Publications by authors named "Francis M Mondimore"

Article Synopsis
  • Accurately diagnosing bipolar disorder (BD) can take around 7 years due to its overlap with unipolar major depressive disorder (MDD), especially since the first manic episode often follows a depressive one.
  • This study uses genome-wide association analyses (GWAS) and polygenic risk scores (PRS) from a large cohort to identify genetic factors that could help differentiate between BD and MDD early on.
  • The results show that while BD and MDD are genetically distinct and share a continuum of genetic risk, larger future studies are needed to enhance the accuracy of these genetic predictors for early diagnosis.
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Article Synopsis
  • Lithium is the primary treatment for bipolar disorder (BD), but how it works and predicts outcomes is not fully understood.
  • A previous study identified key cellular pathways linked to lithium response, including focal adhesion and PI3K-Akt signaling.
  • In this new study, researchers confirmed these pathways in a larger group of 2039 patients but found no connection with the extracellular matrix, suggesting that issues with neuronal growth signaling may impact lithium effectiveness.
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Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores.

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Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients ( = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score.

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Background: Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

Aims: To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

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Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes.

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Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region.

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Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLiGen) study.

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Background: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown.

Methods: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial.

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Objective: The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions.

Methods: Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD.

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Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial.

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Poster abstracts are evaluated based on the following criteria: significance of the problem to healthy aging or medication management; innovativeness of ideas, methods, and/or approach; methodological rigor of methods and approach; presentation of finding; implications identified for future research, practice, and/or policy; and clarity of writing. Submissions are not evaluated through the peer-reviewed process used by . Industry support is indicated, where applicable.

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Objectives: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.

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Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis.

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Background: Medication non-adherence is a critical challenge for many patients diagnosed with mood disorders (Goodwin and Jamison, 1990). There is a need for alternative strategies that improve adherence among patients with mood disorders that are cost-effective, able to reach large patient populations, easy to implement, and that allow for communication with patients outside of in-person visits. Technology-based approaches to promote medication adherence are increasingly being explored to address this need.

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Importance: Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking.

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Article Synopsis
  • - Bipolar disorder (BD) is a complex genetic mental illness with mood and behavioral swings, and previous studies have only identified a small part of its hereditary risk.
  • - The largest genome-wide association study (GWAS) to date analyzed over 9 million genetic variants from nearly 10,000 BD patients and over 30,000 controls, revealing two new significant genetic loci associated with the disorder.
  • - The study highlights the importance of using well-defined patient groups and a larger control sample in genetics research to discover common genetic variants contributing to BD.
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Background: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.

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