Team 1 : Affective disorders: bio-environmental risk and resilience

Marie-Laure Ancelin, Directrice de l'unité

Our main research projects aim to characterize risk and protective factors (resilience) of neuropsychiatric disorders, to identify biomarkers and to study mental health service delivery. We aim to better understand the mechanisms underlying neuropsychiatric pathologies and their heterogeneity by developing valid etiological models of pathological processes. Our approach is based on several epidemiological and clinical studies with a wide range of biological, environmental, psychosocial, pharmacological and clinical data, as well as brain imaging. Based on this information, it will be possible to formulate innovative intervention and prevention strategies and improve clinical management.

1. The ESPRIT-GENEPI project evaluates the role of stress and (epi)genetic factors in the onset of late affective disorders (depressive and anxiety). It is based on the ESPRIT general population cohort; 1863 participants aged 65 years and over followed-up for more than 14 years, undergoing neuropsychiatric and cardiovascular examinations, MRI, a polysomnographic record with salivary and blood samples for a DNA bank. Our hypothesis is that accumulation of traumas throughout the lifespan and inappropriate stress management in genetically vulnerable people could lead to dysfunction of stress-related biological systems and to increased risk of affective disorders. These Gene x Environment interactions could be mediated by epigenetic mechanisms that will be evaluated through two approaches; Epigenome Wide Association Study (EWAS) of the whole epigenome and methylation of candidate genes. Pathophysiological markers of stress (cortisol, sleep, MRI...) will be examined as potential intermediate endophenotypes between (epi)genetic factors and psychiatric phenotypes.

2. The predicting role of a large number of markers of stress regulation systems, e.g. biological (Hypothalamic-Pituitary-Adrenal axis, Autonomic Nervous System, allostatic load), psychological (peritraumatic), and clinical factors, is evaluated within 2 clinical cohorts. The PHOENIX study for the onset and chronicization of post-traumatic and depressive symptoms following exposure to a severe life event and EVEREST for the evolution of these symptoms in patients treated with EMDR therapy (Eye Movement Desensitization and Reprocessing). In parallel, we are interested in the biological and psychosocial factors of resilience, which facilitate recovery following traumatic exposure or remission following a psychotherapy.

3. The REMEMBER/13 November longitudinal study (coll. with Inserm U1077, F Eustache) focuses on the structural and functional neurobiological markers predicting post-traumatic stress disorder in 180 subjects (60 non-exposed controls and 120 subjects exposed to the attacks of 13 November 2015). We will mainly focus on the involvement of spatial contextual memory in the development and chronicization of re-experiencing symptoms and post-traumatic stress disorder.

4. The consequences of psychiatric disorders and pharmacological treatments (psychotropic drugs) on chronic pathologies (including dementia), incapacity, and mortality are examined in the Three-City study (9000 older adults followed-up for 14 years). The interactions between socio-environmental factors and psychiatric disorders are also studied there as well as in primary care in the British cohort UPBEAT (803 patients with high cardiovascular risk, followed-up twice a year for 3 years).

5. A prevention program for Alzheimer's disease, PREVENT, based on potentially modifiable risk factors, such as depression, vascular factors or stress markers, was implemented in collaboration with Imperial College, London and the University of Edinburgh. Five "prevention" clinics have been set to study preclinical biomarkers in 700 adults at high genetic risk, to identify protective factors for neurodegenerative evolution.

6. Another aspect of our work focuses on the evaluation of the management of psychiatric disorders. SESAME examines psychiatric care administered by general practitioners in the adult regional community with a view to improving diagnosis and treatment. STEP evaluates the modalities of schizophrenic management in a specialized hospital setting and their influence on the evolution of symptoms and remission. The multidimensional aspects of apathy and insight in schizophrenia are studied in 2 other clinical studies and a national cohort (FACE-SZ, FondaMental) to develop profile-specific psychotherapy programs adapted to patient symptoms.

Biologist and Epidemiologist Research Director Inserm

Biologist and Epidemiologist Senior Research Fellow Inserm

Epidemiologist Neuropsychologist Emeritus Research Director Inserm, Visiting Professor Imperial College

Psychiatrist Hospital Practitioner

Psychiatrist, University Professor / Hospital Practitioner, Responsible for the medical team of the University Department of Adult Psychiatry, Coordinator of the Department of Adult Psychiatry, Deputy Head of the H-U Department of Psychiatry (Hôpital La Colombière)

Ophtalmologist, University Professor / Hospital Practitioner

Biochemist

Hospital Practitioner

Clinical Research Assistant University Personnel

Psychiatrist, Director of IXICO

Psychiatrist, Professor at King's College, London

Hospital doctoral student

Statistician and Epidemiologist Senior Research Assistant Inserm

Biologist and Epidemiologist Research Assistant Inserm

Statistician and Epidemiologist Senior Research Assistant Inserm

Data manager, Research Assistant Inserm

Contact:

Epidemiologist
Post-doctoral Research Fellow

Publications: 

MOST REPRESENTATIVE PUBLICATIONS IN THE LAST 5 YEARS (IF: 5-year impact factor)

  • Ryan J, Carriere I, Carcaillon L, Dartigues JF, Auriacombe S, Rouaud O, Berr C, Ritchie K, Scarabin PY, Ancelin ML. Estrogen receptor polymorphisms and incident dementia: The prospective 3C study. Alzheimers Dement 2014;10:27-35 (IF: 12.06)
  • Ancelin ML, Farre A, Carriere I, Ritchie K, Chaudieu I, Ryan J. C-reactive protein gene variants: independent association with late-life depression and circulating protein levels. Transl Psychiatry 2015;5:e499 (IF: 5.47)
  • Januar V, Ancelin ML, Ritchie K, Saffery R, Ryan J. BDNF promoter methylation and genetic variation in late-life depression. Transl Psychiatry 2015;5:e619 (IF: 5.47)
  • Zhang X, Norton J, Carriere I, Ritchie K, Chaudieu I, Ancelin ML. Risk factors for late-onset generalized anxiety disorder: results from a 12-year prospective cohort (the ESPRIT study). Transl Psychiatry 2015;5:e536 (IF: 5.47)
  • Raffard S, Gutierrez LA, Yazbek H, Larue A, Boulenger JP, Lançon C, Benoit M, Faget C, Norton J, Capdevielle D. Working Memory Deficit as a Risk Factor for Severe Apathy in Schizophrenia: A 1-Year Longitudinal Study. Schizophr Bull 2016;42:642-51. (IF: 8.05)
  • Gandubert C, *Scali J, *Ancelin ML, Carriere I, Dupuy AM, Bagnolini G, Ritchie K, Sebanne M, Martrille L, Baccino E, Hermes A, Attal J, Chaudieu I. Biological and psychological predictors of posttraumatic stress disorder onset and chronicity. A one-year prospective study. Neurobiol Stress 2016;3:61-7 (IF: 5.73)
  • Ritchie K, Carriere I, Berr C, Amieva H, Dartigues JF, Ancelin ML, Ritchie CW. The clinical picture of Alzheimer's disease in the decade before diagnosis: clinical and biomarker trajectories. J Clin Psychiat 2016;77:e305-e11 (IF: 5.16)
  • Ryan J, Chaudieu I, Ancelin ML*, Saffery R* (*co-last authors). Biological underpinnings of trauma and post-traumatic stress disorder: focusing on genetics and epigenetics. Epigenomics 2016;8:1553-69 (IF: 4.49) [Review]
  • Ancelin ML, Ryan J. 5-HTTLPR x stress hypothesis: is the debate over? Molr Psychiatry 2017:1-2 (IF: 12.43).
  • Ritchie K, Carriere I, Su L, O'Brien JT, Lovestone S, Wells K, Ritchie CW. The midlife cognitive profiles of adults at high risk of late-onset Alzheimer's disease: The PREVENT study. Alzheimers Dement 2017;13:1089-97 (IF: 12.06)
  • Carriere I, Norton J, Farré A, Wyart M, Tzourio C, Noize P, Peres K, Fourrier-Reglat A, Ritchie K, Ancelin ML. Antidepressant use and cognitive decline in community-dwelling elderly people - The Three-City Cohort. BMC Med 2017;15:1-9 (IF: 9.41)
  • Ancelin ML, Scali J, Norton J, Ritchie K, Dupuy AM, Chaudieu I, Ryan J. The effect of an adverse psychological environment on salivary cortisol levels in the elderly differs by 5-HTTLPR genotype. Neurobiol Stress 2017;7:38-46 (IF: 5.73)
  • Ancelin ML, Scali J, Norton J, Ritchie K, Dupuy AM, Chaudieu I, Ryan J. Heterogeneity in HPA axis dysregulation and serotonergic vulnerability to depression. Psychoneuroendocrinology 2017;77:90-4 (IF: 5.52)
  • Lam D, Ancelin ML, Ritchie K, Saffery R, Ryan J. DNA methylation and genetic variation of the angiotensin converting enzyme (ACE) in depression. Psychoneuroendocrinology 2017;88:1-8 (IF: 5.52)
  • Zhang X, Norton J, Carriere I, Ritchie K, Chaudieu I, Ryan J, Ancelin ML. Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder. Sci Rep 2017;7:42676 (IF: 4.60)
  • Carriere I, Farré A, Proust-Lima C, Ryan J, Ancelin ML, Ritchie K. Chronic and remitting trajectories of depressive symptoms in the elderly. Characterisation and risk factors. Epidemiol Psychiatr Sci 2017;26:146-56 (IF: 4.56)
  • Norton J, Oude Engberink A, Gandubert C, Ritchie K, Mann A, David M, Capdevielle D. health service utilisation, detection rates by family practitioners, and management of patients with common mental disorders in French family practice. Can J Psychiatry 2017;62:521-30. (IF: 4.28)
  • Fransquet PD, Lacaze P, Saffery R, McNeil J, Woods R, Ryan J. Blood DNA methylation as a potential biomarker of dementia: A systematic review. Alzheimers Dement 2018;14:81-103 (IF: 12.06) [Review]
  • Ritchie K, Carriere I, Howett D, Su L, Hornberger M, O'Brien JT, Ritchie CW, Chan D. Allocentric and Egocentric Spatial Processing in Middle-Aged Adults at High Risk of Late-Onset Alzheimer's Disease: The PREVENT Dementia Study. J Alzheimers Dis 2018;65:885-96 (IF: 3.79)
  • Ancelin ML, Norton J, Canonico M, Scarabin PY, Ritchie K, Ryan J. Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression. Depress Anxiety 2019 Nov 15. doi: 10.1002/da.22974. (IF: 5.78)
  • Ancelin ML, Carriere I, Artero S, Maller J, Meslin C, Ritchie K, Ryan J, Chaudieu I. Lifetime major depression and gray matter volume. J Psychiatry Neurosci 2019;44:45-53. (IF: 5.53)
  • Johnson J, Chaudieu I, Ritchie K, Scali J, Ancelin ML*, Ryan J* (co-last authors). The extent to which childhood adversity and recent stress influence all-cause mortality risk in older adults. Psychoneuroendocrinology 2019;111:104492. (IF: 5.52)
  • Norton J, Carriere I, Peres K, Gabelle A, Berr C, Ritchie K, Ancelin ML. Sex-specific depressive symptoms as markers of pre-Alzheimer dementia: findings from the Three-City cohort study. Transl Psychiatry 2019;9:291. (IF: 5.47)