Hope and Depression

Hopelessness is a defining symptom of depression. It is also a risk factor for suicide independent of depression. To what extent does a depressed person’s inability to experience hope interfere with his ability to anticipate benefit from treatment? How much does this account for lack of motivation and treatment nonadherence? Are patients with depression able to experience placebo responses based on hope of benefit?

Among the issues Peter Kramer takes up in his latest book, Ordinarily Well: The Case for Antidepressants, is whether depressed patients experience what he calls classical placebo effects, that is, symptom improvement based on hopeful expectation of benefit from treatment. He argues from indirect evidence, mostly antidepressant discontinuation studies, that they do not. Bret Rutherford and his colleagues, whose work on expectancy I discussed last week , marshals other indirect as well as some direct evidence, in which expectancy was measured, to show at least some expectancy effect in antidepressant placebo responses. Rutherford’s group also references psychological studies of reduced response to monetary reward in patients with depression.

George Vaillant, in Spiritual Evolution: How We Are Wired for Faith, Hope, and Love, which I discussed several months ago, makes a number of cogent observations about hope: the ability to look forward to a better future is rooted in past experience of things getting better, which requires intact memory. Merely thinking of a better future is fantasy, which offers little comfort, while hope has a strong emotional element as well. He illustrates this with music: how much more convincing than the lyrics alone are songs like Bernstein’s “There’s a Place for Us,” Beethoven’s “Ode to Joy,” the civil rights anthem “We Shall Overcome,” and Paul McCartney’s “Let It Be.” He also argues that hope has an interpersonal aspect as well: while it can’t be given, it can be shared.

Fabrizio Benedetti, whose work on placebo responses I have discussed, notes difficulties in studying the neurophysiology of hope. Hopelessness is often considered together with helplessness, but they are not the same, even though animal models of “learned helplessness” are used in depression research. He notes that reduced binding to 5-HT2a receptors in the prefrontal cortex of suicide attempters is associated with higher levels of hopelessness, suggesting a role for serotonin.

A perusal of PubMed references to depression, hopelessness, expectancy, and reward does not turn up clear answers to the question of how a depressed patient’s limited ability to anticipate reward plays out in her seeking, accepting, and following through with treatment. Expectation may need to be distinguished from anhedonia, the inability to experience pleasure, since anhedonia may interfere with the expectation of future pleasure.

In my experience, depressed patients often doubt that treatment will help. Sometimes they personalize it—that even though other people respond to treatment, their own depression is uniquely untreatable. I try to address this belief directly, with words like, “I understand you think treatment won't help. You think that way because you're depressed. My experience treating patients and my knowledge of the research convinces me that treatment is very likely to help you. For now, you’ll have to take it from me on faith, but once you start to feel better I think you’ll feel more hopeful.” My sense is that patients sometimes identify, perhaps unconsciously, with my hope for their recovery, and that this provides some relief. That is reminiscent of Vaillant’s idea of sharing hope. It also implies that there is some part of the patient that is capable of relating to hope.

Hope, anticipation, and expectation seem easier to recognize and experience than to define and understand. Untangling their neurobiology will be a challenge. Memory, unconscious learning, the reward system, pleasure, and interpersonal comfort may all be involved. It seems likely that Kramer is partly right, that anticipation of benefit from treatment is impaired to some extent at least in some depressed patients, but that in some, the systems involved are at least partially intact.

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