INVITED COMMENTARY Diagnosing and Treating Depression Earlier and Preventing Recurrences: Still Neglected After All These Years John F. Greden, MD Address University of Michigan, D epartment of Psychiatry, 1500 East Medical Center Drive, MCHC, 6246, Ann Arbor, MI 48109, USA. E-mail: gredenj@ umich.edu Current Psychiatry Reports 2004, 6: 401–402 Current Science Inc. ISSN 1523-3812 Copyright © 2004 by Current Science Inc. More than 8 years ago, the World Health Organization doc- umented that depressive and bipolar illnesses were the most burdensome and disabling of the world’s medical disorders [1]. This undesirable distinction existed despite four decades of advances in neuroscience, the availability o f mo re than 40 antidepressant and mood stabilizing medications, at least two effective psychotherapies (cognitive behavioral therapy and interpersonal therapy), and an array of studies showing that combinations of pharmacotherapy and psychotherapy probably work better than either alone [2,3]. What accounts for our prolonged failures to make meaningful public health reductions in the burdens of depressive and bipolar illnesses during the past 40 years? Greden [4] listed eight intertwined contributions: wide- spread prevalence, early symptom onset, underdiagnosis and undertreatment, stress-genetic effects [5], poor treat- ment adherence and stigma [6], frequent recurrences and worsening course with time, inadequate attention to recur- rence prevention [7], and brain morphologic changes in those with chronic illnesses, apparently as a result of altered neurogenesis [8,9]. Three of these causes are attacked primarily by estab- lished pillars of preventive medicine, namely diagnosing earlier, treating earlier and effectively, and preventing recurrences. Sadly, each remains neglected for depression and bipolar disorders. We have known for decades that onset peaks for depres- sion and bipolar symptoms between 15 and 24 years [10], that the larger 12-month prevalence of depression among women results largely from their higher risk of early onset [11], that undertreatment for all types of depression is the prevailing national pattern in America [12], and that when early onset is undetected and untreated, the patient is at greater risk for major problems in subsequent years [13]. Experts in the treatment of comparable chronic dis- eases such as cardiovascular disorders have clearly docu- mented the benefits of early diagnostic screening and preventive interventions such as exercise, low-dose aspirin, and statins. Similar principles using different treatments should be applied to depressive and bipolar illnesses. However, routine care still emphasizes starting treatment for major depressive disorder and bipolar disorder only after the “first diagnosed episode.” Unfortunately, a “first episode” diagnosis of depression commonly is made only after years of incipient, progressively worsening symptoms or a series of gradually worsening minor episodes of depression or hypomania. Sometimes, diagnoses of dys- thymia or adjustment reactions have been given, but more often than not, these diagnoses obfuscate the future course and lead to “watchful waiting” rather than active treat- ment. Years later, by the time a “first episode” is diagnosed, underlying brain “sensitization and kindling,” cycle accel- eration (greater frequency of episodes), hypothalamic- pituitary-adrenal dysregulation, clinical chronicity, treat- ment resistance, and hippocampal and amygdala changes [8,9] already have done considerable damage. Such changes seem analogous to the cardiovascular conse- quences that follow years of elevated cholesterol and hypertension. Is it not time to learn from our cardiovascu- lar colleagues that the onset of symptoms or abnormal lab- oratory variables (which perhaps we should start reemphasizing) for those with genetic vulnerabilities is the optimal time to begin interventions, rather than waiting to make an arbitrary nosological diagnosis that relies on severity or duration thresholds? Earlier preventive treat- ment is better treatment. Greater attention to detailed fam- ily histories should be emphasized while we continue to search for usable genetic testing. Confounding the problems of failure to screen and treat earlier for those at highest risk is that when “first epi- sodes” are diagnosed, they routinely are not treated to the point of remission and few receive ongoing treatments to prevent recurrences despite strong evidence that the longi- tudinal courses are checkered with recurrences. Again, the consequences are profound. Judd et al. [14] reported that those with residual symptoms after treatment reported