Alexandre Y. Dombrovski

Lethal Forethought: Delayed Reward Discounting Differentiates High- and Low-Lethality Suicide Attempts in Old Age

BACKGROUND The decision to commit suicide may be impulsive, but lethal suicidal acts often involve planning and forethought. People who attempt suicide make disadvantageous decisions in other contexts, but nothing is known about the way they decide about the future. Can the willingness to postpone future gratification differentiate between individuals prone to serious, premeditated and less serious, unplanned suicidal acts? METHODS Four groups of depressed participants aged 60 and older made choices between smaller immediate and larger delayed monetary rewards: 15 who had made high-lethality suicide attempts, 14 who had made low-lethality suicide attempts, 12 who seriously contemplated suicide, and 42 people with depression, but no history of suicidal thoughts. The reference group was 31 psychiatrically healthy elders. RESULTS Individuals who had made low-lethality attempts displayed an exaggerated preference for immediate rewards compared with nonsuicidal depressed and healthy control subjects. Those who had carried out high-lethality suicide attempts were more willing to delay future rewards, compared with low-lethality attempters. Better planned suicide attempts were also associated with willingness to wait for larger rewards. These effects were unchanged after accounting for education, global cognitive function, substance use disorders, psychotropic medications, and possible brain injury from attempts. Discount rates were correlated with having debt, but were not significantly associated with income, hopelessness, depressive severity, premorbid IQ, age at first attempt, or choice of violent means. CONCLUSIONS Although clinicians often focus on impulsivity in patients at risk for suicide, these data suggest that identifying biological characteristics and treatments for nonimpulsive suicidal older people may be even more important.

Cognitive performance in suicidal depressed elderly: preliminary report.

OBJECTIVE Deficits in executive functions may play an important role in late-life suicide; however the association is understudied. This study examined cognitive function in general and executive functioning specifically in depressed elderly with and without suicidal ideation and attempts. DESIGN Case-control study. SETTING University-affiliated psychiatric hospital. PARTICIPANTS We compared 32 suicidal depressed participants aged 60 and older with 32 non-suicidal depressed participants equated for age, education, and gender. MEASUREMENTS We assessed global cognitive function and executive function with the Dementia Rating Scale (DRS) and the Executive Interview (EXIT25), respectively. RESULTS Suicidal and non-suicidal depressed groups were comparable in terms of severity of depression and burden of physical illness. Suicidal participants performed worse on the EXIT25, and on the DRS total scale, as well as on Memory and Attention subscales. The differences were not explained by the presence of dementia, substance use, medication exposure, or brain injury from suicide attempts. CONCLUSIONS Poor performance on tests of executive function, attention, and memory is associated with suicidal behavior in late-life depression.

The temptation of suicide: striatal gray matter, discounting of delayed rewards, and suicide attempts in late-life depression

BACKGROUND Converging evidence implicates basal ganglia alterations in impulsivity and suicidal behavior. For example, D2/D3 agonists and subthalamic nucleus stimulation in Parkinsons disease (PD) trigger impulse control disorders and possibly suicidal behavior. Furthermore, suicidal behavior has been associated with structural basal ganglia abnormalities. Finally, low-lethality, unplanned suicide attempts are associated with increased discounting of delayed rewards, a behavior dependent upon the striatum. Thus, we tested whether, in late-life depression, changes in the basal ganglia were associated with suicide attempts and with increased delay discounting. METHOD Fifty-two persons aged ≥ 60 years underwent extensive clinical and cognitive characterization: 33 with major depression [13 suicide attempters (SA), 20 non-suicidal depressed elderly] and 19 non-depressed controls. Participants had high-resolution T1-weighted magnetization prepared rapid acquisition gradient-echo (MPRAGE) magnetic resonance imaging (MRI) scans. Basal ganglia gray matter voxel counts were estimated using atlas-based segmentation, with a highly deformable automated algorithm. Discounting of delayed rewards was assessed using the Monetary Choice Questionnaire (MCQ) and delay aversion with the Cambridge Gamble Task (CGT). RESULTS SA had lower putamen but not caudate or pallidum gray matter voxel counts, compared to the control groups. This difference persisted after accounting for substance use disorders and possible brain injury from suicide attempts. SA with lower putamen gray matter voxel counts displayed higher delay discounting but not delay aversion. Secondary analyses revealed that SA had lower voxel counts in associative and ventral but not sensorimotor striatum. CONCLUSIONS Our findings, although limited by small sample size and the case-control design, suggest that striatal lesions could contribute to suicidal behavior by increasing impulsivity.

When the solution is part of the problem: problem solving in elderly suicide attempters

Depression, loss, and physical illness are associated with suicide in the elderly. However, the nature of individual vulnerability remains poorly understood. Poor problem solving has been suggested as a risk factor for suicide in younger adults. Unresolved problems may create an accumulation of stressors. Thus, those with perceived deficits in problem‐solving ability may be predisposed to suicidal behavior. To test this hypothesis, we investigated whether elderly suicide attempters perceived their problem solving as deficient.

Sex differences in correlates of suicide attempt lethality in late life

OBJECTIVE Suicide attempts are more lethal in men than in women and this sex difference is more pronounced in old age, when suicide rates in men are highest in most countries, including the United States. To understand this sex difference, the authors assessed correlates of suicide attempt lethality in older men and women. METHOD Our cross-sectional study enrolled 125 adults (84 aged 50-69 and 41 aged 70 and older) with major depression and a suicide attempt admitted to community and university hospitals in Rochester, NY. and Pittsburgh, PA. Assessments included a structured diagnostic interview, the Lethality Scale, the Suicide Intent Scale, the Cumulative Illness Rating Scale (CIRS) measuring burden of physical illness, and the Mini-Mental Status Examination (MMSE). RESULTS Attempt lethality was higher in older (70+) than in younger (50-69) men and lower in older than in younger women. Association between suicidal intent and attempt lethality was the strongest in older men compared with the other groups. Higher attempt lethality in older men was partly explained by their higher levels of intent, and not by CIRS, MMSE, substance use disorders, or living alone. In younger, but not in older women, suicide intent was correlated with attempt lethality. CONCLUSION Older men act more decisively on their suicidal intent than older women and this difference is more pronounced with increasing age. These findings might partially explain the sex differences in suicide deaths worldwide.

Empirically derived decision trees for the treatment of late-life depression.

OBJECTIVE Several predictors of treatment response in late-life depression have been reported in the literature. The aim of this analysis was to develop a clinically useful algorithm that would allow clinicians to predict which patients will likely respond to treatment and thereby guide clinical decision making. METHOD A total of 461 patients with late-life depression were treated under structured conditions for up to 12 weeks and assessed weekly with the 17-item Hamilton Rating Scale for Depression (HAM-D-17). The authors developed a hierarchy of predictors of treatment response using signal-detection theory. The authors developed two models, one minimizing false predictions of future response and one minimizing false predictions of future nonresponse, to offer clinicians two clinically useful treatment algorithms. RESULTS In the first model, early symptom improvement (defined by the relative change in HAM-D-17 total score from baseline to week 4), lower baseline anxiety, and an older age of onset predict response at 12 weeks. In the second model, early symptom improvement represents the principal guide in tailoring treatment, followed by baseline anxiety level, baseline sleep disturbance, and--for a minority of patients--the adequacy of previous antidepressant treatment. CONCLUSIONS Our two models, developed to help clinicians in different clinical circumstances, illustrate the possibility of tailoring the treatment of late-life depression based on clinical characteristics and confirm the importance of early observed changes in clinical status.

Alone? Perceived social support and chronic interpersonal difficulties in suicidal elders.

BACKGROUND Social networks may protect depressed elders against suicidal behavior. However, conflict in important relationships may undermine the sense of social support, potentially negating the protective effects. Thus, we investigated the role of chronic interpersonal difficulties and perceived social support in depressed elders with and without suicidal thoughts and attempts. METHODS 106 individuals aged 60 years and older participated in this cross-sectional, case-control study. They were placed in three groups: suicidal depressed, non-suicidal depressed and non-depressed. Following a detailed clinical characterization, we assessed perceived social support (Interpersonal Support Evaluation List), and chronic interpersonal difficulties (Inventory of Interpersonal Problems). Using general linear models, we explored the relationship between suicidal thoughts/attempts, social support, and chronic interpersonal difficulties. We also examined whether lower perceived social support explained the relationship between chronic interpersonal difficulties and suicidal thoughts/attempts. RESULTS Suicidal depressed elders reported the lowest levels of perceived social support (belonging, tangible support, and self-esteem) and higher levels of chronic interpersonal difficulties (struggle against others and interpersonal hostility), compared to both non-suicidal depressed and non-depressed elders. The relationship between chronic interpersonal difficulties and suicidal behavior was partially explained by low perceived social support. CONCLUSIONS The experience of strong affects, interpersonal struggle, and hostility in relationships may undermine the sense of social support in depressed elders, possibly leading them to contemplate or attempt suicide. Depressed elders with a history of interpersonal difficulties need to be carefully monitored for suicidal behavior.

Reinforcement learning models and their neural correlates: An activation likelihood estimation meta-analysis

Reinforcement learning describes motivated behavior in terms of two abstract signals. The representation of discrepancies between expected and actual rewards/punishments—prediction error—is thought to update the expected value of actions and predictive stimuli. Electrophysiological and lesion studies have suggested that mesostriatal prediction error signals control behavior through synaptic modification of cortico-striato-thalamic networks. Signals in the ventromedial prefrontal and orbitofrontal cortex are implicated in representing expected value. To obtain unbiased maps of these representations in the human brain, we performed a meta-analysis of functional magnetic resonance imaging studies that had employed algorithmic reinforcement learning models across a variety of experimental paradigms. We found that the ventral striatum (medial and lateral) and midbrain/thalamus represented reward prediction errors, consistent with animal studies. Prediction error signals were also seen in the frontal operculum/insula, particularly for social rewards. In Pavlovian studies, striatal prediction error signals extended into the amygdala, whereas instrumental tasks engaged the caudate. Prediction error maps were sensitive to the model-fitting procedure (fixed or individually estimated) and to the extent of spatial smoothing. A correlate of expected value was found in a posterior region of the ventromedial prefrontal cortex, caudal and medial to the orbitofrontal regions identified in animal studies. These findings highlight a reproducible motif of reinforcement learning in the cortico-striatal loops and identify methodological dimensions that may influence the reproducibility of activation patterns across studies.

Maintenance treatment for old-age depression preserves health-related quality of life: a randomized, controlled trial of paroxetine and interpersonal psychotherapy.

OBJECTIVES: To determine whether maintenance antidepressant pharmacotherapy and interpersonal psychotherapy sustain gains in health‐related quality of life (HR‐QOL) achieved during short‐term treatment in older patients with depression.

Impaired Executive Function in Contemplated and Attempted Suicide in Late Life

OBJECTIVE: Executive deficits may play an important role in late-life suicide. Yet, current evidence in this area is inconclusive and does not indicate whether these deficits are broadly associated with suicidal ideation or are specific to suicidal behavior. This study examined global cognition and specifically executive function impairments as correlates of suicidal ideation and suicidal behavior in depressed older adults, with the goal of extending an earlier preliminary study. DESIGN: Case-control study. SETTING: University-affiliated psychiatric hospital. PARTICIPANTS: All participants were age 60+: 83 depressed suicide attempters, 43 depressed individuals having suicidal ideation with a specific plan, 54 nonsuicidal depressed participants, and 48 older adults with no history of psychiatric disorders. MEASUREMENTS: Global cognitive function was assessed with Dementia Rating Scale (DRS) and executive function with Executive Interview (EXIT). RESULTS: Both suicide attempters and suicide ideators performed worse than the two comparison groups on the EXIT, with no difference between suicide attempters and suicide ideators. On the DRS total score, as well as on Memory and Attention subscales, suicide attempters and ideators and nonsuicidal depressed subjects performed similarly and were impaired relative to nonpsychiatric control subjects. Controlling for education, substance use disorders, and medication exposure did not affect group differences in performance on either the EXIT or the DRS. CONCLUSIONS: Executive deficits, captured with a brief instrument, are associated broadly with suicidal ideation in older depressed adults but do not appear to directly facilitate suicidal behavior. Our data are consistent with the idea that different vulnerabilities may operate at different stages in the suicidal process.