ABSTRACT
OBJECTIVES: Statins have recently been linked to having effects on cognition and mood in mood disorders, though results are mixed. In this paper, we use data from a recent randomized controlled trial (RCT) to examine the effect of statins on cognition and mood in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). METHODS: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (nâ¯=â¯60) originally designed to examine the effect of atorvastatin (nâ¯=â¯27) versus placebo (nâ¯=â¯33) for lithium-induced diabetes insipidus in BD and MDD patients who were using lithium. For this analysis, the primary outcome was global cognition Z-score at 12-weeks adjusted for baseline. The secondary cognition outcomes were (1) Screen for Cognitive Impairment in Psychiatry (SCIP), and (2) executive function Z-score. The primary mood outcome (secondary outcome of this analysis) was depression relapse during 12-week follow-up (Mongomery Asberg Depression Rating Scale (MADRS) ≥10). The secondary mood outcomes were (1) relapse rate into a manic episode, and (2) relapse rate into any mood episode. RESULTS: After 12 weeks follow-up, atorvastatin and placebo groups did not differ in terms of global cognition Z-score (ß = -0.009287 (-0.1698,0.1512), p-value = 0.91). Similarly, composite Z-scores for SCIP and executive functions did not differ significantly. Depression relapse during 12-week follow-up was not significantly different between the groups (χ2 (1) = 0.148, p-value = 0.70). Similarly, there was no difference between groups regarding relapse into mania. CONCLUSION: In BD and MDD patients with lithium-induced nephrogenic diabetes insipidus randomized to atorvastatin or placebo, we found no significant differences in cognition and mood outcomes at 12-week follow-up.
Subject(s)
Affect/drug effects , Atorvastatin/pharmacology , Bipolar Disorder/drug therapy , Cognition/drug effects , Depressive Disorder, Major/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Adult , Bipolar Disorder/psychology , Depressive Disorder, Major/psychology , Double-Blind Method , Executive Function , Female , Humans , Male , Middle Aged , Treatment OutcomeSubject(s)
Anxiety Disorders/therapy , Anxiety/therapy , Depression/therapy , Mindfulness , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Health Questionnaire , Treatment OutcomeABSTRACT
Heterozygous loss-of-function mutations in GRIN2B, a subunit of the NMDA receptor, cause intellectual disability and language impairment. We developed clonal models of GRIN2B deletion and loss-of-function mutations in a region coding for the glutamate binding domain in human cells and generated neurons from a patient harboring a missense mutation in the same domain. Transcriptome analysis revealed extensive increases in genes associated with cell proliferation and decreases in genes associated with neuron differentiation, a result supported by extensive protein analyses. Using electrophysiology and calcium imaging, we demonstrate that NMDA receptors are present on neural progenitor cells and that human mutations in GRIN2B can impair calcium influx and membrane depolarization even in a presumed undifferentiated cell state, highlighting an important role for non-synaptic NMDA receptors. It may be this function, in part, which underlies the neurological disease observed in patients with GRIN2B mutations.
