Clinical Highlights and summary of Chapter• Episodes of depression and bipolar illness progress in two ways:faster recurrences as a function of number of prior episodes, andgreater autonomy (decreased need for precipitation by stressors(Episode Sensitization)• Recurrent stressors result in increased reactivity to subsequent stressors(Stress sensitization) and bouts of stimulant abuse increase in severity with repetition(Stimulant-induced behavioral sensitization)• Each type of sensitization cross-sensitizes to the others and drives illness progression• Each type of sensitization involves specific memory-like epigenetic processes as well as nonspecific cellular toxicities• Childhood onset depression and bipolar illness have a more adverse course than adult onset illness and are increasing in incidence via a cohort (year of birth) effect• As opposed to genetic vulnerability, each type of sensitization can be prevented with appropriate clinical intervention and prevention, which should lessen illness severity and progression• Seeing depression and bipolar disorder as progressive illnesses changes the therapeutic emphasis away from acute treatment and instead to long term prophylaxis• Preventing recurrent depressions will likely protect the brain, the body, and the personWord count with Named refs = 6,417>Depression and bipolar disorder are illnesses which tend to progress with each new recurrence. Stressors, mood episodes, and bouts of substance abuse each sensitize (show increased reactivity) upon their repetition and cross-sensitization to the others. These sensitization processes appear to have a memory-like and epigenetic basis, in some instances conveying lifelong increased vulnerability to illness recurrence and progression. Greater numbers of episodes are associated with faster recurrences, lesser need for stress precipitation, cognitive dysfunction, pathological changes in brain, treatment refractoriness, and loss of many years of life expectancy, predominantly from cardiovascular disease. Such a perspective emphasizes the need for greater awareness of higher incidence of psychiatric and medical comorbidities in the United States compared to many European countries, and the need for earlier intervention and more sustained long term prophylaxis to prevent illness progression and its adverse consequences on brain and body.
The Challenges of Children with Bipolar Disorder