Adolescent – Onset Bipolar Disorder

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The onset and first diagnosis of bipolar disorder frequently occur in adolescence. For the most part, adolescent-onset bipolar disorder is clinically similar to adult bipolar disorder. 

Despite current awareness, adolescent bipolarity often was not recognized as such in the past. Diagnostic errors were common, reflecting the biases of the time. These biases included the above noted reluctance to accept the existence of youthful onset of bipolar disorder and a common tendency to assume that psychotic symptoms as thought disorder, grandiosity and bizarre delusional and hallucinatory phenomenon are pathognomonic of schizophrenia. 

Additionally, morbid preoccupations, frenzied behavior, moodiness or rapid mood swings, irritability, defiance and a host of other disturbances were often regarded as exaggerations if not typical manifestations of adolescence. 

As discusses earlier, moreover, even when recognized as clearly pathological, disturbed behaviors in youths have been difficult to distinguish from alcohol and drug abuse behaviors and personality disorders. these challenges remain today

In recent years however, several factors have contributed to the increasing recognition and accurate diagnosis of adolescent bipolar disorder. These factors include the greater awareness of the existence of severe mood pathology in adolescents, improving diagnostic criteria, and interview methods for identifying depression and mania in younger populations and increased availability of effective pharmacological and psychotherapeutic treatments for mood disorders. 

Increasingly adult diagnostic criteria are being applied reliably and effectively to the diagnosis of bipolar in adolescence. 

There is a general consensus that adolescent onset bipolar disorder in a relatively common presentation and that as noted, it essentially resembles the disorder in adults. 

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Symptoms and Clinical Presentation: Diagnosis

Adolescent onset of bipolar-I disorder may first present with major depression, mania or a mixed state. 

Manic episodes provide the most unambiguous indicator of bipolar disorder.  Symptoms such as elated mood, grandiosity, excessive activity, decreased need for sleep, hypersexuality, and racing thoughts are similar in both adolescents and adults, with differences only in developmental presentation. 

Geller and Luby 1997, describe grandiose beliefs in adolescents who despite a lack of talent believe they can become a rock star, whose excessive activity takes the form of making curtains, illustrating a book rearranging furniture and making multiple phone calls all within a relatively brief period of time; or whose reduced need for sleep may take the form of sneaking out and partying all night. 

Engagement in high-risk pleasurable activities may involve a heightened interest in sex and risky sexual experiences, excessive spending through the use of parent’s credit cards, taking dares, or driving more recklessly than their peers. 

The assessment of bipolar illness in adolescents can be complicated. Tillman and colleagues found poor concordance between the symptom descriptions of parents and their kids. Children and adolescents report the presence of racing thoughts and decreased need for sleep significantly more than do their parents, perhaps reflecting the reality that external and disruptive behaviors are more likely to be noted by parents. 

Other researchers have found high rates of bipolar spectrum in young people with recurrent depression, findings consistent with those of studies showing that adults with bipolar disorder tend to under report hypomanic symptoms and impairment. 

Supplemental assessment measures such as the General Behavior Inventory the Young Mania Rating scale add to diagnostic validity. 

Manic Features

Although the phenomenology of adolescent-onset mania, has been studied incompletely existing research clearly indicates a heterogeneity that may reflect different subgroups. Pooled data from several investigations of mania in adolescents have revealed pressured speech euphoria, and hyperactivity to be the most common symptoms, similar to what has been found in adults. Faeda 1995.

Lewinsohn 1995, noted a much higher frequency of elevated expansive mood than irritability in their community sample (which however consisted primarily of those with bipolar spectrum rather than BP-I). Faraone 1997, on the other hand found relatively high rates of irritability and low rates low rates of euphoria in their clinical sample of young manic patients. 

Both Lewisohn and Faraone subjects reported high rates of increased activity, grandiosity and distractibility. 

In an analysis of the symptoms of mania in 115 adolescents with manic or subsyndromal manic episodes, Lewinsohn 1995 identified two factors: 

1. 1. behavioral disorganization, consisting of decreased need for sleep, flight of ideas, distractibility, and poor judgement. 
   2. inflated self-esteem and increased activity. 
      
      

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The former factor was correlated more highly than the later with functional impairment (school, family and social, and the authors speculated the individuals scoring high on this factor might be more likely to experience psychotic symptoms during severe manic episodes. 

Even in adolescents with only subthreshold BP, Lewinsohn 2003, noted substantial impairment, comorbidity, and increased risk of suicide attempts 18% compared with 3% in never mentally ill controls. 

Mania in adolescents often includes psychotic features (see chapter 2). Several studies have found that between 1/3 and ½ of adolescent BP patients have prominent psychotic symptoms. Kafantaris 1998, found that half of BP youths in their study who presented with psychotic mania had no prior psychotic history, and appeared to have experienced an acute onset after having functioned relatively well to that point. 

The authors suggest that this sudden onset psychotic subgroup psychotic subgroup may represent “classic” bipolar disorder.  A recent study or 43 BP adolescents, found that in most, the prodromal onset was either slow with gradual deterioration 47% or slow with quick worsening 39%. Rapid onset of illness was relatively uncommon 14%, Correll 2005. 

There is suggestive evidence that there are ethnic differences in psychotic features expressed during mania. A recent study compared of 17 BP African American adolescents and 61 BP white kids, fully 90 % of the black kids had psychotic symptoms as compared to only 30% of white kids. These results are consistent with differences found between white and black adult BP patients. 

Mixed mania and rapid cycling are also common in adolescents with BP. Kutcher 1998 studies a small and carefully ascertained clinical sample of 28 BP kids and found that the majority had mixed mania 74%, rapid cycling 76% or both during their first (retrospectively assessed) episode. 

Fewer than 10% of the sample demonstrated classic euphoric mania during their initial manic episode. 

Mixed episodes were reported by Faraone 1997, in 71% of a sample of 17 patients with adolescent onset of mania. 

McElroy 1997, found that adolescents with BP had a higher frequency of mixed episodes than was the case among comparison adult BP patients, but the investigators did not distinguish between childhood and adult onset in their adolescent sample.

Findling 2001, compared 56 children and 34 adolescents with BP-I and found that 56%. of the adolescents had rapid cycling and 21% had mixed states; proportions among children with BP-I were similar. However, many adolescents with BP in that study appeared to have had childhood onset. 

Finally, Strober 1995, reported that the index episode in their inpatient sample which was the 1st episode in 56% of the cases studied was mixed in 19% and rapid cycling in 19%, with the other cases being “pure” depression or mania. 

An unresolved issue is whether rapid cycling or mixed states are particularly associated with BP adolescents with childhood onset, a typical developmental manifestation of BP illness in young people or a subtype of BP-I marking a course that may differ from more “classic” cycling episodes. 

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Depressive Features

For a substantial number if not the majority of individuals with adolescent BP, the illness started with depression, thereby delaying recognition and diagnosis of the BP course. Kutcher 1998, found that depressions were the first affective episodes in 75% of their sample of adolescents with BP-I.

Likewise, a community sample of adolescents with BP spectrum revealed that 61% had experienced an initial depressive episode before the manic or hypomania had occurred, (Lewinsohn 1995). 

And among those who responded to a volunteer survey of members of the National Depressive and MDI Association (now called the Depression and Bipolar support Alliance), both early age at onset and female gender were associated with higher rates of initial depressive symptoms or both depressive and manic symptoms Lish 1994. 

The studies of Kutcher 1998, and Lewinsohn 1995, did not evaluate initial symptoms presentation by gender status. 

The switch rate of adolescent major depression to eventual mania or hypomania is quite variable across studies. Interpretation of this variation is complicated by the above noted common practice of mixing children and adolescents in the same study samples. 

For instance, in a review of seven studies of more than 250 depressed children and adolescents followed for 2-4 years, Faedda 1995, found a mean rate of switch from depression to eventual mania of about 25 %.  A review by Kovacs 1996 yielded a switch rate of 8-37%; her own longitudinal study of 92 depressed children followed for 5-10 years yielded a rate of 21%. 

More recently Birmaher 2006 conducted a 2-year prospective study of 263 children and adolescents (mean age 13),

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with BP-I, BP-II and BP NOS. 

• Of the BP II subjects, 21% converted to BP-I, 
• 20% of the BP-NOS converted to BP-I and10% converted to BP-II
• Females were more likely to convert than males.

These findings are of considerable interest but somewhat difficult to interpret because of the mixed age range of the sample. Such variations in rates of switching among studies may depend on the mean age and age ranges of the sample, the diagnostic criteria used. The ascertainment source (whether the study involved community, outpatient or inpatient populations) and the extent to which the initial depressive episode was treated with antidepressants (see chapter 23).

In contrast to the high switch rate in Kovac’s childhood sample, Weissman 1999 revisited 10-15 years later an outpatient sample that had been diagnosed with major depression during adolescence and found that only 4.1% developed BP-I and 1.4 developed BP-II. As discussed earlier, severe depression in childhood (rather than adolescence) may portent higher rated of eventual bipolarity (Geller 1994). 

Further studies are needed not just on adolescent depression switch rates but also on characteristics that link adolescent and childhood and childhood depression to eventual BP disorder. Strober and Carlson 1982 studied 60 inpatient depressed adolescents and identified several features predictive of eventual bipolarity: 

• rapid onset of a depressive episode

• psychomotor retardation

• psychotic features

•  family history of mood disorders (i.e., BP) and

• antidepressant onset of mania or hypomania

It should be noted however, that a recent study of switching during a 2 year among adults with first onset psychotic depression showed no association of switching with medication use, earlier age at onset, or family history of BP, DeBello 2003.

A 15 year follow up study of 74 young adults hospitalized for MDD, average age 23, found that 27% of the study group had experienced at least one episode of hypomania and another 10% had an episode of mania. (Goldberg 2001). 

Psychosis during the depressive episode was significantly correlated with a switch into manic states. (See chapter 19). Predicting BP switching in cases of adolescent depression is an important area for further study because of speculation that treatment with ADs in the absence of knowledge of underlying bipolarity precipitates switches from depression to mania or hypomania and predicts a more adverse course of BP with rapid cycling. (See chapter 19).

Depressive symptoms in adolescents with BP tend to be quite similar to those seen in adults, although psychotic features are more common in the younger age group Carlson 1979 and others). Preoccupation with death and thoughts of suicide are common and suicide attempts are frequent (see box 6-2 for BP girl’s account of her depressive experience during a suicidal depression, “Drowning in my Personal Hell”. 

Lewinsohn 2003, found that 44% of BP adolescents in their sample had attempted suicide: in comparison 22% of adolescents with MDD attempted suicide as had 18% of those with subsyndromal BP syndrome (defined as abnormally and persistently elevated mood, expansive or irritable mood plus one other DSM-III-R manic symptoms but never having met criteria for full BP. 

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Course of Disorder

Longitudinal studies of youths with BP-I are rare, therefore most data on the course of the illness come from retrospective accounts or short-term treatment outcome studies. The later studies certainly document the likelihood of further episodes and hospitalizations, but more information is needed to clarify the predictors of relatively better or worse outcomes and responsiveness to treatment in patients with adolescent onset. 

Strober 1995, conducted one of the few longitudinal studies, a 5-year naturalistic follow up of 54 adolescents, mean age 16, who had been inpatients diagnosed with BP (although age at diagnosis of first episode was not reported). The rate of recovery from first index episode was high (96%) with only 2% of patients failing to achieve recovery during the 5-year period.

However, time to recovery was affected by the polarity of the index episode: median time to recovery was significantly longer for those who had pure depressive episodes (26 weeks) compared with those who had pure mania (9 weeks or mixed (11 weeks) episodes.  The majority, 56% of those recovered remained free from of major depressive relapses during the follow-up period, and the probability of relapse did not vary with polarity of the index episode (although among those who had multiple relapses, most had mixed or cycling index episodes. 

Suicide attempts sufficient to require medical attention occurred on 20% of the adolescents on the 5-year study, Strober 1995. None of the clinical or demographic factors that were evaluated in the study significantly predicted relapse, and all participants were treated aggressively. Thus, it is important to note that the information on course derived from this study cannot be generalized to untreated BP in adolescents. 

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A 2-year prospective study of adolescent psychotic disorders by McClellan and colleagues 1999, included comparisons of a small group of BP youths with patients who had schizophrenia. The results indicated that 50% of the BP youths had an episodic course, and 40% were chronically impaired (but fared significantly better than the schizophrenic youths). Rakeev 2003, observed adolescent patients with BP mania for 6 months; like Strober but unlike McClellan, they found 96% recovery and very little chronicity. 

Recently researchers at U. of Pittsburg, Brown U and UCLA conducted a longitudinal study of 263 BP children and adolescents av age 13; they interviewed their subject on an average of every for 95 weeks using Longitudinal Interval Follow -up Evaluation. Although 2/3 rds. of the subjects recovered from the index episode, 50% had at least one syndromal occurrence, Birmaher 2005.

 Subjects were symptomatic for the majority (60%) of the follow-up period; almost one quarter, (22%) of the time spent in full syndromic episodes.

Additional research is needed on predictors of treatment responsiveness in BP adolescents, see chapter 23). Moreover, given the potential for misdiagnosis of BP in youths, further studies on potentially adverse effects of antidepressants and stimulants for ADHD are warranted.

Pre and Postmorbid Adjustment of Functioning

Premorbid adjustment would appear to be an important clue to the possible presence of subclinical symptoms in childhood prior to the onset or diagnosis of BP, see chapter 4). However relatively few studies have reported information on prior adjustment. In the study by Kutcher 1998, 905 patients with BP-I with adolescent onset had excellent or average peer relationships and more than 60% had good to excellent academic achievement before their diagnosis. 

Such findings suggest that many youths with adolescent onset BP had relatively good functioning before being diagnosed. In the study by McClellan 1999, better premorbid functioning predicted higher levels of functioning over 2 years and was a more significant predictor then diagnosis in a sample of schizophrenic and BP adolescents. 

Once initiated, however, the course of BP in adolescents is associated with considerable impairment.  Kutcher 2000, found that a BP adolescent onset sample followed for 4.6 years after their initial manic episode had lower rates of HS graduation and lower FSIQ scores than those of UP and non-ill controls, see Quackenbush 1996. They also had significantly worse problems with peers and greater dissatisfaction with peer relationships than comparison groups. Like-wise in a cross-sectional study that included adolescents with mania and distinguished between childhood and adolescent onset, Faraone 1997, found significantly worse functioning on most social, peer, recreational and family variables as well as school performance, among BP youths compared with normal controls. 

Few differences in functioning were observed between childhood and adolescent onset BP youths, except that manic adolescent generally had worse relationships with parents, than did manic children.  A recent comparison or 18 BP adolescents and 18 normal controls found that adolescents with BP displayed significantly more deficit in social skills performance; however, no significant differences emerged between the groups in social skills knowledge Goldstein 2006. 

Thus, whereas some individuals with adolescent onset BP—especially those with severe childhood psychopathology—may have a relatively poor course of illness and adjustment, many cases of more “classic” BP disorder emerge in adolescents. Such individuals may have relatively favorable outcomes in the long run, and adequate if not excellent adjustment in the short run. 

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Comorbidity

Comorbidity complicated the diagnostic and clinical picture of adolescent BP as it does for childhood illness. Tables 6-3 and 6-4 display the results of major studies of comorbidity among adolescent onset and combined samples of adolescent and child onset BO subjects. Nowhere is the question of the meaning of comorbidity more complex than with adolescent BP disorder, because of the co-occurrence of psychiatric syndromes can be due to several factors. 

there are for example indistinct diagnostic boundaries and overlapping symptoms. Irritability, impulsivity and excessive activity are symptoms shared by BP and other syndromes. Moreover, there is a causal relationship between BP and other disorders in that symptoms of mania or depression may lead to substance abuse or alcohol abuse. also, substance abuse can precipitate mood disorders. 

Also, there are shared genetic or other risk factors such as parental assertive mating, and similar or related genes may be implicated in both ADHD and BP. Considerable research including carefully designed longitudinal studies is needed to clarify the meaning of co-morbid conditions in those with childhood and adolescent BP. comorbid conditions that commonly complicate the differential diagnosis are drug and alcohol abuse, Conduct, ADHD all of which may involve manic like symptoms of irritability, disruptiveness, hostility and impulsiveness, distractibility and antisocial behavior and the like. 

Psychotic symptoms may be mistaken for schizophrenia, and drug and alcohol abuse may obscure and complicate the diagnosis of mania, depression, or mixed states. 

Comorbidity with personality disorders may also complicate the diagnosis of BP in adolescents. Although relatively few studies of Axis II disorders in BP adolescents have been conducted this important topic should be pursued because personality pathology not only makes the differential difficult it also affects the interpretation of studies of course and treatment outcome. 

A small study by Kutcher 1990, revealed a rate of 15% for BPD among euthymic BP adolescents and the presence of thar disorder predicted worse outcome to lithium. 

Mood instability, impulsiveness an inclination to suicide, irritability and other characteristics of BPD represents a conceptual challenge in determining the boundary between severe mood disorder and personality pathology. Such issues are pursued in greater detail in chapter 10.

It is likely that mood instability and cognitive and behavioral due to BP in childhood and adolescence contribute to the development of personality pathology. 

Studies vary in the rates of comorbid diagnosis reported among individuals with adolescent onset- BP. Lewinson 1995, 2003, found high rates of comorbid anxiety disorders (33%), substance abuse and disruptive behavior disorders (22%), as well as ADHD (11%) in their community sample of youths with BP spectrum disorders. Kutcher 1998, found that 61& of their adolescent onset sample had no psychiatric diagnosis other than mood disorders; among those who did, GAD 21%, ADHD 21%, and CD 11%. were observed most frequently. 

Findling 2001, also observed high levels of comorbidity 76% overall including 62% with ADHD among Adolescents with BP (many of whom however probably had childhood onset). 

ADHD as a comorbid condition is of particular interest as discussed earlier, because of the problem of differential diagnosis, markedly different treatment strategies, and the possibility that co-morbid ADHD may identify a genetic subtype and predict a worse course and poor response to lithium. (Strober 1998).

A recent European study of 98 consecutively referred BO children and adolescents found that 38% were comorbid for ADHD (Masi, et.al. 2006). The mean age of onset for BP was 10.0 +- 3.2 years.  the BP patients with ADHD were predominately male 73%, and younger, has an early age at onset of BP 8.1 +- 2.8 years, vs. 11.1 +- 2. years, were more likely to exhibit a chronic rather than episodic course 67 vs 36% and were likely to have overall greater psychiatric impairment. As the authors of the study point out, these differences are important:

An identification of ADHD may help to identify a specific subgroup of patients, with a more homogenous course, outcome, and response to treatment. From a neurological standpoint, the identification of common biological pathways may help to more deeply define the links in the pathophysiology of both disorders, which are still under question. p 389 and Geller 2006. 

To be covered in Part 5

• Neurodevelopmental aspects of adolescent BP and the issue of puberty. 

• Conclusions