Psychiatric Hospital for Children and Adolescents, Aarhus University Hospital, Denmark
National Centre for Register-Based Research, Aarhus University, Denmark
Department of Biostatistics, Aarhus University, Denmark
Psychiatric Hospital for Children and Adolescents, Aarhus University Hospital, Denmark
Correspondence: Søren Dalsgaard, Psychiatric Hospital for Children and Adolescents, Harald Selmersvej 66, 8240 Risskov, Aarhus University Hospital, Denmark. E-mail: sda{at}buh.aaa.dk
Supported by The Danish Medical Council Research Foundation, Fru Hermansens Mindelegat and Rosalie Petersen Foundation.
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ABSTRACT |
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Aims To identify predictors for adult psychiatric outcome of children with ADHD, including gender and comorbidity.
Method Children aged 4-15 years, referred for hyperactivity/inattention and treated with stimulants were included (n=208). The Psychiatric Case Register provided follow-up data on psychiatric admissions in adulthood until a mean age of 31 years.
Results A total of 47 cases (22.6%) had a psychiatric admission in adulthood. Conduct problems in childhood were predictive (hazard ratio HR=2.3; 95% CI 1.22-4.33). Girls had a higher risk compared with boys (HR=2.4; 95% CI 1.1-5.6).
Conclusions Girls with ADHD had a higher risk of adult psychiatric admission than boys. Conduct problems were also associated with a higher risk. Girls with ADHD with conduct problems had a very high risk of a psychiatric admission in adulthood.
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INTRODUCTION |
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METHOD |
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Reliability
Reassessment of 191 case records for ADHD or hyperkinetic disorder and ODD
or conduct disorder was performed blindly by two independent raters: a
resident child and adolescent psychiatrist (rater 1); and an experienced
senior child psychiatrist (rater 2). The first 23 case records were included
in a consensus rating. After the consensus rating, the two raters did not
discuss their ratings of the remaining 168 cases. This reliability study of
ADHD diagnoses from 168 records showed a satisfactory agreement of 76% with a
corresponding Cohen's kappa of 0.51. The agreement on hyperkinetic disorder
was slightly better, at 77% and a kappa of 0.54. In diagnosing conduct
disorder and ODD, higher agreement percentages were found, in the range 73-92%
and kappas in the range 0.44-0.70. There were no gender differences in the
reliability of the diagnosis of ADHD in this reassessment. There was no
systematic difference in the rating of any of the specific ADHD or
hyperkinetic disorder items nor was there any significant difference in
associations between correlated items between the two raters. Rater 1
reassessed the complete sample of 208 cases and this rating was used as the
final diagnostic conclusion.
Assessment of adult psychiatric admissions
Data from the Danish Psychiatric Central Register (DPCR;
Munk-Jorgensen & Mortensen,
1997) gave complete follow-up information on all probands
regarding any in-patient and day patient psychiatric admissions. DPCR is a
nationwide computerised register containing data on all admissions to Danish
psychiatric in-patient facilities since April 1969 and also including
out-patient consultations at psychiatric departments since 1995. The register
contains data on dates of admissions, and discharges, terms of admissions,
ICD8 diagnoses (World Health
Organization, 1967) for the period 1969-1993 and ICD10
diagnoses (World Health Organization,
1992) from January 1994. Because all included patients had at
least one previous psychiatric admission, the index follow-up event was
defined as the first in-patient admission to a psychiatric hospital ward after
the age of 15 years. Data were censored on either the date of the first
psychiatric admission after the age of 15, date of death or 15 June 2000,
whichever came first. In terms of lifetime diagnosis of four disorders
schizophrenia, personality disorder, mood disorder and substance use disorder
during the 10- to 38-year follow-up period data were censored using
the same criteria. Cases with a lifetime diagnosis of one of these four
diagnoses were censored on the date of their first adult psychiatric admission
and those without a lifetime diagnosis of any of these four disorders but with
other disorders, were censored on the date of their first other adult
psychiatric admission.
Diagnostic groups
The follow-up register data included both ICD8 and ICD10
diagnoses. Eight different diagnostic groups were formed using the guidelines
provided by the World Health Organization
(1999): schizophrenia and
schizophreniform psychosis (295.09-295.99, 297.09-297.99, 298.39 and F20-29);
affective psychosis (296.09-296.99, 298.09, 298.19 and F30-39); antisocial
personality disorder (301.79, 301.39, 301.82, 301.83 and F60.2); other
personality disorders (301 and F60-69 except F60.2); mental retardation
(310-315 and F70-79); abuse of alcohol (291, 303 and F10.x); substance misuse
disorder (304 and F11-19); and finally the last group, including all other
diagnoses.
Statistical analysis
Follow-up data were analysed using survival analyses. KaplanMeier
survival plots were used in univariate analyses, and to test equality in
survival distributions for gender and conduct problems log rank tests were
applied. Hazard ratios (HRs) by Cox regression were used in the predictor
analyses, giving crude HRs with 95% confidence intervals for baseline
variables. In the multivariate analyses odds ratios were adjusted for gender
and conduct problems. Possible interactions between gender and conduct
problems and other potential long-term predictors were tested using Wald
tests. The SPSS 9.0 (SPSS Inc.,
1998) and STATA 6.0
(StataCorp, 1999) statistical
packages were used in the analyses.
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RESULTS |
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The most prevalent diagnosis at the first adult psychiatric admission was any personality disorder (accounting for 29% of the cases), half of which were antisocial personality disorder. The second most prevalent single diagnosis at first adult psychiatric admission was mood disorder. Personality disorder was also the most prevalent lifetime diagnosis in this follow-up until a mean age of 31 years. Although only two cases were given a diagnosis of schizophrenia at the first adult psychiatric admission, the lifetime prevalence for schizophrenia was much higher (3.8%), as shown in Table 2. The lifetime prevalence of antisocial personality disorder was 4.8%.
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Long-term predictors
Gender was the single most important predictor for a psychiatric admission
in adulthood. Thirty-two per cent of the female probands had a psychiatric
admission in adulthood. Being female was associated with a significantly
higher risk for a later admission (HR=2.42; 95% CI 1.05-5.62). A comorbid
diagnosis of either ODD or conduct disorder in childhood was also predictive
(HR=2.29; 95% CI 1.22-4.33). Most other comorbid disorders in childhood,
including learning and communication disorders and motor skills disorder,
lowered the risk of later psychiatric admissions, although not in a
statistically significant manner. A high total IQ was associated with a small
but statistically significantly higher risk. When adjusted for gender and
conduct problems the tendency was not significant. The adult psychiatric
outcome of children with definite ADHD was not different from the outcome of
children with sub-threshold or possible ADHD. The number of inattentive,
hyperactive or impulsive symptoms in childhood was not predictive nor was the
socio-economic status of the parents. A severe global impairment in childhood,
measured as a CGAS score below 50, did not increase the risk for an adult
psychiatric admission when adjusted for gender and conduct problems. Among
probands without conduct problems, 12% experienced a psychiatric admission in
the follow-up compared with 27% of the probands with conduct problems
(P=0.017). The overall results of the predictor analyses are shown in
Table 3. Duration of treatment
with stimulants in childhood was not associated significantly with the adult
psychiatric outcome, and did not predict later psychotic episodes or substance
misuse disorder.
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Gender and conduct problems
Girls with ADHD and comorbid conduct problems had a much higher risk of an
adult psychiatric admission compared with those without conduct problems
(HR=6.0; 95% CI 1.21-30.09). Of the 25 female probands, 10 had had comorbid
conduct problems in childhood. Sixty per cent of these females with ADHD and
comorbid conduct problems experienced an adult psychiatric admission. The
survival analysis according to both gender and the presence of ODD or conduct
disorder are shown in Fig. 1.
Independent of gender, the severity of the conduct problems also showed a
doseresponse relationship with adult psychiatric outcome. Mild conduct
problems tended to predict a higher risk; however, moderate or severe conduct
problems predicted a much higher risk and the poorest adult psychiatric
outcome (HR=3.10; 95% CI 1.35-7.16) compared with having no conduct problems.
The three most important ODD or conduct disorder symptoms in predicting poor
adult psychiatric outcome seem to be: has deliberately destroyed
others' property (other than fire setting) (OR=2.6; 95% CI 1.1-6.2);
is often truant from school, beginning before age 13 years
(OR=2.5; 95% CI 1.1-5.5); and often initiates physical fights
(OR=2.0; 95% CI 1.1-3.6). The last of these was a frequent comorbid symptom,
present in more than half the cases, whereas the first two symptoms were less
common. In a test for any possible interactions, tic disorder and gender was
the only significant interaction identified. Girls with comorbid tic disorder
had a significantly higher risk compared with boys with comorbid tics. Other
potential long-term predictors were also tested but no significant
interactions were identified.
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Predictors for lifetime diagnoses
The 10 cases with a later diagnosis of antisocial personality disorder all
had some conduct problems in childhood and a diagnosis of conduct disorder
predicted antisocial personality disorder (HR=3.78; 95% CI 1.06-13.44).
Antisocial personality disorder was not predicted by gender, IQ, duration of
stimulant treatment, or the degree of inattention, hyperactivity or
impulsivity in childhood. Being female predicted a lifetime diagnosis of
schizophrenia (HR=6.56; 95% CI 1.39-30.94). A comorbid diagnosis of ODD or
conduct disorder in childhood also tended to increase the risk, although not
statistically significantly when adjusted for gender. Comorbid anxiety in
childhood was not associated with later schizophrenia. Having mild or moderate
global impairment in childhood, with a CGAS above 50, tended to increase the
risk for a lifetime diagnosis of schizophrenia, compared with having severe
impairment. There was a higher risk for a lifetime diagnosis of a mood
disorder among girls (HR=5.30; 95% CI 1.24-22.67). Mood disorder was not
predicted by anxiety in childhood. Substance misuse disorder was associated
with being female (HR=18.33; 95% CI 3.17-105.96) and also predicted by ODD or
conduct disorder (HR=23.69; 95% CI 3.40-165.39).
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DISCUSSION |
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The present study does have limitations. First, the cases included were all referred to the same child and adolescent psychiatric clinic and were all treated with stimulants. Accordingly, our results might not be generalisable to community-based samples of children with ADHD. Second, in this historical follow-up study, the more specific characteristics of the cases in childhood were reassessed from case records, based upon secondary data. However, an interrater-reliability study was performed showing good quality of these data (Dalsgaard et al, 2001). Finally, as the study also aims to evaluate the long-term outcome of girls with ADHD and the predictive value of gender, it is a limitation to have included only 25 girls.
Psychiatric status in previous follow-up studies of children with
ADHD
Numerous follow-up studies have reported on the adolescent outcome of
children with ADHD, especially boys. Only three studies have focused on the
adult mental status. However, no studies have identified convincing, sturdy
predictors of adult mental outcome.
The Montreal Study conducted a 15-year follow-up study of 104 clinically referred probands (Weiss et al, 1985). Only 49-61% of the initial sample completed the follow-up at age 25 years. No specific variable predicted psychiatric outcome; however, low IQ and socio-economic status, emotional instability, aggressiveness and poor parental mental health predicted a poor global outcome (Hechtman et al, 1984). The New York studies were performed on clinical samples of boys with hyperactivity without any conduct problems, with follow-up at age 24 and 26 years (Mannuzza et al, 1993, 1998). Neither IQ nor parental psychopathology was predictive of adult outcome. Because children with comorbid conduct problems were excluded from these studies, the findings suggest that even children without conduct problems have a higher risk of antisocial personality disorder in adulthood compared with controls. A small subsample of hyperactive girls (n=12) were followed into adolescence (Mannuzza & Gittelman, 1984), and compared with male controls. The girls with ADHD had poorer outcome in terms of social, academic and behavioural functioning in adolescence. Unpublished data indicated that females in adulthood had better outcome than males, with lower risk of antisocial personality disorder and substance misuse disorder (Mannuzza & Klein, 2000). The Göteborg Community-Based Study (Rasmussen & Gillberg, 2000) was a long-term follow-up of 55 cases at age 22 years. A prediction analysis was not published but the poorest outcome was actually seen in cases with developmental coordination disorder only, without ADHD. The Loney Study found low IQ in childhood to be the strongest predictor of antisocial personality disorder and alcoholism (Loney et al, 1983). Aggression in childhood was associated with later weapon use, police contacts and the use of hallucinogens, but not with adult mental status.
The present study compared with previous follow-up studies
The prevalence of any psychiatric disorder in adulthood was slightly lower
in our study (23%) compared with previous studies (33-52%). This could be
explained by the fact that only psychiatric admissions to hospitals in
adulthood were used as a measure of outcome in the present study. Probands
might have developed psychiatric disorders in adulthood without being admitted
and the prevalence could thereby be underestimated. This could also explain
why the prevalence of antisocial personality disorder was lower than in
previous studies. Personality disorders and substance/alcohol misuse disorder
being the two most prevalent diagnoses at adult follow-up is very much
consistent with previous findings. The low prevalence rates of mood disorders
were also comparable. Both present and lifetime diagnoses of schizophrenia
were elevated in the present study compared with the previous studies; this
could be explained by the longer follow-up and the complete follow-up on all
probands in our study. Patients with psychosis are more likely to have been
missed because of attrition in previous long-term follow-up studies.
Comparison of predictors
No solid childhood characteristics have previously been found to predict
adult psychiatric outcome. IQ and parental socio-economic status have
previously been found to be associated negatively with a poorer global adult
outcome. Conduct problems in childhood have previously been found to predict
antisocial behaviour in adolescence but the previous longer follow-up studies
have not been able to conclude on the predictive value of such comorbidity.
The findings from the present study on the importance of conduct problems in
childhood in predicting adult psychiatric outcome is supported by the
short-term follow-up studies. In differentiating between conduct problems, not
only the aggressive symptoms seem to increase the risk of adult psychiatric
admissions.
When adjusting for gender and presence of conduct problems in childhood parental socio-economic status did not predict poor psychiatric outcome. The severity of inattentiveness, hyperactivity and impulsivity did not predict adult psychiatric status, nor did global impairment measured with CGAS when adjusted for gender and conduct problems. Duration of stimulant treatment was not randomised in the present study and the association between long duration and later adult psychiatric admissions is most likely to be caused by higher severity or more impairment of the cases treated longer (Hechtman et al, 1981). Regarding IQ, the present study found a very small but significant association but the direction of this was opposite to previous findings, as a higher IQ predicted a poorer outcome (crude HR=1.22; 95% CI 1.01-1.47 per 10 IQ points). Indeed, IQ was not a strong predictor in the present study. In the interpretation of the results it is important to emphasise that the predictive value of a large number of variables was tested in the present study. In the systematic analyses of interactions, the small sample size in the different groups gives very little data and limited information on interactions.
Gender as a predictor
Girls with ADHD often differ from boys in terms of lower levels of
hyperactivity and lower rates of externalising behaviours. Although boys more
often have comorbid conduct problems, girls with ADHD and ODD or conduct
disorder might have more social problems than boys
(Carlson et al, 1997;
Gaub & Carlson, 1997; Faraone et al, 2000).
It has also been suggested that girls with ADHD are less vulnerable to
deficits in executive functions than boys with ADHD
(Seidman et al,
1997). A recently published brain imaging study suggests that some
of the morphological differences seen in boys with ADHD are also seen in girls
with ADHD (Castellanos et al,
2001). Overall, the research on gender differences in ADHD have
not established any good biological differences, although girls with ADHD have
different neuropsychological profiles, patterns of comorbidity, severity of
core symptoms and impairment in social functioning compared with boys with
ADHD.
Our study suggests that girls with ADHD might have a poorer adult psychiatric outcome than boys with ADHD. However, the gender differences in risk of a psychiatric admission in adulthood found in the present study might only reflect a high risk for women in general. The finding could also be explained by a true biological gender difference in the disorder or a different threshold for referral for girls. Although girls seldom exhibit comorbid conduct problems, such comorbidity in girls seems to be far more important in predicting adult psychiatric outcome than IQ, parental socio-economic status, global impairment and severity of core symptoms of ADHD. More long-term studies on larger samples of girls with ADHD, are needed to confirm this.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication January 2, 2002. Revision received May 8, 2002. Accepted for publication May 29, 2002.
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