The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomized controlled trials

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.     

1064 nm Nd:YAG laser light affects transmembrane mitochondria respiratory chain complexes

Photobiomodulation (PBM) is a non‐plant‐cell manipulation through a transfer of energy by means of light sources at the non‐ablative or thermal intensity. Authors showed that cytochrome‐c‐oxidase (complex IV) is the specific chromophore's target of PBM at the red (600‐700 nm) and NIR (760‐900 nm) wavelength regions. Recently, it was suggested that the infrared region of the spectrum could influence other chromospheres, despite the interaction by wavelengths higher than 900 nm with mitochondrial chromophores was not clearly demonstrated. We characterized the interaction between mitochondria respiratory chain, malate dehydrogenase, a key enzyme of Krebs cycle, and 3‐hydroxyacyl‐CoA dehydrogenase, an enzyme involved in the β‐oxidation (two mitochondrial matrix enzymes) with the 1064 nm Nd:YAG (100mps and 10 Hz frequency mode) irradiated at the average power density of 0.50, 0.75, 1.00, 1.25 and 1.50 W/cm² to generate the respective fluences of 30, 45, 60, 75 and 90 J/cm². Our results show the effect of laser light on the transmembrane mitochondrial complexes I, III, IV and V (adenosine triphosphate synthase) (window effects), but not on the extrinsic mitochondrial membrane complex II and mitochondria matrix enzymes. The effect is not due to macroscopical thermal change. An interaction of this wavelength with the Fe‐S proteins and Cu‐centers of respiratory complexes and with the water molecules could be supposed.      

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

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Dispersal patterns in a medium‐density Irish badger population: Implications for understanding the dynamics of tuberculosis transmission

European badgers (Meles meles) are group‐living mustelids implicated in the spread of bovine tuberculosis (TB) to cattle and act as a wildlife reservoir for the disease. In badgers, only a minority of individuals disperse from their natal social group. However, dispersal may be extremely important for the spread of TB, as dispersers could act as hubs for disease transmission. We monitored a population of 139 wild badgers over 7 years in a medium‐density population (1.8 individuals/km²). GPS tracking collars were applied to 80 different individuals. Of these, we identified 25 dispersers, 14 of which were wearing collars as they dispersed. This allowed us to record the process of dispersal in much greater detail than ever before. We show that dispersal is an extremely complex process, and measurements of straight‐line distance between old and new social groups can severely underestimate how far dispersers travel. Assumptions of straight‐line travel can also underestimate direct and indirect interactions and the potential for disease transmission. For example, one female disperser which eventually settled 1.5 km from her natal territory traveled 308 km and passed through 22 different territories during dispersal. Knowledge of badgers' ranging behavior during dispersal is crucial to understanding the dynamics of TB transmission, and for designing appropriate interventions, such as vaccination.     

Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons

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Next steps after 15 stimulating years of human gut microbiome research

Gut microbiome research has bloomed over the past 15 years. We have learnt a lot about the complex microbial communities that colonize our intestine. Promising avenues of research and microbiome-based applications are being implemented, with the goal of sustaining host health and applying personalized disease management strategies. Despite this exciting outlook, many fundamental questions about enteric microbial ecosystems remain to be answered. Organizational measures will also need to be taken to optimize the outcome of discoveries happening at an extremely rapid pace. This article highlights our own view of the field and perspectives for the next 15 years.     

Induction of drug metabolizing enzymes: a survey of in vitro methodologies and interpretations used in the pharmaceutical industry--do they comply with FDA recommendations?

The FDA has published guidelines by which to carry out and interpret in vitro induction studies using hepatocytes but do researchers in pharmaceutical companies actually follow these to the letter? In a survey of 30 participants in the pharmaceutical industry, 19 questions were posed regarding the species investigated, methodologies and interpretations of the data. Also addressed was the in-house decision making processes as a result of in vitro induction data. The survey showed that, although the basic methods were similar, no two researchers carried out and interpreted induction assays in exactly the same way. No single method was superior but all included enzyme activities as the major end point. Hepatocytes from animal species were used to confirm animal in vivo data but only human hepatocytes were used to predict human induction responses. If a compound was found to be positive in an in vitro induction assay, few would halt the development of the compound. The majority would consider other properties of the compound (bioavailability, clearance and therapeutic concentrations) and follow the FDA recommendation to conduct clinical drug-drug interaction studies. Overall, the results from this survey indicate that there is no standard pharmaceutical industry method or evaluation criterion by which in vitro assays are carried out. Rather than adhering to the FDA guidelines, some adapt methods and interpretation according to their own experience and need (whether screening or lead optimisation). There was general consensus that studies using human hepatocyte cultures currently provide the best indication of the in vivo induction potential of NCEs. In addition, the assessment of in vitro induction data from the literature suggest that the two-fold induction threshold and the percent of positive control criteria may not be the best methods to accurately assess the in vivo induction potential of a drug. Although the two-fold induction criterion is now obsolete, more predictive models for determining the clinical induction potential are needed. Alternative models are proposed and discussed herein.     

Endoglin is required for myogenic differentiation potential of neural crest stem cells

Genetic studies show that TGFbeta signaling is essential for vascular development, although the mechanism through which this pathway operates is incompletely understood. Here we demonstrate that the TGFbeta auxiliary coreceptor endoglin (eng, CD105) is expressed in a subset of neural crest stem cells (NCSCs) in vivo and is required for their myogenic differentiation. Overexpression of endoglin in the neural crest caused pericardial hemorrhaging, correlating with altered vascular smooth muscle cell investment in the walls of major vessels and upregulation of smooth muscle alpha-actin protein levels. Clonogenic differentiation assay of NCSCs derived from neural tube explants demonstrated that only NCSC expressing high levels of endoglin (NCSC(CD105+)) had myogenic differentiation potential. Furthermore, myogenic potential was deficient in NCSCs obtained from endoglin null embryos. Expression of endoglin in NCSCs declined with age, coinciding with a reduction in both smooth muscle differentiation potential and TGFbeta1 responsiveness. These findings demonstrate a cell autonomous role for endoglin in smooth muscle cell specification contributing to vascular integrity.     

Functional roles for beta1,4-N-acetlygalactosaminyltransferase-A in Drosophila larval neurons and muscles

Adult Drosophila mutant for the glycosyltransferase beta1,4-N-acetlygalactosaminyltransferase-A (beta4GalNAcTA) display an abnormal locomotion phenotype, indicating a role for this enzyme, and the glycan structures that it generates, in the neuromuscular system. To investigate the functional role of this enzyme in more detail, we turned to the accessible larval neuromuscular system and report here that larvae mutant for beta4GalNAcTA display distinct nerve and muscle phenotypes. Mutant larvae exhibit abnormal backward crawling, reductions in nerve terminal bouton number, decreased spontaneous transmitter-release frequency, and short, wide muscles. This muscle shape change appears to result from hypercontraction since the individual sarcomeres are shorter in mutant muscles. Analysis of muscle calcium signals showed altered calcium handling in the mutant, suggesting a mechanism by which hypercontraction could occur. All of these phenotypes can be rescued by a transgene carrying the beta4GalNAcTA genomic region. Tissue-specific expression, using the Gal4-UAS system, reveals that neural expression rescues the mutant crawling phenotype, while muscle expression rescues the muscle defect. Tissue-specific expression did not appear to rescue the decrease in neuromuscular junction bouton number, suggesting that this defect arises from cooperation between nerve and muscle. Altogether, these results suggest that beta4GalNAcTA has at least three distinct functional roles.