Publications by authors named "William Coryell"
Article Synopsis
- Bipolar disorder (BD) features disrupted sleep patterns and nerve cell loss, with lithium being a common but variably effective treatment.
- Research focused on how certain circadian genes and their interactions influence cell survival and lithium response using neurons from BD patients and regular controls.
- Findings indicated that certain gene knockdowns affected cell survival differently between lithium responders and non-responders, suggesting complex roles of circadian rhythms in BD and lithium treatment efficacy.
Bipolar disorder (BD) is characterized by mood episodes, disrupted circadian rhythms and gray matter reduction in the brain. Lithium is an effective pharmacotherapy for BD, but not all patients respond to treatment. Lithium has neuroprotective properties and beneficial effects on circadian rhythms that may distinguish lithium responders (Li-R) from non-responders (Li-NR).
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- Lithium is recognized as a leading treatment for bipolar disorder, but predicting who will respond to it remains a challenge, leading researchers to investigate the genetic and functional differences between lithium responders and non-responders.
- A study analyzing iPSC-derived neurons found 41 genes significantly expressed differently between these groups, and further gene prioritization identified over a thousand candidate genes related to lithium response.
- The research highlighted the role of focal adhesion and the extracellular matrix in response mechanisms, indicating that differences in these areas may have a more significant impact on lithium treatment efficacy than the drug itself.
Article Synopsis
- The study investigates the genetic and phenotypic traits associated with age at onset (AAO) and polarity at onset (PAO) in bipolar disorder to enhance understanding of the illness and develop screening tools.
- Results indicate that an earlier AAO is linked to more severe symptoms, such as psychosis and suicidality, as well as variations in educational success and living situations.
- The research reveals a significant relationship between higher polygenic risk scores for other mental disorders and earlier AAO, although no significant associations were found for PAO, highlighting considerable variability across different cohorts.
Background: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%-40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms.
View Article and Find Full Text PDFTargeting the coronavirus nucleocapsid protein through GSK-3 inhibition.
Proc Natl Acad Sci U S A
October 2021
The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome-CoV, and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors, including lithium.
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- - The rise of clinics offering intravenous ketamine for treatment-resistant depression (TRD) reflects its potential efficacy, despite ketamine being FDA-approved only as an anesthetic, which raises safety concerns.
- - A review focuses on the challenges of implementing ketamine infusions, emphasizing the need for stakeholder engagement, standardized procedures, and training for treatment teams.
- - Key considerations for developing a ketamine clinic include thorough patient assessments, dosing guidelines, and safety monitoring to balance meeting demand with ensuring safe treatment practices.
Background: Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response.
View Article and Find Full Text PDFBipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of "clock genes" and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms.
View Article and Find Full Text PDFUnlabelled: The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors including lithium.
View Article and Find Full Text PDFLithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1-5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index].
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