Family history of bipolar disorder itself is associated with a range of psychopathological problems compared to controls; the risk of bipolar spectrum disorder (BSD) may vary by as much as 24 times in children of the same bipolar disorder patient; children of bipolar disorder patients should be considered “ultra-high risk” if they present with mood swings and anxiety/depression symptoms This is especially true if the parent has an early onset of the disorder. Bipolar disorder is highly heritable and children of patients can be considered at high risk for bipolar disorder. In this context, researchers from the University of Pittsburgh and other institutions have explored symptomatological predictors of new-onset bipolar spectrum disorder (BSD) in “high-risk” adolescents at familial risk for bipolar disorder, based on data from the Pittsburgh Bipolar Offspring Study (BIOS). The study was published online Feb. 19 in the American Journal of Psychiatry. The study included 359 children aged 6-18 years of patients with bipolar I and II and 220 community control children. At baseline, 8.4% of the former group already had BSD, including bipolar I, bipolar II, and bipolar disorder NOS; after 8 years, that number rose to 14.7% (44/299), with 15 of them clearly having bipolar I or II. Using factor analysis, the investigators gradually narrowed the range of factors collected at baseline and during follow-up and explored the predictive value of the factors of interest for new-onset BSD. Their findings: 1. Compared to control children, children with high-risk BSD at baseline had significantly higher levels of anxiety/depression, attention-deficit/disinhibition, externalizing problems, subclinical mania, and mood lability, suggesting that a family history of bipolar disorder itself can contribute to a range of psychopathological problems; 2. The strongest predictors of new-onset BSD included baseline anxiety/depression levels, baseline and recent (within 2 years prior to onset) mood lability. The strongest predictors of new-onset BSD included baseline anxiety/depression levels, baseline and recent (within 2 years prior to onset) mood instability, and recent subclinical manic symptoms (p<0.05); 3. 5. Early onset of parental affective disorder (e.g., <18 years of age) was also significantly associated with an increased risk of child morbidity; 6. The risk of developing BSD for children without anxiety/depression, mood swings and mania (as well as late onset of mood disorders in one parent), i.e., the relatively "safest" children, was 2%, compared to 49% for those with all of the above risk factors. The researchers note that these findings are significant: studies have shown that a range of psychopathological symptoms are associated with a family history of bipolar disorder, but some of these symptoms are also predictive of BSD onset; such as anxiety/depression and mood lability, and once at-risk adolescents develop these symptoms, they should be alerted to conversion to BSD later in life, especially if their parents had an earlier onset of mood disorders. Over time, the persistence of mood lability in these adolescents, as well as the presence of manic symptoms, significantly increases the likelihood of developing BSD in the following years. From a clinical perspective, the relatively high specificity of these symptoms may help identify adolescents who may benefit most from early pharmacological/psychosocial interventions; from a research perspective, the definition of "ultra-high risk" may help identify potential biomarkers and facilitate the evaluation of early interventions. Such research may eventually lead to a definition of "prodromal bipolar disorder".