Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults

BackgroundSystemic inflammation has emerged as a risk factor for cognitive decline and Alzheimer’s disease, but inflammation’s effect on distributed brain networks is unclear. We examined the relationship between peripheral inflammatory markers and subsequent functional connectivity within five large-scale cognitive networks and evaluated the modifying role of cortical amyloid and APOE ε4 status.MethodsBlood levels of soluble tumor necrosis factor-alpha receptor-1 and interleukin 6 were assessed in 176 participants (at baseline mean age: 65 (SD 9) years; 63% women; 85% cognitively normal, 15% mild cognitive impairment (MCI)) and were combined to derive an Inflammatory Index. Approximately six years later, participants underwent resting-state functional magnetic resonance imaging to quantify functional connectivity; a subset of 137 participants also underwent ¹¹C Pittsburgh compound-B (PiB) PET imaging to assess cortical amyloid burden.ResultsUsing linear regression models adjusted for demographic characteristics and cardiovascular risk factors, a higher Inflammatory Index was associated with lower connectivity within the Default Mode (β = −0.013; 95% CI: −0.023, −0.003) and the Dorsal Attention Networks (β = −0.017; 95% CI: −0.028, −0.006). The strength of these associations did not vary by amyloid status (positive/negative). However, there was a significant interaction between Inflammatory Index and APOE ε4 status, whereby ε4-positive participants with a higher Inflammatory Index demonstrated lower connectivity. Inflammatory Index was unrelated to connectivity within other large-scale cognitive networks (Control, Limbic, and Salience/Ventral Attention networks).ConclusionPeripheral pro-inflammatory signaling in older adults without dementia, especially among APOE ε4-positive individuals, is associated with altered connectivity within two large-scale cognitive networks.     

Association between psychological measures with inflammatory anddisease-related markers of inflammatory bowel disease

Objective: This study aimed at investigating the associations between inflammatory mediators, symptoms and psychological disturbances in inflammatory bowel disease (IBD) patients.

Methods: IBD patients and patient controls were examined during a single visit to a gastroenterology clinic. Disease activity was assessed using the Mayo index for ulcerative colitis (UC), inflammatory bowel disease questionnaire (IBDQ), Crohn’s disease activity index (CDAI) and Crohn’s disease endoscopic index of severity (CDEIS). Gene expression of inflammatory mediators were measured in intestinal biopsies and whole blood samples along with circulating concentrations of interleukin (IL)-6, interferon (IFN)γ, C-reactive protein (CRP), kynurenine and tryptophan. Validated depression, anxiety and quality of life scores were used to assess psychological well-being.

Results: Patients who were symptomatic had the highest depression and anxiety scores, together with increased intestinal expression of IL-1β, IL-6 and matrix metalloproteinase-9, increased circulating IL-6 and CRP, and an increased circulating kynurenine:tryptophan ratio. Increased Hamilton depression (HAM-D) scores in IBD patients were observed independent of the psychological impact of acute symptoms.

Conclusions: Active IBD is associated with symptoms of depression and anxiety and with a raised circulating inflammatory mediator profile. Patients with active IBD exhibiting psychological symptoms should undergo psychological evaluation to ensure the psychological aspects of the condition are considered and addressed.     

A factor analysis of chronic fatigue symptoms in a community-based sample

Background This study examined characteristics of fatigue in individuals with chronic fatigue from a community-based study. Most studies of chronic fatigue have been based on patients recruited from primary or tertiary care settings. Samples such as these might not be representative of patients within the general population. The purpose of this study was to determine the factor structure of participants' symptoms in a random community sample of individuals with chronic fatigue. Method A random sample of 18,675 respondents in Chicago received a brief telephone questionnaire designed to identify individuals with chronic fatigue. A group of 780 (4.2 %) with chronic fatigue received further interview via telephone questionnaire involving characteristics of their fatigue. The analyses for this study were based on those people identified with having chronic fatigue. A factor analysis was conducted on responses to questionnaire items, and a four-factor solution emerged. Mean factor scores were derived and analyzed in relation to sociodemographic characteristics and sample subgroups. Results The four factors were labeled: Lack of Energy, Physical Exertion, Cognitive Functioning, and Fatigue and Rest. Conclusions Results indicated that individuals with chronic fatigue have symptoms that can be differentiated into theoretically distinct factors. Accepted: 12 November 2001     

Social factors associated with chronic depression among a population-based sample of women in rural Pakistan

Abstract Objective Previous studies have reported a high prevalence of depression in women in Pakistan. This paper investigates whether risk factors for chronic depression established in studies performed in Western countries can explain this high prevalence. Method A two–phase survey using the self–rating questionnaire (SRQ) for common mental disorders and the Psychiatric Assessment Schedule was performed on a general population sample in rural Pakistan. Demographic data and results of the Life Events and Difficulties Schedule were analysed in relation to SRQ score and psychiatric disorder. Results A total of 145 women were screened. High SRQ score was associated with low educational status, not having a confidant, having four or more children, being older, not being married and living in a house with more than three people per room. Regression analysis demonstrated that the first three of these independently contributed to SRQ score. In the interviewed sample (74 women), only educational level independently contributed to the presence of depression. In addition, the least educated group experienced the greatest number of marked difficulties: 67% of them had experienced both marked housing and financial difficulties compared to 28% and 25% of the other educational groups (p = 0.005). Experiencing both housing and financial difficulties was a significant risk factor for depression in women with secondary education, but not for those without secondary education. Conclusions This study suggests that high levels of social adversity and low levels of education are strongly associated with depression in women in Pakistan. The other vulnerability factors found in the West (such as lack of a confidant, the presence of three or more young children at home, or loss of mother during childhood) may be of lesser importance in this population.     

Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

Background  

Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS) however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood.     

Association between smoking and attention-deficit/hyperactivity disorder symptoms in a population-based sample of young adults

CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk of smoking, and some studies have suggested that inattentive symptoms specifically may underlie this risk. Few studies, however, have examined ADHD symptoms in nonclinical samples to determine the extent to which the number of symptoms-independent of the full diagnosis-confer risk for smoking-related outcomes. OBJECTIVE: To evaluate the relation between smoking-related variables and the number of retrospectively reported ADHD inattentive and hyperactive/impulsive symptoms in a population-based sample of young adults. DESIGN, SETTING, AND PARTICIPANTS: The study population consists of 15 197 eligible participants from wave III of the National Longitudinal Study of Adolescent Health, a nationally representative sample of adolescents followed from 1995 to 2002. MAIN OUTCOME MEASURES: Logistic regression was used to examine the relation between self-reported ADHD symptoms and the lifetime likelihood of being a regular smoker, defined by having smoked at least 1 cigarette a day for 30 days. For individuals reporting regular smoking, we also examined the extent to which ADHD symptoms predicted age at onset of regular smoking and number of cigarettes smoked. RESULTS: A linear relation was identified between the number of self-reported inattentive and hyperactive/impulsive symptoms and smoking outcome measures (P<.001 for each symptom domain). Controlling for demographic and conduct disorder symptoms, each reported inattention and hyperactivity/impulsivity symptom significantly increased the likelihood of ever regular smoking (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.08-1.14 and OR, 1.16; 95% CI, 1.13-1.19, respectively). For those reporting lifetime regular smoking, reported symptoms decreased the estimated age at onset and increased the number of cigarettes smoked. CONCLUSIONS: Self-reported ADHD symptoms were found to be associated with adult smoking outcome variables in this nationally representative sample, providing further evidence of a likely link between ADHD symptoms and risk for tobacco use.     

The association between sleep characteristics and prothrombotic markers in a population-based sample: Chicago Area Sleep Study

Background and aimShort sleep duration and poor quality sleep are associated with coronary heart disease (CHD) mortality; however, the underlying pathophysiologic process remains unclear. Sleep apnea may confound the association because of its relationship with formation of thrombi, the vascular occlusive process in CHD. We tested whether sleep duration and quality were associated with prothrombotic biomarkers in adults with a low probability of apnea.MethodsWe included adults aged 35–64 years recruited from the community and who had an apnea hypopnea index <15 after one night of screening (n = 506). Sleep duration and maintenance were determined from 7 days of wrist actigraphy; daytime sleepiness was estimated using the Epworth Sleepiness Scale. Factor VIII (FVIII), von Willebrand factor (vWF), thrombin antithrombin (TAT) complexes, and plasminogen activator inhibitor-1 (PAI-1) were measured in fasting blood.ResultsSleep duration, maintenance, and daytime sleepiness were not associated with FVIII, vWf, or TAT. Sleep maintenance was modestly inversely associated with higher levels of log-transformed PAI-1 (β = −0.07, standard error (SE) = 0.03 per 4.8%, p = 0.04) following adjustment for demographic characteristics, cardiovascular risk factors, and body mass index (BMI).ConclusionsMild impairment in sleep was modestly associated with activation of coagulation; further study is needed to evaluate the role of fibrinolytic factors in sleep-mediated coronary thrombosis.     

Status epilepticus in a population-based Virginia twin sample

PURPOSE: To characterize status epilepticus (SE) and estimate its frequency of first occurrence, as well as to assess the contribution of genetic factors to risk of SE occurrence in a sample of Virginia-born twins ascertained from the population-based Mid-Atlantic Twin Registry. METHODS: The occurrence of SE was determined in 13,506 unselected Virginia-born twin pairs ascertained from birth records. Twins included in the study were between ages 2 and 75 years when surveyed. History of seizures and SE was validated through medical records and by detailed personal or parental interviews. RESULTS: Among 381 twins included in 332 pairs with a verified history of seizures, 70 (18.4%) were validated to have had at least one episode of SE. The frequency of first SE in this sample was 309 per 100,000 twins. First SE occurred in conjunction with 21 of 158 febrile and 49 of 223 afebrile seizure cases, respectively. Mean length of SE episode was 76.2 +/- 14.9 min. Age at first SE occurrence ranged from 2 months to 59 years. All concordant twin pairs in the sample were monozygotic (MZ), with a proband-wise concordance rate estimated for SE in this population of 0.31 [95% confidence interval (CI), 0.14-0.52) overall, and 0.67 (95% CI, 0.35-0.90) in pairs concordant for epilepsy. CONCLUSIONS: These results provide a direct estimate of the frequency of SE in a defined population of twins and afford further evidence for a genetic contribution to risk for SE.     

Cognitive functioning in a population-based sample of young adults with anxiety disorders

Objective

Cognitive functioning in anxiety disorders has received little investigation, particularly among young adults and in non-clinical samples. The present study examined cognitive functioning in a population-based sample of young adults with anxiety disorders in comparison to healthy peers.

Methods

A population-based sample of 21–35-year-olds with a lifetime history of anxiety disorders (n = 75) and a random sample of healthy controls (n = 71) derived from the same population were compared in terms of performance in neuropsychological tests measuring verbal and visual short-term memory, verbal long-term memory, attention, psychomotor processing speed, and executive functioning.

Results

In general, young adults with anxiety disorders did not have major cognitive impairments when compared to healthy peers. When participants with anxiety disorder in remission were excluded, persons with current anxiety disorder scored lower in visual working memory tests. Current psychotropic medication use and low current psychosocial functioning associated with deficits in executive functioning, psychomotor processing speed, and visual short-term memory.

Conclusion

Lifetime history of anxiety disorders is not associated with cognitive impairment among young adults in the general population. However, among persons with anxiety disorders, current psychotropic medication use and low psychosocial functioning, indicating more severe symptoms, may associate with cognitive impairments.     

The impact of sample processing on inflammatory markers in serum: Lessons learned

Abstract

Objectives: To investigate the effect of sample handling on inflammatory cytokines in serum and highlight challenges with using samples pre-collected from biobanks for biomarker research.

Methods: Cytokine concentrations (IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, and IFNγ) were measured in serum samples of 205 patients with bipoldar disorder (BD) from the Mayo Clinic Bipolar Disorder Biobank and 205 non-psychiatric controls from the Mayo Clinic Biobank. As cytokine concentrations varied by recruitment site, post-hoc models were used to test the effect of clinical variables and pre-processing time on cytokines. To evaluate the effect of pre-processing time experimentally, cytokines were assayed in serum and plasma from 6 healthy volunteers processed at different time points.

Results: Cytokine levels were significantly higher in the BD group. However, both cytokine levels and pre-processing times differed by recruitment site, and post-hoc analyses revealed that pre-processing time was significantly associated with several cytokines. An experiment using samples from healthy volunteers confirmed that concentrations for most cytokines increased with longer pre-processing times.

Conclusions: Delays in processing influence cytokine concentrations in blood samples. Given the increasing use of biobanks in research, this study highlights the need to carefully evaluate sample collection and handling methods when designing biomarker studies.     

Assessing the reliability of the five minute speech sample against the Camberwell family interview in a chronic fatigue syndrome sample

PurposeThe current study aimed to examine the reliability of the Five Minute Speech Sample (FMSS) for assessing relative Expressed Emotion (EE) compared with the Camberwell Family Interview (CFI) in a sample of relatives of adult patients with Chronic Fatigue Syndrome (CFS).Method21 relatives were recruited and completed both assessments. The CFI was conducted first for all participants, with the FMSS conducted approximately one month later. Trained raters independently coded both EE measures; high levels of rating reliability were established for both measures. Comparisons were conducted for overall EE status, emotional over-involvement (EOI) and criticism.FindingsThe distribution of high and low-EE was equivalent across the two measures, with the FMSS correctly classifying EE is 71% of cases (n = 15). The correspondence between the FMSS and CFI ratings was found to be non-significant for all categorical variables. However, the number of critical comments made by relatives during the FMSS significantly correlated with the number of critical comments made during the CFI. The poorest correspondence between the measures was observed for the EOI dimension.ConclusionThe findings suggest that the FMSS may be a useful screening tool for identifying high-EE, particularly criticism, within a sample of relatives of patients with CFS. However, the two measures should not be assumed equivalent, and the CFI should be used where possible, particularly with respect to understanding EOI.     

ADHD medication use in a population-based sample of twins

OBJECTIVE: To determine treatment patterns for youth attention-deficit/hyperactivity disorder (ADHD) symptoms in a general population sample of 1,610 twins. METHOD: Twin pairs ages 7 to 17 years and parents ascertained from birth records in the state of Missouri were interviewed using the Missouri Assessment of Genetics Interview for Children between 1996 and 2001. Multivariate logistic regression analyses were used to determine which factors were significant in answering three questions about treatment for ADHD. RESULTS: Of 302 boys, 177 (58.6%) and 26 of 57 girls (45.6%) who met full DSM-IV criteria for ADHD received stimulant medication in this sample. Of 314 youths, 111 (35.4%) who received stimulant medication did not meet DSM-IV criteria for ADHD. When controlling for comorbidity and other factors, the number of impairing ADHD symptoms and having a cotwin who was also brought to treatment for ADHD correlated with referral or treatment in youths without ADHD. Youths without ADHD who were treated had a large number of ADHD symptoms. CONCLUSION: As is shown in earlier studies, children with ADHD are being undertreated. Complex factors, including comorbid disorders and family history of ADHD treatment, affect treatment patterns in the general population.     

Combined peripheral nerve and central nervous system demyelination in a patient with chronic inflammatory demyelinating polyneuropathy

We report the case of a 49-year-old woman suffering combined central and peripheral demyelination, with serial magnetic resonance images scans illustrating the development of central demyelination in a patient with established chronic inflammatory demyelinating polyneuropathy. This is the sixth patient with this rare overlap syndrome reported to date. We review the available literature and argue that an inherited predisposition to both diseases is the most likely explanation for its occurrence.     

Coping strategies in twins with chronic fatigue and chronic fatigue syndrome

Objectives: Individuals with chronic fatigue and chronic fatigue syndrome (CFS) face debilitating symptoms as well as stressful life situations that may result from their condition. The goal of this study was to examine the coping strategies used by fatigue-discordant twin pairs. Methods: We utilized a co-twin design to assess how twin pairs discordant for chronic fatigue and CFS cope with stress. All twin pairs were administered the Revised Ways of Coping Checklist. Results: Overall, the pattern of coping strategies was similar for fatigued and non-fatigued twins. However, twins with chronic fatigue or CFS utilized more avoidance strategies than their non-fatigued counterparts; those with chronic fatigue also used more avoidance relative to problem-focused coping than their co-twins. Conclusions: These results suggest that while fatigue-discordant twins generally exhibit similar behavior patterns in order to cope with stress, there may be an association between fatigue and avoidance coping. Future research should focus on the role of avoidance and its relationship to fatiguing illnesses.