At its worst, depression leaves few corners of the human mind unscathed. Many people suffering from this chronic illness lose their appetites, their ability to sleep normally, their sex drive, and the very ability to enjoy the simplest pleasures. Among the more conspicuous of the casualties is memory. Scientists are probing the connection between depression and memory-some in hopes of improving treatments, others to improve understanding of the deep connections between mind, mood, and memory. Using brain imaging techniques, we are even beginning to see some of those connections.

Hobbling the executive brain
Memory is but one of a suite of higher or "executive" brain functions hobbled by depression. In addition to becoming forgetful, a person suffering from major depression may have trouble initiating tasks, making decisions, planning future actions, or organizing thoughts. This is thought to trace to imbalances in the chemicals, called neurotransmitters, that enable individual brain cells to "talk" to each other and store new memories.

One of the ways that depression affects memory is by skewing the types of memories people tend to recall while in the grip of melancholy. We all tend to remember happy events when we are happy and sad events when we are sad, explains Norman Rosenthal, MD, a professor of clinical psychiatry at Georgetown University Medical School. A depressed person tends to recall mostly the negative, unhappy experiences. This can appear to family and friends as a loss of memory. It also reinforces the person's drab and negative view of life, fueling the depression.

Coordination of memory
It is also well known that depression impairs the ability to create long-term memories. It really comes down to a lack of attention and concentration, explains Constantine Lyketsos, MD, director of neuropsychiatry at the Johns Hopkins School of Medicine. For example, a depressed man agrees to meet a spouse or friend at a certain address. An hour later, he realizes he has "forgotten" the address. But perhaps due to a lack of attention and concentration-a hallmark of the depressed mental state-he never really formed an enduring memory of the address in the first place.

This type of event reflects a loss of coordination between working, short-term, and long-term memory. Imagine these forms of memory as a series of bins, explains Lyketsos. The working memory bin keeps track of events as they happen, but only for a short time. At a picnic, working memory registers your conscious experiences as you find a seat, eat, and watch the volleyball game.

But only a few of these experiences will become permanently stored in your brain. A few exciting or important events, such as a fantastic play in the volleyball game, might get passed from working memory into short-term memory-the bin where we store memories for minutes or hours. The rest of the events will fade, displaced from working memory by more recent events. Over time, some items in the short-term memory are moved into the final bin, long-term memory, where they may endure for a lifetime.

A depressed person, Lyketsos explains, may be too inattentive and unfocused to file passing events in short-term memory. In this case, it isn't so much that the depressed person has forgotten, but that the memory was never stored in the first place.

Restoring memory
Depression is a highly treatable condition. There are many approaches, including medication and psychotherapy, which can reduce depressive symptoms. Unfortunately, many "older-generation" antidepressant medications alleviated the mood disorder but made memory problems worse. It is hoped that today's generation of medications (SSRIs and MAO inhibitors) will be better able to treat depression with fewer side effects.

There is some scientific evidence that treating depression can indeed help reduce memory complaints. One recent study, conducted by Finnish researchers, involved 174 adults with major depression. At the start of the study, the depressed patients performed poorly on several neuropsychological tests of memory, including the ability to repeat short stories or lists from memory. For the next six months, the patients were given treatment for their depression, including medication and/or therapy. At the end of this period, patients whose depression had been reduced also reported fewer memory problems. Their performance on the memory tests also improved.