Reduction in cortical presynaptic markers, notably parvalbumin (PV), for the chandelier subtype of inhibitory γ-amino-butyric acid (GABA) interneurons is a highly replicated post-mortem finding in schizophrenia. Evidence from genetic and pharmacological studies implicates hypofunction of N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic signaling as a critical component of the pathophysiology of schizophrenia. Serine racemase (SR) produces the endogenous NMDAR co-agonist D-serine, and disruption of the SR gene results in reduced NMDAR signaling. SR null mutant (−/−) mice were used to study the link between NMDAR hypofunction and decreased PV expression, assessed by immunoreactive (IR) cell density in the medial prefrontal cortex and hippocampus and protein levels in brain homogenates from the frontal cortex and hippocampus. Contrary to expectations, SR −/− mice showed modest elevations in PV-IR cell density and no difference in PV expression in brain homogenate. To control for these surprising results, we investigated PV expression in mice and rats following subchronic phencyclidine or ketamine treatments in adulthood. PV expression was not affected by drug these treatment in either species, failing to reproduce previously published findings. Our findings challenge the hypothesis that pathological deficits in PV expression are simply a consequence of NMDAR hypofunction.

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BACKGROUND: In patients hospitalized with heart failure (HF) exacerbations, physicians routinely supplement potassium to maintain levels ≥4.0 mEq/L. The evidence basis for this practice is relatively weak. We aimed to evaluate the association between serum potassium levels and outcomes in patients hospitalized with HF. METHODS: We identified patients admitted with acute HF exacerbations to hospitals that contributed to an electronic health record-derived dataset. In a subset of patients with normal admission serum potassium (3.5-5.0 mEq/L), we averaged serum potassium values during a 72-hour exposure window and categorized as follows: <4.0 mEq/L (low normal), 4.0-4.5 mEq/L (medium normal), and >4.5 mEq/L (high normal). We created multivariable models examining associations between these categories and outcomes. RESULTS: We included 4,995 patients: 2,080 (41.6%), 2,326 (46.6%), and 589 (11.8%) in the <4.0, 4.0-4.5, and >4.5 mEq/L cohorts, respectively. After adjustment for demographics, comorbidities, and presenting severity, we observed no difference in outcomes between the low and medium normal groups. Compared to patients with levels <4.0 mEq/L, patients with a potassium level of >4.5 mEq/L had a longer length of stay (median of 0.6 days; 95% CI = 0.1 to 1.0) but did not have statistically significant increases in mortality (OR [odds ratio] = 1.51; 95% CI = 0.97 to 2.36) or transfers to the intensive care unit (OR = 1.78; 95% CI = 0.98 to 3.26). CONCLUSIONS: Inpatients with heart failure who had mean serum potassium levels of <4.0 showed similar outcomes to those with mean serum potassium values of 4.0-4.5. Compared with mean serum potassium level of <4.0, mean serum levels of >4.5 may be associated with increased risk of poor outcomes.