Abstract: Pediatric Bipolar Disorder BD is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania.
Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania.
In Between Euphoria and Melancholy
Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers.
Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder. E , later reported by Esquirol in the early s and then by Kraepelin and his contemporaries [ 1 ].
In recent times, converging evidence supports the notion that pediatric bipolar disorder is a highly morbid pediatric psychiatric disorder and that its prevalence is around 1. Pediatric BD PBD is consistently and significantly associated with family psychiatric history of mood disorders [ 3 ], with increased risk in subjects who have a loaded more than three members affected and a multigenerational family history of mood disorder or a family history of mania [ 4 , 5 ].
The diagnosis of PBD is complicated by a highly debated clinical picture and very high rate of comorbidity with other juvenile psychiatric disorders attention deficit and hyper- activity, oppositional defiant and conduct disorders with frequently overlapping symptomatology [ 6 ]. The clinical phenomenology and course of illness of PBD often differs from the classical episodic presentation of manic-depressive illness with clear cycling and periods of inter-morbid high functioning and instead often resembles the more severe and treatment resistant adult forms of BD with rapid-cycling course and mixed features with irritability, dysphoria and high risk of suicidal behaviors [ 1 , 6 , 7 ].
Age of onset can be identified during the preschool years with an age-dependent developmentally distinct symptomatology. Initial symptoms appearing during the preschool years often include irritability, moodiness, sleep. Course pattern is mostly rapid or ultra-rapid with frequent mood shifts during a same day, whereas the classical episodic course is less common during juvenile years [ 1 , 7 - 10 ].
Pediatric onset of BD is associated with elevated risks for substance abuse and addiction, anxiety, conduct and antisocial disorders, with high levels of morbidity and disability, as well as an increased risk of suicide [ 11 - 13 ]. Reported latency between initial affective symptoms and a first major affective episode in BD is 8—12 years, with up to another 9 years from a first affective episode to initiation of appropriate mood-stabilizing treatment [ 14 - 16 ].
More research is needed to identify early manifestation of pediatric mania in the youngest individuals, improve its differential diagnosis with other juvenile disorders such as ADHD and delineate the potential predictors of diagnostic stability and continuity between pediatric and adult bipolar disorder. According to the Diagnostic and Statistical Manual for Mental Disorders DSM V [ 17 ], mania can be characterized by a severe and impairing abnormal mood state that is either euphoric or irritable.
These two sides of mania have been observed and well described in clinical descriptions of bipolar children and adolescents. Euphoria is characterized by an elated, high-energy state with grandiose feelings and ideas. Children in this state appear cheerful, over-the-top funny, sometimes hilarious, and frequently show immature-giddy behaviors that are difficult to be contained by both parents and peers.
These children may also be grandiose with over-confidence, taking on unrealistic projects and defying adult authority to an extreme degree [ 18 ].
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The other mood state of mania is characterized by irritability. In adult patients, clinicians frequently diagnose impairing mixed states or dark mania with extreme irritability. In children or adults, these mood states can appear as nastiness, blaming, demanding, whining, or viciousness, characterized by explosive rages that can be physically abusive, destructive and dangerous [ 18 ]. Irritability, though highly debated as characteristic of many disorders, is as an important manic feature.
When occurring frequently and intensely, the quality and quantity of irritability can distinguish a bipolar diagnosis. Even in the presence of other classic symptoms of melancholy and euphoria, irritability is often the most impairing aspect of the clinical picture and often forms the chief complaint for referral to psychiatric services. Irritability without euphoria has been reported as the most common mood presentation in children presenting with PBD [ 7 ], with high levels of impairment and morbidity and is often associated with impulsive and reckless behaviors, violent gestures and impulsive suicidal thoughts, threats and behaviors [ 7 , 19 - 21 ].
Mixed states with high levels of irritability have been commonly reported in adults with bipolar disorder. For these patients, psychosis, aggressive behaviors and psychomotor agitation can be a primary cause of hospitalization [ 6 ]. From the identified articles, additional articles were noted in the reference sections. Of the articles, eighteen were identified which reported the number of subjects with either irritability or elation as the presenting mood symptom in samples of subjects younger than age 18 years old.
While all studies report high rates of both euphoria and irritability, 14 of the 18 studies report irritability as a predominant mood symptom. Eight studies provide information on cycling patterns, with rapid cycling or chronic course most commonly reported. Notes: a.
The rates of irritability, elated mood, and grandiosity were not significantly different between pre-pubertal and pubertal BD subjects; h. Irritable mood: BD vs. Elated mood: BD vs. Grandiosity: BD vs. In subjects with chronic course , the duration of the illness was at least 6 months , but usually the subjects remained clearly symptomatic for 1 or 2 years.
The Episodic course was more frequent in patients with elated mood, while Chronic course was more frequent in patients with irritable mood; l. Table 1 shows the prevalence of symptoms reported by parent only or child only or both informants; n. No difference were found between Irritable only vs.
Our report summarizing the predominant mood presentation in youth with mania supports the importance of irritability in diagnosing pediatric bipolar disorder. Some investigators [ 10 , 22 , 23 ] have argued that euphoria as opposed to irritability is unique to bipolar disorder and therefore should be considered the defining mood disturbance of bipolar children. Findings from two meta-analysis support this latter view and found high rates of irritability in all age groups with mania suggesting that irritability may be a marker of mania in children and that euphoria and grandiosity are usually less common in children than in adults [ 1 , 29 ].
The prevalence of irritable mood varies in relation to the inclusion criteria of the analyzed sample. In fact in some reports bipolar subjects had been included only if presenting with one of the two cardinal symptoms elation or grandiosity. Some studies reported a severity rating for these symptoms. Some authors reported that pediatric subjects with irritable mania are significantly younger than those presenting euphoric mania [ 30 , 31 ] and that the irritability score significantly decreased linearly with age [ 32 ].
Accordingly, retrospective studies found that irritability, mood lability and impulse dyscontrol may be the predominant psycho- pathological features of pediatric bipolar disorder at onset [ 33 , 34 ]. A possible explanation of this finding might be that irritability is generally a highly prevalent psychopathological feature during pediatric age. Moreover, several independent laboratories have shown that bipolar youth with predominantly irritable mood do not significantly differ from those presenting with euphoric mood in their profile of symptoms of mania, measures of social functioning and long-term outcome [ 20 , 35 ].
Some authors suggest that patterns of comorbidity may be different with prevalently irritable subjects, who have higher rates of comorbidity with ADHD and other externalizing disorders and a chronic course, whereas euphoric manic subjects more frequently show an episodic course and a comorbid anxiety disorder [ 30 ]. Despite debate regarding chronicity and episodicity in pediatric mania, only half the studies reviewed reported on number of episodes or cycling patterns. The duration of manic episodes can range from brief tantrum-like affective storms lasting minutes or hours to longer episodes persisting for several days or months.
The existence of very short episodes of mania lasting minutes or hours and the consequent identification of a ultra-ultra-rapid course pattern of pediatric bipolar disorder characterized by more than cycles per year at least one mood shift per day or ultra-rapid course pattern with 5— cycles per year is another highly debated point among authors analyzing pediatric mood disorder phenomenology [ 24 ].
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Current DSM-V criteria and also the previous DSM-IV criteria for mania include the duration criteria of at least 4—7 consecutive days of abnormal mood state respectively for hypomania and mania [ 17 ]. For this reason, many juvenile bipolar subjects are currently classified as Bipolar Not Otherwise Specified NOS for which several research groups have operationalized symptom criteria aimed at classifying brief and severe manic and hypomanic episodes [ 36 ].
Explosive temper outbursts that are considered by many authors as a common manifestation of short episodes of irritable mania, have been included in DSM-V as the new syndrome Disruptive Mood Dysregulation Disorder DMDD that is classified among unipolar depressive mood disorders with the aim of differentiating subjects presenting with chronic versus episodic irritability. This new category stands in contrast to the very high rate of ultra-ultra-rapid and ultra-rapid cycling bipolar course characterized by ultradian mood cycling described by several authors as the most common presentation of bipolar disorder during pre-pubertal and early adolescent age [ 7 , 9 , 24 ].
Moreover several longitudinal course studies showed that bipolar patients spend most of the time suffering from a sub-syndromal mixed and depressive symptomatology, miming the chronic mood dysregulation [ 35 , 37 , 38 ]. Patients with a chronic course were reported to be younger, mostly irritable when manic, with an earlier onset of BD and with more comorbid externalizing disorders when compared to juvenile subjects with an episodic bipolar disorder [ 39 ].
Findings from retrospective studies of adult bipolar disorder patients indicate that between one-third to more than half had experienced early psychopathological symptoms during childhood or adolescence [ 16 , 34 , 40 ]. Perlis et al. These reports suggest that pediatric mania can and does persist into the adult years.
Typical reported early features include mood swings, early depressive symptoms, dysregulated mood, activity and sleep patterns, irritability and disordered behaviors including aggression [ 33 , 42 ]. Longitudinal, including high risk family studies, are consistent with retrospective studies in identifying that sub-syndromal depressive and hypomanic symptoms often precede bipolar disorder by several years [ 33 , 43 ] with a reported latency between initial affective symptoms and the first identified major affective episode in BD between 8 to 12 years [ 34 ], with another 8 to 10 years from the first affective episode to the initiation of an appropriate mood-stabilizing treatment [ 14 - 16 ].
An important clinical and prognostic aspect of undiagnosed and untreated early BD is an elevated risk of substance misuse, anxiety disorders as well as conduct and antisocial disorders, with high levels of morbidity, disability and suicide [ 12 , 44 ]. Also, adult mood disorders with a juvenile onset are more severe and more recurrent than similar illnesses starting in adult years [ 12 , 15 , 41 ]. Particularly, childhood onset BD was associated with a greater number of episodes, higher percent time ill, a higher risk of rapid cycling and more severe manic and depressive episodes [ 12 , 41 ], as well as with greater rates of other psychiatric disorders, especially with comorbid anxiety disorders and substance abuse, with greater likelihood of suicide attempts and violent behaviors [ 41 ].
The fact that untreated and early onset bipolar disorder results in a worse clinical outcome highlights the importance of a closer linkage between pediatric and adult psychiatry, to clarify the natural history of childhood disorders by their outcomes and in order to predict the diagnosis, course and prognosis of adult mood disorders, with the possible aim of improving long term adult outcomes.
Some authors have reported findings strongly supporting continuity between pediatric and adult bipolar disorders. Geller and colleagues followed for 8 years PBD-I subjects presenting on average at age 11 years with a manic or mixed episode [ 37 ]. At the end of the 8 year follow-up period, results showed that subjects spent Wozniak and colleagues documented a highly persistent course of bipolar disorder in youth. These authors followed-up after 4 years 78 PBD-I subjects who were an average age of This data indicates the importance of considering the full range of persistence in longitudinal samples beyond continued BP-I disorder in order to understand the extent of ongoing morbidity in this population [ 45 ].
At the end of follow up most bipolar youth experienced both irritability and elation irrespective of history at baseline and irritable only youth were found to be at similar risk for persistence of mania compared to elated only or irritable and elated subjects. Few studies stratified follow up by the symptoms of irritability and elation or by chronicity versus episodic course, but in this study irritable only subjects experienced a greater depressive morbidity during follow-up than did subjects who were both irritable and elated [ 35 ]. Brotman and colleagues followed prospectively children meeting criteria for severe mood dysregulation until age 18 and they found that severe mood dysregulated youth were significantly more likely to be diagnosed with a depressive disorder at age 18 when compared to youth with no severe mood dysregulation.
Similarly, Copeland and colleagues reported that young adults with a history of DMDD had elevated rates of anxiety and depression relative to comparison subjects with no history of DMDD and that participants with a history of DMDD were more likely to have adverse health outcome including police contact.
The low rates of bipolar disorder in these studies may not be surprising since the exclusionary criteria for DMDD list any symptoms of mania beyond irritability. Axelson and colleagues suggested that DMDD could not be distinguished from oppositional defiant disorder and conduct disorder and was not associated with mood disorders at all [ 49 ].
However, since the onset of a major depressive disorder by age 18 has been reported to be a strong predictor of later conversion to bipolar disorder [ 33 , 50 ] and since, similarly, a unipolar major depressive disorder with associated antisocial behaviors and great functional impairment has been reported to have a high risk to switch to bipolar disorder [ 42 , 51 ], it seems likely that bipolar disorder would be an outcome of at least some subset of childhood DMDD cases.