The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in the pathophysiology of mood and anxiety disorders and is a potential treatment target in major depressive disorder (MDD). This study compared brain mGluR5 binding in elderly patients suffering from MDD with that in elderly healthy volunteers using positron emission tomography (PET) and [11C]ABP688. Twenty elderly (mean age: 63.0±6.3) subjects with MDD and twenty-two healthy volunteers in the same age range (mean age: 66.4±7.3) were examined with PET after a single bolus injection of [11C]ABP688, with many receiving arterial sampling. PET images were analyzed on a region of interest and a voxel level to compare mGluR5 binding in the brain between the two groups. Differences in [11C]ABP688 binding between patients with early- and late-onset depression were also assessed. In contrast to a previously published report in a younger cohort, no significant difference in [11C]ABP688 binding was observed between elderly subjects with MDD and healthy volunteers. [11C]ABP688 binding was also similar between subgroups with early- or late-onset depression. We believe this is the first study to examine mGluR5 expression in depression in the elderly. Although future work is required, results suggest potential differences in the pathophysiology of elderly depression versus depression earlier in life.

Objective To determine which outcome measures could detect early progression of disease in school‐age children with mild cystic fibrosis (CF) lung disease over a two‐year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements. Methods Thirty‐six school‐age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1 second (ppFEV1) 99 [12.5]) were evaluated by serial spirometer‐controlled chest CT scans and spirometry at baseline, 3‐month, 1‐ and 2‐years. Results No significant changes were noted at 3‐month for any variable except for decreased ppFEV1. Mucus plugging score (MPS) and QATA1 and A2 increased at 1‐ and 2‐years. The bronchiectasis score (BS), and total score (TS) were increased at 2‐year. All variables tested with the exception of bronchial wall thickness score, parenchymal score (PS), and ppFEV1, were consistent with longitudinal worsening of lung disease. Multivariate analysis revealed baseline PS, baseline TS, and 1‐year changes in BS and air trapping score were predictive of 2‐year changes in BS. Conclusions MPS and QATA1‐A2 were the most sensitive indicators of progressive childhood CF lung disease. The 1‐year change in the bronchiectasis score had the most positive predictive power for 2‐year change in bronchiectasis.

Overall, no consistent effects of AQW051 on brain regions involved in the performance of a WMT or EMT were observed; however, this study presents a model for evaluating potential response to pharmacological interventions for cognitive impairment in schizophrenia.

Aims TAK‐041 (NBI‐1065846), an orally available, investigational, small molecule agonist of GPR139, an orphan G‐protein‐coupled receptor, has shown promise in preclinical studies for the treatment of symptoms associated with schizophrenia. Here, we report the results from a phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK‐041 in healthy adults and exploratory efficacy assessment of TAK‐041 as adjunctive therapy to antipsychotics in adults with stable schizophrenia (http://ClinicalTrials.gov: NCT02748694). Methods The study comprised 4 parts: parts 1–3 were undertaken in healthy adults and part 4 in patients with stable schizophrenia. Part 1 was a single‐rising‐dose study, part 2 was a multiple‐rising‐dose study that assessed plasma exposure and accumulation, part 3 evaluated the bioavailability of tablet formulation versus oral suspension, and part 4 was a repeat multiple‐dose study in patients with stable schizophrenia. Results No serious adverse events were reported. TAK‐041 had a nearly linear pharmacokinetics profile, with rapid absorption and long half‐life of 170–302 hours across all doses tested. Bioavailability was similar between the tablet formulation and oral suspension, and no meaningful food effect was detected. Systemic exposure was 22–30% lower for patients with schizophrenia than for healthy volunteers. A potential signal of improvement was detected in the anxiety–depression scale of the Positive and Negative Syndrome Scale (P = .0002, not corrected for multiplicity) and the Temporal Experience of Pleasure Scale in patients with schizophrenia. Conclusion TAK‐041 was generally well tolerated in healthy volunteers and adults with schizophrenia. Further investigation of TAK‐041 in individuals with schizophrenia is supported.