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Comorbidities are commonly associated with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder (HKD) in children, adolescents and adults.1-8

How does the aetiology and the pathology of ADHD vary across different patients? | Dr Matt McConkey | South Eastern Health and Social Care Trust, Northern Ireland, UK


Children and adolescents

The large European ADORE (Attention-Deficit Hyperactivity Disorder Observational Research in Europe) study was a 24-month naturalistic longitudinal observational study in 10 European countries of children (aged 6–18 years). In total, 1478 patients were analysed, of whom 84% were male.2

Results found substantial ‘co-existing psychiatric disorders’, the most common being oppositional defiant disorder (67%) and conduct disorder (46%) (Figure).1 The ADORE study did not perform a detailed assessment of the psychiatric disorders co-existing with ADHD, but rather collected overall clinical ratings of the disorders, which may in part explain the high prevalence rates.1

Co-existing psychiatric disorders associated with ADHD in children and adolescents in the ADORE study (n=1478)1

Co-existing psychiatric disorders associated with ADHD in children and adolescents in the ADORE study

The comorbidity profile across the sample of this study was similar between genders,3 and the study also found that the presence of multiple psychiatric comorbidities impacted overall health-related quality of life more than the presence of ADHD alone.1

A Danish study of 14,825 children and adolescents (aged 4–17 years) found that 52% of the study population had at least one comorbid psychiatric disorder, and 26.2% had two or more comorbid disorders.4

The most frequently reported comorbid conditions included:4

  • Conduct disorders (16.5%)
  • Specific developmental disorders of language, learning and motor skills (15.4%)
  • Autism spectrum disorder (12.4%)
  • Intellectual disability (7.9%).

In a US community-based investigation of children with ADHD (aged 4–15 years), the prevalence of comorbid disorders was reported for study sites in South Carolina and Oklahoma (Table). Children with ADHD and comorbid anxiety/mood disorders were significantly more likely to have below average academic performance (odds ratio [OR]: 10.8; 95% confidence interval 2.4–49.1).5

Prevalence of comorbid disorders in children with ADHD from a US community-based sample by study site. Reproduced with kind permission.5

Comorbidity South Carolina

(n=99)

Oklahoma

(n=160)

Conduct disorder 13.5% 26.8%
Oppositional defiant disorder 44.3% 59.3%
Anxiety/mood disorder 18.0% 20.5%
Generalised anxiety disorder 6.4% 7.3%

Adults

The National Comorbidity Survey Replication of US adults (aged 18–44 years) identified 3199 cases of adult ADHD using a two-part diagnostic interview.6

Commonly reported comorbidities and their associated ORs included:6

  • Bipolar disorder (OR: 7.4)
  • Social (OR: 4.9) and specific (OR: 2.8) phobia
  • Intermittent explosive disorder (OR: 3.7)
  • Generalised anxiety disorder (OR: 3.2)
  • Substance use disorder (alcohol/drugs) (OR: 3.0)
  • Major depressive disorder (OR: 2.7).

The Swedish STAGE (Study of Twin Adults: Genes in Environment) study assessed 17,899 adults for ADHD symptoms using a self-reported questionnaire based on Diagnostic and Statistical Manual of Mental Disorders – 4th Edition (DSM-IV) diagnostic criteria.7 In total, 227 (1.27%) participants with ADHD were identified, and this group was associated with an increased risk for symptoms of:7

  • Bipolar disorder (OR: 8.0)
  • Generalised anxiety disorder (OR: 5.6)
  • Obsessive-compulsive disorder (OR: 3.9)
  • Major depression (OR: 2.8)
  • Alcohol dependence (OR: 2.6).

No significant differences were seen between genders.7

The observational CAT (Comorbilidad en Adultos con TDAH) study of newly diagnosed adults (aged ≥18 years) with ADHD (n=367) in Spain found that on average, 2.4 comorbidities were present at the time of first diagnosis, and that 66.2% of the sample had at least one psychiatric comorbidity.8 The most frequently reported comorbidities were substance abuse disorders, anxiety disorders and mood disorders.8

Preliminary evidence suggests that young adults and adolescents with ADHD and comorbid major depression have an increased risk of subsequently developing bipolar disorder.9

Researchers conducted a longitudinal follow-up study using data from the Taiwan National Health Insurance Research Database. A total of 1193 patients (aged <30 years) with major depression and comorbid ADHD participated over the study period.9

Compared with patients with major depression without comorbid ADHD, the ADHD group had an increased incidence of subsequent bipolar disorder (18.9% vs 11.2%; p<0.001).9

  • Comorbid ADHD was an independent risk factor for subsequent bipolar disorder (hazard ratio: 1.50; 95% confidence interval 1.30–1.72).9

ADHD comorbidity and gender

Independent, long-term longitudinal case-controlled studies have assessed psychiatric outcomes in groups of male and female patients with ADHD.10,11 In total, 110 boys with ADHD were followed-up after a 10-year study period10, and 140 girls with ADHD were followed-up after 11-years.11 In both studies, males and females had high lifetime risk for comorbid antisocial, addictive, mood and anxiety disorders compared with controls.10,11

Males

The lifetime prevalence for all categories of psychopathology was significantly greater in males with ADHD compared with controls, with hazard ratios and 95% confidence intervals of:10

  • Major psychopathology (mood disorders and psychosis): 6.1 (3.5–10.7)
  • Anxiety disorders: 2.2 (1.5–3.2)
  • Antisocial disorders (conduct, oppositional-defiant and antisocial personality disorder): 5.9 (3.9–8.8)
  • Developmental disorders (elimination, language and tics disorder): 2.5 (1.7–3.6)
  • Substance dependence disorders (alcohol, drug and nicotine dependence): 2.0 (1.3–3.0).

Females

The lifetime prevalence for all categories of psychopathology was significantly greater in females with ADHD compared with controls, with hazard ratios and 95% confidence intervals of:11

  • Antisocial disorders: 7.2 (4.0–12.7)
  • Mood disorders: 6.8 (3.7–12.6)
  • Anxiety disorders: 2.1 (1.6–2.9)
  • Developmental disorders: 3.2 (2.0–5.3)
  • Addictive disorders: 2.7 (1.6–4.3)
  • Eating disorders: 3.5 (1.6–7.3).

ADHD subtype and comorbidity

Data from STAGE were used to assess psychiatric comorbidity in each of the three presentations of ADHD. Patients with predominantly hyperactive-impulsive type ADHD had a lower risk for comorbidities, particularly anxiety disorder and major depression (Figure).7

Association of ADHD symptoms with psychiatric disorders in adult patients with ADHD (n=17,899). Reproduced with kind permission.7

Association of ADHD symptoms with psychiatric disorders in adult patients with ADHD

Further evidence for ADHD subtype differences in comorbidities comes from a study in which DSM-IV subtypes were reterospectively determined from DSM-III-R criteria. From a sample of 149 clinically referred adults with ADHD (mean age 37 years), it was found that combined type ADHD was associated with higher incidence of oppositional, bipolar and substance abuse disorders when compared with inattentive type ADHD.12 Only three patients with hyperactive-impulsive type ADHD participated in the study, meaning that meaningful conclusions on the incidence of comorbid conditions could not be made in this group.12

A study of adult (age 18–55 years) outpatients with ADHD (n=107) used DSM-IV diagnostic criteria to identify ADHD subtypes, and evaluated psychiatric comorbidity as a secondary outcome.13 Patients with combined type ADHD had higher lifetime incidence rates of conduct disorder (36% vs 12%), bipolar disorder (23% vs 6%) and psychosis (15% vs 0%) than patients with inattentive type ADHD (p=0.01, 0.04, 0.01, respectively).13

The correlation between ADHD subtype and comorbid psychiatric symptom severity was investigated in a study of 487 clinically referred and 900 community-sampled adults.14

In the community sample, patients with combined type ADHD had more severe symptoms of anorexia, bulimia, dissociation, major depressive disorder and post-traumatic stress disorder than patients with inattentive type ADHD.14

Similarly, patients with hyperactive type ADHD had more severe symptoms than patients with inattentive type ADHD for anorexia, bulimia and mania.14

Overall, patients with combined type ADHD had highest rates of comorbid symptom severity.14

A study of 118 clinically referred adult patients (aged 18–59 years) with ADHD assessed psychiatric comorbidity in two of the DSM-IV-defined presentations – combined and predominantly inattentive ADHD – and in a third subtype, ‘inattentive anamnestically combined’, which defines adults with combined ADHD symptoms during childhood who present with primarily inattentive symptoms in adulthood.15

The prevalence of psychiatric disorders overall was higher in all three examined ADHD subtypes compared with controls.15

  • Lifetime substance abuse disorders were more prevalent in patients with combined, or inattentive anamnestically combined type ADHD than patients with predominantly inattentive type ADHD.15

ADHD and obesity

A meta-analysis of data from 42 studies examining the association between obesity and ADHD has indicated that children, adolescents and adults with ADHD may have an elevated risk of obesity.16

In total, 48,161 patients with ADHD from studies in 17 countries were included in the meta-analysis.16

  • Pooled prevalence of obesity was increased by 70% in adults with ADHD relative to adults without ADHD16
  • Children with ADHD were 40% more likely to be obese compared with children without ADHD.16
  1. Steinhausen HC, Novik TS. ADORE Study Group. Co-existing psychiatric problems in ADHD in the ADORE cohort. Eur Child Adolesc Psychiatry 2006; 15: I/25-I/29.
  2. Preuss U, Ralston SJ, Baldursson G, et al. Study design, baseline patient characteristics and intervention in a cross-cultural framework: results from the ADORE study. Eur Child Adolesc Psychiatry 2006; 15(Suppl 1): I/4-I/14.
  3. Novik TS, Hervas A, Ralston SJ, et al. Influence of gender on attention-deficit/hyperactivity disorder in Europe–ADORE. Eur Child Adolesc Psychiatry 2006; 15(Suppl 1): I/15-I/24.
  4. Jensen CM, Steinhausen HC. Comorbid mental disorders in children and adolescents with attention-deficit/hyperactivity disorder in a large nationwide study. Atten Defic Hyperact Disord 2015; 7: 27-38.
  5. Cuffe SP, Visser SN, Holbrook JR, et al. ADHD and psychiatric comorbidity: functional outcomes in a school-based sample of children. J Atten Disord 2015; Epub ahead of print.
  6. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163: 716-723.
  7. Friedrichs B, Igl W, Larsson H, et al. Coexisting psychiatric problems and stressful life events in adults with symptoms of ADHD–a large Swedish population-based study of twins. J Atten Disord 2012; 16: 13-22.
  8. Piñeiro-Dieguez B, Balanzá-Martinez V, García-García P, et al. Psychiatric comorbidity at the time of diagnosis in adults with ADHD: the CAT study. J Atten Disord 2016; 20: 1066-1075.
  9. Chen MH, Chen YS, Hsu JW, et al. Comorbidity of ADHD and subsequent bipolar disorder among adolescents and young adults with major depression: a nationwide longitudinal study. Bipolar Disord 2015; 17: 315-322.
  10. Biederman J, Monuteaux MC, Mick E, et al. Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study. Psychol Med 2006; 36: 167-179.
  11. Biederman J, Petty CR, Monuteaux MC, et al. Adult psychiatric outcomes of girls with attention deficit hyperactivity disorder: 11-year follow-up in a longitudinal case-control study. Am J Psychiatry 2010; 167: 409-417.
  12. Millstein RB, Wilens TE, Biederman J, et al. Presenting ADHD symptoms and subtypes in clinically referred adults with ADHD. J Atten Disord 1997; 2: 159-166.
  13. Wilens TE, Biederman J, Faraone SV, et al. Presenting ADHD symptoms, subtypes, and comorbid disorders in clinically referred adults with ADHD. J Clin Psychiatry 2009; 70: 1557-1562.
  14. Sprafkin J, Gadow KD, Weiss MD, et al. Psychiatric comorbidity in ADHD symptom subtypes in clinic and community adults. J Atten Disord 2007; 11: 114-124.
  15. Sobanski E, Bruggemann D, Alm B, et al. Subtype differences in adults with attention-deficit/hyperactivity disorder (ADHD) with regard to ADHD-symptoms, psychiatric comorbidity and psychosocial adjustment. Eur Psychiatry 2008; 23: 142-149.
  16. Cortese S, Moreira-Maia CR, St FD, et al. Association between ADHD and obesity: a systematic review and meta-analysis. Am J Psychiatry 2016; 173: 34-43.
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