Journal of Affective Disorders 172 (2015) 417421

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Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research report

Diagnostic stability in pediatric bipolar disorder

Lars Vedel Kessing a,n, Eleni Vradi b, Per Kragh Andersen b
a
Psychiatric Center Copenhagen, Department O, 6233 Blegdamsvej 9, 2100 Copenhagen, Denmark and University of Copenhagen, Faculty of Health and
Medical Sciences, Copenhagen, Denmark
b
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

art ic l e i nf o

a b s t r a c t

Article history:
Received 25 March 2014
Received in revised form
20 October 2014
Accepted 20 October 2014
Available online 29 October 2014

Background: The diagnostic stability of pediatric bipolar disorder has not been investigated previously. The
aim was to investigate the diagnostic stability of the ICD-10 diagnosis of pediatric mania/bipolar disorder.
Methods: All patients below 19 years of age who got a diagnosis of mania/bipolar disorder at least once in a
period from 1994 to 2012 at psychiatric inpatient or outpatient contact in Denmark were identied in a
nationwide register.
Results: Totally, 354 children and adolescents got a diagnosis of mania/bipolar disorder at least once; a
minority, 144 patients (40.7%) got the diagnosis at the rst contact whereas the remaining patients (210;
59.3%) got the diagnosis at later contacts before age 19. For the latter patients, the median time elapsed
from rst treatment contact with the psychiatric service system to the rst diagnosis with a manic episode/
bipolar disorder was nearly 1 year and for 25% of those patients it took more than 2 years before the
diagnosis was made. The most prevalent other diagnoses than bipolar disorder at rst contact were
depressive disorder (21.4%), acute and transient psychotic disorders or other non-organic psychosis (19.2%),
reaction to stress or adjustment disorder (14.8%) and behavioral and emotional disorders with onset during
childhood or adolescents (10.9%). Prevalence rates of schizophrenia, personality disorders, anxiety disorder
or hyperkinetic disorders (ADHD) were low.
Limitations: Data concern patients who get contact to hospital psychiatry only.
Conclusions: Clinicians should be more observant on manic symptoms in children and adolescents who at
rst glance present with transient psychosis, reaction to stress/adjustment disorder or with behavioral and
emotional disorders with onset during childhood or adolescents (F9098) and follow these patients more
closely over time identifying putable hypomanic and manic symptoms as early as possible.
& 2014 Elsevier B.V. All rights reserved.

Keywords:
Mania
Bipolar disorder
Diagnostic stability
ICD-10
Children and adolescents

1. Introduction
One criterion for validating psychiatric diagnoses is that of diagnostic stability (Robins and Guze, 1970). Diagnostic stability may be
dened as the degree to which a diagnosis is conrmed at subsequent
assessment points (Fennig et al., 1994). Surprisingly, the diagnostic
stability of the diagnosis of pediatric bipolar disorder has never been
investigated in any larger long-term study. The National Institute of
Mental (NIMH) funded Phenomenology and Course of Pediatric
Bipolar Disorder study (Geller and Tillman, 2005; Geller et al.,
2008) has never addressed in detail what proportion of the sample
continues to have the same diagnosis, as recently highlighted (Carlson,
2011), although it is mentioned that subjects remained bipolar and
did not develop schizophrenia, ADHD or other psychiatric disorders
during 4-year prospective follow-up (Geller and Tillman, 2005). In
fact, there is one study only including 91 children and adolescents
with bipolar disorder, which found that 86% fullled criteria for mania
n

Corresponding author. Tel.: 45 38 64 70 81.

E-mail address: lars.vedel.kessing@regionh.dk (L. Vedel Kessing).

http://dx.doi.org/10.1016/j.jad.2014.10.037
0165-0327/& 2014 Elsevier B.V. All rights reserved.

or hypomania at 6-month follow-up, but this study presented no data

on diagnostic shift (Geller et al., 2000). Only two studies on children
and adolescents with rst episode psychosis have included bipolar
disorder patients and reported on diagnoses during follow-up. One
study including 13 patients with rst episode psychotic bipolar
disorder found a 92% diagnostic stability after -year follow-up
(Castro-Fornieles et al., 2011) and another study including 8 patients
with rst episode psychotic bipolar disorder revealed a 57% diagnostic
stability after 1 year (Fraguas et al., 2008).
Based on the importance of the question of diagnostic stability
and the very limited amount of research within the area we nd it
important to report data from Danish psychiatric case registers on
all children and adolescents diagnosed with mania/bipolar disorder within psychiatry and during a period of 16 years.
The aim of the present study was to investigate the diagnostic
stability of the ICD-10 diagnosis of pediatric mania/bipolar disorder as made by clinicians within psychiatry using a nationwide
register based sample of out- and inpatients from psychiatric
settings and further to estimate the gender and age associations
with time to rst diagnosis of bipolar disorder.

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L. Vedel Kessing et al. / Journal of Affective Disorders 172 (2015) 417421

two independent groups. Po0.05 was used to indicate statistical

signicance.

2. Method
2.1. The register
The Danish Psychiatric Central Research Register (DPCRR) is
nation-wide with registration of all psychiatric hospitalizations in
Denmark for the 5.3 million inhabitants (Munk-Jorgensen and Mortensen, 1997). From January 1, 1995 the register included information
on patients in psychiatric ambulatories and community psychiatry
centers, also. General practitioners and private practicing psychiatrist
do not report to the DPCRR.
All inhabitants in Denmark have a unique person identication
number (Civil Person Registration number, CPR-number) that can be
logically checked for errors; so it can be established with great
certainty if a patient has had contact to psychiatric service previously,
irrespective of changes in name etc.
No private psychiatric inpatient hospitals or department are in
operation in Denmark, all are organized within public services and
reporting to the DPCRR. The International Classication of Diseases, 10th Revision (World Health Organization, 1992) has been
used in Denmark from January 1, 1994.

3. Results
Totally, 354 patients below 19 years of age got a main diagnosis of a
manic episode (F30) or bipolar affective disorder (F31) at least once
during the study period from 1994 to 2012. The annual rate of incident
mania or bipolar disorder was approximately 0.003% in 2010 for both
sexes. Fig. 1 shows age at rst diagnosis of mania/bipolar disorder for
boys and girls. There was no signicant difference between boys and
girls at age at rst diagnosis of mania/bipolar disorder (P0.6).
Among the 354 patients, 144 patients (40.7%) got the main
diagnosis at the end of the rst contact period whereas the remaining
patients (21059.3%) got the diagnosis at later contacts. There was no
difference in the proportions of boys and girls who got the diagnosis of
mania/bipolar disorder at rst contact (36.7% of girls versus 45.8% of
boys, P0.08).

3.1. Change from bipolar disorder to other diagnoses

2.2. The sample
The study sample was dened as all children and adolescents o19
years with a contact as outpatient (patients in psychiatric ambulatories
and community psychiatry centers) or inpatient (patients admitted
during daytime or overnight to a psychiatric hospital) with at least one
main diagnosis of mania/bipolar disorder (ICD-10, code DF30-31.9)
during the study period from January 1, 1994 to December 31, 2012.
Outpatients were included in a period from January 1, 1995 to
December 31, 2012 (as these data are available for this period, only)
and inpatients in the entire ICD-10 period (from January 1, 1994 to
December 31, 2012).
2.3. Statistical analysis
Categorical data were analyzed with the chi-square test (2-sided)
and continuous data were analyzed with the MannWhitney test for

Among the 144 patients with the diagnosis of mania/bipolar

disorder at the rst contact ever in a period from 1994 to 2012, 60
(41.7%) were treated during outpatient settings and 84 (58.3%) during
psychiatric hospitalization; 50.7% were girls. Median age at rst
contact was 17.4 years (quartiles: 16.318.2 years) and follow up time
from rst contact with a diagnosis of mania/bipolar disorder to end of
study or 19th birthday was 1.31 years (quartiles: 0.652.48).
Table 1 presents main diagnoses at subsequent contact periods for
the 144 patients with a main diagnosis of mania/bipolar disorder at
rst contact. As can be seen, 98 patients had a second contact period,
41.7% had a third contact period, etc. At the end of the second contact
period, 79.6% got a main diagnosis of bipolar disorder and this
proportion was rather stable at subsequent contact period. The most
prevalent other diagnosis during follow-up was within neurotic,
stress-related and somatoform diagnoses with an increase to 9.1% at
the 5th psychiatric contact. There was no tendency to an increase in
other main diagnoses for which the prevalence was 5% or below.

Fig. 1. Age at rst diagnosis of mania/bipolar disorder for boys and girls.

L. Vedel Kessing et al. / Journal of Affective Disorders 172 (2015) 417421

419

Table 1
Main diagnoses at subsequent contact periods for 144 patients with a main diagnosis of a manic episode/bipolar disorder at rst contact.
N 144

2nd contact

3rd contact

4th contact

5th contact

Number of patients (% of total)

Organic
Psychoactive substance use
Schizophrenia, schizotypal and delusional
Bipolar disorder
Affective disorders, other (F3239)
Neurot, stress-rel. and somatof.
Personality disorders
Pervasive development disorders (F8489)
Behavioral and emotional disorders (F9098)

98 (68.1)
0
2.1
3.1
79.6
5.1
4.1
3.1
1.0
2.0

60 (41.7)
0
3.3
1.7
76.7
5.0
8.3
0
0
5.0

36 (25)
0
0
5.6
83.3
2.8
2.8
2.8
0
2.8

22 (15.3)
0
4.6
4.6
77.3
4.5
9.1
0
0
0

Table 2
Main diagnoses at rst contact for 210 patients with a main diagnosis of a manic episode/bipolar disorder at subsequent contact periods.
%, total for group
Organic F0009
Psychoactive substance use F1019

0
2.9

Schizophrenia, etc. F2029

22.9

Affective disorder F3239

22.9

Neurot, stress-rel. and somatof. F4049

19.5

Personality disorders F6069

1.0

Pervasive developmental disorders (F8489)

7.1

Behavioral and emotional disorders (F9098)

10.9

Major sub-diagnoses within group

% of total

Dementia (F00039)
Alcohol use (F10)
Cannabinoids (F12)
Cocaine (F14.55)
Multiple drug or psychoactive substances (F19)
Schizophrenia (F20)
Schizotypal disorder (F21)
Persistent delusional disorder (F22)
Acute and transient psychotic disorders (F23)
Schizoaffective disorders (F25)
Other non-organic psychosis (F28.9 29.9)
Depressive episode or recurrent depressive disorder (F3233)
Affective disorder, unspecied (F38.8 39.9)
Phobic anxiety disorders (F40)
Other anxiety disorders (F41)
Obssesivecompulsive disorder (F42)
Reaction to severe stress, and adjustment disorders (F43)
Dissociative disorders (F44)
Somatoform disorders (F45)
Emotionally unstable personality disorder, borderline type (F60.31)
Schizoid personality disorder (F60.1)
Personality disorder, unspecied (D60.9)
Childhood autism, atypical autism (F84.084.1)
Rett's syndrome (F84.2)
Others
Hyperkinetic disorders (F90)
Conduct disorder (F9192)
Emotional disorders (F93)
Disorders of social functioning (F94)
Others

0
0
1.0
0.5
1.4
1.4
0.5
1.4
14.8
0.5
4.3
21.4
1.5
0
2.9
1.4
14.8
0.5
0
0
0.5
0.5
1.4
0
5.7
3.8
2.9
1
1.9
1.3

3.2. Change from other diagnoses to bipolar disorder

4. Discussion

Table 2 presents data the other way around as the main diagnosis
at rst contact for the 210 patients who got a main diagnosis of mania/
bipolar disorder at subsequent contact periods but not at the rst
contact period. A large proportion of the patients got a main diagnosis
of depressive episode or recurrent depressive disorder (22.9%) at rst
discharge. However, 22.9% got a main diagnosis within F20mainly
acute and transient psychotic disorder (14.8%) and other non-organic
psychosis (4.3%). Notably, only 1.4% got a diagnosis of schizophrenia at
rst contact. A total of 19.5% got a main diagnosis within neurotic,
stress related and somatoform disorder (F40), among which the major
proportion was reaction to stress or adjustment disorder (14.8%).
For the 210 patients who got the diagnosis at later contacts, the
median time from the rst diagnosis with a manic episode/bipolar
disorder back to rst treatment contact within the psychiatric
service system was 0.93 years (quartiles: 0.382.52). This time lag
was numerically longer for boys (1.04 years (quartiles: 0.292.67))
than for girls (0.87 years (quartiles: 0.432.32)) but the difference
was not statistically signicant (P 0.9).

This is the rst study investigating the diagnostic stability of pediatric mania/bipolar disorder in clinical practice. The study included a
Danish nationwide sample of all in- and outpatients treated for
pediatric mania/bipolar disorder at least once in psychiatric settings.
In Denmark, doctors are obliged to make a diagnosis when a treatment period is terminated, i.e. at discharge from hospital or at the
end of an ambulatory treatment period, and all diagnoses are
reported to the Danish Psychiatric Central Research Register.
The most striking nding is that only 40.7% of the patients got the
diagnosis of mania/bipolar disorder at the rst in- or outpatient
contact whereas 59.3% got the diagnosis at later contacts. This 40.7%
proportion of pediatric patients who got the diagnosis at rst contact
was substantially lower than the corresponding proportion among
adult patients in a similar study from our group with exactly the same
design and type of analyses, namely 56.2% (Kessing, 2005).
In the present study, for the patients who got their rst diagnosis
of a manic episode/bipolar disorder at a later contact, the median time
elapsed since rst treatment contact with the psychiatric service

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L. Vedel Kessing et al. / Journal of Affective Disorders 172 (2015) 417421

system was nearly 1 year and for 25% of the patients it took more
than 2 years before the diagnosis was made. These gures are very
similar to those found in the study among adult patients (Kessing,
2005), and although this diagnostic lag is critical for all individuals
regardless of age it may be even more critical for children and
adolescents with as untreated mania or bipolar disorder may have
substantial negative inuence on the development of personality,
intellectual and school capability and social competencies. The most
prevalent other diagnoses than bipolar disorder at rst contact were
depressive disorder (21.4%), acute and transient psychotic disorders or
other non-organic psychosis (totally 19.2%), reaction to stress or
adjustment disorder (14.8%) and behavioral and emotional disorders
with onset during childhood or adolescents (10.9%, F9098). Also
among adults, the most frequent misdiagnosis of bipolar disorder is
unipolar depression (Hirschfeld et al., 2003; Kessing, 2005) although
acute and transient psychotic disorders as well as reaction to stress or
adjustment disorders also are frequent initial diagnoses prior to the
diagnosis of mania/bipolar disorder (Kessing, 2005). The high prevalence of depressive episodes is in accordance with the natural
history of bipolar disorder with prevalent onset of depressive episodes prior to rst hypomania/mania. However, the other gures
illustrate great difculties in identifying initial presentations of mania/
bipolar disorder, which seems even more pronounced among children and adolescents than among adults. This may be due to
uncertainty among doctors or psychiatrists so they do not identify
possible manic symptoms or bipolar disorder behind these syndromes or alternatively that bipolar disorder in a substantial proportion of cases initially present with prodromal syndromes such as
transient psychosis, reaction to stress/adjustment disorder or behavioral and emotional disorders (F9098) and that these conditions
later on may develop into bipolar disorder. In addition, for some
children and adolescents symptoms of mania may emerge more
slowly and with mixed and/or shifting depressive and manic symptoms complicating the diagnostic process (Youngstrom et al., 2008). It
is most likely that these phenomena may co-occur.
In contrast to this diagnostic uncertainty, clinicians did not seem
to be unsure regarding differentiation of mania/bipolar disorder
from schizophrenia, personality disorders, anxiety disorder or
hyperkinetic disorders (ADHD). Thus, as can be seen from Table 2,
remarkably few patients had a main diagnosis of schizophrenia
(1.4%) or schizoaffective disorder (0.5%) at rst contact and only 1.0%
were diagnosed with a main diagnosis of personality disorders and
1.4% with OCD and 2.9% with other anxiety disorder. In addition,
hyperkinetic disorders (corresponding to the DSM ADHD diagnosis)
were surprisingly low at rst contact (3.8%, Table 2) and at
subsequent contacts (25%, Table 1). Although early studies have
suggested high comorbidity between ADHD and child and adolescents mania/bipolar disorder (Geller et al., 1995; Geller and Luby,
1997) longitudinal data (Craney and Geller, 2003; Youngstrom et al.,
2008) as well as studies with more careful diagnostic sorting of
symptoms (Arnold et al., 2011) have revealed lower comorbidity
and supported the differentiation of child and adolescents mania/
bipolar disorder from hyperkinetic disorder/ADHD in accordance
with our ndings. As argued by Arnold et al. (2011), Indeed, if one
automatically count such symptoms as hyperactivity and impaired
attention towards both disorders without noting association with
mood episodes, and especially if one does not require episodicity for
bipolar disorder it may articially inate the comorbidity rate. To
identify episodicity longitudinal observation is an advantage. In this
way our longitudinal results seem to conrm the observation that
even though the symptoms may not be so different between mania
and ADHD, the clinical presentation and the illness course with an
episodic course in bipolar disorder and a more chronic course in
ADHD differ between the disorders (Carlson and Klein, 2014).
When the diagnosis of mania/bipolar disorder was made at rst
psychiatric contact, this diagnosis was rather stable over successive

contacts as 7683% also got this diagnosis during follow-up in this

way suggesting that the initial diagnosis was correct (the follow up
time from rst contact with a diagnosis of mania/bipolar disorder to
end of study or 19th birthday was 1.31 years (quartiles: 0.652.48)).
No other studies have presented data on diagnostic shifts of patients
initially diagnosed with mania/bipolar disorder; however, a study of
91 children and adolescents with bipolar disorder found that 86%
fullled criteria for mania or hypomania at 6-month follow-up (Geller
et al., 2000). In addition, two studies on children and adolescents with
rst episode psychotic bipolar disorder revealed 92% diagnostic
stability after -year follow-up of 13 patients (Castro-Fornieles
et al., 2011) and 57% diagnostic stability after 1 year of 8 patients
(Fraguas et al., 2008). These three mentioned studies used research
based DSM-IV diagnoses according to the Kiddie-Schedule for Affective disorders and Schizophrenia (Kaufman et al., 1997) but the level
of diagnostic stability among patients with a rst diagnosis of mania/
bipolar disorder was rather similar to the diagnostic stability in our
study, in this way validating the clinical diagnoses made in our study.
4.1. Advantages of the present study
Diagnostic stability has never been systematically investigated
before but compared to three mentioned follow-up studies above,
the sample size was considerable larger and the study period longer
in our study. The study comprises an observation period of up to 16
years of the whole Danish population (5.3 million inhabitants) and
further, the population is ethnically and socially homogeneous and
with a very low migration rate. The entire population (approximately 100%) of patients treated in psychiatric settings in a whole
country during in- or outpatient settings was included. Psychiatric
care is well developed in Denmark so persons with mania or bipolar
disorder can easily come in contact with psychiatric community
centers or hospitals. Also, as psychiatric treatment in Denmark is
free of charge, the study is not biased by socioeconomic differences.
4.2. Limitations of the present study
It may be argued that the psychiatrists who made the clinical
diagnoses were not blinded for diagnoses given at previous contacts
and that the study consequently may have overestimated the diagnostic stability of bipolar disorder. We do not nd, however, that the
clinical situation in this respect differs from the situation making
research based diagnoses using e.g. the Kiddie-Schedule for Affective
disorders and Schizophrenia, as the latter diagnoses also are best
estimate diagnoses based on all available data frequently including case
les and diagnoses from previous contacts or detailed information
from the patient regarding such data. Nevertheless, it should be
emphasized that the clinical ICD-10 diagnoses of mania/bipolar disorder used in the Danish Psychiatric Central Research Register has not
been validated against research based diagnoses such as the KiddieSchedule for Affective disorders and Schizophrenia. Despite these
caveats, the diagnostic stability was rather similar in our study as in
the three other studies that have used research based diagnoses and
presented data on the level of diagnostic stability among patients with
a rst diagnosis of mania/bipolar disorder (Geller et al., 2000; CastroFornieles et al., 2011; Fraguas et al., 2008), also for the only study that
used a blinded approach (92% at -year follow-up, (Geller et al., 2000)).
It should be noted that the study included patients who have
passed the threshold for treatment to psychiatric outpatient settings
(psychiatric ambulatories and community centers) or to psychiatric
hospitalization, only. Although the vast majority of children and
adolescents with bipolar disorders are treated in these hospital setting
as in- or outpatients some patients with milder types of the illness
may be treated within private psychiatric practice. Such patients are
not included in the study, as private psychiatric practice does not

L. Vedel Kessing et al. / Journal of Affective Disorders 172 (2015) 417421

report to the DPCRR. General practitioners do not treat children and

adolescents with bipolar disorder in Denmark.
As the Danish Psychiatric Central Research Register started to
include information on out-patient treatment in January 1, 1995,
some patients may have had an outpatient psychiatric contact before
this date without this being recorded in the register. Thus, a minor
proportion of these patients and of the patients who were recorded
in the register with a rst hospitalization contact may have had an
out-patient contact before January 1, 1995. We cannot exclude the
possibility that the diagnostic stability is underestimated somewhat
in the present study due to this minor misclassication but we do not
believe that it has substantially affected our results.
The causal relation between diagnostic stability and the number of psychiatric contacts is unknown. Patients who have many
psychiatric contacts may present with more unstable psychiatric
illness leading to more diagnostic variation. On the other hand, it
may be that clinicians have problems with diagnosing some
patients accurately and that this may lead to less effective treatment and more psychiatric contacts for these patients.
It should be noted that the diagnosis of bipolar disorder in ICD10 includes both bipolar disorder I and bipolar disorder II but does
not discriminate between the two subtypes, as ICD-10 bipolar
disorder is dened as a disorder with at least two mood episodes
among which at least one is a hypomanic or a manic episode. It is
most likely that the majority of the 354 patients in the present
study suffered from bipolar disorder, type I, as patients were
included via their contact to hospital psychiatric settings.
Frequent comorbid conditions in bipolar disorder such as
anxiety disorders, hyperkinetic disorders and substance use may
complicate the diagnostic process. It should be stressed that the
present study focused on the diagnostic change in the main
diagnoses as the aim was to investigate changes in the main
diagnostic picture over time as evaluated in clinical practice. The
main diagnosis is given for the main illness leading to investigation and treatment. The main diagnoses are given according to the
diagnostic hierarchy in ICD-10 giving priority to diagnoses with
lower ICD-10 codes (World Health Organization, 1992). According
to the diagnostic guidelines, a comorbid illness should be recorded
as an auxiliary diagnosis only when the comorbid illness is
independent of the primary illness. Auxiliary diagnoses are seldom
recorded in Denmark. Thus among patients with a main diagnosis
of bipolar disorder at rst contact, only between 20.8% (at the rst
contact) and 13.6% (at the 5th contact) got an auxiliary diagnosis of
any kind. Including such small gures of auxiliary diagnoses in the
analyses would only have changed our results marginally.
5. Conclusion
In conclusion, in a nationwide sample of all children and
adolescents who got an ICD-10 diagnosis of mania/bipolar disorder
at least once in a period from 1994 to 2012 during in- or outpatients
psychiatric treatment it was found that a minority of patients (40.7%)
got the diagnosis at the initial contact and the majority (59.3%) got
the diagnosis at later contacts. Approximately 24% of patients with an
initial diagnosis of mania/bipolar disorder eventually changed diagnosis during follow-up. Substantial proportions of patients initially
presented with depression or prodromal syndromes such as acute
and transient psychosis, reaction to stress/adjustment disorder or
mental or behavioral and emotional disorders with onset during
childhood or adolescents that subsequently developed into bipolar
disorder. Clinicians should be more observant on hypomanic and
manic symptoms who as rst glance present with these conditions
and follow these patients more closely over time identifying putable
hypomanic and manic symptoms as early as possible. On the other

421

hand, clinicians seem to be able to differentiate child and adolescent

mania/bipolar disorder from schizophrenia, anxiety disorders and
hyperkinetic disorder/ADHD.

Role of funding source

The study was funded by a NARSAD Distinguished Investigator Grant 2012,
(Grant no. 19796), New York but the funding source had no role in the design,
analyses or interpretation of the results.

Conict of interest
Lars Vedel Kessing has within the preceding three years been a consultant for
Lundbeck and AstraZenica.
Eleni Vradi and Per Kragh Andersen report no nancial disclosure and competing
interests.

Acknowledgment
None.

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