Bipolar disorder (BP) is a recurrent illness that usually has its onset during adolescence and is associated with substantial morbidity and impairment (1). Nonetheless, there is often a delay of up to a decade from the onset of the mood symptoms until proper diagnosis and treatment of BP (1, 2) increasing the risk of worse outcomes (2–4). Therefore, identification of early BP symptomatology could aid in earlier treatment and better psychosocial outcome. Retrospective studies of youth and adults with BP consistently indicate increased irritability, mood lability, subclinical mood and anxiety symptomatology, and behavior and sleep problems may be potential prodromal symptoms of BP (5–12). Of these symptoms, mood lability, defined as sudden, exaggerated, unpredictable and developmentally inappropriate changes in mood, is one of the strongest potential prodromal symptoms for BP. However, it is important to note that as used in the literature, mood lability is an umbrella term that captures pathological changes across several mood states including irritability. Among the studies that reported mood lability (or irritability) as a prodromal for BP, Angst and colleagues (7) in a large prospective adult community study reported that, independent of family history, unstable mood regulation was the strongest risk factor for BP. Also, Egeland and colleagues (13) in a well-characterized sample of 58 Amish bipolar I disorder (BP-I) adults whose medical records from childhood were available, reported that the most frequently symptoms included episodic changes in depressed, irritable, anger, and increased energy. In this study, there was a 9–12-year time interval between appearance of the first symptoms and the onset of the BP-I. Finally, Correll and colleagues (14) also reported a long symptomatic prodromal phase prior to the first manic episode manifested by mood lability (including anger outbursts), subclinical manic and depressed symptoms, anxiety, and social isolation. To obviate the biases encountered with retrospective investigations, and since the single most significant vulnerability factor for the development of BP is a family history of BP, studies have evaluated the prevalence of psychopathology in child and adolescent offspring of parents with BP. Using categorical as well as dimensional measurements, cross-sectional studies have reported higher levels of mood lability (including irritability and other rapid mood fluctuations), negative affect, depressed mood, anxiety, aggressive behaviors, and attention and sleep problems in offspring of parents with BP when compared with offspring of controls (8, 9, 12, 15–22). In the Pittsburgh Bipolar Offspring Study (BIOS) (18), from which the sample for the present study is derived, the offspring of parents with BP, particularly those offspring who already developed BP, had higher scores in the Total, Internalizing, Anxious/Depressed, Withdrawn/Depressed, and Aggressive Behavior scales of the Children Behavior Checklist (CBCL), the CBCL–Dysregulation Profile (CBCL-DP), and a sum of CBCL items associated with mood lability than the offspring of the control parents (17), independent of child and parental non-BP psychopathology. Using the Child Hostility Inventory, Farchione and colleagues (23) also reported high levels of irritability and hostility in the BIOS offspring of parents with BP when compared with offspring of the controls. The above literature suggest that mood lability and its components (e.g., irritability) as well the presence of subclinical mood and anxiety symptoms are a potential prodromal phenotype for BP. However, these symptoms, and in particular mood lability, are ubiquitous among psychiatric disorders (24–28). In fact, whereas some have found mood lability to be associated with the development of BP (5, 11, 14, 29–32), others have reported that it increases the risk for anxiety and depressive disorders, antisocial behaviors, and suicidality, but not BP (33–38). Thus, further investigations with more clear definitions or instruments to ascertain mood lability and its components are warranted to clarify the association of these symptoms with pediatric BP in high-risk populations without full-blown BP. Different methods have been used to ascertain mood lability such as single items and a composite of symptoms derived from instruments not specifically designed to ascertain mood lability, like the CBCL (e.g., 24, 26, 39–41). We therefore decided to use a parent-report (about their children) scale specifically developed to assess mood lability in youth, the Children’s Affective Lability Scale (CALS) (42). To compare and expand the original factor analysis of the CALS which was carried out with school children among whom there is less likelihood of mood symptomatology, and because the primary aim of our study was to identify prodromal symptoms of mania, a new factor analysis was performed. In this study, we sought to investigate the prevalence of mood lability and its components in non-BP offspring of BP parents, BP offspring of BP parents, and offspring of community control parents. These comparisons will help to clarify whether excessive mood lability only exists in the BP offspring of BP parents or is also increased in the non-BP offspring of parents with BP. Moreover, since some control parents are healthy whereas others have non-BP psychopathology, we will be able to evaluate if excessive mood lability is associated with having a parent with BP or is non-specifically associated parental overall psychopathology. Based on the literature and prior BIOS results it was hypothesized that after adjusting for confounding factors (e.g., effect of parental and offspring non-BP psychopathology) non-BP offspring of BP parents will have significantly higher scores on the parent and child CALS and its subscales than the offspring of community control parents. In addition, after adjusting for confounding factors, BP offspring of BP parents will show higher CALS scores than the non-BP offspring of BP parents and the offspring of the control parents.