In this large sample of youth with BP spectrum disorders, both adolescent groups had their first episodes meeting criteria for major depression, and were more likely to have a lifetime history of a major depressive episode. In contrast, younger children were more likely to have had subsyndromal manic/hypomanic symptoms as their first episode. After adjusting for sex, SES, and duration of illness, more “typical” and severe symptomatology was observed in both adolescent groups while manic, especially those with adolescent-onset BP. In contrast, mood lability was more frequent in children and adolescents with childhood-onset BP than adolescents with adolescent-onset BP. While depressed, also both adolescent groups showed more severe depressive symptoms and higher rates of melancholic, atypical depressive symptoms, and suicide attempts than children with BP. Irritability was the only symptom that was moderately higher in depressed children when compared with adolescents with adolescent-onset BP.
As expected, earlier-onset of BP was most commonly associated with lifetime comorbid ADHD. In contrast, older age was associated with higher rates of lifetime panic, conduct, and substance use disorders.
Before discussing the above-noted results it is important to note the limitations of this study. First, recollection bias may have influenced the reported rate of symptoms. However, to minimize this problem this study focused on the worst lifetime (present or past) manic and depressive symptoms. Second, the frequency and quality of the symptoms may change from one episode to the next and may vary with the reporter (child vs. parent) 24
. Future papers using prospective longitudinal data will address the two above-noted issues. Third, the base rates of some symptoms (e.g., lifetime delusions) were low. Fourth, the data analyzed for this report included only the worst lifetime (current or past) symptoms. These symptoms did not necessarily represent the mood symptomatology experienced by the child during her/his first mood episodes. Fifth, as depicted in and , some symptoms, although significantly different, showed low effect sizes. Nevertheless, even if these symptoms are not taken into account or after adjusting for multiple comparisons, the main story of this paper holds: older age was associated with more typical and severe manic and depressive symptoms. Sixth, lifetime comorbid disorders were not necessarily present during the same time period as the worst mood symptoms. Nevertheless, after adjusting for duration of illness, the types and rates of comorbid disorders follow the expected developmental trajectory (e.g., more ADHD in childhood-onset BP and more SUD in adolescents). Finally, since most subjects included in this study were recruited from outpatient clinics and were Caucasian, the results of this study may not apply to other populations.
It appears that mood lability, as defined in this study by the K-MRS19
(“rapid mood variation with several mood states within a brief period of time which appears internally driven without regard to the circumstances”) and to a lesser degree irritability/anger, are more characteristic of childhood-onset rather than adolescent-onset mania even when adjusting for potential confounding factors such as comorbid disorders. Mood “swings” or lability is often described by parents of children with BP and has been reported in other cross-sectional and longitudinal prospective pediatric BP studies 16,2–5, 13
. However, it is important to note that these mood changes are not equivalent to the DSM “rapid cycling” classification and that not every child with severe mood lability, especially if the symptoms are not episodic, has BP. 4, 6, 7, 9, 25
In contrast with prior reports 11, 26, 27
, this study found that DSM manic symptoms were more severe in adolescents, particularly in those with adolescent-onset BP, than in children with BP. The reasons for this discrepancy are unclear, but it may be accounted for by methodological differences such as sample size, subject age, instruments used to ascertain symptoms, diagnostic criteria and thresholds used to classify a symptom as positive and counting symptoms that overlap between disorders as positive for two or more disorders without taking into account the overall clinical picture of the child. It is also possible that early-onset BP has a different trajectory than adolescent-onset BP which appears to be more similar to adult BP. Ongoing prospective follow-up of this early-onset group potentially will answer this question.
Speculatively, the greater prominence of cognitive elements of mania such as grandiosity may simply reflect the more advanced cognitive operations that are normatively associated with adolescent development. Also, differentiating abnormal grandiosity from normal fantasy is less difficult in adolescents that in younger children 7
. The presence of these symptoms and the increased ability of an adolescent to express his or her affective state as compared to a younger child may explain, at least in part, why it is easier and more acceptable to diagnose BP in adolescents than in children. However, it remains for future more refined neuropsychological research on prospectively observed samples to determine if very early onset of illness compromises the acquisition of more complex cognitive structures which in turn impact on the phenomenology of BP.
Both the duration of illness and the transition into adolescence affected the rates and severity of depressive symptoms with both adolescent groups having their first episode as major depression, higher rates of lifetime major depressive episodes and more melancholic and atypical depressive symptomatology and suicidality when compared to children. In contrast, children showed less severe depressive symptomatology and more irritability. Thus, similar to the unipolar depression literature, the expression of major depression seems to be related to developmental pubertal changes and early age of onset 28–32
. There is only one other study that carried out a post-hoc analysis of the symptoms of BP depression in a sample of youth with BP depression and ADHD compared to youth with unipolar depression and ADHD. 33
This study reported higher familial loading for mood disorders and more severe symptomatology, suicide behaviors, anxiety, and conduct disorders in the depressed BP/ADHD youth.
The rates of lifetime comorbid disorders reported in this study are consistent with developmental correlates of psychopathological disorder with childhood-onset BP having higher rates of ADHD and adolescents showing higher rates of substance abuse, and conduct disorders than children. Also, comparable to other pediatric and adult studies of BP anxiety disorders were common across groups, with panic disorder being found most frequently in adolescents 34–36
. Interestingly, the rate of comorbid disorders in this study tended to be lower than those reported in some studies.4
This may be due to fact that in COBY, a comorbid diagnosis was not assigned if overlapping symptoms presented only during a mood disorder episode.
This and other studies have reported that early-onset BP has a somewhat different phenotype, higher familial load for mood disorders, and a different picture of comorbid disorders. 7, 9, 26, 37–39
These findings have suggested that early age of onset may carry a different genotype for BP that differentially influences disease phenotype, course, patterns of comorbidity, and functional outcome. However, we cannot determine from this analysis whether the differences found between child and adolescent age of onset subgroups are an independent effect of age when illness begins, or affected by susceptibility genes that confer early age of onset. However, interestingly, studies of adult BP have noted heterogeneity of linkage associated with psychotic features and anxiety 40
, as well as familiality of a range of phenotypic characteristics in families with BP 41
. Whatever the reason for these differences, it will be crucial for ongoing molecular, genetic, neuroimaging, and treatment studies to take into account the age of BP onset, maturational effects, as well as the presence of comorbid disorders and differential exposure to stress to fully explicate research findings.
In summary, older age was associated with more severe and typical mood symptomatology. However, there are differences and similarities in the type, intensity, and frequency of BP symptoms as well as comorbid disorders in youth depending, at least in part, on the age of onset and duration of their BP and their level of psychosocial development. These factors together with the normal difficulties children have expressing and modulating their emotions may explain the existing complexities in diagnosing and treating BP in this population and suggest the need for developmentally sensitive pharmacological and psychosocial treatments.
The presence of comorbid disorders and sometimes their respective treatments may further complicate the identification and treatment of BP and be associated with worse prognosis 42, 43
. Thus, it is critical that these disorders are identified and differentiated from the symptoms of BP, and if appropriate, promptly treated. For example, clinicians should be aware of the possibility that an adolescent with childhood-onset BP may also have ADHD since some symptoms of ADHD tend to improve with age (e.g., hyperactivity). Furthermore, the selective serotonin reuptake inhibitors are efficacious for the treatment of anxiety disorders in youth, but they may induce mood destabilization in youth with BP.
Clinicians should be aware that BP, particularly in adolescents, often initially presents with an episode of major depression posing an important clinical dilemma since the treatment of these youth with antidepressants may worsen their clinical outcome. In these cases the presence of psychosis, pharmacologically induced mania/hypomania, and high familial loading for BP may indicate increased risk to develop BP 44–46
. Finally, after puberty the frequency and severity of depression as well as potentially lethal suicide behaviors and substance abuse become more common, indicating the need for early identification and treatment of this disorder to avoid its serious consequences.