A: We were surprised to find changes in brain function so early in the course of treatment that were related to how a person improved many weeks later. For several decades, clinical scientists have wondered about the time lag of several weeks between starting to treat a patient with an antidepressant and the point when the person feels and looks improved; our data indicate that changes in brain function are happening soon after starting treatment, even though clinical improvement may take some time to be visible. These changes in activity were seen exclusively in the frontal parts of the brain, so future studies may need to examine these particular brain structures to determine how the brain changes lead to clinical improvement.

Our work is the first to report that the amount of change in brain wave activity was related to the amount of clinical improvement, so this is also surprising and new. It is an appealing concept - that brains that show a lot of change in response to treatment will translate this into a lot of improvement - but no one has measured this effect before. The cordance measure of brain activity appears to detect subtleties that other measures do not.

A: We don't yet know. In our report in Neuropsychopharmacology, we examined people treated either with fluoxetine (Prozac) or with venlafaxine (Effexor). These medications both affect the level of serotonin, one of the brain's chemical messengers or neurotransmitters; venlafaxine additionally affects the level of norepinephrine, another neurotransmitter involved in mood disorders like depression. We're currently examining other medications to see if they, too, show this pattern of early EEG change predicting later clinical response - particularly whether this holds for treatments in general or if it works only for serotonin-selective drugs. We don't yet have data on how psychotherapy ("talk therapy") may alter brain function, though others have looked at this question using other methods (PET scans, etc).

A: There are a number of implications, both for clinical care and for the development of new medications. Clinically, it may soon be possible to perform an EEG test before starting treatment and after a brief trial of medication, and say whether the patient is taking a medication likely to lead to improvement, or if the EEG is not changing in the way associated with remission. Showing the change would support continuing with that treatment, while not showing the change would suggest that a different treatment might merit a trial. Other researchers will need to try this technique in their own clinics to confirm our findings.

Another implication is that the discovery of new antidepressants might be accelerated with the technique. Rather than studying potentially-useful medications primarily with prolonged clinical experiments of 8 weeks or longer, it might be possible for researchers to see within a week whether or not a potential medication appeared to have antidepressant properties. The most promising candidates would then be studied in larger-scale trials. This might have an impact both on the time to develop new medications and on the cost.

A: Depression is a common illness that can return more than once. It can cause problems with work, at school, with family and friends, and with substance abuse. Some warning signs of depression include:

• no longer enjoying things that are normally fun
• feelings sad, down, or irritable most of the time
• trouble with sleep and/or appetite
• trouble concentrating
• withdrawing from family and friends
• feelings of guilt
• thoughts of death or suicide
• low self-esteem

Effective treatments CAN help relieve the suffering for depression and restore a person to wellness. This is best accomplished by working closely with a healthcare professional.

A: At this time, the cordance method to process the EEG recordings is a research tool; we hope that other researchers will confirm its usefulness in studying response to treatment for depression and that clinicians will be able to use it within the next few years.

Information about our current research projects in depression can be viewed here.

A: If you are in the Los Angeles area, there is a team of psychiatrists at UCLA who are skilled in helping people with depression. The number to call for an appointment is (310) 825-9989 or (800) 825-9989.

If you are not in the Los Angeles area, you may be able to find a referral to an appropriate mental health practitioner at www.mentalhealth.org from the US Department of Health and Human Services, or from the public information area of the American Psychiatric Association's website.

If you wish to participate in a research program, the National Institutes of Health has set up a web site www.ClinicalTrials.gov which lists many government-funded studies in depression.