Preliminary Transcriptome Analysis in Lymphoblasts from Cluster Headache and Bipolar Disorder Patients Implicates Dysregulation of Circadian and Serotonergic Genes.
Bipolar disorder (BD) and cluster headache (CH) are distinct conditions with important similarities such as a temporal pattern of disturbances, dysregulation of the sleep-wake cycle, and response to lithium treatment in a proportion of patients. Aiming to identify common transcription signatures in these two disorders, we carried out an exploratory microarray gene expression analysis in lymphoblasts from 8 CH and 10 BD I patients selected for positive response to lithium and 10 healthy controls (CO). Gene expression levels of BD and CH were compared with CO to create two lists of differentially expressed genes. We then matched the two lists and focus on genes showing statistically significant difference and same change direction in both disorders. RNA binding motif protein 3 (RBM3) was the most significantly altered gene in the list (3.17 × 10(-13) in BD, 9.44 × 10(-14) in CH). Pathway analysis identified protein processing in endoplasmic reticulum as the most significantly enriched. For validation with quantitative reverse transcription PCR (qRT-PCR) using the same samples, we selected seven genes. Among these, we were able to validate the RBM3, nuclear receptor subfamily 1, group D, member 1 (NR1D1), and tryptophan hydroxylase 1 (TPH1). These genes encode for elements involved in circadian rhythm regulation (RBM3 and NR1D1) and in serotonin synthesis (TPH1), processes previously involved in both disorders, and in the mechanism of action of lithium.
Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Sp 8 Sestu-Monserrato, Km 0.700, 09042, Monserrato, Cagliari, Italy.
Marta
M
Costa
Alessio
A
Squassina
Ignazio Stefano
IS
Piras
Claudia
C
Pisanu
Donatella
D
Congiu
Paola
P
Niola
Andrea
A
Angius
Caterina
C
Chillotti
Raffaella
R
Ardau
Giovanni
G
Severino
Erminia
E
Stochino
Arianna
A
Deidda
Antonio M
AM
Persico
Martin
M
Alda
Maria
M
Del Zompo
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D057906:Circadian Clocks / Q000235:genetics*; D003027:Cluster Headache / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000235:genetics*; D059467:Transcriptome; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C099506:RBM3 protein, human; D016601:RNA-Binding Proteins; D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase