Lithium-associated transcriptional regulation of CRMP1 in patient-derived olfactory neurons and symptom changes in bipolar disorder

Charlee K. McLean, Soumya Narayan, Sandra Y. Lin, Narayan Rai, Youjin Chung, Maria Mananita S. Hipolito, Nicola G. Cascella, John Nurnberger, Koko Ishizuka, Akira S. Sawa, Evaristus A. Nwulia

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

There is growing evidence that lithium used in the treatment of bipolar disorder (BD) affects molecular targets that are involved in neuronal growth, survival, and maturation, but it remains unclear if neuronal alterations in any of these molecules predict specific symptom changes in BD patients undergoing lithium monotherapy. The goals of this study were to (a) determine which molecular changes in the olfactory neurons of symptomatic patients receiving lithium are associated with antimanic or antidepressant response, and (b) uncover novel intraneuronal regulatory mechanisms of lithium therapy. Twenty-two treatment-naïve non-smoking patients, with symptomatic BD underwent nasal biopsies for collection of olfactory tissues, prior to their treatment and following a 6-week course of lithium monotherapy. Sixteen healthy controls were also biopsied. Combining laser capture microdissection with real-time polymerase chain reaction, we investigated baseline and treatment-associated transcriptional changes in candidate molecular targets of lithium action in the olfactory neuroepithelium. Baseline mRNA levels of glycogen synthase kinase 3 beta (GSK3β) and collapsin response mediator protein 1 (CRMP1) genes were significantly associated with BD status and with severity of mood symptoms. Among BD subjects, treatment-associated downregulation of CRMP1 expression was most predictive of decreases in both manic and depressive symptoms. This study provides a novel insight into the relevance of CRMP1, a key molecule in semaphorin-3A signaling during neurodevelopment, in the molecular mechanism of action of lithium, and in the pathophysiology of BD. It supports the use of human-derived olfactory neuronal tissues in the evaluation of treatment response of psychiatric disorders.

Original languageEnglish (US)
Article number81
JournalTranslational Psychiatry
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Bipolar Disorder
Lithium
Neurons
Therapeutics
Antimanic Agents
Semaphorin-3A
Laser Capture Microdissection
collapsin response mediator protein-1
Nose
Antidepressive Agents
Psychiatry
Real-Time Polymerase Chain Reaction
Down-Regulation
Depression
Biopsy
Messenger RNA
Survival
Growth
Genes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Lithium-associated transcriptional regulation of CRMP1 in patient-derived olfactory neurons and symptom changes in bipolar disorder. / McLean, Charlee K.; Narayan, Soumya; Lin, Sandra Y.; Rai, Narayan; Chung, Youjin; Hipolito, Maria Mananita S.; Cascella, Nicola G.; Nurnberger, John; Ishizuka, Koko; Sawa, Akira S.; Nwulia, Evaristus A.

In: Translational Psychiatry, Vol. 8, No. 1, 81, 01.12.2018.

Research output: Contribution to journalArticle

McLean, CK, Narayan, S, Lin, SY, Rai, N, Chung, Y, Hipolito, MMS, Cascella, NG, Nurnberger, J, Ishizuka, K, Sawa, AS & Nwulia, EA 2018, 'Lithium-associated transcriptional regulation of CRMP1 in patient-derived olfactory neurons and symptom changes in bipolar disorder', Translational Psychiatry, vol. 8, no. 1, 81. https://doi.org/10.1038/s41398-018-0126-6
McLean, Charlee K. ; Narayan, Soumya ; Lin, Sandra Y. ; Rai, Narayan ; Chung, Youjin ; Hipolito, Maria Mananita S. ; Cascella, Nicola G. ; Nurnberger, John ; Ishizuka, Koko ; Sawa, Akira S. ; Nwulia, Evaristus A. / Lithium-associated transcriptional regulation of CRMP1 in patient-derived olfactory neurons and symptom changes in bipolar disorder. In: Translational Psychiatry. 2018 ; Vol. 8, No. 1.
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