Senior’s Suicide Tied to Brain Signaling Defect

Published: Aug 11, 2013

By Salynn Boyles, Contributing Writer, MedPage Today

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

Action Points

·         Impaired signaling in a region of the brain associated with decision making and reward was linked to an increased risk of suicidal behavior in depressed older people.

·         Note that the finding reinforces the idea that impaired decision competence is a significant contributor to suicidal thoughts and actions.

Impaired signaling in a region of the brain associated with decision making and reward was linked to an increased risk of suicidal behavior in depressed older people, new brain imaging research showed.

Impulsivity and a history of suicide attempts in older, depressed subjects was associated with a weakened reward signal in the paralimbic cortex, as measured by functional magnetic resonance imaging (MRI), according to a study published online in the journal JAMA Psychiatry.

A similar disruption in reward signaling has been shown in people with addictions to drugs and gambling, and the finding reinforces the idea that impaired decision competence is a significant contributor to suicidal thoughts and actions, said researcher Alexandre Y. Dombrovski, MD, associate professor of psychiatry at the University of Pittsburgh.

"In the clinic, decision competence has been largely neglected when evaluating patients (for suicide risk)," he told MedPage Today. " But it is emerging as an important risk factor for suicide and also addiction."

Depressed elderly patients in the study also exhibited disrupted corticostriatothalamic encoding of unpredicted rewards, which in turn predicted behavioral oversensitivity to punishment.

The identification of these two neural patterns associated with disrupted control over reward-guided behavior suggests that the common view of suicide as a deliberate and strategic choice may be faulty in depressed, older people, Dombrovski said.

"This research together with existing evidence suggests that moment to moment decisions may be just as important contributors to suicide," he said. "This means that in suicidal crisis, very small distortions in how people react to conflict, punishment or pain can make the difference."

The study involved 53 people who were age 50 or older, including 15 depressed patients who had attempted suicide, 18 depressed patients with no history of suicide attempts and 20 psychiatrically healthy controls.

While undergoing functional MRI, the study subjects participated in tests designed to assess reward learning behavior.

On each of 300 trials, the participants were asked to choose between two pictures, such as a picture of a house or dandelion. One picture had an 80% probability of reward, while the other was associated with a 20% reward probability. Every 25 trials, however, the reward probability between the two pictures was switched.

"On this task, one needs to trade off staying with the previously reinforced stimulus despite occasional misleading (probabilistic) feedback and switching when a true reversal occurs," the researchers wrote. "The tendency to stay too long after reversal while ignoring negative feedback leads to perseverative errors. Conversely, the tendency to switch after a single misleading punishment results in probabilistic switch errors, previously linked to depression."

To estimate abstract reward signals from the participants' reinforcement history and behavior, the researchers developed a computational predictive model based on the Rescorla-Wagner reinforcement learning model.

Impulsivity was assessed using several standard measures including the Impulsive/Careless Style subscale of the Social Problem-Solving Inventory, the Nonplanning and Attention/Cognitive subscales of the Barratt Impulsiveness Scale and bets against the odds on the Cambridge Gamble Task (CGT).

The study revealed that depressed participants whose paralimbic structures were less responsive to expected reward were more likely to ignore negative feedback after reversal.

"Confirming our hypothesis in depressed participants, weak paralimbic response to high expected reward was related to nonplanning impulsivity (r₂₇ = −0.43 [P = .03]; after excluding one outlier, r₂₆ = −0.50 [P = .01]) and bad choices on the CGT (ρ₂₇ = 0.50 [P=.01])," the researchers wrote. "The correlation with impulsive/careless problem-solving style was not significant (r₃₁ = −0.20 [P=.29]) but became more apparent after excluding one outlier (r₃₀ =−0.43[P=.02])."

The failure to track reinforcement history accurately was seen mostly in study participants who had made unplanned suicide attempts.

The tendency of depressed study participants to overreact to negative feedback was related to blunted representation of positive prediction errors in the cingulo-opercular and frontoparietal networks (r₃₃ = -0.40 [P=.02]).

"As a group, depressed participants displayed weaker modulation by positive prediction error in the right thalamus, bilateral superior temporal gyrus, bilateral operculoinsular cortex, bilateral postcentral gyrus and the bilateral supplementary motor area (P<.05), and these effects were not related to a history of suicide attempts," the researchers wrote.

The study was funded by the National Institutes of Mental Health and the Foundation for Suicide Prevention.

The findings suggest that clinical interventions targeting impulsivity and impaired reward signaling could reduce suicidal behaviors in elderly, depressed people, Dombrovski said.

"Perhaps we can construct an environment for these people that would make the suicide option harder by stressing positive behaviors such as hope and coping," he said.

This research was funded by grants from the National Institute of Mental Health and the American Foundation for Suicide Prevention.

The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review or approval of the manuscript.

Primary source: JAMA Psychiatry
Source reference: Dombrovski AY, et al "Reward signals, attempted suicide, and impulsivity in late-life depression" JAMA Psychiatry 2013; DOI: 10.1001/jamapsychiatry.2013.75.

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