Different types of psychosocial stressors have long been recognized as potential precipitantsof both unipolar and bipolar affective episodes and the causative agents in posttraumatic stressdisorder (PTSD). New preclinical data have revealed some of the neurobiological mechanismsthat could convey the long-term behavioral and biochemical consequences of early stressors.Depending on the timing, quality, quantity, and degree of repetition, maternal deprivation stress inthe neonatal rodent can be associated with lifelong anxiety-like behaviors, increases in stresshormones and peptides, and proneness to drug and alcohol administration, in association withacute changes in the rate of neurogenesis and apoptosis (preprogrammed cell death) anddecrements in neurotrophic factors and signal transduction enzymes necessary for learning andmemory. Patients with bipolar illness who have a history of early extreme adversity (physical orsexual abuse in childhood or adolescence), compared with those without, show an earlier onset ofillness, faster cycling frequencies, increased suicidality, more Axis I and Axis II comorbidities(including alcohol and substance abuse), and more time ill in more than 2 years of prospectivefollow-up. These findings are subject to a variety of interpretations, but to the extent that themore severe course of bipolar illness characteristics are directly and causally related to these earlystressful experiences, early recognition and treatment of high-risk children could be crucial inhelping to prevent or ameliorate the long-term adverse consequences of these stressors.