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Published on: February 24, 2023
Gene expression and association analysis of LIM (PDLIM5) in major depression
Jun-ichi Iga1, Shu-ichi Ueno, Ken Yamauchi
1Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Abstract:
LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n=130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant.
Insights
Lower LIM mRNA expression in leukocytes is linked to depression. Treatment with paroxetine normalized LIM mRNA levels, suggesting it may serve as a biomarker for mood disorders.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- LIM (PDLIM5) protein interacts with key signaling molecules like protein kinase C-epsilon and N-type calcium channels.
- Altered LIM mRNA expression has been observed in postmortem brains and lymphoblastoid cells of mood disorder patients.
- LIM mRNA expression in peripheral leukocytes is proposed as a potential biological marker for mood disorders.
Purpose of the Study:
- To investigate the association between LIM mRNA expression levels in peripheral leukocytes and major depressive disorder.
- To examine the effect of antidepressant treatment on LIM mRNA levels in patients with major depression.
- To explore the potential of LIM gene single nucleotide polymorphisms (SNPs) in relation to major depression.
Main Methods:
- Quantitative analysis of LIM mRNA levels in peripheral leukocytes from 20 drug-naive major depressive patients and age/sex-matched controls.
- Assessment of LIM mRNA level changes after 4-week paroxetine treatment in depressive patients.
- Genotyping of three LIM gene SNPs in 130 major depression patients and 130 controls.
Main Results:
- Significantly lower LIM mRNA levels were found in leukocytes of drug-naive depressive patients compared to controls.
- A significant increase in LIM mRNA levels was observed after 4-week paroxetine treatment, returning to control levels.
- No significant association was found between the studied LIM gene SNPs and major depression.
- Hamilton Depression Rating Scale (HAM-D) scores improved by approximately 50% after treatment, but changes did not correlate with mRNA level alterations.
Conclusions:
- Reduced LIM mRNA expression in peripheral leukocytes is associated with the depressive state.
- The recovery of LIM mRNA levels following antidepressant treatment suggests an adaptive response.
- LIM mRNA expression in leukocytes may serve as a potential biomarker for monitoring depression and treatment response.
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