RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium’s clinical efficacy

Elena Milanesi, Irena Voinsky, Adva Hadar, Ala Srouji, Carlo Maj, Tatyana Shekhtman, Michael Gershovits, Shlomit Gilad, Caterina Chillotti, Alessio Squassina, James B. Potash, Thomas G. Schulze, Fernando S. Goes, Peter Zandi, John R. Kelsoe, David Gurwitz

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objectives: Lithium remains the oldest and most effective treatment for mood stabilisation in bipolar disorder (BD), even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA sequencing information derived from lymphoblastoid cell lines (LCLs) of lithium-responsive (LR) versus lithium non-responsive (LNR) BD patients, to assess gene expression variations that might bear on treatment outcome. Methods: RNA sequencing was carried out on 24 LCLs from female BD patients (12 LR and 12 LNR) followed by qPCR validation in two additional independent cohorts (41 and 17 BD patients, respectively). Results: Fifty-six genes showed nominal differential expression comparing LR and LNR (FC ≥ |1.3|, P ≤ 0.01). The differential expression of HDGFRP3 and ID2 was validated by qPCR in the independent cohorts. Conclusions: We observed higher expression levels of HDGFRP3 and ID2 in BD patients who favourably respond to lithium. Both of these genes are involved in neurogenesis, and HDGFRP3 has been suggested to be a neurotrophic factor. Additional studies in larger BD cohorts are needed to confirm the potential of HDGFRP3 and ID2 expression levels in blood cells as tentative favourable lithium response biomarkers.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalWorld Journal of Biological Psychiatry
DOIs
Publication statusE-pub ahead of print - 2017

Fingerprint

RNA Sequence Analysis
Nerve Growth Factors
Bipolar Disorder
Lithium
Cell Line
Biomarkers
Neurogenesis
Genes
Blood Cells

Keywords

  • Bipolar disorder
  • HDGFRP3
  • lithium
  • lymphoblastoid cell lines
  • RNA sequencing

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium’s clinical efficacy. / Milanesi, Elena; Voinsky, Irena; Hadar, Adva; Srouji, Ala; Maj, Carlo; Shekhtman, Tatyana; Gershovits, Michael; Gilad, Shlomit; Chillotti, Caterina; Squassina, Alessio; Potash, James B.; Schulze, Thomas G.; Goes, Fernando S.; Zandi, Peter; Kelsoe, John R.; Gurwitz, David.

In: World Journal of Biological Psychiatry, 2017, p. 1-13.

Research output: Contribution to journalArticle

Milanesi, E, Voinsky, I, Hadar, A, Srouji, A, Maj, C, Shekhtman, T, Gershovits, M, Gilad, S, Chillotti, C, Squassina, A, Potash, JB, Schulze, TG, Goes, FS, Zandi, P, Kelsoe, JR & Gurwitz, D 2017, 'RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium’s clinical efficacy', World Journal of Biological Psychiatry, pp. 1-13. https://doi.org/10.1080/15622975.2017.1372629
Milanesi, Elena ; Voinsky, Irena ; Hadar, Adva ; Srouji, Ala ; Maj, Carlo ; Shekhtman, Tatyana ; Gershovits, Michael ; Gilad, Shlomit ; Chillotti, Caterina ; Squassina, Alessio ; Potash, James B. ; Schulze, Thomas G. ; Goes, Fernando S. ; Zandi, Peter ; Kelsoe, John R. ; Gurwitz, David. / RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium’s clinical efficacy. In: World Journal of Biological Psychiatry. 2017 ; pp. 1-13.
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abstract = "Objectives: Lithium remains the oldest and most effective treatment for mood stabilisation in bipolar disorder (BD), even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA sequencing information derived from lymphoblastoid cell lines (LCLs) of lithium-responsive (LR) versus lithium non-responsive (LNR) BD patients, to assess gene expression variations that might bear on treatment outcome. Methods: RNA sequencing was carried out on 24 LCLs from female BD patients (12 LR and 12 LNR) followed by qPCR validation in two additional independent cohorts (41 and 17 BD patients, respectively). Results: Fifty-six genes showed nominal differential expression comparing LR and LNR (FC ≥ |1.3|, P ≤ 0.01). The differential expression of HDGFRP3 and ID2 was validated by qPCR in the independent cohorts. Conclusions: We observed higher expression levels of HDGFRP3 and ID2 in BD patients who favourably respond to lithium. Both of these genes are involved in neurogenesis, and HDGFRP3 has been suggested to be a neurotrophic factor. Additional studies in larger BD cohorts are needed to confirm the potential of HDGFRP3 and ID2 expression levels in blood cells as tentative favourable lithium response biomarkers.",
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AU - Milanesi, Elena

AU - Voinsky, Irena

AU - Hadar, Adva

AU - Srouji, Ala

AU - Maj, Carlo

AU - Shekhtman, Tatyana

AU - Gershovits, Michael

AU - Gilad, Shlomit

AU - Chillotti, Caterina

AU - Squassina, Alessio

AU - Potash, James B.

AU - Schulze, Thomas G.

AU - Goes, Fernando S.

AU - Zandi, Peter

AU - Kelsoe, John R.

AU - Gurwitz, David

PY - 2017

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N2 - Objectives: Lithium remains the oldest and most effective treatment for mood stabilisation in bipolar disorder (BD), even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA sequencing information derived from lymphoblastoid cell lines (LCLs) of lithium-responsive (LR) versus lithium non-responsive (LNR) BD patients, to assess gene expression variations that might bear on treatment outcome. Methods: RNA sequencing was carried out on 24 LCLs from female BD patients (12 LR and 12 LNR) followed by qPCR validation in two additional independent cohorts (41 and 17 BD patients, respectively). Results: Fifty-six genes showed nominal differential expression comparing LR and LNR (FC ≥ |1.3|, P ≤ 0.01). The differential expression of HDGFRP3 and ID2 was validated by qPCR in the independent cohorts. Conclusions: We observed higher expression levels of HDGFRP3 and ID2 in BD patients who favourably respond to lithium. Both of these genes are involved in neurogenesis, and HDGFRP3 has been suggested to be a neurotrophic factor. Additional studies in larger BD cohorts are needed to confirm the potential of HDGFRP3 and ID2 expression levels in blood cells as tentative favourable lithium response biomarkers.

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