Publications

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, cognitive impairments, and autonomic disturbances is not well understood. Objectives The current study aims to delineate whether the remitted phase of RRMS is accompanied by activated immune-inflammatory pathways and if the latter, coupled with erythron variables, explain the chronic fatigue and mood symptoms due to RRMS. Material and Methods We recruited 63 MS patients, 55 in the remitted phase of RRMS and 8 with secondary progressive MS, and 30 healthy controls and assessed erythron variables and used a bio-plex assay to measure 27 serum cytokines. Results A significant part of the MS patients (46%) displayed activation of the immune-inflammatory response (IRS) and compensatory immune response (CIRS) systems, T helper (Th)1 and Th-17 cytokine profiles. Remitted RRMS patients showed increased chronic fatigue, depression, anxiety, physiosomatic, autonomic, and insomnia scores, which could partly be explained by M1 macrophage, Th1, Th-17, growth factor, and CIRS activation, as well as aberrations in the erythron including lowered hematocrit and hemoglobin levels. Conclusions Around 50% of remitted RRMS patients show activation of immune-inflammatory pathways in association with mood and chronic-fatigue-like symptoms. IRS and CIRS activation as well as the aberrations in the erythron are new drug targets to treat chronic fatigue and affective symptoms due to MS.

Background: Physiosomatic symptoms are an important part of schizophrenia phenomenology. The aim of this study is to examine the biomarker, neurocognitive and symptomatic correlates of physiosomatic symptoms in schizophrenia. Methods: We recruited 115 schizophrenia patients and 43 healthy controls and measured the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) scale, schizophrenia symptom dimensions, and the Brief Assessment of Cognition in Schizophrenia. We measured neuro-immune markers including plasma CCL11 (eotaxin), interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box 1 protein (HMGB1) and endogenous opioid system (EOS) markers including κ-opioid receptor (KOR), µ-opioid receptor (MOR), endomorphin-2 (EM2) and β-endorphin. Results: Patients with an increased FF score display increased ratings of psychosis, hostility, excitement, formal though disorders, psychomotor retardation and negative symptoms as compared with patients with lower FF scores. A large part of the variance in the FF score (55.1%) is explained by the regression on digit sequencing task, token motor task, list learning, IL-10, age (all inversely) and IL-6 (positively). Neural network analysis shows that the top-6 predictors of the FF score are (in descending order): IL-6, HMGB1, education, MOR, KOR and IL-10. We found that 45.1% of the variance in a latent vector extracted from cognitive test scores, schizophrenia symptoms and the FF score was explained by HMGB-1, MOR, EM2, DKK1, and CCL11. Conclusions: FF symptoms are an integral part of the phenome of schizophrenia. Neurotoxic immune and neurodegenerative pathways and to a lesser extent the EOS appear to drive FF symptoms in schizophrenia.

A general method is described for the use of tumor-inducing (Ti) plasmids as experimental gene-vectors for plant cells. Intermediate vectors, containing specific Ti plasmid sequences and capable of replication in both E. coli and Agrobacterium strains, were constructed and used for the in vitro introduction of isolated DNA fragments into predetermined sites of the T-region derived fragments. Site-specific inserts and/or deletions-substitutions in Ti plasmids were produced by exchange of the modified T-region sequences for the wild-type sequence by in vivo recombination between intermediate vectors and resident Ti plasmids. This method was applied for the isolation of mutant Ti plasmids affecting either morphogenetic properties or opine synthesis in crown gall tumors. Foreign DNA, inserted at different sites in the T-region of both octopine and nopaline Ti plasmids, was shown to be cotransferred with the T-DNA and to be stably maintained in the transformed plant cells.

Sluzewska, A1; Rybakowski, J K1; Bosmans, E3; Maes, M4; Sobieska, M2 Author Information

Central serotonergic vulnerability indicated by altered mood and neuroendocrine responses to an intravenous (i.v.) tryptophan (Trp) challenge was assessed in healthy adult unaffected first-degree relatives of bipolar disorder (BD) patients (n = 30) (family history; FH). The effects of a single dose of 7.0 g Trp on mood, cortisol and prolactin (Prl) in FH subjects were compared with healthy matched controls (n = 15) in a placebo-controlled, double blind cross-over design. Prl and cortisol responses increased following Trp. Overall, Trp lowered mood. Hormonal and mood effects did not differ between FH and controls. Results show some evidence for differences in serotonergic vulnerability between relatives of type I BD patients and relatives of type II BD patients.