Open access Research First incidence, age of onset outcomes and risk factors of onset of DSM-5 oppositional defiant disorder: a cohort study of Spanish children from ages 3 to 9 Lourdes Ezpeleta,1 J Blas Navarro,2 Nuria de la Osa,1 Eva Penelo,2 Josep Maria Domènech2 To cite: Ezpeleta L, Navarro JB, Abstract de la Osa N, et al. First Objective To examine the 1-year first incidence and Strengths and limitations of the study incidence, age of onset prevalence of oppositional defiant disorder (ODD), the outcomes and risk factors of ►► The length of the follow-up period (7 years) includ- outcomes on psychopathology and functioning by age of onset of DSM-5 oppositional ing two different developmental stages, preschool onset and the risk factors of onset of ODD from ages 3 to 9 defiant disorder: a cohort and childhood. study of Spanish children in children from the Spanish general population. ►► The information on risk factors and outcomes ob- from ages 3 to 9. BMJ Open Design Longitudinal with seven follow-ups and double tained from parents and teachers. 2019;9:e022493. doi:10.1136/ cohort (ODD and non-ODD children). ►► The consideration of risk factors in Cox regression bmjopen-2018-022493 Setting General population of preschool and elementary models as time-dependent covariates instead of school children in Barcelona (Spain). ►► Prepublication history and fixed covariates. Participants On a first phase, the parent-rated Strengths additional material for this ►► The lower participation of low socioeconomic status paper are available online. To and Difficulties Questionnaire conduct problems scale families and the non-random attrition for some out- view these files, please visit plus ODD Diagnostic and Statistical Manual of Mental comes may have led to bias in the estimates. the journal online (http://​dx.​doi.​ Disorders, fourth version, symptoms were used to screen ►► The low incidence of oppositional defiant disorder org/​10.​1136/​bmjopen-​2018-​ for behavioural problems. The second phase sample size (ODD) made necessary to cluster ages (3–5 and 022493). contained 622 cases at age 3 and, at age 9, 418 remained 6–9) for the analysis of the influence of ODD age of in the study. Received 22 February 2018 onset on psychopathology and functioning. Results The probability of the onset of ODD showed Revised 22 January 2019 increasing values at ages 4 (R=2.7%) and 5 years Accepted 11 February 2019 (R=4.4%). These values decreased until age 7 (R=1.9%) and increased again until age 9 (R=3.6%). Up to 9 early identification and prevention of mental years old, the cumulative risk of new cases of ODD was disorders. 21.9%. Early onset was associated with a higher risk Oppositional defiant disorder (ODD), a of depression comorbidity and later onset with higher © Author(s) (or their pattern of negativistic, defiant, disobedient functional impairment and symptomatology. Subthreshold employer(s)) 2019. Re-use and hostile behaviour, is one of the most prev- permitted under CC BY-NC. No ODD, high scores in irritability and headstrong dimensions, attention deficit/hyperactivity disorder and other alent disorders from preschool age to adult- commercial re-use. See rights and permissions. Published by comorbidity, negative affectivity until age 7, difficulties hood.3 4 The pooled prevalence is 3.6% up BMJ. in inhibit and emotional control, punitive parenting and to age 18.1 ODD is accompanied by various 1 Unitat d’Epidemiologia i de maternal internalising problems were risk factors of a first concurrent disorders (attention deficit/ Diagnòstic en Psicopatologia del episode of ODD during this 7-year period. hyperactivity disorder [ADHD]), succes- Desenvolupament, Departament Conclusions The risk of new cases of ODD in the sive comorbidity (conduct disorder, anxiety, de Psicologia Clínica i de la general population at preschool age and during childhood depression, substance use)5 6 and functional Salut, Universitat Autònoma de is high. Preschool age is a target period for preventive Barcelona, Bellaterra, Barcelona, impairment.7 8 Symptomatology is stable interventions. Identified risk factors are objectives for Catalunya, Spain and sufferers have difficulties in the transi- targeted and indicated interventions. 2 Unitat d’Epidemiologia i de tion to adulthood.9 The amount of children Diagnòstic en Psicopatologia del and families affected and the severe conse- Desenvolupament, Departament quences that compromise healthy mental de Psicobiologia i Metodologia de les Ciències de la Salut, Introduction development underscore the need to know Universitat Autònoma de According to epidemiological studies, the when the first onset occurs and the factors Barcelona, Bellaterra, Barcelona, proportion of children and adolescents with that predict this onset in order to plan appro- Catalunya, Spain mental health problems is 13.4%.1 These priate preventive strategies. Correspondence to disorders are stable and continue into later Currently, we know how many children Dr Lourdes Ezpeleta; life with adverse adults outcomes.2 There- in the population are affected by ODD at a ​Lourdes.​Ezpeleta@​uab.​cat fore, childhood is a target period for the given point in time, that is, the prevalence, Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 1 Open access a measure of the status of the disease. We do not know, however, how many new cases appear at different devel- opmental stages, that is, incidence, a measure of newly occurring cases of the disease during a specific develop- mental period.10 Because there is often a low number of incident cases, incidence studies require cohort designs with large size samples. Literature shows that there is a dearth of studies about the incidence of psychiatric disorders in childhood and adolescence. The available data on ODD mostly focus on adolescents and youths. Roberts11 reported that the risk of new cases of ODD for adolescents in a 12-month period was 1.56%, and Benjet12 found a 5% 8-year incidence for 19- to 26-year-old youth. There are no studies on the incidence of ODD during preschool and childhood. Neither do we know the differential consequences of the disorder according to age of onset. Literature on general mental disorders has reported that early onset is associated with greater severity, persistence and lack of response to treatment.13 Age of onset is an important data to advise on mental health policies.14 Several risk factors have been reported in the literature Figure 1 Design of the study. DSM-IV, Diagnostic and on ODD. Child risk factors include genetic influences,15 Statistical Manual of Mental Disorders, fourth version; difficult temperament,16 difficulties in processing social ODD, oppositional defiant disorder; SDQ, Strengths and information,17 sex18 and ADHD.19 The contextual factors Difficulties Questionnaire. reported include socioeconomic status (SES), parenting practices, parental psychopathology, family conflict and poor attachment.15 20 Incidence figures, which report Method on new cases of disease, are more useful for identifying Participants risk factors than prevalence studies, which include both The initial sample consisted of 2283 children randomly chronic and new cases.21 No previous studies have exam- selected from early childhood schools in Barcelona ined the risk factors of ODD by considering new cases. (Spain).25 A two-phase design was employed. In the Only Roberts11 adopted this approach in adolescents, first phase of sampling, 1341 families (58.7%) agreed to reporting that a younger age, poor family satisfaction, participate (33.6% high SES, 43.1% middle and 23.3% passive coping and low mastery, school and economic low; 50.9% boys). To ensure that children with possible stress and poor relations with parents were predictors of behavioural problems participated, the parent-rated incident cases of ODD. Strengths and Difficulties Questionnaire (SDQ3-4) conduct Furthermore, ODD is a continuous disorder that starts problems scale26 plus ODD Diagnostic and Statistical early in life and persists into adulthood.9 It is therefore Manual of Mental Disorders, fourth version (DSM-IV) symp- imperative to know for prevention purposes how the early toms were used to screen. Two groups were considered: manifestations of ODD symptomatology affect the defi- screen positive (all children with SDQ scores ≥4, percentile nite appearance of the full disorder. Several dimensions of 90, or with a positive response to any of the eight DSM-IV ODD have been identified to explain its underlying struc- ODD symptoms) and screen-negative (a random group ture: irritable (including loses temper, angry and touchy); comprising 28% of children who did not reach the positive headstrong (argues, defies, annoys, blames) and hurtful threshold). The sample size was determined for detecting (spiteful-vindictive).22 Rowe20 showed how ODD dim OR ≥1.8 between psychopathology and risk factors, using a ensions predict full ODD diagnosis. Moreover, the liter- test of hypothesis for risk α=0.05 and power of 0.80. As the ature has shown that subthreshold conditions are risk planned follow-up was 12 years long, the sample size was factors for developing similar (homotypic) or different increased 50% for losses. (heterotypic) full syndrome23 and that they constitute a The final sample for the follow-ups (second phase) major public mental health burden.24 included 622 children (figure 1) comprising all the The objective was to study annually the proportion children from the screen-positive group whose fami- of incident cases of ODD from ages 3 to 9 (preschool lies accepted to participate (n=417; 49.4% boys) and a through childhood), to ascertain the differential random sample from the screen-negative group (n=205; outcomes by age of onset and to test if previously 51.2% boys). To select participants from screen-nega- reported risk factors associated with ODD are prospec- tive group, children of each classroom were alphabeti- tive risk factors of incident cases at these developmental cally numbered without including the name of the child stages. nor the school. Then they were randomly permutated 2 Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 Open access Rowe’s20 ODD dimensions were used (irritable and head- Table 1 Demographic characteristics of the sample at age 3 (n=622) strong). Interinterviewer agreement in the diagnoses ranged from kappa coefficients from 0.83 to 1 (mean Age (mean; SD) 3.8 (0.33) kappa 0.92; being 0.84 for ODD), indicating a good to Sex; n (%) excellent agreement between interviewers. Male 311 (50.0) SDQ26 assesses emotional and behavioural problems Race/ethnicity; n (%) with 25 items with three response options organised in five scales. It was answered by the parents and teachers. Non-Hispanic White 557 (89.5) Cronbach’s alpha for parents range from 0.55 (conduct) Hispanic-American 46 (7.4) to 0.85 (hyperactivity) and for teachers from 0.69 Other 19 (3.1) (conduct) to 0.88 (total). Socioeconomic status; n (%) The Children’s Global Assessment Scale28 is a global High 205 (33.0) measure of functional impairment rated by the inter- viewer. Scale scores range from 1 (maximum impairment) Middle 280 (45.0) to 100 (normal functioning). Scores above 70 indicate Low 137 (22.0) normal adaptation. Children’s Behaviour Questionnaire Short Form and using SPSS random number generator, and the first Very Short Form29 measure reactive and self-regulative 30% was selected. The percentage of dropouts at annual temperament with 94 and 36 items, respectively, on a follow-up from ages 4 to 9 was similar in the two screen seven-point Likert-type scale. These were answered by groups (χ2 = 0.72, p=0.798 at age 4; χ2=0.31, p=0.575 at the parents when the children were 3, 4 and 5 years old age 5; χ2=1.36, p=0.244 at age 6; χ2=0.02, p=0.877 at age (short form) and 7 years old (very short form). The broad 7; χ2=0.49 and p=0.484 at age 8; χ2=0.20 and p=0.652 at dimensions negative affectivity and effortful control were age 9). No differences in sex (χ2 =0.07; p=0.793) or type considered. Cronbach’s alpha in the sample ranged of school (χ2 =0.72; p=0.396) were found on comparing from 0.71 for effortful control at age 7 to 0.85 for negative completers and dropouts during the 7 years of annual affectivity at age 5. follow-ups. However, the SES of those leaving the study The Behaviour Rating Inventory of Executive Function until age 9 was lower (χ2 =20.89; p<0.001). Finally, to assess preschool version,30 answered by teachers when children randomness of attrition, the outcome scores at age 3 were 3 years old, assesses behaviours reflecting the exec- between cases and dropouts at age 9 were compared. For utive functions in daily life. The broad dimension that 6 out of the 16 outcomes, scores at age 3 were higher for combine inhibit (control of impulses and behaviour) and dropouts than for completers at age 9. emotional control (appropriate modulation of emotional From the initial 622 children, 65 who presented an responses) (Inhibitory Self-Control Index; ISCI) was used ODD diagnosis at the start of the study (age 3) and 18 (Cronbach’s alpha: 0.94). who left the study at the second follow-up (age 4) were The Alabama Parenting Questionnaire-Preschool excluded for the analysis of risk factors because of lack (APQ-Pr)31 measures parental practices in three dimen- of information (n=539). Decrements in sample size at sions (24 items): positive discipline techniques, incon- successive follow-ups were either due to attrition or to the sistent parenting and punitive parenting.32 They were exclusion of children who had already presented a first obtained at ages 3 and 6. Cronbach’s alpha for the three ODD diagnosis. Demographic characteristics are shown dimensions was 0.75, 0.62 and 0.42 at age 3 and 0.74, 0.66 in table 1. and 0.52 at age 6, respectively. The Adult Self-Report33 assesses dimensional psychopa- Measures thology (126 items) in adults. The mothers answered the Diagnostic interview of children and adolescents for parents of questionnaire when the children were 3 and 8 years old. preschool children Internalising and externalising scale scores were analysed The diagnostic interview of children and adolescents for (Cronbach’s alpha 0.85 and 0.80, respectively, at the last parents of preschool children27 is a computerised semi- follow-up). structured interview which generates diagnoses through algorithms following DSM-V. The diagnosis of ODD was Patient and public involvement statement obtained annually. The interviews in the first assessment ODD is a social problem and families and schools gathered data from the first 3 years of life. ADHD, major complain about how to manage disruptive behaviour depression, any anxiety disorders (separation, gener- disorders at home and in school. We wanted to investigate alised, social anxiety or specific phobias) and comor- about the development of this problem to know the best bidity (ADHD, conduct disorder, major depression or developmental moments and their risk factors to help any anxiety plus ODD) were obtained at each age from the families and the teachers to prevent oppositionality. 3 to 9 years old. Subthreshold ODD was defined as cases Families and schools were freely and actively involved in that did not meet the threshold criteria of four symptoms the study. Families and schools were informed yearly of for the diagnosis but presented impairment or distress. the results of the previous follow-up and were oriented Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 3 Open access about what to do to improve the behaviour when neces- Table 2 DSM-V ODD prevalence from 3 to 9 years old sary. Every 3 years, they received a written report about the evolution and development of the child. Teachers Age (years) Total cases ODD cases Prevalence* % received a 15-hour course about How to manage disrup- 3 622 65 6.03 tive behaviour disorder at the school-room at the beginning of 4 604 63 7.08 different school levels (preschool: age 3, elementary:ages 5 535 46 7.09 6 and 9). 6 509 47 7.04 Procedure 7 456 41 6.99 Families were recruited in schools and gave written 8 469 35 6.09 consent. The families who agreed to participate and 9 418 40 8.83 met the screening criteria were contacted each year and *Weighted by screen-positive or screen-negative membership: interviewed in school. Interviewers were trained and were number of children with ODD divided by the total sample size at blind to the screening group. All the interviews were that age. audiorecorded and supervised. The data were collected DSM-V, Diagnostic and Statistical Manual of Mental Disorders, fifth between November 2009 and July 2016. version; ODD, oppositional defiant disorder. Statistical analysis The data were analysed with Stata V.15 for Windows. Since of an ODD diagnosis and to the characteristics of the all the data were collected using a double-phase screening sample, with neither deaths nor physical comorbidities design, all analyses were weighted by assigning each child that prevented an ODD diagnosis. Proportional hazard a value that was inverse to the probability of random selec- assumption was verified by calculating the significance tion in the second phase of sampling. Cases with missing value of the interaction between predictors and time. In data were excluded separately for each analysis (pairwise the presence of significant interaction, the HR for the deletion). The incidence proportion was calculated for involved predictor was obtained separately for each year 1 year time periods beginning at 4 years old by dividing of follow-up, corresponding to ages 3 to 8. For each Cox the number of new cases of first ODD diagnosis (inci- regression model, Harrell’s C index36 was calculated to dent cases) by the number of children at risk, that is, the evaluate the adequacy of the predictions (values ≥0.70 are number of cases at the beginning of the period excluding considered good). those who had previous diagnoses of ODD. This ratio is also called Risk (R) and it estimates the ‘probability of Results an event during a specified period of time’.10 Cumulative Prevalence of ODD from 3 to 9 years old risk estimates the risk of ODD from 0 years old to each Table 2 presents the number of children in the study, the time period; because of the lost cases across the study, number of ODD diagnoses and the prevalence for each cumulative risk was computed by the Kaplan-Meier prod- age. Prevalence oscillated between 6.0% (age 3) and uct-limit estimation34 using the weighted annual risk. 8.8% (age 9). The analysis of differences in psychopathology and functioning by age of onset of ODD was made by anal- First incidence and cumulative risk of ODD from 4 to 9 years ysis of variance for raw scores of quantitative outcomes old and logistic regression for binary outcomes. Age of onset The first three columns in table 3 show the cases at risk was grouped into preschool (ages 3-5) and school (ages (without an ODD diagnosis) at the beginning of each year 6-9) periods. The group without ODD was also consid- period, the number of new cases diagnosed with ODD ered and post hoc comparisons corrected by Bonferroni during that year and the incidence. The probability of for multiple comparisons were estimated. Treatment for the appearance of ODD showed a cubic shape, with risk ODD at any time, current ODD diagnosis and number of increasing from age 4 to age 5 (R=2.7% to 4.4%), followed years with an ODD diagnosis were introduced as covari- by a decrease until age 7 (R=1.9%) and a new increase at ates to adjust for confounding effects. ages 8 and 9 (R=2.9%, 3.6%). The last column in table 3 To analyse the predictors of the risk of an ODD diag- shows the cumulative risk of having a first ODD diagnosis nosis, several Cox proportional hazard regression models up to 9 years old, which reached 21.9%. Figure 2 shows were estimated, grouping predictors (risk factors) by the prevalence of ODD and incidence of first ODD diagnosis measurement instrument and adjusting estimates by sex by age. and SES. Predictors were considered as time dependent between ages 3 and 8 to benefit from the most recent Outcomes of age of onset of ODD available information. As a consequence and because of Table 4 shows the scores and percentages of psychopa- the multiple-record structure of the data matrix (each thology and functioning for children with onset of ODD child had one data record for each follow-up period), at 3–5 and 6–9 years old and for those without ODD, the robust variance estimator35 was used. No compet- as well as the multiple comparisons between the three itive events were considered due to the high specificity groups with the mean difference (MD) or the OR and 4 Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 Open access ODD dimensions of irritability (HR=1.56, 95% CI 1.13 to Table 3 ODD 1-year first incidence and cumulative risk from 0 to 9 years old 2.12) and headstrong (HR=2.33, 95% CI 1.84 to 2.96), comorbidity (HR=2.21, 95% CI 1.13 to 3.53), specifically Incident First ODD diagnosis of ADHD (HR=2.64, 95% CI 1.42 to 4.93), higher nega- Age Cases at ODD Risk† Cumulative tive affectivity (HR=3.73, 95% CI 2.21 to 6.29 at age three (years) risk cases* % risk‡ (%) to HR=1.68, 95% CI 1.27 to 2.23 at age 7), difficulties in 0 to 3 6.0 inhibition and emotional control (HR=1.04, 95% CI 1.02 4 541 23 2.71 8.6 to 1.07), higher scores in punitive parenting (HR=1.22, 5 463 20 4.39 12.6 95% CI 1.08 to 1.38) and mother’s internalising problems 6 419 13 2.65 14.9 (HR=1.06, 95% CI 1.02 to 1.10). The capability to predict new ODD first-incident cases 7 367 10 1.88 16.5 from the subsets of risk factors was low in general. Only the 8 373 11 2.92 18.9 first model with ‘being an ODD subthreshold’ as predictor, 9 325 13 3.61 21.9 and the second model with ‘ODD Irritability and Head- *Incident cases (after excluding children with previous strong’ scores as predictors showed Harrell’s C ≥ 0.70. diagnoses of ODD). †Weighted by screen-positive or screen-negative membership. ‡Computed by Kaplan-Meier product-limit estimation using Discussion weighted annual risk. To our knowledge, this is the first study reporting on not ODD, oppositional defiant disorder. only the 1-year incidence of ODD in a 7-year follow-up design covering ages 3 to 9 and the effects of different age their 95% CI. Controlling by current ODD diagnosis, ranges of onset, but also their risk factors and the DSM-V the number of years of duration of ODD and treatment prevalence. We found that the probability of the appear- received, children with onset at 3–5 years old scored lower ance of ODD shows a cubic shape with higher values for on functional impairment, which indicates worse func- the preschool period, a decrease at the start of childhood tioning (MD=−7.17), and presented higher comorbidity (ages 6 and 7) and another increase when approaching with major depression (OR=5.76) in comparison to chil- puberty (ages 8 and 9). Prevalence was around 6%–7% dren without ODD. Children with onset of ODD at 6–9 between ages 3 and 8, increasing to 8.8% by age 9. An years old scored higher on all the scales of parent’s SDQ early onset of ODD is more closely associated with the except prosocial (MD between 0.63 for conduct and 1.68 presence of depressive comorbidity, but the functional for hyperactivity) and on total (MD=3.95), and presented impairment of those with later onset is most marked and worse functioning (MD=−13.06) in comparison with chil- their parents report higher symptomatology. Risk factors dren without ODD. There were differences in the total of incidence were identified. SDQ score (MD=2.99) and in peer problems (MD=0.66) Throughout development, prevalence was high and between preschooler and late ODD onset, the latter very stable (6%–7%), with the highest value at 9 years old. showing higher scores. Moreover, children with onset of These percentages indicate the need to allocate resources ODD at 6–9 years old presented higher functional impair- such as services and training to the parents, teachers and ment than those with onset at 3–5 years old (MD=−5.89). professionals involved with the children in these age ranges that have already developed the disorder. Risk factors of incident ODD diagnosis from 3 to 9 years old 2.7 and 4.4 out of 100 preschoolers aged 4 and 5, respec- HR for each risk factor with the 95% CI, its p value and tively, and between 1.9 and 3.6 out of 100 children aged 6 to Harrell’s C for each model were calculated (see online 9 will develop a first episode of ODD in 1 year. It is remark- supplementary table 1). The hazard of having an ODD able that at the end of the follow-ups, the cumulative risk was diagnosis was increased by subthreshold ODD symptom- high, indicating that up to 9 years old, the risk of presenting atology (HR=6. 27, 95% CI 3.85 to 10.21), high scores on ODD is 21.9%. This risk is highest in the preschool period, which cumulates 12.6% of the risk, the remaining 9.3% occurring in childhood. These values are noteworthy in terms of public mental health indicators if one considers the short-term impact ODD has on the lives of children, families, teachers and schools,8 as well as the long-term effects until adulthood.9 Specifically, these results point to the need to pay attention to the preschool period if the goal is to prevent ODD. On the one hand, preschool age is when the child is acquiring important skills related to ODD, such as self-regulation and executive functioning, and when parents adjust their parenting practices.37 It is important to Figure 2 Prevalence and first incidence (risk) of oppositional intervene in this period when the early signs of dysfunction defiant disorder diagnosed from 3 to 9 years old. become apparent. On the other hand, programmes that Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 5 6 Table 4 Outcome of age of onset on psychopathology and functioning (n=461) Open access Age onset Age onset No ODD 3–5 years old 6–9 years old Missing (n=305) (n=113) (n=43) 3–5 versus no ODD* 6–9 versus no ODD* 6–9 versus 3–5* years old values Mean (SD) Mean (SD) Mean (SD) MD (95% CI) p value MD (95% CI) p value MD (95% CI) p value SDQ-Parent  Emotional 4 1.01 (0.88) 1.92 (1.52) 2.18 (1.42) 0.29 (−0.35 to 0.92) 0.379 0.82 (0.27 to 1.36) 0.003 0.53 (−0.16 to 1.22) 0.133  Conduct 15 1.18 (0.84) 3.00 (1.54) 2.87 (1.32) 0.42 (0.02 to 0.82) 0.040 0.63 (0.18 to 1.08) 0.006 0.22 (−0.24 to 0.67) 0.353  Hyperactivity 4 3.01 (2.08) 4.28 (2.36) 4.95 (2.33) 0.65 (−0.28 to 1.57) 0.171 1.68 (0.78 to 2.57) <0.005 1.03 (−0.01 to 2.07) 0.052  Peer 4 0.69 (0.75) 1.35 (1.24) 1.65 (1.17) 0.09 (−0.33 to 0.51) 0.679 0.75 (0.25 to 1.25) 0.004 0.66 (0.07 to 1.25) 0.027  Prosocial 4 1.47 (1.04) 2.14 (1.22) 1.90 (1.57) 0.30 (−0.32 to 0.91) 0.340 0.17 (−0.40 to 0.73) 0.560 −0.13 (−0.85 to 0.59) 0.719  Total 4 5.89 (3.29) 9.90 (5.33) 11.64 (3.97) 0.97 (−0.81 to 2.75) 0.286 3.95 (2.47 to 5.44) <0.001 2.99 (1.20 to 4.77) 0.001 SDQ-Teacher  Emotional 2 1.28 (1.02) 1.84 (1.44) 2.14 (1.89) 0.47 (−0.25 to 1.18) 0.201 0.61 (−0.23 to 1.44) 0.153 0.14 (−0.78 to 1.06) 0.762  Conduct 14 1.22 (1.21) 2.00 (1.81) 2.25 (1.92) 0.16 (−0.41 to 0.72) 0.587 0.37 (−0.40 to 1.14) 0.347 0.21 (−0.60 to 1.02) 0.604  Hyperactivity 2 2.86 (2.29) 3.71 (2.32) 4.39 (2.90) 0.18 (−0.82 to 1.17) 0.730 1.22 (−0.16 to 2.60) 0.082 1.05 (−0.40 to 2.49) 0.157  Peer 2 1.11 (1.01) 1.48 (1.19) 1.87 (1.36) 0.05 (−0.36 to 0.47) 0.799 0.50 (0.02 to 0.97) 0.041 0.44 (−0.05 to 0.94) 0.080  Prosocial 2 2.43 (1.43) 3.05 (1.78) 3.28 (2.16) −0.25 (−0.84 to 0.34) 0.400 0.09 (−0.74 to 0.92) 0.835 0.34 (−0.47 to 1.16) 0.411  Total 2 6.47 (4.26) 8.68 (5.20) 10.46 (6.40) 0.35 (−1.56 to 2.26) 0.721 2.44 (−0.38 to 5.26) 0.089 2.09 (−0.84 to 5.03) 0.162  CGAS 0 78.33 (5.73) 66.99 (7.60) 59.03 (7.24) −7.17 (−10.0 to −4.31) <0.001 −13.06 (−6.1 to −9.99) <0.001 −5.89 (−9.16 to −2.62) <0.001 DSM-5 % % % OR (95% CI) p value OR (95% CI) p value OR (95% CI) p value ADHD 25 15.5% 51.8% 39.3% 2.55 (0.93 to 6.97) 0.068 2.53 (0.91 to 7.03) 0.076 0.99 (0.34 to 2.85) 0.986 Major 47 1.5% 9.4% 7.1% 5.76 (1.15 to 28.8) 0.033 4.06 (0.56 to 29.51) 0.166 0.70 (0.11 to 4.50) 0.712 depression Any anxiety 37 26.0% 57.8% 26.7% 2.23 (0.91 to 5.46) 0.079 1.20 (0.40 to 3.58) 0.747 0.54 (0.16 to 1.81) 0.316 disorder In bold are significant p values after Bonferroni correction for multiple comparison. *Comparison between ages of first ODD diagnosis are adjusted by: having or not ODD treatment, current ODD diagnosis and number of years with an ODD diagnosis. ADHD, attention deficit/hyperactivity disorder; CGAS, Children’s Global Assessment Scale; DSM-V, Diagnostic and Statistical Manual of Mental Disorders, fifth version; MD, mean difference; ODD, oppositional defiant disorder; SDQ, Strengths and Difficulties Questionnaire Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 Open access have been shown to effectively treat ODD38–40 and prevent some limitations must be considered when interpreting the it41 42 are currently available. results. The diagnostic information, based on data from just An early age of onset has typically been associated with one source, the parents and the lower participation of low worse mental health outcomes.13 This is also true for ODD SES families may have led to bias in the estimates. A second regarding comorbidity. Specifically, the risk of depression limitation refers to the non-randomness of attrition in 6 in children who debut ODD at preschool age multiplies out of the 16 outcomes analysed as risk factors of first ODD by 5.76 compared with children without ODD. Comparing diagnose. However, as shown in several populations, attri- early versus later onset after strict control by confounding tion is associated with adverse psychosocial variables and variables, later onset increases the risk of higher symptom- high levels of psychological distress.44 45 Also, some of the atology (general and in peer problems) and difficulties in scales of the APQ-Pr presented low internal consistency and functioning. One of the contributions of studying age of the results should thus be interpreted with caution. Finally, onset is to have available information for targeting preven- as the number of incident cases diminished with age, the tion that focuses on early intervention in incipient mental statistical power may be limited. disorders and on primary prevention of secondary disor- Synthesising, oppositional defiant disorder is one of the ders.13 Thus, our results once again suggest the need to most prevalent disorders in our society. It has important intervene at early ages. This implication is also supported consequences in the development of the child and in the by the finding that for those starting later (ages 6–9), the functioning of the family. It starts very early in life but we do impairment in functioning and in symptomatology is more not know how many new cases appear every year, nor the severe. Therefore, paying attention to prodromal indicators consequences it has depending on the age of onset. Our and risk factors to prevent the full development of ODD is study reports that the probability of appearance of opposi- crucial. tional defiant disorders is highest by age 5 and, afterwards, Regarding risk factors, our goal was to confirm the risk by age 9, when approaching to puberty. Most of the new of first onset of ODD using some of the main risk factors cases of oppositional disorder appeared in preschool age reported previously in the literature. No previous studies (12.6%). By age 9, there is a cumulative risk of new onset of have been carried out with incident cases. The strength of 21.9%. Early onset at preschool age is associated with comor- the association for some of the predictors is remarkable. We bidity with depression and functional impairment; child- found that premorbid forms of ODD (subthreshold, high hood onset is associated with higher symptomatology and scores in the ODD dimensions irritability and headstrong) functional impairment. These results indicate the burden were the strongest predictor of onset of full ODD. Iden- of oppositional disorder for public health and point to the tifying premorbid cases is of great value for the indicated need of focusing in preschool age for preventive purposes. prevention of ODD, given that the group at risk presents To allocate resources in this developmental period and objective markers (ODD symptoms). Similarly, children paying attention to prodromal indicators and risk factors to with other psychopathology, and specifically ADHD, and prevent the full development of ODD is crucial. Our results individual characteristics, such as difficulties in inhib- are generalisable to Spanish children mostly from mean it-emotional control are also at risk of onset of ODD. Also, and high-mean socioeconomic levels until age 9. our results indicate that difficulties regulating negative emotions are at a higher risk of ODD onset, especially from Acknowledgements We would like to thank the participating schools and families. very early ages, while the risk diminishes with age. Last, Contributors LE designed the study and wrote the paper with JBN. JBN analysed unsupportive environments, such as punitive parenting data. JMD contributed to data analysis. NdlO and EP collaborated in the writing and practices and maternal internalising problems, predicted editing of the manuscript. All the authors contributed to reviewing the final version of the manuscript. the emergence of an ODD diagnosis, which is also in line with previous literature.15 43 Predictive capability assessed by Funding This work was supported by the Spanish Ministry of Economy and Competitiveness [grants PSI2012-32695 and PSI2015-63965-R (MINECO/FEDER)] Harrell’s C was generally low to moderate, indicating that and the Secretaria d’Universitats i Recerca, Departament d’Economia i Coneixement to predict first-incident ODD cases, other predictors are of the Generalitat de Catalunya [grant 2014 SGR 312]. needed in addition to the clinical risk factor considered. Competing interests None declared. However, it is necessary to consider the low number of Patient consent for publication Parental/guardian consent obtained. predictors included in each model. Strengths of the study are that the diagnostic informa- Ethics approval The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional tion was obtained via semistructured interviews based committees on human experimentation and with the Helsinki Declaration of on DSM-V criteria, the length of the follow-up period (7 1975, as revised in 2008, and by the Ethics Committee for Human and Animal years), the inclusion of two different developmental stages, Experimentation of the Universitat Autònoma de Barcelona. preschool and childhood, and the fact that the estimates Provenance and peer review Not commissioned; externally peer reviewed. of incidence were not overestimated, given that previous Data sharing statement Data cannot be publicly available due to ethical diagnoses until age 3 were also made. Age of onset studies restrictions protecting the confidentiality of the families involved. Data are have been carried out mostly through retrospective design, available to interested researchers after signing a consent of confidentiality form as the authors had previously signed to obtain the data from the families of the which is a limitation. We studied age of onset through a sample. Researchers must be working in clinical child psychology in a public- prospective design. Furthermore, the information on risk funded project. To request the anonymous data, please contact the corresponding factors was obtained from parents and teachers. However, author. Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493 7 Open access Open access This is an open access article distributed in accordance with the disorder (ADHD) and oppositional defiant disorder (ODD). J Abnorm Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which Psychol 2016;125:154–67. permits others to distribute, remix, adapt, build upon this work non-commercially, 20. Rowe R, Costello EJ, Angold A, et al. Developmental pathways in oppositional defiant disorder and conduct disorder. J Abnorm and license their derivative works on different terms, provided the original work is Psychol 2010;119:726–38. properly cited, appropriate credit is given, any changes made indicated, and the use 21. de Graaf R, ten Have M, Tuithof M, et al. First-incidence of DSM-IV is non-commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. mood, anxiety and substance use disorders and its determinants: results from the Netherlands Mental Health Survey and Incidence Study-2. J Affect Disord 2013;149(1-3):100–7. 22. Stringaris A, Goodman R. Three dimensions of oppositionality in youth. J Child Psychol Psychiatry 2009;50:216–23. References 23. Shankman SA, Lewinsohn PM, Klein DN, et al. Subthreshold 1. Polanczyk GV, Salum GA, Sugaya LS, et al. Annual research conditions as precursors for full syndrome disorders: a 15-year review: a meta-analysis of the worldwide prevalence of mental longitudinal study of multiple diagnostic classes. J Child Psychol disorders in children and adolescents. J Child Psychol Psychiatry Psychiatry 2009;50:1485–94. 2015;56:345–65. 24. Roberts RE, Fisher PW, Turner JB, et al. Estimating the burden of 2. Copeland WE, Wolke D, Shanahan L, et al. Adult functional outcomes psychiatric disorders in adolescence: the impact of subthreshold of common childhood psychiatric problems: a prospective, disorders. Soc Psychiatry Psychiatr Epidemiol 2015;50:397–406. longitudinal study. JAMA Psychiatry 2015;72:892–9. 25. Ezpeleta L, de la Osa N, Doménech JM. Prevalence of DSM-IV 3. La Maison C, Munhoz TN, Santos IS, et al. Prevalence and disorders, comorbidity and impairment in 3-year-old Spanish risk factors of psychiatric disorders in early adolescence: 2004 preschoolers. Soc Psychiatry Psychiatr Epidemiol 2014;49:145–55. Pelotas (Brazil) birth cohort. Soc Psychiatry Psychiatr Epidemiol 26. Goodman R. Psychometric properties of the strengths and 2018;53:685–97. difficulties questionnaire. J Am Acad Child Adolesc Psychiatry 4. Nock MK, Kazdin AE, Hiripi E, et al. Lifetime prevalence, correlates, 2001;40:1337–45. and persistence of oppositional defiant disorder: results from the 27. Ezpeleta L, de la Osa N, Granero R, et al. The Diagnostic Interview National Comorbidity Survey Replication. J Child Psychol Psychiatry of Children and Adolescents for Parents of Preschool and Young 2007;48:703–13. Children: psychometric properties in the general population. 5. Drabick DA, Ollendick TH, Bubier JL. Co-occurrence of ODD and Psychiatry Res 2011;190:137–44. anxiety: shared risk processes and evidence for a dual-pathway 28. Shaffer D, Gould MS, Brasic J, et al. A children's global assessment model. Clin Psychol 2010;17:307–18. scale (CGAS). Arch Gen Psychiatry 1983;40:1228–31. 6. Mikolajewski AJ, Taylor J, Iacono WG. Oppositional defiant disorder 29. Putnam SP, Rothbart MK. Development of Short and Very Short dimensions: genetic influences and risk for later psychopathology. J Forms of the Children's Behavior Questionnaire. J Pers Assess Child Psychol Psychiatry 2017;58:702–10. 2006;87:102–12. 7. Boekamp JR, Liu RT, Martin SE, et al. Predictors of partial hospital 30. Gioia GA, Espy KA, Isquith PK. Behavior rating inventory of executive readmission for young children with oppositional defiant disorder. function - preschool version. Lutz, FL: Psychological Assessment Child Psychiatry Hum Dev 2018;49:505–11. Resources, 2003. 8. Burke JD, Rowe R, Boylan K. Functional outcomes of child and 31. Frick PJ. Alabama parenting questionnaire, 1991. adolescent oppositional defiant disorder symptoms in young adult 32. de la Osa N, Granero R, Penelo E, et al. Psychometric properties of men. J Child Psychol Psychiatry 2014;55:264–72. the Alabama Parenting Questionnaire – Preschool revision (APQ- 9. Leadbeater BJ, Ames ME. The Longitudinal Effects of Oppositional Pr) in 3 year-old Spanish preschoolers. Journal of Child and Family Defiant Disorder Symptoms on Academic and Occupational Studies 2014;23:776–84. Functioning in the Transition to Young Adulthood. J Abnorm Child 33. Achenbach TM, Rescorla LA. Manual for the ASEBA adult forms & Psychol 2017;45:749–63. profiles. Burlington, VT: University of Vermont, Research Center for 10. Greenland S, Rothman KJ. Measures of occurrence. In: Rothman KJ, Children, Youth & Families, 2003. Greenland S, Lash TL, eds. Modern epidemiology. Philadelphia, PA: 34. Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Lippincott Williams & Wilkins, 2008:32–50. Observations. J Am Stat Assoc 1958;53:457–81. 11. Roberts RE, Roberts CR, Chan W. One-year incidence of psychiatric 35. Lin DY, Wei LJ. The Robust inference for the cox proportional disorders and associated risk factors among adolescents in the hazards model. J Am Stat Assoc 1989;84:1074–8. community. J Child Psychol Psychiatry 2009;50:405–15. 36. Newson RB. Comparing the Predictive Powers of Survival Models 12. Benjet C, Borges G, Méndez E, et al. Eight-year incidence of Using Harrell's C or Somers’ D. Stata J 2010;10:339–58. psychiatric disorders and service use from adolescence to early 37. Eisenberg N. Emotion, regulation, and moral development. Annu Rev adulthood: longitudinal follow-up of the Mexican Adolescent Mental Psychol 2000;51:665–97. Health Survey. Eur Child Adolesc Psychiatry 2016;25:163–73. 38. Fossum S, Handegård BH, Adolfsen F, et al. A meta-analysis of long- 13. Kessler RC, Amminger GP, Aguilar-Gaxiola S, et al. Age of onset of term outpatient treatment effects for children and adolescents with mental disorders: a review of recent literature. Curr Opin Psychiatry conduct problems. J Child Fam Stud 2016;25:15–29. 2007;20:359–64. 39. Hobbel S, Drugli MB. Symptom changes of oppositional defiant 14. de Girolamo G, Dagani J, Purcell R, et al. Age of onset of mental disorder after treatment with the Incredible Years Program. Nord J disorders and use of mental health services: needs, opportunities Psychiatry 2013;67:97–103. and obstacles. Epidemiol Psychiatr Sci 2012;21:47–57. 40. Kaminski JW, Claussen AH. Evidence base update for psychosocial 15. Lavigne JV, Herzing LB, Cook EH, et al. Gene × environment effects treatments for disruptive behaviors in children. J Clin Child Adolesc of serotonin transporter, dopamine receptor D4, and monoamine Psychol 2017;46:477–99. oxidase A genes with contextual and parenting risk factors on 41. Muratori P, Bertacchi I, Giuli C, et al. Coping Power Adapted as symptoms of oppositional defiant disorder, anxiety, and depression Universal Prevention Program: Mid Term Effects on Children's in a community sample of 4-year-old children. Dev Psychopathol Behavioral Difficulties and Academic Grades. J Prim Prev 2013;25:555–75. 2016;37:389–401. 16. Wichstrøm L, Penelo E, Rensvik Viddal K, et al. Explaining the 42. Winther J, Carlsson A, Vance A. A pilot study of a school-based relationship between temperament and symptoms of psychiatric prevention and early intervention program to reduce oppositional disorders from preschool to middle childhood: hybrid fixed and defiant disorder/conduct disorder. Early Interv Psychiatry random effects models of Norwegian and Spanish children. J Child 2014;8:181–9. Psychol Psychiatry 2018;59:285–95. 43. Tung I, Lee SS. Negative parenting behavior and childhood 17. Matthys W, Vanderschuren LJ, Schutter DJ, et al. Impaired oppositional defiant disorder: differential moderation by positive and neurocognitive functions affect social learning processes in negative peer regard. Aggress Behav 2014;40:79–90. oppositional defiant disorder and conduct disorder: implications for 44. Fischer EH, Dornelas EA, Goethe JW. Characteristics of people interventions. Clin Child Fam Psychol Rev 2012;15:234–46. lost to attrition in psychiatric follow-up studies. J Nerv Ment Dis 18. Demmer DH, Hooley M, Sheen J, et al. Sex differences in the 2001;189:49–55. prevalence of oppositional defiant disorder during middle childhood: 45. Granero R, Ezpeleta L, Doménech JM. Features associated with a meta-analysis. J Abnorm Child Psychol 2017;45:313–25. non-participation and abandonment in mental health epidemiological 19. Harvey EA, Breaux RP, Lugo-Candelas CI. Early development of designs of socially-at-risk children and adolescents. Soc Psychiatry comorbidity between symptoms of attention-deficit/hyperactivity Psychiatr Epidemiol 2007;42:251–8. 8 Ezpeleta L, et al. BMJ Open 2019;9:e022493. doi:10.1136/bmjopen-2018-022493