving was associated with distress as measured by mental health functioning, anxiety, perceived stress, and depression. The overall association between caregiving and distress was confounded by common genes and environment for mental health functioning, anxiety, and depression. Common environment also confounded the association of caregiving and perceived stress. Conclusions: Vulnerability to distress is a factor in predicting caregivers' psychosocial functioning. Additional research is needed to explicate the mechanisms by which common genes and environment increase the risk of distress among informal caregivers. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study examined if associations between body mass index (BMI) and mental and physical health were independent of genetic and familial factors. Method: Data from 2831 twins (66% female) were used in an epidemiological co-twin control design with measures of BMI and mental and physical health outcomes. Generalized estimating equation regressions assessed relationships between BMI and health outcomes controlling for interdependency among twins and demographics. Within-pair regression analyses examined the association of BMI with health outcomes controlling for genetic and familial influences. Results: Adjusted analyses with individual twins found associations in women between BMI and perceived stress (P=.01) and depression (P=.002), and the link between BMI and depression (P=.03) was significant in men. All physical health outcomes were significantly related to BMI. Once genetic and familial factors were taken into account, mental health outcomes were no longer significantly associated with BMI. BMI in women remained related to ratings of physical health (P=.01) and body pain (P=.004), independent of genetic and familial influences. Conclusion: These findings suggest that genetic and familial factors may account for the relationship between increased weight and poor mental health. [Copyright &y& Elsevier]

The University of Washington Twin Registry is a unique community-based registry of twin pairs who join specifically to participate in scientific research. It was founded in 2002 to serve as a resource for investigators throughout the scientific community. Current enrollment exceeds 7,200 pairs, and plans are in place to increase enrollment to 10,000 pairs by 2015. In addition to serving as a recruitment base for new research studies, the registry maintains extensive and continually expanding survey data on physical and mental health, as well as a biorepository that includes DNA from more than 8,800 individual twins. The registry is engaged in linking member data to birth records and to diagnostic and procedure variables for hospital-based care provided to members in Washington State. It also incorporates several innovative variables relevant to the built and social environments, which were created by geocoding twin addresses and linking the resulting coordinates to geospatial information systems databases. This combination of existing data and biospecimens, characterizing a group of twins who are willing to participate in research, is a valuable resource for the new wave of twin studies. These include ‘omics’, epigenetics, gene-by-environment interactions, and other novel methods to understand human health. [ABSTRACT FROM AUTHOR]

Abstract: We used a classical twin design and measures of neighborhood walkability and social deprivation, using each twin''s street address, to examine genetic and environmental influences on the residential location of 1389 same-sex pairs from a US community-based twin registry. Within-pair correlations and structural equation models estimated these influences on walkability among younger (ages 18–24.9) and older (ages 25+) twins. Adjusting for social deprivation, walkability of residential location was primarily influenced by common environment with lesser contributions of unique environment and genetic factors among younger twins, while unique environment most strongly influenced walkability, with small genetic and common environment effects, among older twins. Thus, minimal variance in walkability was explained by shared genetic effects in younger and older twins, and confirms the importance of environmental factors in walkability of residential locations. [Copyright &y& Elsevier]

Abstract: We studied whether self-reported intent to exert cognitive control over eating was associated with differences in brain response to food cues, independent of genetic background. Subjects were ten pairs of identical twins in which one twin was a restrained eater and the co-twin was unrestrained, as classified by the Herman and Polivy Restraint Scale. Before and after ingestion of a milkshake, we used functional magnetic resonance imaging to measure brain response to photographs of objects, “fattening” food, and “non-fattening” food. At baseline, restrained eaters had greater activation in the left amygdala and the right thalamus in response to fattening food cues than did their unrestrained co-twins. When restrained eaters drank a milkshake, activation in response to fattening food photographs decreased across multiple brain areas, whereas activation induced by non-fattening food photographs increased. As compared to their unrestrained co-twins, restrained eaters who drank a milkshake had greater decreases in activation by fattening food images in the left amygdala and occipital lobe, and greater increases in activation by non-fattening food images in the medial orbitofrontal cortex. Because of the discordant monozygotic twin study design, the findings provide a rigorous level of support for the hypothesis that adopting an intention to restrain eating alters brain response to food cues. [Copyright &y& Elsevier]

Background: Studies have found a modest association between depression and obesity, especially in women. Given the substantial genetic contribution to both depression and obesity, we sought to determine whether shared genetic influences are responsible for the association between these two conditions. Methods: Data were obtained from 712 monozygotic and 281 dizygotic female twin pairs who are members of the community-based University of Washington Twin Registry. The presence of depression was determined by self-report of doctor-diagnosed depression. Obesity was defined as body mass index of ≥30 kg/m2, based on self-reported height and weight. Generalized estimating regression models were used to assess the age-adjusted association between depression and obesity. Univariate and bivariate structural equation models estimated the components of variance attributable to genetic and environmental influences. Results: We found a modest phenotypic association between depression and obesity (odds ratio=1.6, 95% confidence interval=1.2–2.1). Additive genetic effects contributed substantially to depression (57%) and obesity (81%). The best-fitting bivariate model indicated that 12% of the genetic component of depression is shared with obesity. Conclusions: The association between depression and obesity in women may be in part due to shared genetic risk for both conditions. Future studies should examine the genetic, environmental, social, and cultural mechanisms underlying the relationship between this association. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain condition with unclear underlying etiology. Our objectives were to determine whether psychological distress was higher in twins with urological symptoms commonly found in IC/PBS than in twins without, and if so, did familial influences contribute to this association. Method: Data from 1165 female twins in a community-based sample were used. Urological symptoms, symptoms of posttraumatic stress disorder (PTSD), depression, anxiety and perceived stress were assessed with standardized questionnaires. Generalized estimating equation (GEE) regression models were used to examine the relationship between psychological distress and urological symptoms. Results: Compared to unaffected twins, twins with urological symptoms were more likely to report PTSD symptoms (OR=3.9; 95% CI=2.6–5.8), depression (OR=3.1; 95% CI=2.0–5.0), anxiety (OR=3.4; 95% CI=2.3–5.2) and perceived stress (OR=3.2; 95% CI=2.1–4.9). After adjusting for familial influences, the within-pair effects remained significant for PTSD symptoms (OR=2.2; 95% CI=1.2–3.8) and perceived stress (OR=2.2; 95% CI=1.2–3.8). Conclusion: Familial influences partially explained the relationship between indicators of psychological distress and urological symptoms. Future research should examine shared environmental and genetic mechanisms that may further explain this relationship and improve diagnosis and treatment of this unexplained clinical condition. [Copyright &y& Elsevier]

Objective: We examined the relative contributions of genetic and environmental influences to restrained eating. Method: Restrained eating was assessed by the Restraint Scale in a survey mailed to all twins enrolled in the University of Washington Twin Registry. We used structural equation modeling to estimate genetic and nongenetic contributions to restrained eating. Results: 1,196 monozygotic (MZ), 456 same-sex dizygotic (DZ) twins, and 447 opposite-sex twins were included in analyses. Restraint Scale scores were more closely correlated in MZ twins (rmale = .55, rfemale = .55) than in same-sex DZ twins (rmale = .31, rfemale = .19). Based on structural equation modeling, the estimated heritability for restrained eating, adjusted for body mass index (BMI) and sex, was 43% (95% confidence interval 35–50%). There was little evidence for common environmental effects. Discussion: These results indicate an inherited component to restrained eating. Genes could influence restrained eating directly or through inherited mediators such as personality factors or tendencies to gain weight. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome. Methods: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs. Results: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology. Conclusions: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS. [Copyright &y& Elsevier]

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects. [ABSTRACT FROM AUTHOR]

Objective. Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS. Design. Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS. Patients and Setting. Fifteen monozygotic twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington. Results. Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain ( P = 0.003) and fatigue ( P < 0.001) by their cotwins without CFS. Conclusions. These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS. [ABSTRACT FROM AUTHOR]

Abstract: Background: : Previous work using quantified EEG has suggested that brain activity in individuals with chronic fatigue syndrome (CFS) and normal persons differs. Our objective was to investigate if specific frequency band-pass regions and spatial locations are associated with CFS using low-resolution electromagnetic brain tomography (LORETA). Methods: : We conducted a co-twin control study of 17 pairs of monozygotic twins where 1 twin met criteria for CFS and the co-twin was healthy. Twins underwent an extensive battery of tests including a structured psychiatric interview and a quantified EEG. Eyes closed EEG frequency-domain analysis was computed and the entire brain volume was compared of the CFS and healthy twins using a multiple comparison procedure. Results: : Compared with their healthy co-twins, twins with CFS differed in current source density. The CFS twins had higher delta in the left uncus and parahippocampal gyrus and higher theta in the cingulate gyrus and right superior frontal gyrus. Conclusions: : These findings suggest that neurophysiological activity in specific areas of the brain may differentiate individuals with CFS from those in good health. The study corroborates that slowing of the deeper structures of the limbic system is associated with affect. It also supports the neurobiological model that the right forebrain is associated with sympathetic activity and the left forebrain with the effective management of energy. These preliminary findings await replication. [Copyright &y& Elsevier]

The University of Washington Twin Registry is a community-based registry of twins identified from the Washington State Department of Licensing. A fortuitous quirk in the Washington State drivers' license and identification number assignment, and collaborative Washington State laws, permitted us to build a statewide registry. Since obtaining approval from the Washington State Attorney General, the Washington State Department of Licensing has provided us with information on over 26,000 newly licensed twins, and we continue to receive computerized records on approximately 80 new twins per week. The University of Washington Twin Registry is assembled by mailing each twin a recruitment packet that includes an information sheet, brochure, brief survey, and nominal gift. Once both members of a twin pair have completed the packet, the pair is enrolled in the registry. As of June 2006, 2287 adult twin pairs have enrolled in the registry; about one half of these are female-female pairs. Among all twins, the average age is 32 years. Based on self-report, 52% of twins are monozygotic, 42% are dizygotic, and zygosity on 6% cannot yet be determined. We also have instituted a clinical protocol for collecting additional data and DNA from all twins participating in research studies requiring an in-person visit. The registry has established policies and procedures to protect the confidentiality of twin data and guidelines for the use of the registry by investigators. Plans for the further growth of the University of Washington Twin Registry and its use are discussed. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue may be accompanied by substantial functional disability. A volunteer sample of twins discordant for fatigue was identified from throughout the US. Fatigued twins were classified using three increasingly stringent definitions: (1) > or = 6 months of fatigue (119 pairs); (2) CFS-like illness based on self-report of the Centers for Disease Control and Prevention CFS research definition criteria (74 pairs); and (3) CFS assessed by clinical examination (22 pairs). Twins with chronic fatigue were compared with their unaffected co-twins on the eight standard scales and two physical and mental component summary scales from the medical outcomes study short-form health survey (SF-36). Substantial impairment was observed for fatigued twins across all levels of fatigue, while scores in the healthy twins were similar to US population values. Mean scores among fatigued twins on the physical and mental component summary scales were below 97 and 77%, respectively, of the US population scores. Diminished functional status was found across increasingly stringent classifications of fatigue and was associated with a dramatic decrement in physical functioning. The symptom of fatigue has a pronounced impact on functional status, especially in the domain of physical functioning. [ABSTRACT FROM AUTHOR]