ArticleTranslational psychiatry2020
Integrative analysis of lithium treatment associated effects on brain structure and peripheral gene expression reveals novel molecular insights into mechanism of action.
Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Investigation of habenula volume in mood disorders: A meta-analytic study.Psychological medicine · 2026Pooled it
- Lithium effects in the frontolimbic circuitry: a systematic review of neuroimaging findings in bipolar disorder.Translational psychiatry · 2026Pooled it
- Brain structural connectomic topology predicts medication response in youth with bipolar disorder: A randomized clinical trial.Journal of affective disorders · 2025Trial
- Investigating seasonal metabolic variations in bipolar disorder: a targeted metabolomics study.BMC psychiatry · 2025Article
- Lithium salts alter the size and morphology of the Madagascar hissing cockroach's neuroendocrine system.Scientific reports · 2025Article
- Circadian clock genes and cell survival in bipolar disorder: Insights into lithium responsiveness and molecular mechanisms in patient-derived neural progenitor cells and mouse neurons.The FEBS journal · 2025Article
- Transcription-Driven Repurposing of Cardiotonic Steroids for Lithium Treatment of Severe Depression.Cells · 2025Article
- Effects of oxidative stress and GDNF on patients with bipolar disorder: a prospective study.BMC psychiatry · 2025Article
- The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder.BMC psychiatry · 2025Article
- Lithium in Drinking Water and its Potential Impact on Mental Health: A Review.Current medicinal chemistry · 2025Review
- New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.Pharmacological reviews · 2024Review
- Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders.Research square · 2024Article
- Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2023Article
- Mania-related effects on structural brain changes in bipolar disorder - a narrative review of the evidence.Molecular psychiatry · 2023Review
- RNA Biomarkers in Bipolar Disorder and Response to Mood Stabilizers.International journal of molecular sciences · 2023Review
- Lithium Biological Action Mechanisms after Ischemic Stroke.Life (Basel, Switzerland) · 2022Review
- Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Chronic lithium treatment alters the excitatory/ inhibitory balance of synaptic networks and reduces mGluR5-PKC signalling in mouse cortical neurons.Journal of psychiatry & neuroscience : JPN · 2021Article
- The effects of lithium chloride and cathodal/anodal transcranial direct current stimulation on conditional fear memory changes and the level of p-mTOR/mTOR in PFC of male NMRI mice.Metabolic brain disease · 2021Article
- A 7 Tesla Amygdalar-Hippocampal Shape Analysis of Lithium Response in Bipolar Disorder.Frontiers in psychiatry · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Lithium is a highly effective medication for bipolar disorder, but its mechanism of action remains unknown. In this study, brain MRI scans and blood samples for gene expression (total of 110 scans and 109 blood samples) were collected from 21 bipolar subjects before and after 2 and 8 weeks of lithium monotherapy and at the same time-points from untreated 16 healthy controls. We used linear mixed-effects models to identify brain structural features and genes with expression changed after lithium treatment, with correction for multiple testing, and correlated their concurrent changes to identify molecular pathways associated with lithium effects. There are significant increases in gray matter fraction, global cortical thickness, and the frontal and parietal cortices after 8 weeks of lithium treatment (corrected p < 0.05). Volume increases were also seen for putamen, hippocampus, thalamic nuclei, and thalamic substructures. Several genes showed significant expression changes, and 14 gene pathways were identified for the present integration analysis. Of these, nine pathways had significant correlations with structural changes (FDR < 0.05). Three neurotrophy-related pathways (GDNF family of ligands, NFAT immune-response, and p53-signaling pathway) correlated with structural changes in multiple regions. Mediation analysis showed that the sphingomyelin metabolism pathway is associated with HAM-D change (p < 0.01), and this effect is mediated via the volume of mediodorsal thalamus (p < 0.03). In summary, the integration of lithium effects on brain structural and peripheral gene expression changes revealed effects on several neurotrophic molecular pathways, which provides further insights into the mechanism of lithium action.
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Registered trials
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