Publications

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota–gut–brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing, analyzed α- (Chao1 and Shannon indices) and β-diversity (Bray–Curtis dissimilarity), and conducted linear discriminant analysis (LDA) effect size (LEfSe) analysis. Neither α- nor β-diversity differed significantly between MDD and controls. Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi, and Clostridium propionicum were significantly enriched in MDD, while Gracillibacteraceae family, Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes, and Gemmiger were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of Ruminococcus, which is depleted in six different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients, with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of Ruminococcus may be a more universal biomarker of MDD that may contribute to increased enteral LPS load, LPS translocation, and gut–brain axis abnormalities.

Pundits and scholars warned that the personalization of the web and in particular of online social networks fosters interaction between likeminded users and amplifies the polarization of political opinions. We criticize, however, that this warning is based on one particular polarization model and that an alternative and equally prominent theory implies the exact opposite effect, predicting that personalization fosters consensus rather than polarization. We develop a general modeling framework to compare the predictions of the competing models. Using agent-based modeling, we formally demonstrate that the two theories make contradicting predictions and study the conditions of polarization. In conclusion, we call for empirical research on the competing assumptions of the two models, discussing major roadblocks and novel methods to overcome them.

Some groups have recently reported higher titers of autoantibodies in depressed subjects than in normal controls. The present study investigates whether depressed patients exhibit increased antiphospholipid antibody titers compared with normal controls. The authors measured the binding index (BI) of antiphosphatidylserine (APSA), antipartial thromboplastin (APTA) and anticardiolipin (ACA) in 22 minor, 23 simple major and 20 melancholic depressives, 10 healthy controls and 104 normal controls with negative autoantibody sera. Depressed subjects exhibited significantly higher APSA and APTA antibody titers compared with normal controls. A large number of depressed subjects (± 54%) showed APTA and APSA positivity, defined as BI≥2 standard deviations above the mean BI of normal controls. There was a significant discrimination (≥2.8 standard deviations) between melancholic subjects and healthy controls with respect to BI of ACA, APSA and APTA. However, by using a more conservative value for phospholipid positivity (i.e., BI≥5 standard deviations above the mean BI of a reference sample of normal sera), the subject's autoantibody titers were, on the whole, within the normal range. Our results point towards a higher expression of antiphospholipid antibodies during depression but a much lower incidence of positive patients than in classical autoimmune disorders, such as systemic lupus erythematosus.

Abstract No precision medicine models of temporal lobe epilepsy (TLE) and associated mental comorbidities were developed to date. This observational 11study aimed to develop a precision nomothetic, data driven comorbid TLE model with endophenotype classes and pathways phenotypes that may have prognostic and therapeutical implications. We recruited forty healthy controls and 108 TLE patients for this research and assessed TLE and psychopathology (PP) features as well as oxidative stress (OSTOX, e.g., malondialdehyde or MDA, lipid hydroperoxides, and advanced oxidation protein products) and antioxidant (paraoxonase 1 or PON1 status, -SH groups, and total radical trapping potential or TRAP) biomarkers. A large part (57.2%) of the variance in a latent vector (LV) extracted from the above TLE and PP features was explained by these OSTOX and antioxidant biomarkers. The PON1 Q192R genetic variant showed indirect effects on this LV which were completely mediated by PON1 activity and MDA. Factor analysis showed that a common core could be extracted from TLE, PP, OSTOX and antioxidant scores, indicating that these features are manifestations of a common underlying construct, i.e., a novel pathway phenotype of TLE. Based on the latter we constructed a new phenotype class that is characterized by increased severity of TLE, PP and OSTOX features and lowered antioxidant defenses. A large part of the variance in episode frequency was explained by increased MDA, lowered antioxidant, and nitric oxide metabolite levels. In conclusion a) PP symptoms belong to the TLE phenome and signal increased severity; and b) cumulative effects of aldehyde formation and lowered antioxidants determine epileptogenic kindling.

There is some evidence that major depression is characterized by systemic immune activation with involvement of phagocytic cells, T cell activation, B cell proliferation and increased autoantibody production. This paper reviews that major depression may be accompanied by higher concentrations of positive and lower concentrations of negative acute phase proteins (APPs). The most prominent abnormalities of APPs in major depression are increased haptoglobin (Hp) plasma levels. The latter are significantly and positively correlated with interleukin (IL)-6 production, various indices of systemic immune activation (e.g. monocytosis, neutrophilia, T cell activation) and with the vegetative symptoms of depression (e.g. anorexia, weight loss, psychomotor retardation, sleep disorders, anergy). Major depression is characterized by an altered distribution of Hp phenotypes and genes suggesting that genetic variation on chromosome 16 may be associated with this illness. It is concluded that increased production of IL-6 and IL-1 in major depression may underlie both immune activation and the "acute" phase response in that illness, and that disorders in Hp may be related to the pathophysiology and pathogenesis of major depression.

Increased gut permeability (leaky gut) with increased translocation of Gram-negative bacteria plays a role in the gut-brain axis through effects on systemic immune-inflammatory processes. Deficit schizophrenia is characterized by an immune-inflammatory response combined with a deficit in natural IgM antibodies to oxidative specific epitopes (OSEs), which are a first line defense against bacterial infections. This study measured plasma IgA/IgM responses to 5 Gram-negative bacteria in association with IgM responses to malondialdehyde (MDA) and azelaic acid in 80 schizophrenia patients (40 with the deficit syndrome and 40 without) and in 38 healthy controls.Deficit schizophrenia was characterized by significantly increased IgA responses to Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii and Klebsiella pneumoniae as compared with non-deficit schizophrenia. The presence of deficit schizophrenia was highly predicted by increased IgA responses to Pseudomonas putida and IgM responses to all 5 Gram-negative bacteria and lowered natural IgM to MDA and azelaic acid with a bootstrap area under the ROC curve of 0.960 (2000 random curves). A large proportion of the variance (41.5%) in the PANSS negative score was explained by the regression on IgA responses to K. pneumoniae and IgM responses to the 5 enterobacteria coupled with lowered IgM antibodies to azelaic acid. There were significant associations between IgA levels to Gram-negative bacteria and Mini Mental State Examination, Boston naming test, Verbal Fluency and Word List Memory test scores.These findings provide further evidence that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by an increased impact of Gram-negative commensal bacteria coupled with a deficit in natural IgM, pointing to aberrations in B1 cells. It is concluded that increased bacterial translocation and deficits in the compensatory immune-regulatory system (CIRS) may drive negative symptoms and neurocognitive impairments, which are hallmarks of deficit schizophrenia.

Aim: There is a strong comorbidity between methamphetamine (MA) and alcohol use whereby MA use may contribute to increased alcohol consumption. This study aims to determine the associations between alcohol drinking and MA-associated behaviors among MA users in relation to mood disorders, suicidal ideation, and health-related quality of life (HR-QoL). Methods: Substance use characteristics were obtained in 106 participants with MA use at a substance abuse treatment center by using the Severity of Dependence Scale (SDS) and the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Current alcohol drinking behaviors were estimated using the Substance Outcomes Profile (SOP), which was developed and translated from the Treatment Outcomes Profile, by computing the number of alcohol units x days per month of alcohol use. The Mini-International Neuropsychiatric Interview (M.I.N.I.) was used to estimate lifetime histories of mood disorders and substance abuse and current suicidal ideation. Results: Current suicidal ideation in MA users is to a large extent predicted by the severity of current alcohol and MA use, female gender, and a lifetime history of mood disorders (major depression, dysthymia, and hypo-mania). Moreover, a lifetime history of mood disorders is positively associated with the severity of MA, but not with alcohol use. Partial least squares (PLS) path modeling shows that lowered HR-QoL in MA users is predicted by the SDS score and alcohol dosing (both inversely) and that lifetime diagnoses of mood disorders and MA use (both inversely) and alcohol dependence (positively) have significant effects on HR-QoL which are completely mediated via the SDS score. Conclusions: In MA users, the severity of dependence, and MA and/or alcohol use exert adverse effects on current suicidal ideation and HR-QoL. Mechanistic explanations are given which may explain the inverse associations between the severity of MA and alcohol use in MA abusers.