There is now evidence that major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are accompanied by partially overlapping pathophysiological mechanisms, i.e. activation of various inflammatory and oxidative & nitrosative (IO&NS) pathways.The aim of the present study was to examine the urinary excretion of 8-hydroxy-deoxyguanosine (8-OhdG), a marker of oxidative damage to DNA, in depression; ME/CFS; and depression and ME/CFS.Toward this end, morning urine was sampled for the assays of 8-OHdG and creatinine, in 44 patients with ME/CFS; 25 with major depression; 23 with depression and ME/CFS; and 17 normal controls. Severity of fatigue and somatic symptoms was measured by means of the Fibromyalgia and CFS Rating (FF) scale.We found that 49.0% of the variance in the urinary excretion of 8-OHdG was predicted by the regression on creatinine. Consequently, the urinary 8-OHdG excretion should be expressed as the residualized 8-OHdG values after partialling out the effects of creatinine and not by computing the 8-OHdG / creatinine ratio. We found that the residualized urinary excretion of 8-OHdG (adjusted for creatinine) was significantly higher in patients with depression and ME/CFS than in normal controls and all other patients. In the patient group, there were significant correlations between the urinary 8-OHdG and the total score on the FF scale and sadness and flu-like malaise.The findings show increased oxidatively generated DNA damage in patients with major depression and ME/CFS and, therefore, further extent the role played by IO&NS pathways in the pathophysiology of both disorders. Since oxidatively damage to DNA is a risk factor for atherosclerosis and neurodegeneration, our results also explain previous findings on increased cardiovascular morbidity in depression and ME/CFS, and neurodegenerative processes in depression.
There is now evidence that major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are accompanied by partially overlapping pathophysiological mechanisms, i.e. activation of various inflammatory and oxidative & nitrosative (IO&NS) pathways.The aim of the present study was to examine the urinary excretion of 8-hydroxy-deoxyguanosine (8-OhdG), a marker of oxidative damage to DNA, in depression; ME/CFS; and depression and ME/CFS.Toward this end, morning urine was sampled for the assays of 8-OHdG and creatinine, in 44 patients with ME/CFS; 25 with major depression; 23 with depression and ME/CFS; and 17 normal controls. Severity of fatigue and somatic symptoms was measured by means of the Fibromyalgia and CFS Rating (FF) scale.We found that 49.0% of the variance in the urinary excretion of 8-OHdG was predicted by the regression on creatinine. Consequently, the urinary 8-OHdG excretion should be expressed as the residualized 8-OHdG values after partialling out the effects of creatinine and not by computing the 8-OHdG / creatinine ratio. We found that the residualized urinary excretion of 8-OHdG (adjusted for creatinine) was significantly higher in patients with depression and ME/CFS than in normal controls and all other patients. In the patient group, there were significant correlations between the urinary 8-OHdG and the total score on the FF scale and sadness and flu-like malaise.The findings show increased oxidatively generated DNA damage in patients with major depression and ME/CFS and, therefore, further extent the role played by IO&NS pathways in the pathophysiology of both disorders. Since oxidatively damage to DNA is a risk factor for atherosclerosis and neurodegeneration, our results also explain previous findings on increased cardiovascular morbidity in depression and ME/CFS, and neurodegenerative processes in depression.
Article Abstract Background: Delivery is accompanied by increases in anxiety levels that are significantly related to an activation of the inflammatory response system (IRS), as indicated by increases in the serum concentrations of interleukin-6 and the interleukin-1 receptor antagonist (IL-1RA) and increases in the activity of prolyl endopeptidase (PEP), a cytosolic endopeptidase that cleaves peptide bonds on the carboxyl side of proline in behaviorally active neuropeptides involved in anxiety. Primiparae may show an immune responsivity differing from that in multiparae. The aims of this study were to examine whether there are differences in anxiety levels, the IRS, and serum PEP values between primiparae and multiparae before and after delivery. Method: We administered the Spielberger State-Trait Anxiety Inventory (STAI) to and assessed serum IL-1RA and soluble CD8 (sCD8) concentrations and serum PEP activity in 48 primiparae and 48 multiparae at the end of term and 1 and 3 days after delivery. Data were gathered in 1996 and 1997. Results: We found that in primiparae (p = .001), but not in multiparae (p = .6), there was a significant increase in the STAI score 3 days after delivery and that primiparae had significantly higher STAI scores than multiparae 3 days after delivery (p = .01). Primiparae showed significantly higher serum IL-1RA levels than multiparae 1 (p = .003) and 3 (p = .02) days after delivery, but not before delivery. Primiparae also had lower serum sCD8 and higher serum PEP activity than multiparae before and after delivery. Conclusions: The results suggest that primiparae suffer greater anxiety and have a different neuroimmune responsivity than multiparae and that the increased anxiety levels in primiparae may be related to changes in the IRS and serum PEP activity.
There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic‐pituitary‐adrenal (HPA) axis, as assessed by means of 24‐h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post‐traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24‐h UC excretion. The aim of the present study was to examine 24‐h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24‐h UC excretion than normal controls and fibromyalgia patients. At a threshold value of ≥240 μg/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24‐h UC excretion with a specificity of 100%. There were no significant differences in 24‐h UC excretion either between fibromyalgia patients and normal controls, or between patients with major depression and PTSD patients. In the three patient groups, no significant correlations were found between 24‐h UC excretion and The HDRS score. In fibromyalgia, no significant correlations were found between 24‐h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24‐h UC excretion and severity of either depression‐avoidance or anxiety‐arousal symptoms. In conclusion, this study found increased 24‐h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24‐h UC were found.
This study investigated the diagnostic performance of the MMPI validity and clinical scales, and especially of Scale 7 ( Pt), for the DSM-III—R obsessive-compulsive personality disorder by comparing the MMPI variables for 24 obsessive-compulsive with those for 58 nonobsessive-compulsive inpatients. Both groups were diagnosed by semistructured interview (SCID-II). The obsessive-compulsive group obtained for the mean MMPI profile a 2-(6-l) ( D-Pa-Hs) code, with a tendency for a lowered Scale 4 ( Pd) score, compared to the nonobsessive-compulsive group. Neither the ROC analysis of the individual MMPI scales, including Scale 7 ( Pt), nor the analyses of frequency of two-point codes and elevated ( T>69) scales showed any clear indications of good diagnostic performance for the DSM-III—R obsessive-compulsive personality disorder.
Abstract Background No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD. Conclusions Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.
The insulin-like growth factors (IGFs) are small peptides that are present in serum and extracellular fluids and stimulate the growth of many cell types. In extracellular fluids the IGFs are bound to carrier proteins that are believed to modify the biological actions of the IGFs. At least three structurally distinct IGF-binding proteins (IGF-BPs) have been identified, and the serum concentrations of one of these has been shown to be regulated by pituitary GH. We report here that this GH responsive protein [39,000–45,000 mol wt (Mr)] can be induced (7-fold) by infusion of IGF-I in hypophysectomized rats or (3.5-fold) in protein-deprived rats, whereas two other forms of IGF-BP e.g. 31,000–34,000 and 24,000 Mr) showed no change in the hypophysectomized animals and minimal increases in the protein-deprived animals. Likewise, GH injections in hypophysectomized animals resulted in a 7-fold increase in the 39,000–45,000 Mr form and no change in the 31,000–34,000 and 24,000 Mr forms. The protein-deprived animals showed a 3.2-fold increase in the 39,000–45,000 Mr and 2.4- to 1.8-fold increases in the 31,000–34,000 and 24,000 Mr forms, respectively. Changes in the larger Mr IGF-BP in these experimental models are paralleled by changes in serum IGF-I, suggesting that the GH dependence of the former protein is mediated at least partially via IGF-I. Our findings also suggest that the secretion of IGF-I and at least one IGF-BP may be linked, providing a mechanism by which their extracellular fluid concentrations are coordinated. Because IGF-BPs are present in extracellular fluids and can modulate IGF-I-receptor interaction, induction of this protein may be an important mediator of IGF action.
