Childhood adversity and cell-mediated immunity in young adulthood: Does type and timing matter?

Childhood adversity can have powerful effects on health over the life course. Persistent changes in cell-mediated immune function may be one pathway linking adverse childhood experiences with later disease risk. However, limited research has examined childhood adversity in relation to cell-mediated immune function, and in particular, immune response to latent viruses in adulthood. The present study investigated the association of two types of childhood adversity, socioeconomic disadvantage during adolescence and abuse prior to age 18, with Epstein–Barr Virus (EBV) antibody titers in a large nationally representative sample of young adults aged 24–32 years. Data were drawn from the National Longitudinal Study on Adolescent Health, Wave 4 (n = 13,162). We examined the associations of three indicators of adolescent SES (parental education, household income, and occupational status) and frequency and timing of physical and sexual abuse with EBV antibodies, controlling for age, sex, race/ethnicity, and presence of a smoker in the household during adolescence. Lower parental occupational status and some categories of lower education were associated with elevated EBV antibodies (p < .05), and individuals who reported sexual abuse that occurred more than 10 times had elevated EBV antibodies relative to individuals who were not sexually abused (p = 0.03). Among individuals exposed to physical abuse, those who were first abused at age 3–5 years had heightened EBV antibodies relative to those first abused during adolescence (p = 0.004). This study extends prior research linking early adversity and immune function, and provides initial evidence that childhood adversity has a persistent influence on immune responses to latent infection in adulthood.     

When should we test for voltage-gated potassium channel complex antibodies? A retrospective case control study

Patients with voltage-gated potassium channel (VGKC)-complex antibodies are increasingly recognized as having central, peripheral or combined phenotypes. With increasing awareness, more patients are tested and the clinical spectrum is expanding. Consequently, clinicians may be uncertain as to which patients should or should not be tested. Previous studies have identified common clinical features, but none has looked at the usefulness of these in predicting seropositive disease. We conducted a case-control study of patients tested for VGKC-complex antibodies over 10 years at a regional tertiary neurology centre determining which clinical/biochemical features were associated with antibody-positive disease. We found a marked increase in the numbers tested, although the percentage positive remained low. Antibody titre was highest in central disease (p < 0.001). Time from presentation to testing was shorter in those with VGKC-disease (p = 0.01). Seizures were present in 11 (69%) of those with VGKC-disease versus three (18%) without (odds ratio [OR] 10.3, 95% confidence interval [CI]: 2.0–52.7, p = 0.005). There was an inverse correlation between the antibody titre and serum sodium. A multivariate model selected seizures and hyponatraemia as predictive of VGKC disease (sensitivity 75% and specificity 82%); faciobrachial dystonic movements were specific but insensitive. Interestingly serum alkaline phosphatase was higher in those with VGKC-disease (p = 0.016) and highest in those with peripheral disease (p = 0.015). An ALP > 70 u/L was strongly associated with antibody positivity (OR 4.11 95% CI: 1.43–11.8, p = 0.007) with a sensitivity of 74.2%. The presence of seizures, faciobrachial movements, and hyponatraemia should raise suspicion of VGKC-disease; alkaline phosphatase may represent a novel biomarker, particularly in those with peripheral disease.     

Cortisol-dependent stress effects on cell distribution in healthy individuals and individuals suffering from chronic adrenal insufficiency

Chronic adrenal insufficiency (CAI) is characterized by a lack of glucocorticoid and mineralocorticoid production due to destroyed adrenal cortex cells. However, elevated cortisol secretion is thought to be a central part in a well-orchestrated immune response to stress. This raises the question to what extent lack of cortisol in CAI affects stress-related changes in immune processes.To address this question, 28 CAI patients (20 females) and 18 healthy individuals (11 females) (age: 44.3 ± 8.4 years) were exposed to a psychosocial stress test (Trier Social Stress Test: TSST). Half the patients received a 0.03 mg/kg body weight injection of hydrocortisone (HC) post-TSST to mimic a healthy cortisol stress response. Catecholamines and immune cell composition were assessed in peripheral blood and free cortisol measured in saliva collected before and repeatedly after TSST.CAI patients showed norepinephrine (NE) stress responses similar to healthy participants, however, epinephrine (E) as well as cortisol levels were significantly lower. HC treatment post-TSST resulted in cortisol increases comparable to those observed in healthy participants (interaction effects – NE: F = 1.05, p = .41; E: F = 2.56, p = .045; cortisol: F = 13.28, p < .001). Healthy individuals showed the expected pattern of stress-related early lymphocyte increase with subsequent decrease below baseline. The opposite pattern was observed in granulocytes. While exhibiting a similar initial increase, lymphocytes kept increasing over the following 2 h in untreated patients. HC treatment buffered this effect (interaction effects – lymphocyte%: F = 7.31, p < .001; granulocyte%: F = 7.71, p < .001).Using CAI in humans as a model confirms cortisol’s central involvement in post-stress lymphocyte migration from blood into immune-relevant body compartments. As such, future studies should investigate whether psychosocial stress exposure may put CAI patients at an increased health risk due to attenuated immune responses to pathogens.     

Low performance in attention testing is associated with reduced grey matter density of the left inferior frontal gyrus in euthyroid patients with Hashimoto’s thyroiditis

Hashimoto’s thyroiditis (HT) can casually co-occur with an encephalopathy associated with autoimmune thyroid disease. Recently we found an increased occurrence of weaknesses in sustained attention and response inhibition in a subgroup of euthyroid patients with HT as obtained by the d2 attention test. Previous studies in healthy subjects and patients with brain lesions demonstrated a pivotal role for the left inferior frontal gyrus (LIFG) in these skills. Therefore, we studied the association between the performance in the d2 test and grey matter (GM) density of the LIFG in 13 euthyroid patients with HT compared to a control group of 12 euthyroid patients with other thyroid diseases. A significant correlation between GM density and d2 test total score was detected for the opercular part of the LIFG in patients with HT (p < 0.001), but not in the control group (p = 0.94). Regression in patients with HT was significantly stronger than in the control group (p = 0.02). Moreover, GM density was significantly reduced when comparing HT patients with control patients that scored in the lower third during d2 attention testing (p < 0.05). It can be concluded that in HT performance in the d2 test correlated with GM density of the LIFG. Particularly low achievement was associated with reduced GM density of this brain region suggesting an influence of autoimmune processes on the frontal cortex in this disease. This could be due to not yet known antibodies affecting brain morphology or an influence of thyroid antibodies themselves.     

Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis

Fatigue in the immune mediated inflammatory disease sarcoidosis is thought to be associated with impaired exercise tolerance. This prospective study assessed fatigue and recuperative capacity after repeated exercise, and examined whether changing concentrations in biomarkers upon exercise are associated with fatigue.Twenty sarcoidosis patients and 10 healthy volunteers performed maximal cardiopulmonary exercise tests on two successive days. Concentrations of cytokines, stress hormones, ACE and CK were assessed before and after the two exercise tests, and 3 days thereafter. All participants completed a sleep diary.Severely fatigued patients showed significant lower VO₂ max (p = 0.038, p = 0.022) and maximal workload (p = 0.034, p = 0.028) on both exercise tests compared to healthy controls. No impairment of maximal exercise testing was demonstrated during the second cycling test in any group. Fatigue was not correlated with changes in concentrations of biomarkers upon exercise. Severely fatigued patients rated both tests as significantly more fatiguing, and reported significant lower mean subjective night sleeping time during the testing period.Fatigue in sarcoidosis patients cannot be objectified by reduction of exercise capacity after repeated maximal exercise testing, and is not correlated with significant changes in biomarkers. Severe fatigue is only and consistently featured by patient reported outcomes.     

Epstein-Barr virus reactivation during pregnancy and postpartum: Effects of race and racial discrimination

ObjectiveAdverse pregnancy outcomes, including preterm birth, are markedly higher among African–Americans versus Whites. Stress-induced immune dysregulation may contribute to these effects. Epstein-Barr virus (EBV) reactivation provides a robust model for examining cellular immune competence. This study examined associations of EBV virus capsid antigen immunoglobulin G (VCA IgG) with gestational stage, race, and racial discrimination in women during pregnancy and postpartum.MethodsFifty-six women (38 African–American, 18 White) were included. African–Americans and Whites did not differ in age, education, income, parity, or body mass index (ps ? .51). During the 1st, 2nd, and 3rd trimester and ～5 weeks postpartum, women completed measures of racial discrimination, perceived stress, anxiety, depressive symptoms and health behaviors. EBV VCA IgG antibody titers were measured via ELISA in serum collected at each visit.ResultsIn the overall sample, EBV VCA IgG antibody titers were lower in the 3rd versus 1st trimester (p = .002). At every timepoint (1st, 2nd, 3rd trimester and postpartum), African–American women exhibited higher serum EBV VCA IgG antibody titers than Whites (ps < .001). This effect was most pronounced among African–Americans reporting greater racial discrimination [p = .03 (1st), .04 (2nd), .12 (3rd), .06 (postpartum)]. Associations of race and racial discrimination with EBV VCA IgG antibody titers were not accounted for by other measures of stress or health behaviors.ConclusionsCompared to Whites, African–American women showed higher EBV VCA IgG antibody titers, indicative of impaired cellular immune competence, across pregnancy and postpartum. This effect was particularly pronounced among African–American women reporting greater racial discrimination, supporting a role for chronic stress in this association. In women overall, EBV antibody titers declined during late as compared to early pregnancy. This may be due to pregnancy-related changes in cell-mediated immune function, humoral immune function, and/or antibody transfer to the fetus in late gestation. As a possible marker of stress-induced immune dysregulation during pregnancy, the role of EBV reactivation in racial disparities in perinatal health warrants further attention.     

The effects of temporal lobe epilepsy on scene encoding

Forty-four patients with temporal lobe epilepsy (TLE) (25 left) and 40 healthy control participants performed a complex visual scene-encoding fMRI task in a 4-T Varian scanner. Healthy controls and left temporal lobe epilepsy (LTLE) patients demonstrated symmetric activation during scene encoding. In contrast, right temporal lobe (RTLE) patients demonstrated left lateralization of scene encoding which differed significantly from healthy controls and LTLE patients (all p ≤ .05). Lateralization of scene encoding to the right hemisphere among LTLE patients was associated with inferior verbal memory performance as measured by neuropsychological testing (WMS-III Logical Memory Immediate, p = 0.049; WMS-III Paired Associates Immediate, p = 0.036; WMS-III Paired Associates Delayed, p = 0.047). In RTLE patients, left lateralization of scene encoding was associated with lower visuospatial memory performance (BVRT, p = 0.043) but improved verbal memory performance (WMS-III Word List, p = 0.049). These findings indicate that, despite the negative effects of epilepsy, memory functioning is better supported by the affected hemisphere than the hemisphere contralateral to the seizure focus.     

A prospective study of C-reactive protein as a state marker in Cardiac Syndrome X

Cardiac Syndrome X (CSX), the presence of angina pectoris despite normal epicardial coronary arteries seen on invasive angiography, is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We sought to establish if C-reactive protein (CRP) levels varied with disease severity and so whether it is a state or trait marker. We studied 16 CSX patients with typical angina pectoris, normal coronary arteries and an electrically positive exercise stress test (EST) and 13 age- and sex-matched healthy controls (HC). CSX patients were followed up at a subsequent visit with repeated exercise stress testing and CRP measurement. We found that CRP levels were significantly higher in the CSX group compared to the HC (1.5 [0.8–4.5] v 0.8 [0.4–1.4] mg/L, p = 0.02). This elevation in CRP persisted throughout the study length. CRP correlated with time to symptoms on EST at enrolment and at the second visit (r = −0.690, df = 10, p = 0.013 and r = −0.899, df = 4, p = 0.015, respectively). At the follow-up visit, 50% of CSX patients developed electrically and symptomatically negative ESTs. The mean CRP of this group was significantly lower than that of the CSX patients with ongoing symptoms and positive ESTs (1.2 ± 0.2 v 2.8 ± 0.6 mg/L, p = 0.018) and did not differ significantly from that of healthy controls. CRP levels also dropped in patients whose symptoms improved while they increased in patients who became more symptomatic (p = 0.027). We conclude that the results of this small study support the concept of CSX being an inflammatory-mediated condition with CRP levels prospectively varying with functional measures of disease severity. This indicates that CRP is a state marker in CSX.     

Soluble mediators in plasma from irritable bowel syndrome patients excite rat submucosal neurons

Background: Episodic bouts of abdominal pain and altered bowel habit are characteristic of irritable bowel syndrome (IBS). Although a comprehensive understanding of IBS pathophysiology remains elusive, support is growing for a primary role for immune activation in disease severity as evidenced by altered cytokine profiles in IBS plasma. Additionally, aberrant stimulation of the stress axis is likely to result in altered plasma constituents. Methods: Whole-mount preparations of submucosal plexus from adult male Sprague Dawley rats were exposed to plasma from IBS patients and healthy controls. Ratiometric calcium imaging recordings were used to measure changes in intracellular calcium ([Ca²⁺]_i) as a marker of neuronal excitability. Key results: IBS plasma stimulated a robust increase in [Ca²⁺]_i (0.09 ± 0.02) whereas plasma from healthy volunteers had little effect (−0.02 ± 0.02, n = 24, p < 0.001). The neuromodulatory actions of IBS plasma were reduced by pre-neutralisation with anti-interleukin (IL)-6 (p < 0.01) but not IL-8, immunoglobulin G or C-reactive protein. Moreover, IBS plasma-evoked responses (0.22 ± 0.06) were inhibited by the corticotrophin releasing factor receptor (CRFR) 1 antagonist, antalarmin (1 μM, 0.015 ± 0.02, n = 14, p < 0.05), but not the CRFR2 antagonist, astressin 2B. Neuronal activation was mediated by ERK/MAPK signalling. Conclusions: These data provide evidence that factors present in IBS plasma modulate neuronal activity in the submucosal plexus and that this is likely to involve CRFR1 activation and IL-6 signalling. These neuromodulatory actions of stress and immune factors indicate a potential mechanism by which immune activation during periods of stress may lead to symptom flares in IBS.     

Serum uric acid level in patients with relapsing-remitting multiple sclerosis

Uric acid (UA) is a hydrophilic antioxidant product associated with multiple sclerosis (MS). We conducted a randomized case-control study to evaluate the serum level of UA in different phases of MS in comparison with levels in a healthy control population. Serum UA was checked in 130 patients with relapsing-remitting MS (85 patients in remitting and 45 patients in relapsing phase) and 50 age-matched controls using a quantitative enzyme-linked immunosorbent assay (ELISA). The mean concentrations of UA in serum was 6.41(±3.18) mg/dL in patients with remitting MS, 4.76(±1.66) mg/dL in patients with relapsing MS and 6.33(±2.94) mg/dL in controls. There was a significant difference between mean UA concentration in relapsing MS and remitting MS (p < 0.001), and between patients with relapsing MS and controls (p = 0.002); however, the difference between levels for patients in the remitting phase of MS and the control group was not significant (p = 0.87). It seems probable that UA has a role in the prevention of disease activity in MS.     

Diagnosis of neuroborreliosis – Improved knowledge base for qualified antibody analysis and cerebrospinal fluid data pattern related interpretations

Recent guidelines do not specify inflammatory CSF pattern, ignore IgM analysis, use unsuitable cut offs and miss the polyspecific immune response for intrathecal antibody interpretation. Insufficient quality of antibody assays together with insensitive evaluations contribute to false positive and false negative interpretations.To improve diagnostic sensitivity and specificity antibody assays are analyzed with external quality assessment (INSTAND survey) and interpretation problems are documented by new CSF statistics.Patient groupsdefinite neuroborreliosis (N = 29), multiple sclerosis (N = 35), seropositives without neuroborreliosis (N = 16) and seropositives with other neurological diseases (N = 36). In acute neuroborreliosis intrathecal immunoglobulin classes IgG/IgA/IgM had a statistical frequency of 59%/41%/100% correspondingly. Predominant intrathecal IgM had a diagnostic sensitivity of 93% and the blood-CSF barrier dysfunction 86%. Sensitivity of Bb-antibodies was 100% (IgG) and 83% (IgM) by corrected borrelia-AI and cut off Bb-AI ≥ 1.5. CSF pattern clearly discriminates borrelia- and VZV-caused facial nerve palsy. 47% of Bb-seropositive MS patients had an intrathecal Bb antibody synthesis. CSF Bb-antibodies without serum antibodies were not found (N = 680). In the neuroborreliosis-survey among 150 participating laboratories we got 4–80% outliers (±30% success-interval) and method-dependent differences between median AI values of a factor three due to different antigen coating.Antigen coating and evaluation by corrected AI is crucial for sensitivity of antibody assays. Specificity depends on a complete CSF data pattern including IgM. The post lyme disease is discussed regarding deficits in analysis, wrong clinical diagnosis, or borrelia as an unspecific trigger of a chronic disease with a multitude of possible causes.     

Evaluation of patients with multiple sclerosis using a combination of morphometrical features and clinical scores

Our aim was to measure cerebellum volume (CV), sclerotic plaque numbers (PN), and plaque surface area (SA) in the parietal lobe, and to investigate the relationship between CV and PN or SA in the parietal lobe, and the clinical status of patients with multiple sclerosis (MS). MRIs were performed in 14 patients with relapsing-remitting MS (RRMS), 13 patients with secondary progressive MS (SPMS), and 26 healthy control participants. The Cavalieri method was used to measure CV and SA. The cerebellum volume was significantly reduced in MS patients compared to controls (p < 0.01). In all patients, CV was negatively correlated with the duration of the disease, relapse number, and Expanded Disability Status Scale (EDSS) scores (p < 0.01). CV was related to mean PN in both the right and left parietal lobes (p < 0.01) and mean SA (p < 0.05) in RRMS patients; CV was also correlated with mean PN (p < 0.01) and mean SA (p < 0.05) in SPMS patients. The progression index (Pi) values were 2.03 ± 0.4 in RRMS patients and 0.83 ± 0.2 in SPMS patients (p = 0.023, t = 2.612) (where Pi = EDSS/time from onset in years). We propose that atrophy begins both in the supratentorial and infratentorial areas simultaneously in the RR stage, and that the Cavalieri method can be used to predict SPMS among patients with RRMS.     

Evaluation of developmental profiles of children with hydrocephalus

ObjectiveThe objective of this study was to compare the developmental characteristics of children with hydrocephalus with those of healthy children.Material and methodsA total of 109 children aged between 2 and 46 months were included in the study, 54 patients diagnosed with hydrocephalus and 55 healthy children were evaluated with demographic data forms and Denver Developmental Screening Test II.ResultsThe mean personal–social (p < 0.001), fine motor-adaptive (p < 0.001), language (p < 0.001), and gross motor subscale scores were significantly lower in children with hydrocephalus than in the control group. Personal–social (p = 0.002) and gross motor (p = 0.029) subscale scores were significantly lower in children with obstructive hydrocephalus than communicating hydrocephalus. There was a significant negative correlation between language scores and ages of the children with hydrocephalus (r = ?0.350, p = 0.009). It was found that children with obstructive hydrocephalus carry a 6.7 folds higher risk of experiencing problems in terms of personal–social development compared to those with communicating hydrocephalus (p = 0.011).ConclusionWe found that patients with hydrocephalus were developmentally retarded compared to the healthy control subjects. Retardation was the most prominent in the obstructive group. Our results showed that neurodevelopmental follow-up should be carried-out regularly in pediatric patients with hydrocephalus, and early intervention should be started in necessary cases.     

Evaluation of periodontitis in hospital outpatients with major depressive disorder. A focus on gingival and circulating cytokines

An imbalance in stimulated cytokine production is associated with the etiopathogenesis of numerous diseases such as major depressive disorder (MDD) and periodontal disease. Increased cytokine levels have been reported in the gingival crevicular fluid (GCF) of patients with MDD. Thirty-six outpatients with MDD participated in this study. Each outpatient was age-matched (±3 years) with a healthy control (n = 36). The patients were controlled for race and smoking habits. Unstimulated and stimulated interleukin 6 (IL-6), interleukin 1β (IL-1β), and interferon-γ (INF-γ) production in whole blood culture (WBC) and IL-6 and IL-1β levels in the GCF were evaluated. Circulating levels of IL-6 and IL-1β (unstimulated) as well as GCF IL-1β were modestly lower in MDD patients, compared to the levels in age-matched controls (Mann–Whitney, p = 0.002, 0.0075, ANCOVA, p = 0.025, respectively). In the unstimulated group, there was no correlation between the levels of circulating IL-6 and GCF IL-6 (r = 0.07, p = 0.67), and between the levels of circulating IL-1β and the IL-1β level in the CGF (r = −0.08, p = 0.63). In the LPS stimulation group, there was no correlation between the levels of circulating levels of IL-6 and GCF IL-6 (r = 0. 02, p = 0.91) or between the circulating IL-1β and GCF IL-1β (r = 0.13, p = 0.42). We observed modest immunosuppression in MDD patients (evaluated by no stimulation whole blood culture [WBC]), especially in patients with melancholic depression, chronic depression, and severe depression.     

A cross-sectional study of clinical management,and provision of health services and their utilisation,by patients with Parkinson’s disease in urban and regional Victoria

Our objective was to evaluate and compare clinical management, utilisation of health services and quality of life (QoL) in patients with Parkinson’s disease (PD) attending clinics in urban and regional Victoria. A cross-sectional survey was conducted on 210 patients with PD attending specialist neurological clinics in a regional area (Ballarat) (n = 97), and an urban area (Melbourne) (n = 113), Victoria. Demographic characteristics of patients with PD, QoL, patterns of disease and management and utilisation of medical and allied health services were analysed. Compared to patients with PD from urban clinics, patients in the regional clinic were significantly older and were diagnosed at a later age with a shorter duration of treatment (all p < 0.05). Despite no significant difference in disease severity (measured by Unified Parkinson’s Disease Rating Scale scores) between the groups, patients in the urban clinic reported a lower QoL (p = 0.003). Patients in the regional clinic were more satisfied with their treatment, despite seeing their medical specialist less frequently (p < 0.001) and having a higher rate of early misdiagnosis (p = 0.015). Patients from regional clinics reported a poorer understanding of their illness than patients in the urban clinic (p = 0.049). Half of all respondents were interested in using telemedicine services. Two-thirds (71%) of all patients used allied health services, with patients in the urban clinic utilising more and desiring greater access to these services (p < 0.05). In conclusion, we found significant differences in the presentation, management and use of health services between patients accessing regional and urban PD clinics in Victoria. Telemedicine may be an effective, and even desirable, method for facilitating improved diagnosis and referral for appropriate therapies.     

Symptomatic brain involvement as the initial manifestation of neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder that predominantly affects the optic nerve and spinal cord; however, symptomatic brain involvement is not rare and is sometimes an initial manifestation in NMO. In this study, we investigated the characteristic features of patients with NMO with symptomatic brain involvement as the initial manifestation of disease (NMO_brain) compared with patients with NMO who presented initially with optic neuritis or myelitis (NMO_ON/myelitis). We retrospectively reviewed 27 consecutive Korean patients with NMO with aquaporin-4 antibodies. Patients with NMO_brain (n = 9) initially presented with intractable hiccup/nausea/vomiting and/or encephalopathy at a younger age than the patients with NMO_ON/myelitis (n = 18) (p < 0.01). During the disease course, the patients with NMO_brain continued to show more frequent symptomatic involvement of the brain than the 18 patients with NMO_ON/myelitis (p < 0.05). At the final visit, the mean age was also significantly lower in patients with NMO_brain than in patients with NMO_ON/myelitis (p < 0.01); however, the Expanded Disability Status Scale scores, used to evaluate disease progression, were not different between the two groups. Our study suggests that patients with NMO who present initially with symptomatic brain involvement may have earlier disease onset and become disabled at a younger age compared to patients with typical NMO. Additional large scale prospective studies are warranted.     

Increased soluble interleukin-2 receptor levels are related to somatic but not to cognitive-affective features in major depression

Cell-mediated immune activation may play a role in the pathogenesis of depression as indicated by findings of increased soluble tumor necrosis factor receptor (sTNF-R) levels and meta-analytic evidence for elevated soluble interleukin-2 receptor (sIL-2R) concentrations. However, little research has been done on how these soluble cytokine receptors are differently related to specific features in patients with depression. We measured levels of the soluble cytokine receptors sIL-2R, sTNF-R1 and sTNF-R2 in 25 non-medicated patients with major depression (DSM-IV) and 22 healthy controls. Psychometric measures included cognitive-affective depressive symptoms, somatoform symptoms, somatic and cognitive dimensions of anxiety and current mood states. While patients with depression showed increased levels of sIL-2R (p < 0.01), differences in sTNF-R1 (p = 0.09) and sTNF-R2 (p = 0.08) marginally failed to reach significance. Increased concentrations of sIL-2R were related to somatic measures such as the severity of somatoform symptoms and somatic anxiety symptoms but not to cognitive-affective measures or current mood states. Our findings may suggest some specificity in the relationship between sIL-2R and symptom dimensions and highlight potential pathways by which T cell mediated immune activation may underpin somatic symptoms in depression.     

Microvascular endothelial function in obstructive sleep apnea: Impact of continuous positive airway pressure and mandibular advancement

ObjectivesEndothelial dysfunction has been proposed as a potential mechanism implicated in the pathogenesis of cardiovascular complications of obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the microvascular endothelial function (MVEV) in OSAS and the impact on MVEF of 2 months of treatment with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD).MethodsMicrovascular reactivity was assessed using laser Doppler flowmetry combined with acetylcholine (Ach) and sodium nitroprusside (SNP) iontophoresis in 24 OSAS patients and 9 control patients. In 12 of the 24 OSAS patients, microvascular reactivity was reassessed after 2 months of CPAP and MAD using a randomized cross-over design.ResultsAch-induced vasodilation was significantly lower in OSAS patients than in matched controls and correlated negatively with apnea hypopnea index (r = ?0.49, p < 0.025) and nocturnal oxygen desaturations (r = ?0.63, p < 0.002). Ach-induced vasodilation increased significantly with both CPAP and MAD. The increase in Ach-induced vasodilation under OSAS treatment correlated with the decrease in nocturnal oxygen desaturations (r = 0.48, p = 0.016).ConclusionOur study shows an impairment of MVEF in OSAS related to OSAS severity. Both CPAP and MAD treatments were associated with an improvement in MVEF that could contribute to improve cardiovascular outcome in OSAS patients.