'A silent epidemic' New findings fromthe Pittsburgh ...
Transcript of 'A silent epidemic' New findings fromthe Pittsburgh ...
10/26/2021
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New findings from the Pittsburgh Longitudinal Research Program in Late-Life Suicide: Implications for identification and treatment
• Presenters:• Katalin Szanto, MD, Professor of Psychiatry Department of Psychiatry
University of Pittsburgh, Pittsburgh, PA
• Emma J O'Brien, BA, Research Specialist University of Pittsburgh Medical Center, Pittsburgh, PA
• Elizabeth Schumacher, BS, Research Specialist University of PittsburghMedical Center, Pittsburgh, PA
gsuicide.pitt.edu
'A silent epidemic'
About 800,000 people die by suicide annually worldwide
48,000 in the US: 130 suicide per day
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In most countries suicide rate is highest among the elderlyWhich of the following populations has the highest suicide rate?
•Men aged 85-89
•Women aged 25-30
•Women aged 60-65
•Men aged 35-40
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True 0r False?In late-life
•Depression is expected
•Quality of life declines
• Satisfaction with life increases
•Decline in crystalized intelligence is expected
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Late-life suicide attempts:"Failed suicides”
• Elderly suicide attempts best in vivo window to death by suicide
• high proportion of medically serious (high lethality) attempts
• Attempt/suicide rate: 4:1 in elderly;
• 10-100: 1 in general population
High mediclate-life
al severity in attempts
Participants: unipolar, non-psychotic,in- and outpatients
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Affective disorder
50-70% of those who die by suicide have current affective disorder (i.e. depression, bipolar)
20-45% of those who die by suicide have
prior suicide attempt
Suicide attempt
Suicide
10% life-time suicide
10% of the attempters die by suicide within 10 years
12 months after an attempt, rates of suicide 37x higher than in matched general population cohort (Olfson, 2017)
Pittsburgh Longitudinal Study for Late-Life Suicide
• Decision-making processes and cognition in late-life suicidal behavioral• Depression, suicidal ideation, suicide attempt, physical health changes over
time
• Attempters, Ideators, Depressed controls, Healthy controls• 70% of those who die by suicide have mood disorder at time of attempt
• Inclusion:• 55+ years of age
• Current depression with or without current suicidal ideation
• MMSE > 21
• No history of stroke, neurological disorder
• No history of psychotic d/o or bipolar
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Socio-CulturalProcesses
Family / EnvironmentalFactors
Intra-Psychic Mechanisms / Temperament
CognitiveNeuroscience
SystemsNeuroscience
Genetics / Molecular Neuroscience
Neuropathology / Neurochemistry
Level of investigations to suicidal behavior
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Who is vulnerable and when?Stress-Diathesis
Model of Suicide (j. Mann)
Cognitive deficits and Late-Life Suicide
• Cognitive and decision-making deficits may contribute to the accumulation of stressors and the perceived/actual inability to solve them.
• Particularly important role due to both normal age-related cognitive decline and dementia
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Early observations/Lab findings:
Williams: Entrapment limits ability to problem solve
1959
Baumeister: Cognitive Deconstruction (concrete, rigid, short-sighted).
1990
2009
Gibbs: Older attempters self-describe as deficient problem solvers
2015
Lower IQ/School performance - attempted and completed suicide decades later (Gunnel 2004, Andersson 2008; Batty
2010, Sorberg 2012, Hung 2015).
Bartfai: Suicidal pts had significantly lower scoresin verbal anddesign fluency.
2001
Keilp: Late Life High-Lethality suicide attempters exhibit worse cognitive control
2005
Jollant: Impaired decision making in attempters
Overlapping contributors to low IQ - also risk factors for mental illness & suicide
Association between low IQ and suicidal behavior is mitigated but remains after adjusting for parental SES, the young adult’s alcohol abuse, smoking status, and mental illness (Batty, 2010)
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With age comes wisdom and cognitive changes,Late-onset depression – as behavioral symptom of dementia
From Dunn & Cassidy-Eagle, Eds (2020)
Depression
Dementia
Taiwan: Elderly who attempted suicide were prone
to developing dementia (Tu, 2016). Late-onset
attempters had a seven-fold increased risk for
subsequent dementia compared to older adults
without a late-life suicide attempt. (Tu, 2016).
Suicide attempters with greater white matter hyperintensities had impaired executive function. Elevated global and periventricular white matter hyperintensities in suicide attempters with LLD. (Li, 2021)
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Dementia and MCI
• Erlangsen, 2008: suicide rate elevated in those diagnosed with dementia, even after controlling for the effect of mood disorders. The risk is highest months after the diagnosis, but remains elevated for years.
• Gunak, 2021: Risk for attempt is significantly higher with a diagnosis of recent MCI (HR:1.73 (CI, 1.34-2.22), and with recent dementia (HR: 1.44 (CI,1.17-1.77).
Dementia, Personality change, Depression, & Suicide
"Robin's was one of the worst Lewy body pathologies [the doctors] had ever seen. […] The massive proliferation of Lewy bodies throughout his brain had done so much damage to neurons and neurotransmitters that in effect, you could say he had chemical warfare in his brain."
-Susan Schneider Williams, "The terrorist inside my husband's brain", Neurology 2016
In hippocampal sections larger number of amyloid deposition and Lewy bodies in suicide brains than in controls (Rubio, 2001)
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• Inhibition deficits: Mid-life HL attempters Keilp, 2001, 2008
Late-life HL attempters, Richard-Devantoy, 2015
• Rule-learning/cognitive flexibility: mid-life and late-life HL attempters (Keilp, 2001, McGirr, 2012)
• Gambling tasks:• Risky choices: in violent attempters, Jollant, 2005
• Choosing unlikely gambles: Clark, 2012
• Impaired reversal learning: in HL attempters, Dombrovski, 2010
Cognitive deficits in older attempters persist after remission of depression and prospectively predict SB
Gujral, S. et al. Course of cognitive impairment following attempted suicide in older adults. Int. J.
Geriatr. Psychiatry 2016.
Szanto, K.,et al.,. Pathways to late-life suicidal behavior: Cluster analysis and predictive validation of
suicidal behavior in a sample of older adults with major depression. J. Clin. Psychiatry 2018..
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C-1: cognitive and dispositional risk factors, and late-onset depression: suggesting a dementia prodrome
HDRS
EXIT
DISCOUNTING
SUNK COST
FRAMING
CARELESSNESS
URGENCY
BURDEN
SELFESTEEM
BELONGING DRS
T.SUPPORTCluster 1
Cluster 2
Suboptimal decision making
• Comorbidity withaddiction, gambling
• Key brain areas related
to value-based decision-making (vmPFC) seem tobe affected in attempted& completed suicide(Arrango 1997; Oquendo 2003;Monkul 2007)
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To know how to grow old is the master-work of wisdom, and one of the most difficult chapters in the great art of living.
Wisdom doesn't necessarily come with age. Sometimes age just shows up all by itself.
Aging & Decision Making
Integrity vs. Despair (Erikson)
Intellectual growth should commence at birth and cease only at death Albert Einstein
Experience, learned heuristics, emotional maturity, shift in self-regarding vs. other-regarding motives.
Positivity bias, however, it may increase the likelihood that elderly are more likely to fall to prey to scams.
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• Elderly use less information and take longer to process it
• Crystallized intelligence remains while fluid intelligence declines
• Use simpler, less cognitively demanding strategies
• Impaired processing information about alternatives, probabilities, risks, rewards.
• Positivity bias, however, it may increase the likelihood that elderly are more likely to fall to prey to scams
Attempters perform poorly on the IOWA gambling task
Meta-analysis Richard-Devantoy, 2014
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Performance on the Iowa Gambling Task:VmPFC Lesion patients, Older adults, Violent suicide attempters.
Left top/bottom: Denburg et al. (2007) Right: Jollant et al. (2005)
Meta-analysis of cognitive markers Richard-Devantoy et al. 2014, 25 studies, 2300 participants
Suicide Attempters vs. Patient ControlsTest Effect size
(Hedges’g)
Significance
Decision making Iowa Gambling Task
Moderate (- 0.47) p < 0.001
Verbal FluencyAnimals
Moderate (- 0.32) p < 0.05
InhibitionStroop
Moderate (- 0.37) p < 0.01
Suicide attempters performed worse in
Making decisions in conditions of uncertainty
Generating words restricted to a given category
Override automatic responses
Cognitive control is the strongest and most consistent cognitive deficit found among suicide attempters, particularly among high-lethality attempters.
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Stability of Findings/ Extension of Initial Studies
Huber, 2019:Review shows that 79% of studies
with a patient control group showed significant cognitive
deficits in SB groups..
Bredemeier, 2015: Executive function and suicidality: A systematic qualitative review.
75% of studies that used depressive disorder samples vs.
54% of mixed diagnostic samples positive findings.
Saffer, 2018:Neurocognitive abilities
(inhibition, decision-making) distinguish attempters from
ideators.
Perrain, 2021:Meta-analysis confirmed riskier
decision-making in suicide attempters (regardless of mood disorder type or age); however, effect sizes were smaller than in
initial studies.
Late-life:Age-related reductions in cognitive abilities may further impair processing of alternatives, probabilities, risks, rewards, social context.
3-arm bandit (Dombrovski, 2018)
Delay discounting (inconsistent responding) (Types, in press)
Social cognition (Szanto, 2012),
Decision competence (framing effect, sunk cost: Szanto, 2015)
Considering social context (Szanto, 2014, Zhang, 2019)
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Due to normal age-related cognitive decline and dementia: are cognitive deficits particularly relevant risk factor for older attempters ?
From Buerke et al., JAD, in press
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Suicidal behavior is heterogeneous- thus, single biological vulnerability is unlikely.
• Heterogeneity among suicide attempters:
• Related to:
• Method of the attempt (violent vs non-violent)
• Medical seriousness of attempt
• Impulsive vs planned attempt
One dimension of heterogeneity may be age of onset of first lifetime attempt.
Chang et al., in progress
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Age at first suicide attempt is a marker for different subtypes of suicidal behavior
findings from the Pittsburgh longitudinal studies
Attempters
L ate- OnsetEarly- Ons et
Personality traits (neuroticism,
introv ers ion, and cluster B traits )
Real- life negativ e decision-making ,
financial, legal, interpersonal
Worse cog nit iv e funct ions
(g lobal cog nit ion, process ing speed,
and m em ory)
(Kenneally et al., 2019) (Szücs et al. 2020) (Perry et al. 2021) (Gujral et al. 2020)
PositFivaemfailmyily hx aggroefgsautiocindoef,of suiMcidoereasttoecmiapl t
andtrsaunicsimdeis, sSioocnial transmission
*
* * *
**
Late-Onset and Early-Onset attempters show worse executive functioning (set-shifting) relative to non-suicidal depressed
older adults
DK
EFS
Trai
lMak
ing
Test
Non-Psych
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NS Depressed
67Ideators
63EO Attempters
48
LO Attempters
44
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RB
AN
SD
ela
yed
Me
mo
ry
Non-Psych NS
Depressed
Ideators EO
Attempters
LO
Attempters
Depressed older adults with Late-Onset suicide attempts exhibit worse memory performance than those with Early-
Onset attempts and those without depression.
RBANS: Repeatable Battery
of Neuropsychological Status
*
Late-Onset attempters show worse global cognitionrelative to non-suicidal depressed older adults.
RB
AN
STo
talS
core
Non-Psych NS
DepressedIdeators EO
Attempters
LO
Attempters
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Cui, in press C
Cognitive/DM deficits: Biomarkers for suicidal behavior?
• Worse cognitive function consistently observed in attempters compared to psychiatric comparison groups
• Can be objectively measured
• Present in unaffected relatives (Ding et al., 2017; Hoehne et al., 2015)• Heritable trait markers?
• Present even when depression remits
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Cognitive/DM deficits are risk factors that differentiate attempters from ideators - in contrast to most well-known risk
factors that do not
Low Self Esteem
High Neuroticism
Hopelessness
Lack of Belonging
Burdensomeness
Current Substance Use
• “Cognitive deficits may be a transdiagnostic risk factor for SB,especially alterations in cognitive control” (Huber, 2019)
• Accumulating evidence that cognitive deficits are trait biomarkers of suicidal behavior, that worsen with aging• More research is needed in adolescence
• Cognitive deficits and DM give information about subtypes of attempters that may need different treatment.
• Age at first suicide attempt is useful for understanding the clinical/cognitive and broader biological heterogeneity of suicidal behavior.
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Summary:
•Cognitive deficits include difficulty shifting attention from compelling but inappropriate stimuli, predisposition to attend to prepotent emotional states, narrowed view of the situation, and reduced consideration of alternatives in a crisis.
• Cognitive and decision-making deficits may contribute to the accumulation of stressors and the perceived inability to solve them.
COVID-19 and Suicide Rates,Perfect storm for mental health consequences?
• Neuroinflammation, Social isolation, Bereavement, Financial difficulties, Disruption in services related to mental health and physical health.
However:
• During the COVID-19 pandemic in the US, death by suicide declined
• In Japan, a 20% decrease in suicide rates was reported in the early months of the pandemic. Similarly to 12 other countries who reported data (Pirkis, 2021).
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Why do suicide rates decline during crises?
• Durkheim’s Anomie in a Time of Crisis speculates why suicide rates may decrease due to an "anomic division of labor" and sense of unity within communities (Durkheim, 1893)
• Increased social cohesion in crises so people who are otherwise marginalized may receive more social support
• Resilience in older adults?• (i.e. WWII, 1973 oil crisis, Vietnam War, 2008 housing crisis)
Why do suicide rates decline during crises?
• Large scale crises may lead to increased social cohesion short-term
• Marginalized people may receive more social support
• Previous life stressors may become less urgent
• Life may feel more precious
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Difficulties in Treatment Engagement during Covid
• Logistic challenges (i.e. technology barriers)
• COVID-19 health concerns in-person
• Ability to deliver services virtually
• Virtual assessment & rapport challenges
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Black –box warning - FDA meta-analysis conclusions
100,000 patients in RTCs
• Ages 65 and older: strong protective effect of antidepressants (Odds Ratio: 0.37, p=0.007)
• 26-64: results initially inconclusive: OR: 0.79, p=0.03
• 25 and younger: may increase risk, OR: 1.62, p=0.07
• No studies in non-unipolar depression.
Generalizability: Age-specific effect, antidepressants reduce long-term suicide risk especially in mid-and late-life
Treatment and Prevention
• Talk about suicide explicitly – destigmatize, use structured assessments, assess family and personal history of suicide
• Be aware of different pathways to suicide
• Assess diathesis (including cognitive performance) and state (depressed mood, psychosis, substance use, intoxication, psychosocial)
• Reduce access to lethal means
• Be aware of clusters/media exposure
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Treatment and Prevention
• Known treatments• Self-help (i.e. exercise)• Therapy and counseling• Medication (i.e. antidepressants, antipsychotics)
• Brain stimulation (i.e. ECT, TMS)
• New approaches• Ketamine• Social engage therapy
Problems in treatment
poor communication with another therapist
permitting patients or relatives to control the
therapy
avoidance of issues related to sexuality
ineffective or coercive actions resulting from the therapist's
anxieties
not recognizing the meaning of the patient's
communications
untreated or undertreated symptoms
Hendin et al., Malsberger, Szanto AJP 2006
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• 50% of psychiatrists experienced the suicide of their patients• Distress after the suicide related to:
• Failure to hospitalize an imminently suicidal patient who then died
• Treatment decision the therapist felt contributed to the suicide
• Negative reactions from the therapist’s institution
• Fear of a lawsuit by the patient’s relatives
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New findings from the Pittsburgh Longitudinal Research Program in Late-Life Suicide: Implications for identification and treatment / Q&A
• Presenters:• Katalin Szanto, MD, Professor of Psychiatry Department of Psychiatry
University of Pittsburgh, Pittsburgh, PA• Emma J O'Brien, BA, Research Specialist University of Pittsburgh Medical
Center, Pittsburgh, PA
• Elizabeth Schumacher, BS, Research Specialist University of PittsburghMedical Center, Pittsburgh, PA
gsuicide.pitt.edu
Thank you! Questions?
We appreciate your referrals to the Pittsburgh Late-Life Suicide Study!
(412) [email protected] gsuicide.pitt.edu
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