Gene expression and association analysis of LIM (PDLIM5) in major depression.
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.
Iga
Jun-ichi
J
Department 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.
Ueno
Shu-ichi
S
Yamauchi
Ken
K
Numata
Shusuke
S
Motoki
Ikuyo
I
Tayoshi
Sumiko
S
Kinouchi
Sawako
S
Ohta
Koshi
K
Song
Hongwei
H
Morita
Kyoko
K
Rokutan
Kazuhito
K
Tanabe
Hirotaka
H
Sano
Akira
A
Ohmori
Tetsuro
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers; D003865:Major Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D060588:LIM Domain Proteins; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D017374:Paroxetine / Q000008:administration & dosage*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016896:Treatment Outcome
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D060588:LIM Domain Proteins; C512485:PDLIM5 protein, human; D017374:Paroxetine