Our weekly roundup of research paper abstracts that have not already appeared on the website
Virol J. 2011 Sep 6;8:423.
XMRV: usage of receptors and potential co-receptors.
Setty MK, Devadas K, Ragupathy V, Ravichandran V, Tang S, Wood O, Gaddam DS, Lee S, Hewlett IK.
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. firstname.lastname@example.org
BACKGROUND: XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC) patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS). Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors.
METHODS: To study the usage of different receptors and co-receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP-Human osteosarcoma) cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR.
RESULTS: Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP.
CONCLUSION: XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.
PMCID: PMC3184104 Free PMC Article
Psychol Health. 2011 Aug;26(8):989-1005. Epub 2011 May 23.
Emotion recognition and emotional theory of mind in chronic fatigue syndrome.
Oldershaw A, Hambrook D, Rimes KA, Tchanturia K, Treasure J, Richards S, Schmidt U, Chalder T.
Section of Eating Disorders, Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King’s College London, London, UK. email@example.com
BACKGROUND: Difficulties with social function have been reported in chronic fatigue syndrome (CFS), but underpinning factors are unknown. Emotion recognition, theory of mind (inference of another’s mental state) and ’emotional’ theory of mind (eToM) (inference of another’s emotional state) are important social abilities, facilitating understanding of others. This study examined emotion recognition and eToM in CFS patients and their relationship to self-reported social function.
METHODS: CFS patients (n=45) and healthy controls (HCs; n=50) completed tasks assessing emotion recognition, basic or advanced eToM (for self and other) and a self-report measure of social function.
RESULTS: CFS participants were poorer than HCs at recognising emotion states in the faces of others and at inferring their own emotions. Lower scores on these tasks were associated with poorer self-reported daily and social function. CFS patients demonstrated good eToM and performance on these tasks did not relate to the level of social function.
CONCLUSIONS: CFS patients do not have poor eToM, nor does eToM appear to be associated with social functioning in CFS. However, this group of patients experience difficulties in emotion recognition and inferring emotions in themselves and this may impact upon social function.
PMID: 21598185 [PubMed – indexed for MEDLINE]
Disabil Rehabil. 2011;33(19-20):1768-75. Epub 2011 Jan 6.
Diagnostic accuracy of symptoms characterising chronic fatigue syndrome.
Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR.
Department of Physical Therapy, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA. firstname.lastname@example.org
PURPOSE: To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS).
METHODS: A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n=16 individuals with CFS; n=14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24h apart.
RESULTS: Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve=0.864, 95% confidence interval [CI]: 0.706-1.00, p=0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p<0.001). A significant binary logistic regression model (p<0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects. CONCLUSIONS: A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.
J Pain. 2011 Feb;12(2):228-35.
Peak and end effects in patients’ daily recall of pain and fatigue: a within-subjects analysis.
Schneider S, Stone AA, Schwartz JE, Broderick JE.
Department of Psychiatry & Behavioral Science, Stony Brook University, Stony Brook, New York 11794-8790, USA. Stefan.Schneider@sunysb.edu
Clinical research often relies on retrospective recall of symptom levels, but the information contained in these ratings is not well understood. The “peak-and-end rule” suggests that the most intense (peak) and final (end) moments of an experience disproportionately influence retrospective judgments, which may bias self-reports of somatic symptoms.
This study examined the extent to which peak and end symptom levels systematically affect patients’ day-to-day recall of pain and fatigue. Rheumatology patients (N = 97) completed 5 to 6 momentary ratings of pain and fatigue per day as well as a daily recall rating of these symptoms for 28 consecutive days.
For pain, peak and end momentary ratings predicted daily recall of average pain beyond the actual average of momentary ratings. This effect was small, yet was confirmed in both between-person and within-person (repeated measures) analyses.
For fatigue, neither peak nor end momentary symptoms significantly contributed to daily recall.
Of note, the evidence for peak- and end-effects in recall of pain and fatigue varied significantly between individual patients. These findings suggest that peak- and end-effects create a small bias in recall reports of pain, but not fatigue. However, there are considerable individual differences in susceptibility to peak and end heuristics.
PERSPECTIVE: The peak-end cognitive heuristic could bias end-of-day recall of pain and fatigue. An effect was shown for pain, but not for fatigue. The effects were small and were unlikely to substantially bias end-of-day assessments. Individuals were shown to differ in the degree that the heuristic was associated with recall.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):730-43. Epub 2010 Aug 5.
Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.
Gardner A, Boles RG.
Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden. email@example.com
For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression.
High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the “affective spectrum disorders”, and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others.
Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders.
The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines.
Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders.
We propose that interactions among monoamines, mitochondrial dysfunction and inflammation can inspire explanatory, rather than mere descriptive, models of these disorder.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):784-94. Epub 2010 Jul 4
An intriguing and hitherto unexplained co-occurrence: De pression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.
Maes Clinics @ TRIA, 998 Rimklongsamsen Road, Bangkok 10310, Thailand. firstname.lastname@example.org
There is a significant ‘comorbidity’ between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy.
This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria.
Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2′-5′ oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS.
Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways.
Depression and ME/CFS are not ‘comorbid’ disorders, but should be regarded as ‘co-associated disorders’ that are clinical manifestations of shared pathways.