Translation to Science to Service: Series on Pediatric Bipolar Disorder Evolution
Gabrielle A. Carlson, MD
Professor of Psychiatry and Pediatrics
Director, Child and Adolescent Psychiatry
Stony Brook University School of Medicine

Overall Vision

It seemed more appropriate for me to talk about where I’ve been since the better part of my career has transpired.  I hope I will be forgiven, then, for not following the format provided.

I owe my interests in bipolar disorder in youth to a young man I’ll call Steve.  Steve was about 19 when I met him as an admission to the mood disorders research unit at the Clinical Center of NIMH many years ago when I was a resident. I was a bit of an anomaly there as I was a woman (and there had never been a woman doctor among psychiatry “clinical associates”), and I was a resident rather than someone doing military service in the public health service as were the male “clinical associates”.  Finally, I was from Washington University and although a couple of men (Drs. David Dunner and Max Baker) had made very positive impressions among the researchers at NIMH at the time, the medical model was not in the forefront of people’s belief systems in Bethesda in the 1970s. 

I was in charge of admissions to our research unit and admitted this young man, in a state of what appeared to me to be hypomania verging on mania.  His history had been that he’d become psychotic every fall for the previous 4 years right before he was to start college, was diagnosed with schizophrenia, and kept home.  His schizophrenia would clear by the winter, he’d prepare to go to college, and have another psychotic episode.  In between he was fine.  His community psychiatrist ultimately thought that an unlikely history for schizophrenia and referred Steve to our research unit, and I wanted to admit him with a diagnosis of manic depression, manic type.  There was considerable resistance because a history of psychosis in a young person was, at the time, always considered to be schizophrenic in origin, and when we stopped Steve’s Thorazine and he went as mad as I’ve ever seen anyone, my already low credibility got even lower. 

Steve, however, not only escalated before everyone’s eyes from looking quite classically manic to being severely psychotic, he also de-escalated over the next several weeks and returned through a fairly manic phase to a euthymic state.  I argued with Dr. Goodwin that mania had stages, the severe psychosis that sometimes culminated was not schizophrenia and, in fact, severely disorganized states were not informative diagnostically.  Moreover, I said severe psychosis could be seen in manic people in general and that it was Steve’s young age that caused him to be considered schizophrenic.

Dr. Goodwin, being a good scientist, challenged me to prove that hypothesis and I was able to do so because of the careful record keeping of the research nurses at NIMH during the prior decades.  The resulting paper, Stages of Mania, (Carlson and Goodwin, Archives of General Psychiatry, 23:221-228, 1973) demonstrated that severe psychosis may be the 3^rd stage of mania in a considerable number of patients and that the phenomenon occurred in manic patients of all ages.  The paper has not only become a classic, it also helped change how people think about severe mania.  Mike Strober and I published similar papers focused specifically on adolescents (Strober and Carlson, Journal of the American Academy of Child Psychiatry, 17:138-153, 1978; Journal of Clinical Psychiatry, 39:63-66, 1978.)

What I found fascinating about Steve, however, has underpinned my clinical research career for the past 30+ years.  The questions I had were: 1) Is it that young people with mania become more psychotic and that is why they were mislabeled with schizophrenia, or was there simply an age bias?  2)  What accounts for a condition in which one can go from absolutely stark-raving mad to normal behavior again and again?  3)  Is there anything prognostic about the psychotic symptoms at the severest point in the manic episode?  4)  And more generally, what is the impact of development on phenomenology and outcome in bipolar disorder?

Among my early papers were those on outcome in adults with bipolar disorder, which demonstrated that about 60% of people with the disorder did reasonably well (they may have had episodes but they returned to their premorbid level of functioning in between) (Carlson et al., British Journal of Psychiatry, 124:134-139, 1974), and age of onset didn’t matter (Carlson et al, American Journal of Psychiatry, 134:919-922, 1977).  The latter sounds surprising in this day and age when age of onset is synonymous for poor outcome.  However, my sample came from NIMH at a time when we were still accepting only relatively classic cases of manic depression (which, in fact, Steve was if you ignored his age), and the diagnosis was made by observation, not just by systematic interview. My mistake was that I relied on people’s memories to date the early age of onset sample, and to equate symptoms with those that caused enough disruption to present for treatment.  This criticism is equally relevant for most age of onset studies of adults even now.  As someone who takes care of psychiatrically hospitalized children, I can say unequivocally that whatever adults remember about their age of onset at 6 or 7 years of age, they absolutely did not have the same level of severity as children who are being admitted to psychiatric hospitals at age 6 and 7.  I find it odd that in a field where good child psychiatrists cannot come to a consensus about the presentation of juvenile bipolar disorder in a child in their clinic that everyone so uncritically accepts information from adults reflecting on their childhood symptoms thirty to forty years earlier.

Current work

The Suffolk County Mental Health Study, a community study of people ages 15-60 hospitalized with a first episode of psychosis has provided a means of further understanding phenomenology, age of onset and psychosis.  According to my research, what ends up being the driving force for poor outcome in early onset “bipolar disorder” is comorbidity with childhood psychopathology (Carlson et al., American Journal of Psychiatry, 157:213-219, 2000; 159:307-309, 2002).  Comorbid childhood behavior disorders (ADHD/ODD/CD) especially make for a poorer outcome.  Classic manic depression with good intermorbid functioning continues to have a reasonably good prognosis.  However, one does not see that condition in children. That is, an otherwise normal child presenting with the sudden onset of mania that lasts several weeks at a time, and returns to a euthymic state without another psychiatric disorder is decidedly rare.  While this is somewhat more common in adolescents, it is still less common than in adults. In the Suffolk County project, which is going into its 16^th year, we continue to demonstrate that observation and are in the process of writing up the 10-year findings (Carlson et al., in preparation).  Basically, childhood psychopathology is a negative predictor for poor functional outcome; age of onset predicts re-hospitalization only. Childhood psychopathology is also more likely to be associated with diagnostic inconsistency (Ruggero et al., submitted). Finally, psychosis — at least during mania — has no impact on outcome. There is some suggestion, though, that some psychotic symptoms are worse in those with adolescent onset.

The Suffolk County project started at age 15 because acutely psychotic younger people are decidedly rare. In my 35+ years of work taking care of the most seriously disturbed children, I can say that cases like “Steve” that I saw at NIMH, and subsequently on the adolescent unit at UCLA, just do not occur in prepubertal children very often.  At the risk of offending colleagues, it is the fact that we don’t see such children on inpatient units, and the fact that they are unlikely to be otherwise at home being managed, that makes me skeptical about what is being identified as childhood mania is the same as post-pubertal mania. That is not to say that some of the depressed children might not go on to develop bipolar disorder, but that what we see in-hospital are not children with acute psychotic mania. That means that the histories being given to those doing structured interviews are unlikely to be what at least I consider to be psychotic mania. 

The question of what constitutes mania in children has long been an interest.  After child and adolescent psychiatrists accepted that adolescent onset bipolar disorder exists, we turned our attention to younger children. Interestingly, the controversy is not a new one (Carlson and Glovinsky, Child and Adolescent Clinics of North America, Apr;18(2):257-71, 2009).  The question has been largely what it is now – is there an alternate form of mania seen in childhood and conversely, if one sees childhood symptoms that look like mania, will they have stability into adulthood as classic mania.

Because of “Steve,” I would have to say that my own interest remains in more classically defined bipolar disorder with acute onset, and clear episodes of mania, depression and euthymia that last long enough that one can clearly see distinct differences in the phases. There are many adults with mood dysregulation, who are being labeled as having bipolar disorder and may have some form of it.  The children to whom we are giving the label of bipolar disorder may well be continuous with this group of adults, who are undoubtedly ill and in need of help.  Understanding those children (and adults) is and will be the task of the doctors comprising The Balanced Mind Foundation’s advisory panel. However, I think it is unwise to come to that diagnosis prematurely for a variety of reasons, not the least of which is that there may be other explanations for the behavior, which are discounted because everyone thinks they know what is wrong.

As the result of a survey I undertook recently with a completely different mission in mind, I have come to understand why my conclusions have been somewhat different from what appears to be the mainstream thinking on juvenile bipolar disorder.  In that regard, we return to “Steve”.  Steve taught me the importance of longitudinal observation of the patient – not just the longitudinal acquisition of information about the patient (which is also important).  The survey asked members of the Society of Professors of Child and Adolescent Psychiatry (the group of directors of child psychiatry training programs) whether or not their programs had an inpatient service for children less than age 13, and if so, what the average length of stay was.

The answer, to my surprise, was that over ¾ [fill in the blank] of the training programs that have any capacity to hospitalize children have lengths of stay of less than 2 weeks, and most have a length of stay of a week or less. Those with longer lengths of stay were usually state hospital programs or those caring for developmentally disabled or eating disordered youth. That means that the situation I have been able to maintain at Stony Brook for the past 20 years, where our length of stay is about 4 weeks, and longer for those who need it, is an anomaly. However, it is an anomaly that has allowed me to observe children with a well-trained staff, and to compare what is described prior to admission with what we see in hospital, often off medication, but within a relatively structured environment. Given that these children often “honeymoon” when hospitalized (i.e. they behave themselves for the first week or so), it is necessary to have them stay longer both to investigate other situations diagnostically, but also to get past the flight into health that is usually transient. 

What has emerged over the years from observations made systematically on this severely ill population follows:

Parent-reported manic symptoms are not necessarily corroborated by a research psychologist doing structured observations and interviews, or by the nursing or school staff who remain with the child all day, every day. The children certainly have complicated and severe psychiatric problems. In their most behaviorally disorganized states, moreover, it is quite difficult to make a diagnosis. Also evident are these observations:

a. They do not respond clearly to lithium (Carlson et al., Journal of Child Psychology and

Psychiatry, 33:411-425, 1992; JAACAP 31:262-270, 1992)

b. They do no worse on stimulants than children with ADHD without manic symptoms (Carlson and Kelly; Journal of Affective Disorders, 51:123-136, 1998)

c. Becoming agitated or disinhibited on stimulants occurs, but does not mean the child has bipolar disorder (Carlson GA and Kelly KL: Journal of Child and Adolescent Psychopharmacology, 13:137-143, 2003)

d. Children younger than 8 and children with developmental disabilities are more likely to become disinhibited on a range of medications (Carlson GA and Mick E:  Journal of Child and Adolescent Psychopharmacology, 13:153-164, 2003)

e. If both parents and teachers observe manic symptoms in children, the children are more likely to have true mania observed by inpatient staff (Carlson GA and Youngstrom EA:  Biological Psychiatry, 53(11):1050-1058, 2003).

f. Half of the children hospitalized with “rages” (severe aggressive episodes at home or at school that require admission through the emergency room, usually) do not have them in hospital.  10% will have 3 or more rages in hospital and are indeed very difficult to treat. (Carlson et al., Journal of Child and Adolescent Psychopharmacology, 2009 Jun;19(3):281-8)

g. One third of children admitted with rages have been given the diagnosis of bipolar disorder by their community clinician; almost 40% of their parents will endorse manic symptoms (though not necessarily episodes) when asked.  Less than 10% of children will actually have mania observed during hospitalization.  (Carlson et al., Bipolar Disorders, in press). Finally, rages structurally are like prolonged tantrums and do not have manic features (Potegal et al., Child Psychiatry and Human Development, in press).

h. It is worth noting that, as far as aggression Vs mood-stabilizing medication treatment is concerned, it doesn’t make much difference whether or not the child gets a bipolar diagnosis.  The difference a bipolar diagnosis makes is whether other conditions are assessed and treated, the kind of IEP the child gets, and what parents expect will happen to the child. (Carlson; American Journal of Psychiatry, 166(1):18-24, 2009)

Going forward

Like my colleagues, I am interested in what happens to children being given the diagnosis of bipolar disorder.  Since the 1980s, I have felt that the presence and definition of episodes is central to the diagnosis of bipolar disorder (Carlson, Journal of Child Psychology and Psychiatry, 31:331-341, 1990). I believe that many children that are given the diagnosis of bipolar disorder have severe problems with mood regulation and executive function. Using data from a longitudinal study begun by Jan Loney, PhD, in the 1960s, I have examined children with what was likely mood dysregulation before age 12, and looked at data from their young adulthoods (Carlson, Loney et al., Journal of Child and Adolescent Psychopharmacology, 10:175-184, 2000). The mood lability/negative-affect symptoms are quite stable. Rates of developing classic bipolar disorder were no different than in the general population. I am hoping to look at data from the mid-life study of that population.

I continue to be interested in assessment, recognizing that not all children should be or will be hospitalized. Over the 20+ years I have been at Stony Brook, I have developed a close relationship with most of the school districts that refer children to us. That means I am able to get teacher-rating scales on close to 90% of children we evaluate and treat. I am currently pursuing the diagnostic implications of widely disparate ratings between the parent and teacher Child Mania Rating Scale (CMRS). These findings were presented at the 2009 conference of the American Academy of Child and Adolescent Psychiatry in Hawaii, and I plan to write them up, too.  Our data suggest that when parents score in the top 75%ile on the CMRS (scores > 15) and teachers score the child in the bottom 25%ile (scores <2), the child is much more likely to have an anxiety or depressive disorder than a bipolar disorder. In other words, they are not having rapid cycles of bipolar disorder. The treatment implications, of course, are far reaching as one treats depression and anxiety differently than one would a manic episode. 

I continue to be interested in the diagnostic stability of symptoms of severe mood dysregulation or ADHD/ODD/mood symptoms. Insofar as the CBCL “bipolar phenotype” is a way to assess that, I have been part of a high-risk study that has examined the stability and diagnostic implications of that clinical picture. It turns out to be highly stable and reflective of comorbidity of behavior and mood disorders, including, but not limited to, bipolar disorder (Meyer SE; et al., J Affective Disorders, 113(3): 227-35, 2009) 

I am part of a study examining the phenotype and stability in a long-term study of a community sample of preschool children. What is elegant about this endeavor is that we have data not only from the Child Behavior Checklist and interviews from parents, but we also have home observations and laboratory observations of the children. They are being followed up at age 6 and, I hope, also at age 9.

I clearly will not have answered all of the questions that got me interested in bipolar disorder in youth before I retire from the field. In terms of understanding what causes a condition, where one can fluctuate from complete madness to complete sanity, and why we do not see it in children, I can only hope the next generation of child and adolescent psychiatrists will be able to discover.

Gabrielle Carlson, MD
Professor of Psychiatry and Pediatrics
Director, Child and Adolescent Psychiatry
Stony Brook University School of Medicine
Putnam Hall-South Campus
Stony Brook, NY  11794-8790
Phone:  (631) 632-8840
Fax:  (631) 632-8953
e-mail:  Gabrielle.Carlson@StonyBrook.edu