ABSTRACT
BACKGROUND: Prevention of age-related cognitive decline and depression is becoming urgent because of rapid growing aging populations. Effects of vagal nerve activation on brain function by food ingredients are inadequately investigated; matured hop bitter acid (MHBA) administration reportedly improves cognitive function and depression via vagal nerve activation in model mice. OBJECTIVE: We investigated the effects of MHBA supplementation on cognitive function and mood state in healthy older adults with perceived subjective cognitive decline. METHODS: Using a randomized double-blind placebo-controlled trial design, 100 subjects (aged 45-69 years) were randomly assigned into placebo (nâ=â50) and MHBA (nâ=â50) groups, and received placebo or MHBA capsules daily for 12 weeks. RESULTS: Symbol Digit Modalities Test (SDMT) score assessing divided attention at week 12 was significantly higher (pâ=â0.045) and ß-endorphin at week 12 was significantly lower (pâ=â0.043) in the subjects receiving MHBA. Transthyretin in serum, a putative mild cognitive impairment marker, was significantly higher at week 12 in the MHBA group than in the placebo group (pâ=â0.048). Subgroup analysis classified by the subjective cognitive decline questionnaire revealed that in addition to improved SDMT scores, memory retrieval assessed using the standard verbal paired-associate learning tests and the Ray Verbal Learning Test at week 12 had significantly improved in the subgroup with perceived subjective cognitive decline and without requirement for medical assistance in the MHBA group compared with that in the placebo group. CONCLUSION: This study suggested that MHBA intake improves cognitive function, attention, and mood state in older adults.
Subject(s)
Affect/drug effects , Cognition/drug effects , Cognitive Dysfunction/drug therapy , Dietary Supplements , Humulus , Mental Status and Dementia Tests , Affect/physiology , Aged , Aging/drug effects , Aging/psychology , Cognition/physiology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Diagnostic Self Evaluation , Double-Blind Method , Female , Humans , Male , Middle Aged , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Stress, Psychological/diagnosis , Stress, Psychological/drug therapy , Stress, Psychological/psychologyABSTRACT
Recent GWAS demonstrated an association between candidate genes located at region 6p22.1 and schizophrenia. This region has been reported to house certain candidate SNPs, which may be associated with schizophrenia at HIST1H2BJ, PRSS16, and PGBD1. These genes may presumably be associated with pathophysiology in schizophrenia, namely epigenetics and psychoneuroimmunology. A three-step study was undertaken to focus on these genes with the following aims: (1) whether these genes may be associated in Japanese patients with schizophrenia by performing a 1st stage case-control study (514 cases and 706 controls) using Japanese tagging SNPs; (2) if the genetic regions of interest for the disease from the 1st stage of analyses were found, re-sequencing was performed to search for new mutations; (3) finally, a replication study was undertaken to confirm positive findings from the 1st stage were reconfirmed using a larger number of subjects (2,583 cases and 2,903 controls) during a 2nd stage multicenter replication study in Japan. Genotyping was performed using TaqMan PCR method for the selected nine tagging SNPs. Although three SNPs situated at the 3' side of PGBD1; rs3800324, rs3800327, and rs2142730, and two-window haplotypes between rs3800327 and rs2142730 showed positive associations with schizophrenia, these associations did not have enough power to sustain significance during the 2nd stage replication study. In addition, re-sequencing for exons 5 and 6 situated at this region did not express any new mutations for schizophrenia. Taken together these results indicate that the genes HIST1H2BJ, PRSS16, and PGBD1 were not associated with Japanese patients with schizophrenia.
Subject(s)
Asian People/genetics , Chromosomes, Human, Pair 6/genetics , Genetic Predisposition to Disease , Histones/genetics , Nerve Tissue Proteins/genetics , Schizophrenia/genetics , Serine Endopeptidases/genetics , Adult , Case-Control Studies , Female , Genetic Association Studies , Genome, Human/genetics , Haplotypes/genetics , Humans , Japan , Male , Open Reading Frames/genetics , Polymorphism, Single Nucleotide/genetics , Reproducibility of Results , Schizophrenia/diagnosis , Sequence Analysis, DNAABSTRACT
Deficits in sensorimotor gating, a function to focus on the most salient stimulus, could lead to a breakdown of cognitive integrity, and could reflect the "flooding" by sensory overload and cognitive fragmentation seen in schizophrenia. Sensorimotor gating emerges at infancy, and matures during childhood. The mechanisms that underlie its development are largely unclear. Here, we screened the mouse genome, and found that tryptophan hydroxylase (TPH) is implicated in the maturation of sensorimotor gating. TPH, an enzyme involved in the biosynthesis of serotonin, proved to be required only during the weaning period for maturation of sensorimotor gating, but was dispensable for its emergence. Proper serotonin levels during development underlie the mature functional architecture for sensorimotor gating via appropriate actin polymerization. Thus, maintaining proper serotonin levels during childhood may be important for mature sensorimotor gating in adulthood.