Epilepsy and bipolar disorder

Knott, Sarah; Forty, Liz; Craddock, Nick; Thomas, Rhys H.

doi:10.1016/j.yebeh.2015.07.003

Cited by 35 publications

(17 citation statements)

References 79 publications

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“…One of the top comparable diseases (based on 236 shared inferred GO-BP terms and no shared genes) was substance-induced psychoses ( Fig 5B ), which is redolent of psychotic disorders, the top comparable disease found via 9 shared genes ( Fig 5A ). Interestingly, many of the other comparable diseases found exclusively using inferred GO-BP terms ( Fig 5B ) were recently confirmed in the literature as comorbidities or medical conditions in bipolar patients, including learning disorders [ 38 ], stomach ulcers [ 39 ], epilepsy [ 40 ], and atherosclerosis with cardiovascular diseases [ 41 ], further validating this approach.…”

Section: Resultssupporting

confidence: 55%

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database

et al. 2016

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Strategies for discovering common molecular events among disparate diseases hold promise for improving understanding of disease etiology and expanding treatment options. One technique is to leverage curated datasets found in the public domain. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) manually curates chemical-gene, chemical-disease, and gene-disease interactions from the scientific literature. The use of official gene symbols in CTD interactions enables this information to be combined with the Gene Ontology (GO) file from NCBI Gene. By integrating these GO-gene annotations with CTD’s gene-disease dataset, we produce 753,000 inferences between 15,700 GO terms and 4,200 diseases, providing opportunities to explore presumptive molecular underpinnings of diseases and identify biological similarities. Through a variety of applications, we demonstrate the utility of this novel resource. As a proof-of-concept, we first analyze known repositioned drugs (e.g., raloxifene and sildenafil) and see that their target diseases have a greater degree of similarity when comparing GO terms vs. genes. Next, a computational analysis predicts seemingly non-intuitive diseases (e.g., stomach ulcers and atherosclerosis) as being similar to bipolar disorder, and these are validated in the literature as reported co-diseases. Additionally, we leverage other CTD content to develop testable hypotheses about thalidomide-gene networks to treat seemingly disparate diseases. Finally, we illustrate how CTD tools can rank a series of drugs as potential candidates for repositioning against B-cell chronic lymphocytic leukemia and predict cisplatin and the small molecule inhibitor JQ1 as lead compounds. The CTD dataset is freely available for users to navigate pathologies within the context of extensive biological processes, molecular functions, and cellular components conferred by GO. This inference set should aid researchers, bioinformaticists, and pharmaceutical drug makers in finding commonalities in disease mechanisms, which in turn could help identify new therapeutics, new indications for existing pharmaceuticals, potential disease comorbidities, and alerts for side effects.

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Section: Resultssupporting

confidence: 55%

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database

et al. 2016

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“…Conversely, for the mood stabilizer lamotrigine, FDA labeling lists hypothyroidism as rare (<1 in 1000 patients) , and recent reviews found little to no evidence for an effect of lamotrigine on thyroid hormones . Despite the overlapping characteristics, and shared pharmacology of BD and epilepsy , we could only find literature on carbamazepine and oxcarbazepine associated with hypothyroidism in epilepsy, a disease in which the pathogenesis may involve thyroid hormones . Evidence from epilepsy studies shows adverse thyroid effects from valproate , carbamazepine , and oxcarbazepine .…”

Section: Discussionmentioning

confidence: 82%

Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort

et al. 2016

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ObjectivesThyroid abnormalities in patients with bipolar disorder (BD) have been linked to lithium treatment for decades, yet other drugs have been less well studied. Our objective was to compare hypothyroidism risk for lithium versus the anticonvulsants and second‐generation antipsychotics commonly prescribed for BD.MethodsAdministrative claims data on 24,574 patients with BD were analyzed with competing risk survival analysis. Inclusion criteria were (i) one year of no prior hypothyroid diagnosis nor BD drug treatment, (ii) followed by at least one thyroid test during BD monotherapy on lithium carbonate, mood‐stabilizing anticonvulsants (lamotrigine, valproate, oxcarbazepine, or carbamazepine) or antipsychotics (aripiprazole, olanzapine, risperidone, or quetiapine). The outcome was cumulative incidence of hypothyroidism per drug, in the presence of the competing risk of ending monotherapy, adjusted for age, sex, physician visits, and thyroid tests.ResultsAdjusting for covariates, the four‐year cumulative risk of hypothyroidism for lithium (8.8%) was 1.39‐fold that of the lowest risk therapy, oxcarbazepine (6.3%). Lithium was non‐statistically significantly different from quetiapine. While lithium conferred a higher risk when compared to all other treatments combined as a group, hypothyroidism risk error bars overlapped for all drugs. Treatment (p = 3.86e‐3), age (p = 6.91e‐10), sex (p = 3.93e‐7), and thyroid testing (p = 2.79e‐87) affected risk. Patients taking lithium were tested for hypothyroidism 2.26–3.05 times more frequently than those on other treatments.ConclusionsThyroid abnormalities occur frequently in patients with BD regardless of treatment. Therefore, patients should be regularly tested for clinical or subclinical thyroid abnormalities on all therapies and treated as indicated to prevent adverse effects of hormone imbalances on mood.

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“…The stronger association with epilepsy than with NNCD indicates an epilepsy-specific effect. A common aetiology has previously been proposed for these two conditions, supported by clinical observations that they both respond to the same drug treatment (212,213). Further, bipolar disorder is a risk factor for onset of epilepsy, and bipolar disorder occurs more often in person with than without epilepsy (76,214).…”

Section: And 5)mentioning

confidence: 78%

Psychiatric comorbidity and social aspects in pregnant women with epilepsy — The Norwegian Mother and Child Cohort Study

Reiter

Veiby

Daltveit

et al. 2013

Epilepsy & Behavior

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Symptoms of depression were associated with epilepsy both during and before pregnancy. Epilepsy was linked to eating disorders before pregnancy. Unemployment, single parenting, and low educational level were linked to epilepsy in young pregnant females. Efforts aiming at treatment and screening for psychiatric comorbidity in pregnant women with epilepsy are important in the follow-up of these patients.

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Epilepsy and bipolar disorder

Cited by 35 publications

References 79 publications

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database

Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort

Psychiatric comorbidity and social aspects in pregnant women with epilepsy — The Norwegian Mother and Child Cohort Study

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