In this population-based propensity score matched (PSM) cohort study, we aimed to investigate the risk of developing dementia with the use of acid suppressants, including proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2 antagonists). Cohorts of PPI users (n = 2,778), H2 antagonist users (n = 6,165), and non-users (n = 86,238) were selected from a dataset covering the years 2000 to 2010 in Taiwan’s National Health Insurance Research Database. Patients in the three groups were PSM at a ratio of 1:1 within each comparison cohort (CC). Three CCs were created: (1) PPI users compared to non-users (CC1, n = 2,583 pairs); (2) H2 antagonist users compared to non-users (CC2, n = 5,955 pairs); and (3) PPI users compared to H2 antagonist users (CC3, n = 2,765 pairs). A multivariable robust Cox proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and the 95% confidence interval (CI) for the risk of developing dementia. The multivariable analysis results show that the aHR of developing dementia during the follow-up period was 0.72 (CC1: 95% CI = 0.51–1.03, P = 0.07) for PPI users and 0.95 (CC2: 95% CI = 0.74–1.22, P = 0.69) for H2 antagonist users, when compared to non-users. Between the patients using acid suppressants, there was no difference between PPI and H2 antagonist users in the risk of developing dementia (CC3: aHR = 0.82, 95% CI = 0.58–1.17, P = 0.28). In conclusion, no association was observed between the use of acid suppressants and the risk of developing dementia in any of the three CCs. Further, randomized controlled trials are warranted to confirm this relationship.

Schizophrenia is a complex mental disorder with a genetic component. The GRIK gene family encodes ionotropic glutamate receptors of the kainate subtype, which are considered candidate genes for schizophrenia. We screened for rare and pathogenic mutations in the protein-coding sequences of the GRIK gene family in 516 unrelated patients with schizophrenia using the ion semiconductor sequencing method. We identified 44 protein-altered variants, and in silico analysis indicated that 36 of these mutations were rare and damaging or pathological based on putative protein function. Notably, we identified four truncating mutations, including two frameshift deletion mutations (GRIK1^p.Phe24fs and GRIK1^p.Thr882fs) and two nonsense mutations (GRIK2^p.Arg300Ter and GRIK4^p.Gln342Ter) in four unrelated patients with schizophrenia. They exhibited minor allele frequencies of less than 0.01% and were absent in 1517 healthy controls from Taiwan Biobank. Functional analysis identified these four truncating mutants as loss-of-function (LoF) mutants in HEK-293 cells. We also showed that three mutations (GRIK1^p.Phe24fs, GRIK1^p.Thr882fs, and GRIK2^p.Arg300Ter) weakened the interaction with the PSD95 protein. The results suggest that the GRIK gene family harbors ultrarare LoF mutations in some patients with schizophrenia. The identification of proteins that interact with the kainate receptors will be essential to determine kainate receptor-mediated signaling in the brain.

Given the frequent concomitance between depression and gastroesophageal reflux disease (GERD), it is important to evaluate the change of depression in patients with GERD, especially considering the presence of esophageal mucosal breaks (MB). This study aimed to examine the change in the levels of depression in patients with GERD during proton-pump inhibitors (PPI) therapy. We designed a prospective cohort study to explore the profile of the alteration in depression with respect to the impact of esophageal MB. This study recruited 172 eligible patients with GERD between February 2016 and May 2018. The change in depression was defined as the difference between the respective Taiwanese Depression Questionnaire (TDQ) scores obtained at baseline and after PPI therapy. Multivariate linear regression models were used to estimate the factors associated with the change in depression. The results revealed statistically significant improvements in the TDQ score (mean score: baseline = 13.2, after PPI therapy = 10.9, p < 0.01, Cohen’s d = 0.30) during PPI therapy for GERD. Moreover, the MB was an independent variable associated with changes in the TDQ score [B = 3.31, 95% confidence interval (CI): (1.12, 5.51), p < 0.01] and the improvement in depression [odds ratio = 0.38, 95% CI: (0.17, 0.86), p = 0.02]. Our findings revealed that depressive symptoms improved slightly following PPI therapy. Moreover, MB was an unfavorable prognostic factor for the improvement in depression.