Sanae Fukuda

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. 11C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (11C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used 11C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. Methods: Nine CFS/ME patients and 10 healthy controls underwent 11C-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, nondisplaceable binding potential (BPND) values were determined using linear graphical analysis with the cerebellum as a reference region. Results: The BPND values of 11C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%–199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BPND values of 11C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BPND values in the cingulate cortex and thalamus positively correlated with pain score, and the BPND value in the hippocampus positively correlated with depression score. Conclusion: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

Relationships between dietary habits and the prevalence of fatigue in medical students

OBJECTIVE Fatigue, which is a common complaint among medical students, is related to poor academic outcomes. Because impaired dietary habits, such as skipping breakfast and taking meals irregularly, are correlated with poor school performances, whether those dietary habits were associated with the prevalence of fatigue was determined in medical students. METHODS The study group consisted of 127 healthy second-year medical students attending Osaka City University Graduate School of Medicine. They completed a questionnaire dealing with fatigue (Japanese version of the Chalder Fatigue Scale), lifestyle, and academic performance. RESULTS On multivariate logistic regression analyses adjusted for age, gender, body mass index, and nocturnal sleeping hours, skipping breakfast (completely skipping breakfast everyday versus having breakfast everyday; odds ratio 7.81, 95% confidence interval 2.00-30.52, P = 0.003) and taking meals irregularly (completely irregular versus always regular; odds ratio 6.89, 95% confidence interval 1.20-39.55, P = 0.030) were positively correlated with the prevalence of fatigue. CONCLUSION Skipping breakfast and taking meals irregularly are associated with the prevalence of fatigue in medical students.

Fatigue Is a Predictor for Cardiovascular Outcomes in Patients Undergoing Hemodialysis

BACKGROUND AND OBJECTIVES Despite potential significance of fatigue and its underlying components in the occurrence of cardiovascular diseases, epidemiologic data showing the link are virtually limited. This study was designed to examine whether fatigue symptoms or fatigues underlying components are a predictor for cardiovascular diseases in high-risk subjects with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 788 volunteer patients under hemodialysis therapy (506 male, 282 female) completed the survey between October and November 2005, with the follow-up period up to 26 months to monitor occurrence of fatal or nonfatal cardiovascular events. The questionnaire consisted of 64 questions, and promax rotation analysis of the principal component method conceptualized eight fatigue-related factors: fatigue itself, anxiety and depression, loss of attention and memory, pain, overwork, autonomic imbalance, sleep problems, and infection. RESULTS 14.7% of the patients showed fatigue scores higher than twice the SD of the mean for healthy volunteers. These highly fatigued patients exhibited a significantly higher risk for cardiovascular events (hazard ratio: 2.17; P < 0.01), with the relationship independent of the well-known risk factors, including age, diabetes, cardiovascular disease history, and inflammation and malnutrition markers. Moreover, comparisons of the risk in key subgroups showed that the risk of high fatigue score for cardiovascular events was more prominent in well-nourished patients, including lower age, absence of past cardiovascular diseases, higher serum albumin, and high non-HDL cholesterol. CONCLUSIONS Fatigue can be an important predictor for cardiovascular events in patients with ESRD, with the relationship independent of the nutritional or inflammatory status.

Personality traits associated with intrinsic academic motivation in medical students

Objectives  Motivation is one of the most important psychological concepts in education and is related to academic outcomes in medical students. In this study, the relationships between personality traits and intrinsic academic motivation were examined in medical students.

Premorbid personality in chronic fatigue syndrome as determined by the Temperament and Character Inventory

BACKGROUND Using the Temperament and Character Inventory (TCI), we examined personality characteristics in patients with chronic fatigue syndrome (CFS) compared with healthy control subjects, and CFS patients with and without psychiatric diseases. There have been no previous reports assessing personality in CFS patients using the TCI. METHODS A total of 211 CFS patients and 90 control subjects completed the TCI and the Chalder Fatigue Scale questionnaires. RESULTS Compared with control subjects, CFS patients demonstrated significantly lower premorbid Novelty Seeking, and higher Harm Avoidance and persistence. The fatigue score for CFS patients with psychiatric diseases was higher than that for CFS patients without psychiatric diseases. Patients with CFS with psychiatric diseases showed lower premorbid Self-Directedness when compared with CFS patients without psychiatric diseases. The fatigue score was negatively correlated with premorbid Self-Directedness and Cooperativeness, and positively correlated with Harm Avoidance among CFS patients. CONCLUSION This study supported the stereotyped image of CFS patients as perfectionists, which is similar to the Persistence score, and neurotics, which is similar to the Harm Avoidance score. Patients displaying greater neuroticisms and poorer social and communication skills, similar to the Self-Directedness and Cooperativeness scores, tend to have intercurrent psychiatry diseases and show more severe symptoms of CFS.

Reliability and Validity of the Japanese Version of the Chalder Fatigue Scale among Youth in Japan

In the present study, the reliability and construct validity of the Japanese version of the Chalder Fatigue Scale was evaluated as a measure of severity of fatigue among young students in Japan. A healthy group comprised 27 Grade 6 primary school students and 28 Grade 1 junior high school students. The severely fatigued group were hospital outpatients with childhood chronic fatigue syndrome (n = 21). Principal components analysis with varimax rotation identified 4 factors which accounted for 63.2% of the total variance, as in the original English version. Internal consistency (Cronbach coefficient α) was .73, and test-retest reliability measured using Spearman rank correlation coefficient was .55. Scale scores of the healthy subjects were lower than those of the patients with childhood chronic fatigue syndrome. The reliability (a) and construct validity of the Japanese version of the scale among healthy students in Japan were satisfactory for research studies among healthy school students.

Relationship between cognitive function and prevalence of decrease in intrinsic academic motivation in adolescents

BackgroundDecrease in intrinsic motivation is a common complaint among elementary and junior high school students, and is related to poor academic performance. Since grade-dependent development of cognitive functions also influences academic performance by these students, we examined whether cognitive functions are related to the prevalence of decrease in intrinsic academic motivation.MethodsThe study group consisted of 134 elementary school students from 4th to 6th grades and 133 junior high school students from 7th to 9th grades. Participants completed a questionnaire on intrinsic academic motivation. They also performed paper-and-pencil and computerized cognitive tests to measure abilities in motor processing, spatial construction, semantic fluency, immediate memory, short-term memory, delayed memory, spatial working memory, and selective, alternative, and divided attention.ResultsIn multivariate logistic regression analyses adjusted for grade and gender, scores of none of the cognitive tests were correlated with the prevalence of decrease in intrinsic academic motivation in elementary school students. However, low digit span forward test score and score for comprehension of the story in the kana pick-out test were positively correlated with the prevalence of decrease in intrinsic academic motivation in junior high school students.ConclusionsThe present findings suggest that decrease in capacity for verbal memory is associated with the prevalence of decrease in intrinsic academic motivation among junior high school students.

Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome--a 6-month follow-up study.

OBJECTIVES Cognitive function was investigated in patients with childhood type chronic fatigue syndrome (CCFS) using the modified advanced trail making test (mATMT). METHODS mATMT was performed on 19 patients with CCFS and 25 healthy controls of comparable age and sex. The effectiveness of combined treatment with cognitive behavioral therapy (CBT) and pharmacotherapy and its relationship to cognitive function was investigated by evaluation of Chalders fatigue scale and behavior state before and after treatment for 6 consecutive months. RESULTS All three tasks (motor skill, selective and alternative attention, and spatial working memory) of the mATMT, especially the difference in reaction time of the alternative attention task, could discriminate CCFS patients from control subjects with 70.5% accuracy (P=0.007). CCFS patients showed significantly lower alternative attention and Chalders fatigue score before treatment (P=0.037 and 0.002, respectively). A significant improvement in performance status scores was found during the 6 months follow-up period with combined treatment with CBT and medication (P<0.001). Improvement of their cognitive symptoms was significantly correlated with improvement of alternative attention (r=0.653, P=0.002). CONCLUSIONS Higher-order level cognitive dysfunction affects CCFS pathogenesis. Alternative attention performance evaluated by the mATMT may be used to monitor improvement in patients with CCFS. Combined treatment with CBT and medication may be effective to improve poor attention characteristics associated with CCFS.

Effort-Reward Imbalance for Learning is Associated with Fatigue in School Children

We examined relationships among fatigue, sleep quality, and effort-reward imbalance for learning in school children. We developed an effort-reward for learning scale in school students and examined its reliability and validity. Self-administered surveys, including the effort reward for leaning scale and fatigue scale, were completed by 1,023 elementary school students (grades 4–6) and 1,361 junior high school students (grades 7–9) at the end of 2006. Effort-reward imbalance for learning was associated with a high incidence of fatigue and sleep problems in elementary and junior high school students of both genders. A good relationship with family was associated with a low fatigue score in junior high school boys, and a good relationship with friends was associated with a low fatigue score in junior high school girls by multiple regression analysis. Fatigue score was associated with effort-reward imbalance and fatigue and quality of sleep in schoolchildren. Fatigue may lead to a decline in school performance, negative health outcomes, or refusal to attend school. These results suggest that it is desirable to consider social support, quality of sleep, and effort-reward imbalance when managing fatigue in school children.

Relationship between cognitive functions and prevalence of fatigue in elementary and junior high school students

BACKGROUND Fatigue is a common complaint among elementary and junior high school students, and is related to poor academic performance. Since grade-dependent development of cognitive functions also influences academic performance, we attempted to determine whether cognitive functions were associated with the prevalence of fatigue. METHODS Participants were 148 elementary school students from 4th- to 6th-grades and 152 junior high school students from 7th- to 9th-grades. Participants completed a questionnaire about fatigue (Japanese version of the Chalder Fatigue Scale) and paper-and-pencil and computerized cognitive tests which could evaluate the abilities of motor processing, immediate, delayed and working memory, selective, divided and alternative attention, retrieve learned material, and spatial construction. RESULTS We found that in multivariate logistic regression analyses adjusted for grade and gender, slow motor processing was positively correlated with the prevalence of fatigue in the elementary school students and decreases in working memory and divided and alternative attention processing were positively correlated with the prevalence of fatigue in the junior high school students. CONCLUSION The grade-dependent development of cognitive function influences the severity of fatigue in elementary and junior high school students.