Publications

Abstract Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data whether, in schizophrenia, activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis and lowered magnesium and calcium levels impact DisQoL scores. This study recruited 90 patients with schizophrenia (including 40 with deficit schizophrenia) and 40 healthy controls and assessed the World Health Association QoL instrument-Abbreviated version and Sheehan Disability scale, Brief Assessment of Cognition in Schizophrenia (BACS), IL-6, IL-23, IL-17, IL-21, IL-22, tumor necrosis factor (TNF)-α, magnesium and calcium. Regression analyses showed that a large part of the first factor extracted from the physical, psychological, social and environmental HR-QoL and interference with school/work, social life, and home responsibilities was predicted by a generalized cognitive deterioration (G-CoDe) index (a latent vector extracted from BACs scores), and the first vector extracted from various symptom domains (“symptomatome”), whereas the biomarkers had no effects. Partial Least Squares analysis showed that the IL6IL23Th17 axis and magnesium/calcium had highly significant total (indirect + direct) effects on HR-QoL/disabilities which were mediated by G-CoDe and the symptomatome (a first factor extracted from negative and positive symptoms). The IL6IL23Th17 axis explained 63.1% of the variance in a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. The latter features are manifestations of a common core, namely the behavioral-cognitive-psycho-social worsening index, which is caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium) thereby producing damage to neuronal circuits underpinning deficit schizophrenia.

This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin - mu opioid receptor (MOR) and immune-inflammatory system.The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males.Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence.Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress.

Abstract Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of δ = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7–12 (difference range − 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13–15 (all differences − 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10. Trial registration: The original IPDMA was registered in PROSPERO (CRD42015024785).

Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data on whether the activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis, and lower magnesium and calcium levels impact DisQoL scores. This study recruited 90 patients with schizophrenia (including 40 with deficit schizophrenia) and 40 healthy controls and assessed the World Health Association QoL instrument-Abbreviated version and Sheehan Disability scale, Brief Assessment of Cognition in Schizophrenia (BACS), IL-6, IL-23, IL-17, IL-21, IL-22, tumor necrosis factor (TNF)-α, magnesium and calcium. Regression analyses showed that a large part of the first factor extracted from the physical, psychological, social and environmental HR-QoL and interference with school/work, social life, and home responsibilities was predicted by a generalized cognitive deterioration (G-CoDe) index (a latent vector extracted from BACs scores), and the first vector extracted from various symptom domains (“symptomatome”), whereas the biomarkers had no effects. Partial Least Squares analysis showed that the IL6IL23Th17 axis and magnesium/calcium had highly significant total (indirect + direct) effects on HR-QoL/disabilities, which were mediated by G-CoDe and the symptomatome (a first factor extracted from negative and positive symptoms). The IL6IL23Th17 axis explained 63.1% of the variance in the behavioral-cognitive-psycho-social (BCPS) worsening index a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. In summary, the BCPS worsening index is partly caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium), thereby probably damaging the neuronal circuits that may underpin deficit schizophrenia.

Little is known of the biochemical processes of cognitive decline during 'healthy' aging. Biological markers in body fluids, such as blood, could provide insight in those processes. In the present studies serum concentrations of different markers have been correlated to cognitive functioning of cognitively healthy aging individuals over a period of six years (mean age 57 years, SD 11, n = 93). Markers were related to mechanisms known to be involved in Alzheimer's disease, including inflammation, cholesterol homeostasis and homocysteine homeostasis. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test), and memory (Word Learning test: Total Words and Delayed Recall). Baseline concentrations of haptoglobine, homocysteine, lathosterol and lanosterol were negatively correlated with cognitive functioning on the Stroop test over the whole follow-up period of six years. Concentrations of all markers, i.e. haptoglobine, C-reactive protein, homocysteine, lathosterol and lanosterol, were also negatively correlated with functioning on the Word Learning test (Delayed Recall and for some markers also with the Total Words) over the whole six-years follow-up period. In conclusion, concentrations of serum markers related to inflammation, homocysteine and cholesterol homeostasis are not only associated with Alzheimer's disease, but also with cognitive functioning in the cognitively healthy aging population.