Social stressors and suicidal behaviour: neurobiology. Philippe Courtet Montpellier

Transcription

1 Social stressors and suicidal behaviour: neurobiology Philippe Courtet Montpellier

2 WHO estimates about 1.5 million deaths by suicide per year worldwide by fold more suicide attempts (Organisation Mondiale de la Santé)

3 The silent epidemiology 1 death every hour France suicides in 2014, Suicide attempts

4 The suicidal process individuals, 17 countries (WHO) Ideation (9,2 % lifetime) Plan (3,1 % lifetime) 60% of transitions within the year Attempt (2,7 % lifetime) 60% of transitions within the year Incidence of Suicide: 15/ Nock et al BJP 2008

5 Stressors related to Suicidal Behaviour Reasons (alleged by patients) Separation, loss Conflict with partner conjoint Other problems in relationship Social problems Illness Psychiatric disorders Depression Schizophrenia Alcoholism Personality (90-97% in psychological autopsiy studies) (Heikkinen et al. 1994)

6 Completed Suicide After a Suicide Attempt: a 37-Year Follow-Up Study (Suominen et al. Am J Psychiatry 2004) 100 patients followed after a suicidal act during 37 years 13 suicides: 6 out of 71 women (8%) 7 out of 27 men (26%) 2/3 happened more than 15 years after the initial act

7 Stress - Vulnerability Model of suicidal behaviour Past history of suicide attempts Family history of suicidal behaviour Impulsive aggression Pessimism Childhood abuse Psychiatric disorders Life events Specific Vulnerability (traits) Stress Suicide Oquendo et al Am J Psychiatry 2004, Romero et al J Clin Psychiatry 2007, Slama et al J Clin Psychiatry, Carballo et al JAD 2008

8 Genetics of suicide «Alcoholism and suicide seem to be something we Hemingways have herited» Margaux Hemingway

9 Gene x Environment Benett et al Mol Psychiatry 2002 Caspi et al Science 2003, Caspi & Moffitt Nature Reviews Neurosciences 2007

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12 Health and care consumption

13 Risky behaviours

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15 Biological stigmata of bullying Methylations of 5HTT gene (MZ twin pairs discordant for bullying CRP (prospective study in general population, n = 1,420), follow up 9-21 yrs Ouellet-Morin et al Psychol Med 2013 Copeland et al PNAS 2014

16 Increased methylations of NR3C1 promoter in childhood abuse Weaver et al 2004, McGowan et al 2009,

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18 Biomarkers of sensitivity to social stressors

19 Environmental events & suicidal behaviour Population attributable risk proportions of trauma among suicidal behaviour: 22% Triggers of suicidal acts: Family problems Loss of a beloved one Job problems, unemployment Financial difficulties Physical illness Social devaluation Heikkinen et al Acta Psychiatr Scand Suppl 1994, Stein et al Plos One 2010

20 Nurses Health Study nurses (46-71 yrs) Social integration index: marital status, social network size, frequency of contact with social ties, participation in religious or other social groups 43 suicide events during more than 1.2 million person-years of follow-

21 Suicide Prevention : restoring social connectedness Postal or telephone contacts have shown efficacy in the prevention of repetition of suicidal behaviour (in RCTs) Motto et al Psychiatr Serv. 2001, Carter et al BMJ 2005, Vaiva et al BMJ 2006, Fleischmann et al Bull World Health Org. 2008

22 Social exclusion - psychological pain - suicide Social adversity Separation Conflict with the spouse Other relational problems Social problems Diseases (physical or mental) Social Exclusion Suicide Psychological pain Inflammation

23 116 women 45 history of depression (euthymic) & Suicide Attempt 43 history of depression (euthymic) & NO Suicide Attempt 28 healthy controls Cyberball Game, fmri

24 Social rejection is associated with inflammatory responses to social stress Acute social stressors Slavich et al PNAS 2010

25 European Neuropsychopharmacology 2015 N = 600 patients admitted for a MDD (Fasting hscrp) Exclusion : CRP>10 mg/l, Hemodialysis, use of interferon-α-based immunotherapy, inflammatory and neurological comorbidities, treatment with Non-steroidal anti-inflammatory drugs, statins, steroids, antibiotics Without any effect of - the time between the sampling - the last suicide attempt - the current suicidal ideation Model 1: adjusted for age, sex, chronic diseases, substances / alcohol misuse, anxiety disorders, smoking, antidepressants intake Model 2: all covariates in model 1+ sexual abuse

26 Batty et al JAMA Psychiatry participants, mean duration of follow-up : 8.6 years <1 mg/l], 1-3mg/L, >3mg/L] Adjusted for age, sex, socioeconomic status, psychological distress, smoking, somatic illness

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28 «Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety» (Ballard et al Journal of Psychiatric Research 2014) (Yang et al Biol Psychiatry 2015)

29 Social ties & suicidal behaviour: inflammation Neural regions involved in processing threats to social connection Stress axis hyper activity Neuroinflammation, microgliosis Trier Social Stress Test Eisenberger & Cole Nat Neurosci. 2012

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31 Social rejection is associated with inflammatory responses to social stress Acute social stressors Slavich et al PNAS 2010

32 116 women 45 history of depression (euthymic) & Suicide Attempt 43 history of depression (euthymic) & NO Suicide Attempt 28 healthy controls Cyberball Game, fmri

33 Social, physical, psychological pains: all present in suicidal behaviour Kross et al PNAS 2011

34 Painkillers and suicidal vulnerability 857 subjects over 65 years old, community dwelling 41 subjects with a lifetime history of w/ SA, 410 affective controls w/o SA, 406 healthy subjects Exhaustive prescribed drugs during 3 years follow up Opioid analgesic consumption associated with SA (OR=2.35 ) adjusted for gender, age, education, chronic diseases, headaches, hospitalization, living alone, subjective health & exclusion of cancer cases Further analysis in a partially overlapping sample (n=858) Suicidal patients : higher rates of opioid prescriptions Non suicidal patients : higher rates of pain Suicidal patients : higher impact of pain Olié et on al 2013, quality Calati of et life al 2017

35 Buprenorphine (-) Social pain (reject / exclusion) (+) Naltroxone μ-opioid receptor (OPRM-1) Suicide

36 Buprenorphine ultra-low dose for treating serious suicidal ideation RCT double blind, buprenorphine sublingual: 0.44 mg/d, n=40 vs pcb n=22, in addition High risk patients : suicidal ideation, suicide attempt in 64,5% Without substance misuse Main objective : suicidal ideation at 4 weeks Yovell et al AJP 2016