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Research paper
Psychiatric symptoms in preclinical behavioural-variant frontotemporal dementia in MAPT mutation carriers
  1. Gayathri Cheran1,
  2. Hannah Silverman1,
  3. Masood Manoochehri1,
  4. Jill Goldman1,
  5. Seonjoo Lee2,
  6. Liwen Wu2,
  7. Sarah Cines1,
  8. Emer Fallon3,
  9. Brendan Desmond Kelly3,4,
  10. Diana Angelika Olszewska3,
  11. Judith Heidebrink5,
  12. Sarah Shair5,
  13. Stephen Campbell5,
  14. Henry Paulson5,
  15. Timothy Lynch3,
  16. Stephanie Cosentino1,
  17. Edward D Huey6
  1. 1G H Sergievsky Center & Taub Institute in the Department of Neurology, Columbia University Medical Center, New York, USA
  2. 2Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York, USA
  3. 3Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland
  4. 4Department of Psychiatry, Trinity Centre for Health Sciences, Trinity College Dublin, Tallaght Hospital, Dublin, Ireland
  5. 5Department of Neurology, The University of Michigan, Ann Arbor, Michigan, USA
  6. 6Departments of Psychiatry & Neurology, Columbia University Medical Center, New York, USA
  1. Correspondence to Dr Edward D Huey, Departments of Psychiatry & Neurology, Columbia University Medical Center, New York, NY 10032, USA; edh2126{at}cumc.columbia.edu

Abstract

Objective To characterise psychiatric symptoms in preclinical and early behavioural-variant frontotemporal dementia (bvFTD), a neurodegenerative disorder whose symptoms overlap with and are often mistaken for psychiatric illness.

Methods The present study reports findings from a systematic, global, prospective evaluation of psychiatric symptoms in 12 preclinical carriers of pathogenic MAPT mutations, not yet meeting bvFTD diagnostic criteria, and 46 familial non-carrier controls. Current psychiatric symptoms, informant-reported symptoms and lifetime prevalence of psychiatric disorders were assessed with The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the Neuropsychiatric Inventory Questionnaire. Fisher exact test was used to compare carriers and non-carriers’ lifetime prevalence of six DSM-IV disorders: major depressive disorder, panic attacks, alcohol abuse, generalised anxiety disorder, panic disorder, and depressive disorder not otherwise specified. Other DSM-IV disorders had insufficient prevalence across our sample for between-group comparisons, but are reported.

Results Non-carriers had greater prevalence of mood and anxiety disorders than has been reported for a general reference population. Preclinical carriers had lower lifetime prevalence of mood and anxiety disorders than non-carriers, except for depressive disorder not otherwise specified, an atypical syndrome comprising clinically significant depressive symptoms which fail to meet criteria for major depressive disorder.

Conclusion Findings suggest that early psychiatric symptoms of emergent bvFTD may manifest as emotional blunting or mood changes not cleanly conforming to criteria for a DSM-defined mood disorder.

  • frontotemporal dementia
  • genetics
  • neuropsychiatry
  • tau
  • frontal lobe

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Footnotes

  • Contributors GC: data acquisition, analyses and interpretation of data, preparation of manuscript. HS: analyses and interpretation of data, preparation of manuscript. MM: critical revision of manuscript for intellectual content. JG, JH and TL: study supervision and critical revision of manuscript for intellectual content. SL and LW: analyses and interpretation of data. SC, EF, SS and SCa: data acquisition. BDK and DAO: data acquisition and critical revision of manuscript for intellectual content. HP: study supervision. SCo: study concept and design, study supervision, analyses and interpretation of data, and critical revision of manuscript for intellectual content. EDH: study concept and design, acquisition of data, study supervision, preparation of manuscript, critical revision for all content.

  • Funding This work was supported by the Association for Frontotemporal Degeneration, and by an R01 grant awarded by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institute of Health (NIH) (5R01NS076837-03). Statistical analyses were supported by grant K01AG051348 awarded by the Research Foundation for Mental Hygiene at the New York State Psychiatric Institute, through the National Institute of Aging. Data presented in this publication was collected at the Irving Institute for Clinical and Translational Research, a resource supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

  • Competing interests None declared.

  • Ethics approval Institutional Review Boards and Ethics Committees at Columbia University Medical Center, University of Michigan, and Dublin Neurological Institute.

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

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