Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), play a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown.Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP) and sulfhydryl (-SH) groups in Depression due to TLE (n=25); Anxiety Disorders due to TLE (n=27); Psychotic Disorder due to TLE (n=25); “pure TLE” (n=27); and healthy controls (n=40).TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899) and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, whilst increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels.These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups play a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology, psychosis, as well as negative and depressive symptoms.
The aims of the present study were to examine serum activities of peptidases, i.e. prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), in patients with fibromyalgia and to examine the effects of subchronic treatment with sertraline on these variables.Serum PEP and DPP IV activity were measured in 28 normal volunteers and 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Tenderness at tender points was evaluated by means of dolorimetry. Fibromyalgia patients had repeated measurements of serum PEP and DPP IV both before and after repeated administration of sertraline or placebo for 12 weeks.Patients with fibromyalgia had significantly lower serum PEP activity than normal volunteers. There were significantly negative correlations between serum PEP activity and severity of pressure hyperalgesia and the non-somatic, cognitive symptoms of the Hamilton Depression Rating Scale. Fibromyalgia patients with severe pressure hyperalgesia had significantly lower PEP activity than normal controls and fibromyalgia patients with less severe hyperalgesia. Fibromyalgia patients with severe non-somatic depressive symptoms had significantly lower serum PEP activity than normal volunteers. There were no significant changes in serum DPP IV activity in fibromyalgia. There were no significant effects of repeated administration of sertraline on serum PEP and DPP IV activity in patients with fibromyalgia.The results show that fibromyalgia, and aberrant pain perception and depressive symptoms in fibromyalgia are related to lower serum PEP activity. It is hypothesized that lower serum PEP activity may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides.
In order to investigate the relationship between the immune apparatus and the hypothalamic-pituitary-adrenal (HPA)-axis activity in depressed patients, we measured in vitro lymphocyte responses to the mitogens Phytohaemagglutinin (PHA), Pokeweed (PWM) and Concanavalin A (Con A) and 8 a.m. baseline cortisol values in plasma, free cortisol excretion in 24 h urine (UFC), basal and post-dexamethasone beta-endorphin values. Major depressed patients with melancholia/psychotic features exhibited a significantly lower mitogen-induced blast transformation as compared to minor and simple major depressed patients. The lymphocyte responses to the three mitogens were significantly inversely related to baseline cortisol values and postdexamethasone beta-endorphin values. The proliferative capacity of lymphocytes to stimulation with PHA and PWM was significantly and positively related to UFC excretion. Up to 45% of the variance in the immune-responses to the mitogens was explained by the baseline cortisol, post-dexamethasone beta-endorphin and UFC values.
Abstract Background Severe or recurring major depression is associated with increased adverse childhood experiences (ACEs), heightened atherogenicity, and immune-linked neurotoxicity (INT). Nevertheless, the interconnections among these variables in outpatient of major depression (OMDD) have yet to be determined. Objectives Determine the correlations among INT, atherogenicity, and ACEs in 66 OMDD patients (of whom thirty-three had metabolic syndrome, MetS) and sixty-seven controls (31 of whom had MetS). Results The free cholesterol/reverse cholesterol transport ratio, apolipoprotein (Apo) B and E, and a comprehensive atherogenicity index were all significantly associated with increased INT in OMDD subjects without MetS. ACEs were substantially correlated with INT in patients with MetS. INT (only in MetS) and atherogenicity indices (only in people without MetS) were significantly associated with the clinical phenome features of OMDD, including the recurrence of illness (ROI, including lifetime suicidal behaviors), the lifetime phenome (neuroticism + lifetime anxiety disorders and dysthymia), and the current phenome (including current suicidal behaviors). A significant proportion of the variability (58.3%) in the lifetime + current phenome could be accounted for by INT, interactions between INT and atherogenicity (labeled "atherommune index"), ApoE, three ACE subtypes (all positively correlated), and age (inversely correlated). A single validated latent construct could be extracted from ROI, lifetime phenome, current phenome, INT, and atherommune index. 36.1% of this factor’s variance was accounted for by three ACE subtypes. Discussion We have developed a novel OMDD model, namely a pathway phenotype, labeled the "atherommune-phenome," which demonstrates that the interplay between INT and atherogenicity is essential to OMDD.
Abstract Background The pathophysiology of amnestic Mild Cognitive Impairment (aMCI) is largely unknown, although some papers found signs of immune activation. Aims To assess the cytokine network in aMCI after excluding patients with major depression (MDD) and to examine the immune profiles of quantitative aMCI (qMCI) and distress symptoms of old age (DSOA) scores. Methods A cross-sectional study was conducted on 61 Thai aMCI participants and 60 healthy old adults (both without MDD). The Bio-Plex Pro human cytokine 27-plex test kit and LUMINEX 200 were used to assay cytokines/chemokines/growth factors in fasting plasma samples. Results aMCI is characterized by significant general immnosuppression, and reductions in T helper 1 (Th)1 and T cell growth profiles, the immune-inflammatory responses system, interleukin (IL)1β, IL6, IL7, IL12p70, IL13, GM-CSF, and MCP-1 as compared with controls. These 7 cytokines/chemokines exhibit neuroprotective effects at physiologic concentrations. In multivariate analyses, three neurotoxic chemokines, CCL11, CCL5, and CXCL8, emerged as significant predictors of aMCI. Logistic regression showed that aMCI was best predicted by combining IL7, IL1β, MCP-1, years of education (all inversely associated) and CCL5 (positively associated). We found that 38.2% of the variance in the qMCI score was explained by IL7, IL1β, MCP-1, IL13, years of education (inversely associated) and CCL5 (positively associated). The DSOA were not associated with any immune data. Discussion A dysbalance between lowered levels of neuroprotective cytokines and chemokines, and relative increases in neurotoxic chemokines are key factors in aMCI. Future MCI research should always control for the confounding effects of affective symptoms.
Summary The thyrotropin-releasing hormone (TRH) test was carried out in 231 depressed patients undergoing a dexamethasone suppression test (DST), and in 63 psychiatric control patients. The patients were classified according to DSM-III. Thyrotropin-secreting hormone (TSH) was determined in basal conditions, 20 and 60 min after the administration of 200 μg TRH. The Δ max TSH values (peak TSH response minus basal TSH) showed no significant difference between psychiatrie Controls and patients with major depression (296.00X2, 296.00X3, 296.00X4) or with depression (major and minor depression; 300,40, 296,82, 309.00). Consequently, the TRH test is not specifie either for depression or for major depression. Within the selected group of depressive patients, major depressives showed significantly ( P< 0.005) lower Δ max TSH responses than minor depressives. The TRH test could barely be used as a clinical diagnostic aid for major depression, since the predictive value for a positive test resuit was too low (maximal 70.2%). To separate major from minor depression, a single DST was more suitable than the TRH test or the combination of both tests. Age showed a negative correlation ( P< 0.005) with the Δ max TSH responses and could be considered as a predisposing factor for a blunted TSH response to TRH in depressive patients.
