Inclusion criteria

Inclusion criteria were ADHD combined subtype (ADHD-C), BD and concurrent ADHD-C and BD (ADHD-C+BD). We included ADHD-C only, because data supporting the validity of other subtypes of ADHD is scarce [31]. Those with BD and ADHD-C were classified as ADHD-C+ BD. Those with BD and other subtypes of ADHD were classified as BD only. BD was defined as BP-I or BP-II according to DSM-IV [32], or BP-NOS according to the Course of Bipolar Youth criteria [33]: "A minimum of elated mood plus 2 associated DSM-IV symptoms, or irritable mood plus 3 DSM-IV associated symptoms, along with a change in the level of functioning, duration of a minimum of 4 hours within a 24-hour period, and at least 4 cumulative lifetime days meeting the criteria". This is a possible bipolar category; 25% percent of children and adolescent fulfilling these criteria are shown to convert into BP-I or BP-II in 2 years [33]. Patients with longer hypomania episodes without depressive episodes and patients with cyclothymic disorder according to DSM-IV were also categorized as BP-NOS.

Exclusion criteria

Mental retardation according to DSM-IV or sequelae of brain injury.

Procedure

Subjects were recruited from a general child and adolescent psychiatry outpatient unit, mainly from one Norwegian community with approximately 25,000 persons <18 years. Inclusion period was December 2004 to April 2008, 1267 subjects (586 females) were referred to the unit in this period. In addition ten subjects were referred from other child and adolescent psychiatry units because of this study. Whenever bipolar disorder was suspected (n = 208) by any of the employees, the patients were evaluated for further assessment. Finally 172 subjects were interviewed by the Kiddie-Schedule for Affective Disorders and Schizophrenia Present and Lifetime version (KSADS)[34]. Caregiver(s) and children > 8 years were interviewed separately by a psychiatrist trained by the child and adolescent psychiatrist responsible for translating and coursing of KSADS in Norway. The taped interviews, supplied with condensed anamnestic information, were validated by a child and adolescent psychiatrist. Interrater agreement (kappa) was 1.0 on bipolar disorder and 0.87 on ADHD-C.

Most of the patients with ADHD-C were recruited from subjects with suspected BD, who fulfilled the ADHD-C criteria only according to the KSADS interview. Ten additional patients with suspected ADHD-C only were selected from patients at the unit to optimize the age, gender and IQ match between the groups. These went through the same diagnostic assessments as the other participants.

In addition to diagnoses of ADHD-C and BD, other diagnoses and background information were recorded from KSADS. All subjects completed an IQ-test (the Wechsler Intelligence Scale for Children-III Norwegian version or the Wechsler Adult Intelligence Scale III Norwegian version, supplied with the Vineland Adaptive Behaviour Scales when required). Further information was obtained from school (Teacher Behaviour Rating Scale [35]), teachers evaluation and in most cases school observation). Subjects received standard treatment; this was not a part of the study but was recorded as clinical information. The final diagnosis was based on KSADS and all available information including response to medication within one month after inclusion, in a discussion with the main researcher and an experienced child psychiatrist (last author).

Subjects

Sixty-six subjects were initially included. Two female BP-I patients were later excluded; one because of drug abuse during testing and one because of possible perinatal brain injury. Sixty-four subjects grouped as ADHD-C, ADHD-C+BD or BD were finally included in the study. Six patients with concurrent ADHD-C and BP-NOS symptoms no longer satisfied the criteria for BP-NOS after stimulant medication; these were reclassified as ADHD-C only. One patient with BP-I successfully treated by a mood stabilizer, switched to mania when adding a stimulant to treat concurrent ADHD symptoms, this patient was therefore classified as BP-I only.

Twenty-six fulfilled the criteria for ADHD-C only, mean age 13.2 years (S.D. = 3.8 years), mean total IQ 91.4 (S.D. = 10.9), 11 females. Fifteen fulfilled the criteria for both ADHD-C and BD (BP-I = 3, BP-II = 4, BP-NOS = 8), mean age 14.0 years (S.D. = 3.6 years), mean total IQ 90.1 (S.D. = 14.7), females 7. Twenty-three fulfilled the criteria of BD (BP-I = 8, BP-II = 7, BP-NOS = 8), mean age 13.8 years (S.D. = 3.8 years), mean total IQ = 95.1 (S.D. = 13.3), females 13. Differences in age and total IQ were non-significant.

Motor examination

The Neuromotor examination for children and adolescents 4-16 years (NUBU) was used [36]. It includes a revised version of the neurological soft sign test from the Isle of Wight Study [37] and motor tests developed from the Oseretsky's test [38]. NUBU is age standardized in a recent study of 272 representative Norwegian children and adolescents without known developmental problems [36]. A soft neurological sign refers to a minor neurological finding, indicating neurological dysfunction depending on age. The soft sign tests in NUBU are the same for all ages; deviations are defined as performance inferior to 85% of the normally developing children. The motor test covers five different domains, each with ten age standardized items. The norms are based on a Rasch model and expressed in terms of age equivalents and percentiles in the range 3.5 to 18 years. In the normative sample, Rasch person reliability was 0.94 and Rasch interrater reliability was 0.99 (Harald Janson, personal communication).

NUBU 4-18 Soft signs; age for all evaluation criteria mastered

1. Total soft signs (summarized test 2-12) 2. 20 jumps on one foot (6 years) 3. Fingertip touch with open (5 years) and closed eyes (6 years) 4. Oculomotor function; coordinated eye movements without head following (7 years) 5. Stretch arms forward for 20 seconds without involuntary or abnormal movements (8 years) 6. Walking heel-toe on line for 20 paces (8 years) 7. Speech; pronunciation and comprehension (8 years) 8. Standing on one foot for 20 seconds (8 years) 9. Diadochokinesis (8 years) 10. Cutting a paper circle (8 years) 11. Fog's test: Walking on lateral sides of feet (11-12 years) 12. Finger opposition (15-16 years)

NUBU 4-18 Motor tests; ten age standardized items of each test

1. Total motor age (mean value of test 2-6) 2. Static coordination (postural control in different positions without moving the feet) 3. Hand-eye coordination (hand-eye coordination and ball tests) 4. Dynamic coordination (postural control in different moving positions) 5. Motor tempo (tempo and precision in hand- and postural movements) 6. Simultaneous movement (motor coordination and sustained rhythm in simultaneous motion)

We used the percentile scores in our group comparisons. The NUBU testing was performed by a psychiatrist trained by the authors of NUBU and by two physiotherapists with special competence in child and adolescent psychiatry, supported by a detailed manual with DVD demonstration of the NUBU tests. Interrater reliability was established by two of the investigators, testing 6 patients together. For motor percentile test, Intraclass Correlation Coefficient range was 0.91-1.00 (single measure). Soft sign tests kappa measure of agreement range was 0.57 - 1.00 (kappa). Inclusion date and test date were not significantly correlated with total soft sign deviations or total motor age.

We attempted to do the test in euthymic and drug free patients. This was impossible in a minority of the subjects because of severity of symptoms (mania or psychosis; n = 9), these were assessed using mood stabilizers. All other medication was discontinued for a minimum of five times the elimination half-life before testing. We had to retest the first included patients (n = 12) after two years because the NUBU scoring algorithms were slightly changed. Missing data: One did not do the dynamic coordination subtest because of discus prolapse and one did not co-operate in the tempo subtest. There were no missing data in the soft sign tests.

Self reported motor problems

The KSADS does not include the diagnostics of DCD, but the introductory part contains questions about motor development and motor difficulties. Answers on these questions were compared with the NUBU findings.

Statistical analysis

Data were analyzed using the Statistical Package for Social Sciences (SPSS), version 16. Analyzed factors were soft sign deviations and motor age percentiles adjusted for possibly confounders (comorbidity and medication). Categorical variables were analyzed using cross table with two-tailed chi square test (with Yates Continuity Correction) or Fisher's exact test when appropriate. Continuous variables were analyzed by Kruskal-Wallis test and if significant, pairwise comparisons using Mann-Whitney U test. ROC curves were used to decide cut off value for presence of ADHD-C diagnosis and corresponding sensitivity, specificity and predictive values. Reported motor problems (from the introductory part of KSADS) were compared with total motor problems and total soft sign deviations by Spearman correlation.

Ethics

The protocol was approved by the Regional Committee for Medical Research Ethics of Southern Norway and the Norwegian Social Science Data Services. All children and their caregivers were given verbal and written information. Caregivers gave formal written consent for all children under age 18 years. Children ≥ 12 years gave formal written consent, younger children gave spoken consent. Data collection was mostly incorporated in routine clinical work. Considering the uncertainty of psychiatric diagnosis in childhood and adolescence, all subjects were offered diagnostic reassessment after 2-3 years and after the age of 18.