Experts Explore Memory as Key Target in Mental Disorders

by Ben Mauk

November 3, 2008

Memory nourishes human existence and informs every aspect of cognition, but its key role in a wide range of mental disorders often goes unremarked.

Two top experts in psychiatry and neuroscience made memory and its dysfunctions in disease the focus of a symposium Oct. 29 at the Pierre Hotel in New York, organized by the Harvard Mahoney Neuroscience Institute and moderated by Emmy Award–winning journalist Charlie Rose.

Memory “gets recruited in a variety of mental disorders,” said Eric R. Kandel, a Nobel Prize–winning professor at Columbia University and a senior investigator at Howard Hughes Medical Institute. The growing list includes such varied members as post-traumatic stress disorder, depression, addiction and schizophrenia, in addition to Alzheimer’s disease. “We now realize,” he said, “[memory] is something that is very susceptible to disease.”

Survival is automatic

Memory serves a vital evolutionary purpose. When one of our species’ ancestors found a food source or encountered a dangerous predator, its memory of the event and the results of any actions it took would influence how it would handle similar events in the future, according to Steven E. Hyman, provost of Harvard University and a professor of neurobiology at Harvard Medical School.

“These are systems in the brain that have to do with survival,” said Hyman. “Survival has to be automatic.”

The process of associating threatening or rewarding situations with an appropriate physiological response produces “implicit” memories, Hyman said, “outside of consciousness.” This is especially true of stressful events.

Stress changes how the brain records events, as hormones such as norepinepherin stamp in otherwise forgettable details. “We always remember where we were when Kennedy was shot,” noted Rose.

By removing the repressors in the brain that normally keep memory in balance, a stressful experience enables what Hyman termed “one-trial learning,” as when a child learns in one trial that he should avoid touching a hot stove and never forgets thereafter. Though vital to survival, this mechanism can go awry to debilitating effect.

Persistence of memory

“In some people, their system becomes too ‘sticky,’ ” Hyman said. “They experience a life-threatening situation,” such as a car accident or act of war, and memory of the incident “becomes intrusive.”

This stickiness describes post-traumatic stress disorder (PTSD). If Alzheimer’s disease is characterized by a deficit of memory, then post-traumatic stress disorder might be described as a surfeit, specifically of traumatic memories that provoke intense cognitive responses.

People who have PTSD exist in a state of constant physiological arousal, Hyman said. The amygdala, an almond-shaped structure in the temporal lobe of the brain linked to both memory and fear processing, becomes hyperactive during negative and even so-called neutral experiences, in which there is no threat. Other brain structures function improperly, as well.

 “Many diseases of the body [such as PTSD] are problems with homeostasis,” said Kandel, meaning that processes are overly excited or inhibited by an imbalance of chemicals, in this case neurotransmitters in the brain.

Such an imbalance occurs in clinical depression, another disorder touched on by the scientists that hinges on emotionally inappropriate responses to memories and events. In both PTSD and depression, researchers have identified some of the chemicals at work, from which they have developed therapies.

People with depression may improve with sessions of cognitive behavioral therapy (CBT), in which the patient and therapist aim to re-evaluate, among other things, the patient’s judgment of past experiences. Patients may also be prescribed pharmaceuticals, or a mixture of therapy and drugs.

“In depression, CBT works quite well,” said Kandel. Even without drugs, behavioral therapy influences brain chemistry, changing how a person experiences—and therefore remembers—events.

Similarly, people with PTSD can work with therapists to develop their ability to reappraise memories of traumatic events, de-emphasizing the stressful aspects and altering the memory itself.

Impermanence of memory

Researchers who study Alzheimer’s disease face the opposite challenges. Patients with this degenerative disorder lose both explicit, episodic memories and the implicit memories that enable us to walk around and communicate.

Outside of treatments that target only a small portion of those who have the disease, “there is no therapy out there” for Alzheimer’s, Kandel said. But a number of potential targets have been identified. These include the toxic clumps of beta-amyloid that cause inflammation related to cell death, as well as other protein structures that malfunction in brains that develop Alzheimer’s.

“We have the hope that we will have treatments in the next decade,” said Kandel, who is the author of the recent award-winning book In Search of Memory: The Emergence of a New Science of Mind.

When asked by Rose what memory-related question each scientist most wished he could answer, both agreed that, as Hyman said,  they would like “to understand for one of the major psychological disorders, say, autism or schizophrenia, exactly what goes wrong in the brain.” Not only would this enable treatments to alleviate suffering, but “these diseases,” Kandel said of the array of disorders discussed at the symposium, “get at the basis of human existence.”

Rose, who interviews politicians, artists and academics on his syndicated television show, added comments and posed questions throughout the evening. He was honored that night with the David Mahoney Prize, presented by the Harvard Mahoney Neuroscience Institute, for his work to increase public awareness of neuroscience and neurodegenerative diseases. The prize and institute are named for the former chairman and CEO of the Dana Foundation.