Download Discovering the individual behind the diagnosis of conduct disorder

Discovering the individual behind the diagnosis of conduct
disorder
Master thesis in Medicine
30 ECTS
Hannah Tolge
Supervisor: Nóra Kerekes, Ph. D
CELAM (Centre for Ethic Law and Mental Heath)
Institute of Neuroscience and Physiology
Program of Medicine
Gothenburg, Sweden 2012
Abstract
Background. Understanding the etiology of conduct disorder (CD) and
commonalities with coexisting psychiatric complications is of essential value
since children with CD have an increased risk for developing most psychiatric
problems in adolescent and adulthood.
Aims. The present study aims a) to compare register information to parental
reports on prevalence of CD; b) to describe the distribution of CD problems and
study the overlap with other neuropsychiatric and birth complications, and c) to
map all coexisting neuropsychiatric and birth complications of probands,
according to zygosity and gender, and to compare these with co-twins.
Method. A cohort was selected from the ongoing twin-study CATSS 9/12, born
between 1st of July 1992 and 31st December 2000, where at least one of the
twins were screened positive for autism spectrum disorder (ASD), CD and/ or
eating disorders, resulting in 2036 children. This database was further merged
with the National Patient Register and the Swedish Medical Birth Register.
.
Results. In this enriched population, 37 % of children had conduct problems
and 9 % reached CD diagnosis but only 1 % had been recognized of the Health
Registers with a diagnose. The prevalence of CD was close to twice as high in
boys than in girls.
While the prevalence of CD declined (both genders) with rising severity, the
prevalence of coexisting disorders (e.g.: oppositional defiant disorder, attention
deficit hyperactivity disorder and/or ASD) were shown to markedly increase.
2 Monozygotic co-twins (both genders) and dizygotic co-twin girls showed
similar number of coexisting psychiatric problems as their twin proband, while
dizygotic co-twin boys had about half as much coexisting problems.
The prevalence of birth complications was not correlated to severity of CD.
Conclusion. This study was able to confirm the over-representation of boys
over girls confined to a CD diagnosis. We have seen that the prevalence of many
other co-existing psychiatric problems increases with the severity of CD. Gender
specific genetic influences are suggested behind the development of CD.
Key words: conduct disorder, twin-study, neurodevelopmental disorders
3 Table of contents
Introduction
-Background
-Swedish Child and Adolescent psychiatry
-Defining (diagnosing) Conduct Disorder
-The risk of developing antisocial personality disorder
Aims/ specific objectives
Material and methods
Results
-Register reports and parental reports
-Distribution of CD problems and prevalence of concurring
complications based on the severity of CD
-Prevalence of neurodevelopmental-, psychiatric problems and
birth complications according to zygosity
Discussion
- Clinical relevance
- Conclusion
Appendix I
DSM-IV Conduct disorder
Appendix II
A-TAC Conduct disorder module
Appendix III
Interventions for treatment of CD
References
4 Introduction
Background
Rarely appearing inappropriate behaviors of children (lying, refusing to comply
and occasionally getting involved in fights) are part of the process of growing up
when occurring in an isolated manner. This normative and often short-lived noncompliance is fueled by the desire to do something autonomously and with the
child’s growing self-assertion. But with active non-compliance (oppositional
behavior) a child resists its caregiver in a more significant, intransigent way
(Matthys and Lochman 2010). In DSM-IV the “mildest” cluster of such
inappropriate behaviors define the diagnose of oppositional defiant disorder
(ODD), one of three diagnoses building up the childhood disruptive behavior
triad of ODD, attention deficit hyperactivity disorder (ADHD) and conduct
disorder (CD). Among the three, conduct disorder represents the most serious
disruptive behavior, consistently and aggressively violating age-appropriate
social expectations and norms. In DSM-IV the disorders ODD and CD alone
constitutes the category known as “disruptive behavior disorders“ (DBD’s).
CD problems, mainly in comorbid diagnose with ADHD, are known to be
associated with an increased long-term risk for antisocial personality disorder
(ASPD) and criminality, substance abuse and most adult types of mental
disorder in general. Previous twin-studies have suggested a strong genetic factor
effect explaining the inter-individual variance in aggressive antisociality,
including CD (Nadder, Rutter et al. 2002; Dick, Viken et al. 2005; Dick, Meyers
5 et al. 2010; Dick, Aliev et al. 2011), proposing that there are common genetic
factors behind CD and criminality.
Supporting the suspected high risk of entering criminality if diagnosed with CD,
a Scandinavian (Norwegian) study of adolescent psychiatric in-patients
(diagnosed with DBD’s, substance abuse disorder (SUD), or a combination of
both) showed a 70% risk of having been convicted of a crime at follow up 15-33
years after admission (Kjelsberg and Dahl 1998). In all, 63% of the males had a
criminality record at follow up which was more than six times the prevalence for
male criminality in the general Norwegian population at that time. Crimes
against property, violence and drug offences were the most commonly
committed offences. The study population also showed a significantly higher
disability rate (38,9 %) than the general population (5,7 %). There was a
significantly higher mortality rate at follow up compared to the general
population. These findings are consistent with previous studies showing that
children referred for antisocial behaviour have a worse outcome than those with
other symptoms at referral (Robins 1996) and with the proposed gender
difference giving greater risk for males with CD of developing ASPD than girls
(Offord and Bennett 1994).
Preliminary results from a recent Swedish population-based epidemiological
study indicate that early age at onset of criminality (defining CD) is one of the
strongest predictors of persistent violence (Falk et al, in preparation). In an ongoing study mapping psychiatric conditions of young adult prisoners (aged 1825), sentenced for violent crime in the Region West of the Swedish Prison and
Probation Services, it is shown that about 70 % of these perpetrators had a CD
diagnose in childhood, 39 % were admitted to youth institutions and 40 % had
6 previous child- and adolescence psychiatric (CAP) contact (unpublished results
from DisCat 2.0 study).
Swedish Child and Adolescent psychiatry
Since 1956 Swedish Child and Adolescent psychiatry (CAP) in Sweden is an
independent member organization of the Swedish Society of Medicine. The
upper age limit for receiving CAP care is 18 years and the modern focus
predominantly lies on out-patient care, a reduction of in-patient beds by nearly
90 % have been shown from 1967-2006, in particular after 1990. The CAP
research tradition includes longitudinal studies from childhood contact with
CAP into juvenile delinquency. In 2007 a Swedish research team (Engqvist and
Rydelius 2007) showed that every third patient leaving treatment from a CAP
unit in Jämtland County (1975-1990) had entered the Register of Persons
Convicted of Offences at the National Council for Crime Prevention (NCCP)
some time before the end of 2003. Several other Swedish prospective and
retrospective longitudinal CAP research studies have pointed out that it is school
problems, behavioural disturbances and dysfunctional family situations that
count for the majority of reasons for families to seek CAP care, and that
problems in adulthood with drug and alcohol abuse as well as registered
criminality can be retro prospectively linked back to this same panorama of
childhood problems in former CAP patients.
7 Defining (diagnosing) Conduct Disorder
DSM-IV
In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR),
(APA 2000), CD is described as ”a repetitive and persistent pattern of behavior
in which the basic rights of others or major age-appropriate societal norms or
rules are violated”. The pattern of incorrect behaviour falls into subcategories of
aggression to people and animals, destruction of property, deceitfulness or theft
and serious violation of rules. For a list of the complete diagnostic criteria, see
Appendix I.
The disturbance must be shown to cause clinically significant impairment in
social, academic or occupational functioning. For individuals aged 18 years or
older, criteria for Antisocial Personality Disorder must not be met. Conduct
Disorder is further subdivided into a Childhood-onset Type with the observed
onset of at least one criterion prior to age 10 years, and an Adolescent-onset
Type where no criteria were met prior to age 10 years.
The severity of Conduct Disorder specifies as mild, moderate and severe
depending on the severity of unique criteria (i.e., considerable harm to others)
and/or number of all criteria met. Most children meeting criteria for Childhoodonset Type CD do also meet criteria for ODD, which is why manifestation of
CD is an exclusion criterion for the ODD diagnose according to the DSM-IV.
For a review see Lahey 1992 (Lahey, Loeber et al. 1992).
The”developmental taxonomic theory” proposes that neurodevelopmental
factors play a critical role in the ethiology of the Childhood-onset Type of CD,
but that the Adolescent-onset Type develops in response to interactions with
8 deviant peers and not as a result of neurobiological factors (Moffitt 1993) . This
theory have recently been challenged in a number of ways showing the same
impairments regardless of subtype of CD concerning affective decision making
(Fairchild, van Goozen et al. 2009), fear conditioning (Fairchild, Van Goozen et
al. 2008) and facial expression recognition (Fairchild, Van Goozen et al. 2009;
Fairchild, Stobbe et al. 2010). There is today substantial evidence of volumetric
differences of sub cortical structures in patients with both early and late onset of
CD showing reduced bilateral grey matter volume in amygdala (independent of
the CD-subtype) in male adolescents regardless of age at onset, found by
structural neuroimaging (MRI). The grey matter volume was reduced in the left
ventral insula and in the left dorsomedial prefrontal cortex and bilaterally in the
caudate nucleus as well, findings in all supporting conduct disorder to stem from
a dysfunction in neural circuits involved in emotional processing (Fairchild,
Passamonti et al. 2011).
ICD-10
The International Classification of Diseases (ICD) represents WHO’s standard
diagnostic tool for epidemiology and health management. Conduct disorders are
here grouped under code F91 with sub-grouping into socialized or nonsocialized, or “confined to the family context” variants. In ICD-10 (2010) CD is
defined as an enduring pattern of behavior (six months or longer) of dissocial,
aggressive or defiant conduct with major violations of age-appropriate social
expectations. The diagnose is based on behaviors that include ”excessive levels
of fighting or bullying, cruelty to other people or animals, severe destructiveness
9 to property, fire-setting, stealing, repeated lying, truancy from school and
running away from home, unusually frequent and severe temper tantrums, and
disobedience.” Any marked behavior is, according to ICD-10, alone sufficient
for the diagnosis - but isolated acting-outs are not.
ODD and CD were formerly quite generally accepted to be different age-related
conditions of the same disorder with CD more often occurring in older
childhood and in adolescents (Loeber, Burke et al. 2000). Interestingly enough,
in ICD-10, ODD is categorized into the conduct disorders group - although CD
is today generally quite accepted being a separate and more serious disorder
than ODD.
A-TAC
Childhood psychiatric problems may be screened for by the Autism- Tics,
ADHD and other Comorbidities inventory (A-TAC), a validated parental
telephone interview instrument (Larson, Anckarsater et al. 2010). The A-TAC
contains 5 gate questions addressing CD, each scored as 1 point for the child if it
is “true”, 0.5 point if “true in some extent”, and 0 point if it is “not true”.
Consequently the most severe cases will have 5 points in A-TAC’s CD module.
Clinical validation of A-TAC’s psychometric properties regarding CD (Kerekes
et al, in progress) gave a 0.95 “Area Under the Curve” for the CD module and
had with the suggested cutoff ≥ 2 for a CD diagnosis, good sensitivity (0.67) and
excellent specificity (0.96). For a closer look at the CD related items in A-TAC,
please see Appendix II.
10 The risk of developing antisocial personality disorder
The presence of CD in adolescence is a prerequisite for the diagnose of ASPD
(DSM-IV), but to rely on CD alone in predicting future ASPD in adulthood have
shown to yield a substantial amount of false positive predictions since not all
CD patients develop ASPD (Storm-Mathisen and Vaglum 1994; Maughan and
Taylor 2001; Lahey, Loeber et al. 2005). ODD in early childhood and CD in
adolescence may predict the possibility of future development of ASPD, but
neither ADHD nor substance abuse seems to have the same potential alone
(Diamantopoulou, Verhulst et al. 2010). Other authors argue that it is the
adolescents’ unique mixture of internalizing (for instance anxiety and
depression) and externalizing problems (acting-outs of aggression and/ or
delinquent behavior) and not the CD per se, that predicts serious antisocial
development (Fombonne, Wostear et al. 2001; Sourander, Jensen et al. 2007).
Yet retrospective studies show that a presence of early childhood CD in ASPD
patients can be up to 75% (Gelhorn, Sakai et al. 2007). A previously mentioned
recent Swedish study has shown that 63% of the violent convictions are received
by the 1% of the population who are persistent (accounting for three convictions
or more) violent offenders. Belonging to this group is foremost predicted by
male sex, any personality disorder, first violent conviction before age 19
(defining CD) and by drug-related offences (Falk et al, in progress).
In conclusion, the pronounced risk for adolescents with CD of becoming a
persistently violent offender, developing ASPD and/or SUD (as well as other
both psychiatric and somatic problems) and the suggested strong genetic
influence on the phenotype (criminality), raise the need for studies both
11 revealing the true prevalence of CD in children and mapping the frequency of
possible psychiatric comorbidities. The genetic component to the development
of CD (and possible contribution to an overlap of other disorders) may be
investigated using twin-sampling where monozygotes (MZ) share 100% of their
genes and dizygotes (DZ) (further subdivided into dizygotes of the same sex
(DZss) or different sex (DZds)) on average share 50% of their genes.
Prevention of the initial onset of conduct problems is an important way of
hindering development of ASPD, according to Tremblay (Farrington and Coid
2003), further motivating the need of early detection. For possible medical and
non-medical interventions in treating CD, see discussion.
12 Aims/ specific objectives
1. To compare information retrieved from registers to parental reports
regarding the prevalence of conduct disorder in an enriched population,
consisting of twin-pairs with at least one twin affected with neuropsychiatric
disorders.
2. To describe the prevalence of affected children (boys and girls separate) and
the overlap with other complications based on the severity of CD.
3. To describe CD probands, according to zygosity and gender, and their cotwins by the prevalence of neurodevelopmental, psychiatric problems and
birth complications.
13 Material and methods
The ongoing longitudinal Child and Adolescent Twin Study in Sweden
(CATSS) accumulates nation-wide data on somatic and mental health problems
in twins during childhood and adolescence, currently including over 20 000
children. CATSS-9/12 allows for systematic assessment of neurodevelopmental
problems at a baseline of nine or twelve years age, when the parents of twins are
asked to participate in a telephone interview about their children’s somatic and
mental health. Children are by this way indirectly screened for childhood
psychiatric problems using the Autism- Tics, ADHD and other Comorbidities
inventory (A-TAC), a validated screening instrument (Larson, Anckarsater et al.
2010).
Briefly, CATSS-9/12 is a twin study that targets all twins born in Sweden since
the 1st of July 1992. In connection with the children’s 9th (or during the first 3
years of the CATSS-9/12 with the children’s 12th) birthdays parents have since
2004 been interviewed by lay interviewers. In the telephone interview many
inventories are used; among others the A-TAC inventory covering all major
clinical diagnostic criteria (according to DSM-IV) in child and adolescent
psychiatry. Parents response rate has (as far as 2010) been high (80 %) with a
dominance of mothers as responders (87,5 %). Questions in the survey are
formulated so that they concern each twin separately and to a life span
perspective. For detailed description of the CATSS, see Anckarsäter
(Anckarsater, Lundstrom et al. 2011).
14 From birth cohorts between 1st of July 1992 and 31st of December 2000, a
number of 1060 twin pairs were selected where at least one of the twins had
been screened positive by the A-TAC for Autism Spectrum Disorders (ASD),
CD and/or eating disorders (ED) (this affected twin referred to as a proband).
Co-twins to the probands were by this way included regardless of being screenpositive or not. For these 1060 twin pairs register data was collected from the
National Health Registers i.e. the National Patient Register (NPR) and the
Swedish Medical Birth Register (MFR) yielding information on in- and (since
2001) outpatient care from private and public caregivers about any possible CD
diagnose according DSM-IV or ICD-10 criteria. The database was by this way
also supplemented with reports on the infants’ prenatal, delivery and neonatal
care (Rosén 2003; Socialstyrelsen 2012; Socialstyrelsen 2012). The screening
for CD was completed with information from parents about any possible
existing CD diagnosis or about placement into Institutional Youth care.
Children with brain damage or known chromosomal aberrations were excluded
from the present study (57 because of brain damage, 25 with chromosomal
aberrations and 2 affected with both) resulting in a working database (the studypopulation) of 2036 children: 1192 boys and 844 girls.
In the study population there were 424 monozygotic (MZ), 808 same-sex
dizygotic (DZss), 50 different-sex dizygotic (DZds) and 754”unknown zygotic”
children. The zygosity was determined either by DNA sampling (saliva) or with
a validated questionnaire having 95 % accuracy. The study population was
further reduced by five children (all boys), who had more than 5 % missing data
in the A-TAC, from 2036 to 2031 children: 1187 boys and 844 girls.
15 The A-TAC inventory contains scales to assess both ODD and CD. It was
developed exclusively for the CATSS with originally 11 items defining
[ODD+CD] joined in a single module ”conduct”. The first validation study of
A-TAC (Hansson, Svanstrom Rojvall et al. 2005) showed an overall inter-rater
and test-retest reliability of 1.00 and 0.93 respectively, but the ODD/CD scales
at this time could not be validated due to a restricted number of affected children
(small study population).
Since the same was true for the next validation study (Larson, Anckarsater et al.
2010), the existing scales were supplemented with additional items while some
items were removed (as they decreased Chronbach’s alpha), and finally the
module was split into two new modules ”Opposition” and ”Conduct”. Later on a
gate structure was established, opening for further questions if partially or fully
endorsing one or several of the ”gate-items”.
The ability of the ”gate scales” to identify children with significant behavior
problems has been tested in the CATSS pilot study and proved successful in
identifying 24 out of 25 children with significant CD problems (96,0 %) and 42
out of 43 children with significant ODD related problems (97,7 %). The
Cronbach’s alphas were 0.552 and 0.841 for the final CD and ODD modules
respectively. Each module has a gate-, a DSM-, and a total score corresponding
to gate items, DSM-IV criteria items and to the sum of all items in the module.
The high correlation between the CD module’s ”gate” and ”total” A-TAC scores
was recently replicated merging A-TAC data on institutionalized adolescents
with controls from the second clinical validation study of the A-TAC (Larson,
Anckarsater et al. 2010). Children with any DSM-IV ODD criterion met to at
least some extent (score ≥ 0,5p) were to 88 % detected by the gate scores alone.
16 With one fully met criterion or two ”to some extent” (score ≥ 1p), 96 % was
detected. For CD the corresponding figures were 86 % and 96 % respectively
indicating that the gate scales have very good screening properties for both
conditions. With the different scales assessed as predictors in Receiver
Operating Characteristics (ROC) curves (using clinical diagnoses of CD as
dependent variables) excellent predictive ability for this disruptive behavior
disorder was shown.
In the present study the revised version of A-TAC was used including 5 gate
questions addressing CD. Further selection of children after gate score variables
was in the present study done by using A-TAC cut-offs of ”CD low” (gate score
≥1, representing signs of conduct problems), and ”CD high” (gate score ≥2,
corresponding to a CD diagnose). These cut-offs have high specificity (0.95 and
0.98) and high to moderate sensitivity (0.84 and 0.55 respectively) and are as
such recommended for screening children for CD in epidemiological studies
(Kerekes et al, 2012, unpublished validation of A-TAC: FV Module O+P).
Psychometric properties of A-TAC CD module is summarized in Table 1.
17 Table 1. Psychometric features of the CD module in A-TAC
Children screened positive for CD (low cut-off) in the A-TAC, and/ or having a
register diagnose of F91 (behavior disorders of acting out), F90.1 (hyperactive
behavior disorder) (ICD-9), 312.8 (conduct disorder), 312.9 (disruptive behavior
disorder) (DSM-IV) and/ or having parent reports on being placed in Youth
Institutional Care for treatment or placed in some ”other care”, were selected as
probands for further descriptive analyses. Children screening positive for CD
high (≥2 gate score points) formed the CD diagnosis group in prevalence
analyses.
All personal data were unidentified, blinded for the researchers and statistically
analyzed using IBM SPSS-19.
18 Results
Register reports and parental reports
In the study population of 2031 children, 37% (N=753) were to any extent
affected by conduct problems (CD_any) of which 750 children were identified
by the A-TAC (CD low cut_off). Of these 753 children 477 were boys and 276
girls.
Further on, 9 % (N=177; 119 boys and 58 girls) met criteria of CD diagnosis (≥2
in the A-TAC) and 17 children scored 4 points or more, constituting the 1% of
the study population (and 2% of the children above low cut_off), that are most
severely affected by CD.
Comparing these figures to the register reports where only seven boys and four
girls were registered with diagnosed CD, a 1 % recognition rate of CD problems
by registers can be concluded.
Distribution of CD problems and prevalence of concurring complications
based on the severity of CD
As already mentioned, 119 boys and 58 girls met the criteria of CD diagnosis in
this study (Figure 1). No girl reached the maximal 5 CD gate points and only
one girl received 4,5p. Regarding the opposite sex, four boys scored 5p, and
three received 4,5p. The declining prevalence with rising severity of CD was
evident (Figure 2).
19 Figure 1: Prevalence of children scoring 2-5p in the A-TAC CD module;
N=177
Figure 2: Numbers of children with CD diagnosis by gender; (N=177; 119 boys
and 58 girls)
20 The overlap of epilepsy (EP) and CD problems was analyzed and showed that of
59 boys and 33 girls in the study population affected by EP (N=92; 4,5 % of the
total study population), 25 boys and 9 girls also had CD problems. The
prevalence of EP was equal (about 4 %) in children without any CD problems,
in children with few CD points and in children with CD diagnosis (Figure 3).
Figure 3: Prevalence of epilepsy in children with defined CD gate points
(N=92).
The prevalence of child psychiatric problems and birth complications were
evaluated in relation to the severity of CD. The prevalence of co-occurring
disorders of ODD, ADHD and ASD were all shown to markedly rise in
adherence to the severity of CD. ODD was present in 100 % of all children
scoring 3p or above in the CD gate questions of A-TAC. The prevalence of Tics,
on the other hand, only discretely rose and that of ED was shown to be constant
with increasing severity of CD (Figure 4)
21 Figure 4.
Mental Retardation (MR) was more frequent in girls affected with CD than it
was in affected boys (Table 2). The amount of birth complications in the study
group was constantly high (42 %) with a close to equal gender distribution
(Figure 4)(Table 2).
The gender wise prevalence of concurring complications to a proposed CD
diagnose (scoring 2p or above in the CD gate questions in the A-TAC) is shown
in Table 2.
Table 2. Prevalence of coexisting problems in probands with a “CD diagnose”
22 Prevalence of neurodevelopmental-, psychiatric problems and birth
complications, according to zygosity
The prevalence of coexisting complications to CD, i.e. the neurodevelopmental
problems of ODD, ADHD, ASD, Tics disorder and ED, as well as the existence
of mental retardation (MR) and/ or birth complications were investigated taking
into account not only the severity of conduct problems, but also zygosity and
gender. All probands with an A-TAC CD gate score of 3 points or more (N=59;
39 boys and 20 girls) and their co-twins were included in this part of the study.
The resulting “color maps” of probands are summarized in Table 3 and for cotwins in Table 4. The sum of co-existing complications is shown in a separate
column, named the “composite” variable. For convenience (and comparability
between probands and co-twins), CD problems (CD_any) count as one
complication in the composite scores.
Table 3. MZ, DZss and DZds probands, their coexisting complications and their
composite measure.
23 24 The mean value of the number of complications in each zygosity-class was
calculated (the mean composite).
MZ probands (N=12) on average showed five complications, including CD,
while DZ probands (N=47; DZss and DZds calculated together) on average had
four. Since zygosity being a proband is of little interest, though, we then
calculated the mean complication rate for all probands to be four.
No gender differences were shown in the mean amount of complications.
The mean value of complications for the MZ co-twins was 4,5 while DZ cotwins (DZss and DZds together) on average had 2 complications, including CD
if present.
Table 4. MZ, DZss and DZds co-twins, their coexisting complications and their
composite measure.
25 26 Finally, the presence of CD problems within twin-pairs was visualized by
accounting for zygosity and gender, resulting in two genograms (Figure 5).
The average point difference between MZ boys and girls were the similar just
between 1 and 1.5 point differences (1.4 for boys and 1.25 for girls). For DZ
however, differences increased between twins, but most obviously for boys (2.7
for boys and 1.9 for girls).
Figure 5.
27 28 Discussion
Main findings
Twin studies make it possible to evaluate genetic and environmental
components of a behavioral trait by comparing the correlations between
monozygotic twin-pairs and dizygotic in terms of hereditability, shared
environmental influence and non-shared environmental influences (influences
that are experienced differently between members of the family).
CD was two times as prevalent in boys as in girls. Male gender is a risk factor
for neuropsychiatric problems (ADHD, ASD) and for aggressive behaviors
(ODD, CD, ASPD) (Gillberg 2010). The paradoxical gender effect or “The
Gender Paradox Hypothesis” saying that boys are more likely to be referred for
treatment than girls while girls seem to be more seriously affected while referred
(Eme 1992; Loeber and Keenan 1994), could though not be confirmed by our
study since the girls on average scored below boys in the A-TAC module. The
skewed gender prevalence of CD, more frequent in boys than in girls at this age,
was though confirmed in this study as previously shown (Bongers, Koot et al.
2004).
Only 6 % of the children scoring positive for a CD diagnose in our study were
also found in the official registers as already being diagnosed by a psychiatrist.
This low detection level could be due to the fact that children whose parents
seek referral for their child may originate from better socioeconomic
environments than others, making the number of unrecorded cases high, or the
fact that there have been a big discrepancy in grouping definitions seen by the
use of DSM-III to DSM-IV, ICD, and other different behavior rating scales. It
29 also seems reasonable to suppose that the significant overlap of childhood
psychiatric disorders (also shown in this study) makes the diagnostic situation
scattered and sometimes obscure.
Prevalence of EP was about the same in children without any CD problems, as
in children with few or very severe CD problems. Our results thereby support
previous findings of no direct association between EP and aggressive behavior
in children (Grunberg and Pond 1957; Caplan, Arbelle et al. 1997; Schoenfeld,
Seidenberg et al. 1999; Dunn 2003). The prevalence of ED and Tics did not
change with severity of CD.
Very high coexistence of ODD and ADHD followed by ASD were shown.
The MZ co-twins to a pronounced CD affected proband (screened >= 3p in the
A-TAC) showed a mean of four comorbidities, including existing diagnostic CD
as one if present. Comparing this to DZ co-twins with a mean value of two
comorbidities, this suggests a pronounced shared genetic vulnerability of
neuropsychiatric disorders in general.
Prevalence of MR in girls affected by CD was higher than in affected boys.
The rate of birth complications were high (though expected when taken into
account that the study population consisted of twins) but did not seem to
correlate with CD or it’s severity, being constant in the whole study population,
independent from existing or not existing CD problems.
30 Clinical implications
The fact that proband children in our study on average had 4-5 coexisting
disorders, including CD, both disorder-specific and possible additive effects
have to be considered in selecting appropriate multimodal interventions.
Having a child with CD causes distress to the family aggravating family
problems that in turn may worsen the CD. Several psychological techniques
have been tried, including behavior modification, working with parenting
techniques and tight supervision, according to Chandler (Chandler 2012), the
best results being shown with ”multisystem therapy”, i.e., working on several
interventions at the same time using pharmacological treatment of co morbid
disorders as well as non-medical strategies (For possible interventions, see
Appendix III). The longer the psychiatric problems go on in childhood and
adolescence the greater the risk of developing personality disorders as adults,
especially Borderline Personality Disorder and Antisocial Personality Disorder
both belonging to cluster B (Kasen, Cohen et al. 1999).
Limitations
Register data is probably partial/ not complete. It is possible that parents only
seek contact with CAP when behavior problems grow extreme. Parents may feel
ashamed to seek help with aggressive children, or lack the ability or insight to
do so due to their own psychiatric problems and/ or problems with drugs or
criminality.
31 The analyses in this study were not controlled for socioeconomic status of the
families, which has been shown to be strongly associated to aggressive behavior
in children, e.i. CD (D'Onofrio, Goodnight et al. 2009), ODD and ADHD
(Diamantopoulou, Verhulst et al. 2010). The study population was enriched to
defined psychiatric problems (CD, ASD and ED) and the study therefore could
not be used to determine the prevalence of CD and other psychiatric problems in
a normal population, but the association between these yet to be studied.
The parental (mainly maternal) reporting may be skewed in favour of the less
affected co-twin (Simonoff, Pickles et al. 1998) or the twin-pair may show
competitive effects where symptoms of one twin reduce the same in the other
(Eaves, Silberg et al. 1997). For this reason it would be desirable to use reports
from teachers as well. Twins do not differ significantly in prevalence of
psychiatric disorders, compared to singletons (Kendler, Martin et al. 1995;
Pulkkinen, Vaalamo et al. 2003), but there is some evidence for small elevations
in childhood and adolescent problem behaviour prevalence in twin-pairs (Gau,
Silberg et al. 1992; Levy, Hay et al. 1996).
The children are evaluated at age 9 or 12 years in this study. Conduct disorder in
its Adolescent form (according to DSM-IV) develops after 10 years of age, and
is thereby in risk of missing out in this study whereas ODD (being a disorder of
primarily early childhood) aught to be more accurately represented.
The developmental continuity model of ODD/ADHD developing into CD and
later ASPD (Loeber, Burke et al. 2000) was recently replicated in a large
community-based sample (the Zuid-Holland-longitudinal study of Verhulst,
1985) where development of CD could be predicted by ODD or [ODD+ADHD]
32 in early childhood (Diamantopoulou, Verhulst et al. 2010). Bearing this in mind,
it is possible that the children in our study not yet fully meeting the screening
criteria for a CD diagnose - but for ODD - are about of developing CD,
especially if charged by further comorbid disorders (ADHD, ASD, MR). Other
studies have though shown that only 50 % of children with ODD as preschoolers will have any remaining psychiatiric disorder by age 8 (Lavigne,
Cicchetti et al. 2001). It would be interesting to further assess and compare data
from probands scoring 2 and 2,5 gate points in the A-TAC CD module, thereby
encompassing all screen-positive children of a CD diagnose to the study. Further
work will be done on that.
Finally, when using cut-offs in epidemiological studies one must not forget the
risk of categorizing individuals based on dichotomous variables alone, since
behavioural studies have shown similar etiological factors behind extreme
scores and the full distribution.
Strength of the study
This study has the advantage of presenting the results of seven psychiatric
disorders, as well as the presence of birth complications, assessed in a single
sample. The comparisons made are therefore not confounded with sample
design or analytic differences. The most important finding of this study was that
children with diagnostic CD had many other coexisting psychiatry problems as
well (on average three). In addition, increasing severity of CD was linked to an
increasing number of coexisting psychiatric problems.
33 All children with pronounced CD (scoring 3 p or more in the A-TAC) also
screened positive for ODD. High overlap between ODD and CD is expected due
to the fact that CD exists in both a Childhood onset Type and an Adolescent
onset type and revisions might be done in the forthcoming DSM-V.
In this study, 62 % of MZ co-twins to a proband with CD (50 % of MZ boys, 75
% of MZ girls) have CD while the prevalence of CD in DZ co-twins was 27 %
(19 % of DZ boys, 44 % of DZ girls). The prevalence of CD in co-twins being
doubled in MZ compared to DZ co-twins, suggests that the development of CD
is coupled with strong genetic background factors. Previous twin studies have
already pointed out the importance of genetic factors but emphasize the effects
of common environmental effects as well (Eaves, Silberg et al. 1997; Dick,
Viken et al. 2005; Ehringer, Rhee et al. 2006; Frisell, Pawitan et al. 2012). One
twin-study conducted with other siblings included, showed a risk of 38 % for a
brother to a proband of being diagnosed with CD, compared to 26 % for a
random male (Ehringer, Rhee et al. 2006). This and our study together show not
only the heritability of the conduct trait but also that the majority of the variation
still is a combination of both genetics and environment.
Ethical considerations
The CATSS-9/12 study has ethical approval from the Karolinska Institute
Ethical Review Board: Dnr 03-672 and 2010/507-31/1.
34 Acknowledgements
I would like to express my gratitude to my supervisor Nóra Kerekes for her dedication and valuable input and to the staff in CELAM, especially to prof. Henrik Anckarsäter and Thomas Nilsson, for their assistance and great ideas that improved the project. And I would also want to thank all cats(s), dogs and horses in my life along with my wonderful children not at least Samuel, born during the project, for their constant well of inspiration.
35 Appendix I: DSM-IV criteria for conduct disorder
In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR),
published by the American Psychiatric Asssociation, CD is described as ”a
repetitive and persistent pattern of behavior in which the basic rights of others or
major age-appropriate societal norms or rules are violated” with at least three of
the following criteria present over the last 12 months and at least one present the
last six months:
Aggression to people and animals
1.
often bullies, threatens, or intimidates others
2.
often initiates physical fights
3.
has used a weapon that can cause serious physical harm to others
(e.g., a bat, brick, broken bottle, knife, gun)
4.
has been physically cruel to people
5.
has been physically cruel to animals
6.
has stolen while confronting a victim (e.g., mugging, purse
snatching, extortion, armed robbery)
7.
has forced someone into sexual activity
Destruction of property
8.
has deliberately engaged in fire setting with the intention of
causing serious damage
9.
has deliberately destroyed others’ property (other than by fire
setting)
36 Deceitfulness or theft
10.
has broken into someone else’s house, building, or car
11.
often lies to obtain goods or favours or to avoid obligations (i.e.,
”cons” others)
12.
has stolen items of nontrivial value without confronting a victim
(e.g., shoplifting, but without breaking and entering; forgery)
Serious violations of rules
13.
often stays out at night despite parental prohibitions, beginning
before age 13 years
14.
has run away from home overnight at least twice while living in
parental or parental surrogate home (or once without returning for
a lengthy period)
15.
often truant from school, beginning before age 13 years
The disturbance must be shown to cause clinically significant impairment in
social, academic or occupational functioning. For individuals aged 18 years or
older, criteria for Antisocial Personality Disorder must not be met. Conduct
Disorder is further subdivided into a Childhood-onset Type with the observed
onset of at least one criterion prior to age 10 years, and an Adolescent-onset
Type where no criteria were met prior to age 10 years.
37 Appendix II: A-TAC: Items regarding symptoms of conduct disorder
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38 Appendix III: Interventions for treatment of CD
Medical interventions
Medical intervention should be considered if treatable comorbidities are present
(ADHD, depression, psychosis, tic disorders or seizures), if non-medical
interventions have proved unsuccessful and when the CD symptoms are very
severe (Chandler 2012). Studies have shown that treating ADHD/CD with
stimulants reduces the symptoms of both conditions (Klein, Abikoff et al. 1997).
The drugs of choice should be proven safe in children and given in an initially
low dose, slowly increasing while closely monitoring for possible side effects.
Usually atypical antipsychotics are tried first (risperidone, olanzapine,
quetiapine), with possible side effects of weight gain, drug induced Parkinsons,
elevated serum cholesterol, diabetes or tardive dyskinesia. Risperidon has been
demonstrated to be superior to placebo in ameliorating aggression in children
with CD (Findling, McNamara et al. 2000), and in children with subaverage IQ
and severe forms of aggression (Buitelaar, van der Gaag et al. 2001). In clinical
practice atypical antipsychotics are often combined with psychostimulants
(Findling, Newcorn et al. 2007). The second drugs of choice are older mood
stabilizers (valproic acid, Lithium) initially used for bipolar illness but also tried
in people violent from brain damage, personality disorders or ODD/CD
(Chandler 2012). Of the two Lithium has been tested the most, its side effects
are possible weight gain, acne, nausea and kidney damage. It has known antiaggressive properties shown in adolescents and children with CD (Campbell,
Small et al. 1984; Malone, Delaney et al. 2000). Valproic acid is an
anticonvulsant drug found to have great effect on treating rapid cycling bipolar
39 illness in adults. It has been tested to some extent for the same indication in
children and could be of interest when the CD child has a strong family history
of bipolar illnesss (Chandler 2012), since it has also shown to be an efficacious
treatment for mood lability and explosive temper in children with DBD’s
(Donovan, Stewart et al. 2000). The third line of drugs includes Clonidine
(originally a cardiovascular drug, an adrenergic agonist), according to Chandler
(Chandler 2012) used to treat Tics, severe ADHD and sometimes autism with
hyperactivity). Clonidine and psychostimulants in combination have shown to
reduce conduct symptoms but not hyperactivity symptoms in children with
ADHD/CD (Hazell and Stuart 2003). Occasionally (when all other fails) new
mood stabilizers (lamotrigine, gabapentin, toprimate) might be of interest - of
which there unfortunately are no good studies showing that they actually work
(Chandler 2012).
Non-medical interventions
The caregivers will need some help in fostering the child with CD. If social
security networks fail (grandparents, friends, cousins e.t.c), respite foster care or
hospitalization might be necessary and useful. The child must not learn that
violence or intimidation works, which is the case with parents or teachers that
are afraid.
It has been discussed that children with CD frequently have learning disorders,
may have grown up in abusive homes and most of them lack social skills to get
along with peers (Chandler 2012). Addressing these problems with individually
designed psycho-educative treatment and counseling may help the child to in
time ”outgrow” the CD.
40 The CD child needs structure, supervision and involvement all around the clock.
Candler suggests fulltime parenting (no job) or foster care, residental care or
hospitalization and argues that the most impressive changes are shown under
such circumstances (Chandler 2012). The combined use of behavioral parent
training and child training programs enhancing cognitive problem-solving skills
have shown more effective than programs providing intervention only to the
child with disruptive behavior (Kazdin, Esveldt-Dawson et al. 1987; Kazdin,
Siegel et al. 1992).
In the US “The Incredible Years Training Series”, originally developed as a
parent training program for the treatment of DBD’s in childhood (WebsterStratton 2001; Webster-Stratton and Taylor 2001; Webster-Stratton 2002;
Kazdin and Weisz 2003), today also includes the “Dinosaur School” and a
teacher component for strengthening home-school connections, improving the
teachers’ management and discipline skills and reinforcement of socialemotional skills in the classroom. The Incredible Years intervention have shown
to produce significant reductions in conduct problems shown at home and in
school and increases in social problem-solving skills, compared to waiting-list
controls (Webster-Stratton, Reid et al. 2001).
Multicomponent programs are many such as “Dinosaur School” training
program for children and teachers (Webster-Stratton and Hammond 1997;
Webster-Stratton, Reid et al. 2004), Fast Track (Conduct Problems Prevention
Research Group, 1992), Family Check-Up (Shaw, Dishion et al. 2006), PSSTPMT (Kazdin, Siegel et al. 1992), Coping Power program (Lochman and Wells
2002), and LIFT (Snyder, Reid et al. 2002). In early adolescence multisystemic
therapy (MST) can be used, implemented with chronic and violent juvenile
41 offenders, being an individualized intervention focusing on the interaction
between the adolescent and the multiple environmental systems influencing the
antisocial behavior, such as peers, family, community and school (Henggeler,
Melton et al. 1992). CBT therapy have recently shown to be effective for adults
with ADHD (Weiss, Murray et al. 2012), with or without stimulant therapy, but
similar psychological treatments of ADHD in childhood have only added a
small margin of benefits over medication alone (MTA 1999). The reason for that
might be the adults’ greater insight into their individual problems with ADHD
and as such being more receptive learning new coping strategies.
42 Populärvetenskaplig sammanfattning (svenska)
Uppförandestörning (Conduct Disorder; CD) är en beteendestörning hos barn
och ungdomar som kännetecknas av betydande brott mot sociala normer och
regler; aggressivt beteende mot människor och djur, skadegörelse samt stöld
och/ eller trotsande av föräldrars/ lärares regler (skolk och rymning från
hemmet). Barn med CD har ökad risk för att utveckla missbruk, kriminellt
beteende och att drabbas av olika vuxenpsykiatriska problem, oftast antisocial
personlighetsstörning (ASPD). I tidigare studier har man sett att så mycket som
75 % av alla vuxna som har ASPD, även hade uppförandestörning i tonåren.
Nyligen har en annan studie visat att 1 % av den svenska befolkningen står för
63 % av alla domar som gäller våldsbrott, och att CD i barndomen är en stark
riskfaktor för att tillhöra den gruppen. Därför är det viktigt att samla in så
mycket information som man kan om barn med CD och deras familjer.
I den här studien samlades information in om 9/12 åriga barns (tvillingars)
psykiska hälsa, från Nationella Hälsoregistret, från föräldrarna, samt med hjälp
av ett strukturerat och validerat screening instrument. Sammanställd data
analyserades och förekomsten av psykiatriska problem (så som trotssyndrom,
uppmärksamhetsstörning/ hyperaktivitet (ADHD), Autism, Tics, svåra
inlärningssvårigheter och ätstörningar) hos barn med CD bestämdes, samt även
frekvenserna av dessa och av CD hos tvilling-syskonen till dessa barn.
Resultaten visar att endast 1 % av barn i 9/12- års ålder med CD problem har
fångats upp av sjukvården. CD drabbar dubbelt så många pojkar som flickor.
43 Det var vanligare att båda syskonen i ett enäggstvillingpar var drabbade av CD,
än vad det var i de syskonpar som var tvåäggstvillingar. Dessutom har
enäggstvillingar i genomsnitt lika många psykiatriska problem var, vilket inte
sågs vad det gäller tvåäggstvillingar.
Sammanfattningsvis: CD är kopplat med många andra psykiatriska problem hos
barn och deras syskon. En stark genetisk faktor antas ligga bakom utvecklingen
av CD. Den kliniska relevansen av studien ligger i att den visar betydelsen av
noggrann psykiatrisk utredning av barn med beteendeproblem.
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