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Letter
Evidence for increased completed suicide in first-degree relatives of LRRK2 G2019S mutation Parkinson’s disease
  1. Roberto Angel Ortega1,2,
  2. Mark Groves1,2,
  3. Anat Mirelman3,4,5,6,
  4. Roy N Alcalay7,
  5. Deborah Raymond1,2,
  6. Sonya Elango1,2,
  7. Helen Mejia-Santana7,
  8. Nir Giladi3,5,6,
  9. Karen Marder7,8,
  10. Susan B Bressman1,2,
  11. Rachel Saunders-Pullman1,2
  1. 1 Department of Neurology, Mount Sinai Beth Israel Medical Center, New York City, New York, USA
  2. 2 Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
  3. 3 Center for the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Medical Center, Tel Aviv, Israel
  4. 4 Laboratory of Early Markers of Neurodegeneration, Tel Aviv Medical Center, Tel Aviv, Israel
  5. 5 Department of Neurology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  6. 6 Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
  7. 7 Department of Neurology, Columbia University Irving Medical Center, New York City, New York, USA
  8. 8 Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA
  1. Correspondence to Roberto Angel Ortega, Department of Neurology, Mount Sinai Beth Israel, New York City, NY 10003, USA; Roberto.Ortega{at}mountsinai.org

https://doi.org/10.1136/jnnp-2018-319364

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    Introduction

    Mutations in the l eucine-rich repeat kinase 2 (LRRK2) gene are an important monogenic cause of Parkinson’s disease (PD). Reported non-motor features of LRRK2 PD include depression, anxiety and bipolar disorder,1 but suicide has not been systematically investigated. As part of our LRRK2 Ashkenazi Jewish Consortium study we assessed the history of death by suicide in probands and first-degree relatives with and without LRRK2 G2019S mutations.

    Methods

    The sample comprised participants from the Ashkenazi Jewish LRRK2 Consortium study sites in Tel Aviv (Tel Aviv Medical Center) and New York (Columbia University Irving Medical Center and Mount Sinai Beth Israel).2 PD probands were screened for the LRRK2 G2019S mutation.3 Genetic status of the first-degree relatives was not known. Questionnaire and pedigree information was systematically collected on LRRK2 PD and non-LRRK2 mutation, idiopathic PD (IPD) probands, and evaluated for suicide as cause of death among first-degree relatives. The odds of suicide among first-degree relatives was compared using a logistic generalised estimating equation, accounting for family membership, site and sex using Stata V.14 (StataCorp, 2015, Stata Statistical Software: Release 14. College Station, TX).

    Results

    No LRRK2 PD or IPD was known to commit suicide during the course of the study. (Study follow-up ranged from 0 to 5 years, and the mean duration among those with at least one follow-up visit was 3.4 years). LRRK2 PD probands were more likely to report a death in a first-degree …

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    Footnotes

    • Contributors Study concept and design: RAO, RSP, SBB, NG, AM, KM, RNA and MG. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: RAO, RSP and SBB. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: RAO and RSP. Administrative, technical or material support: RAO, RSP, HMS, AM, RNA, SE, DR, NG and SBB. Study supervision: RSP, SBB, NG and KM. Obtained funding: RSP, KM, NG and SBB.

    • Funding This study was funded by the Michael J Fox Foundation for Parkinson’s Research and the National Institute of Neurological Disorders and Stroke (NINDS-K02NS073836).

    • Competing interests SBB and RS-P have received consulting fees from Denali Therapeutics Inc. RNA has received consulting fees from Denali, Biogen and Genzyme/Sanofi. NG serves as a member of the Editorial Board for the Journal of Parkinson's Disease. He serves as consultant to Sionara, Accelmed, Teva, NeuroDerm, IntecPharma, Pharma2B, Denali and Abbvie. He receives royalties from Lysosomal Therapeutics (LTI) and payment for lectures at Teva, UCB, Abbvie, Sanofi-Genzyme, Bial and Movement Disorder Society. NG received research support from the Michael J Fox Foundation, the National Parkinson Foundation, the European Union 7th Framework Program and the Israel Science Foundation as well as from Teva NNE program, Biogen, LTI, and Pfizer.

    • Patient consent Not required.

    • Ethics approval Tel Aviv Medical Center Ethical Committee, CUIMC Institutional Review Board and Mount Sinai Beth Israel Institutional Review Board.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data were taken from the MJFF-funded Ashkenazi Jewish LRRK2 Consortium study.