ADHD is becoming much prevalent in childhood and adolescent , comorbidities like learning disability, anxiety, depression, autism spectrum disorder and tourette syndrome . Regarding the treatment we have to put in mind the comorbid disorder . Amphetamine Methylphenidate, Atomoxetine and behavioral treatment are considered of value in treating ADHD and comorbidities , ,

1. Heterogeneity in ADHD:
neuropsychological pathways,
comorbidity and symptom
domains.
Heba Essawy, MD
Prof Of Psychiatry
Ain Shams University

2. Roadmap
• What is ADHD?
• Prevalence of ADHD.
• ADHD mimicry.
• ADHD Comorbidity.
• Treatment of ADHD and Comorbidities

3. Introduction
• ADHD is a complex disorder of higher brain
functioning, characterized by inattention, motor over-
activity and difficulty inhibiting impulsive behaviors
• ADHD is one of the most prevalent disorders in
childhood and adolescence, affecting an estimated 3-
9% of school-age children

4. Introduction
• Symptoms occur at an early age, occur in most areas of
a child’s life, and persist over time, frequently into
adulthood
• The precise constellation of symptoms changes as
children grow and develop

5. Introduction
• ADHD is often inherited
• Imaging, electrophysiological and neuropsychological
tests, and now, genetic analysis, all point to
disturbances in specific neurotransmitter systems,
affecting specific areas of the brain

6. Introduction
• ADHD is frequently associated with other psychiatric
and learning problems, which complicate diagnosis,
treatment and prognosis
• ADHD is a heterogeneous disorder with many known
causes, all of which mediate similar or identical effects
on brain functioning

7. Prevalence of ADHD in Children
and Adolescents
• The world wide prevalence of ADHD in children and
adolescents is 5.29%1
• Children: 5%-8%
• Adolescents: 2.5%-4%
• The pooled prevalence of DSM-IV ADHD is (5.9%-7.1%)2
• Inattentive is the most common subtype (3.4%-3.6%)
• followed by combined (2.2%-2.3%)
• impulsive subtypes (1.1%-1.3%)
• Higher prevalence in males than females (2.4:1)
1. Polanczyk et al. Am J Psychiatry 2007;164(6):942-8.
2. Willcutt. Neurotherapeutics 2012;9(3):490-9.

8. Prevalence of ADHD Across the World by Age
and Gender
a22 studies of subtypes (total N = 52,622)
b10 studies of subtypes (total N = 10,882)
Willcutt. Neurotherapeutics 2012;9(3):490-9.
Age Range
Total Studies
(Total N)
Total ADHD ADHD-C ADHD-H ADHD-I
% M:F % M:F % M:F % M:F
3-5 years 12 (9,339) 10.5 1.8:1 2.4 2.5:1 4.9 1.9:1 2.2 1.0:1
6-12 years 24 (56,088)a 11.4 2.3:1 3.3 3.6:1 2.9 2.3:1 5.1 2.2:1
13-18 years 6 (5,010) 8.0 2.4:1 1.1 5.6:1 1.1 5.5:1 5.7 2.0:1
19+ years 11 (14,081)b 5.0 1.6:1 1.1 2.0:1 1.6 1.4:1 2.4 1.7:1

9. ADHD Mimicry
• In assessing and diagnosing ADHD, it is
important to consider that there are a variety
of conditions that can mimic ADHD.
• These include both physical conditions and
psychological problems.

10. Conditions that Can Mimic ADHD
Symptoms
• Sensory Impairments
• Medication side effects
• Phenobarbital
• Dilantin
• Some Asthma Medications
• Seizure Disorder
• RTH (Resistance to Thyroid Hormone)
• PTSD
• Bipolar Disorder
• Anxiety Disorders
• Depressive Disorders

11. What is Comorbidity?
• A variety of definitions of comorbidity have been
offered.
• From a medical epidemiology perspective, Feinstein
has defined comorbidity as any distinct additional
entity that has existed or that may occur during the
clinical course of a patient who has the index disease
under study.
• Blashfield has referred to comorbidity as the co-
occurrence of different diseases in the same individual.
• Likewise, Caron and Rutter have defined comorbidity
as the simultaneous occurrence of two or more
unrelated conditions.

12. Number of Comorbidities in US Children
with ADHD
Larson et al. Pediatrics 2011;127(3):462-70
ADHD
alone
ADHD
alone 31%
At least one33%
Two
16%
N = 5028
Three or more
ADHD
33%
18%

13. Comorbid Conditions and ADHD
• A number of these conditions will be
considered :
• Learning Disabilities
• Oppositional Defiant and Conduct Disorder
• Anxiety Disorders
• Mood Disorders
• ASD
• Tourette’s Syndrome
• Other Related Characteristics

14. Learning Disabilities
• Children with ADHD show problems in the academic
environment.
• These problems include
 behaviors that interfere with learning,
 lowered levels of school achievement,
 specific learning disabilities.
• They show more grade repetitions and more frequent
placement in special classes.
• Follow-up studies have also found that the academic
and learning problems of such children often persists
into adolescence and are associated with chronic
underachievement and school failure.

15. Learning Disabilities
• Biederman, et al found the degree of overlap between
ADHD and “learning disabilities” ranged from a low of
10 % to a high of 92% (??).
•
• Barkley (1998) has suggested that the best estimate of
comorbidity is likely to be 19 to 26 % when learning
disability is “conservatively” defined (i.e., significant
delay in reading, math, or spelling relative to IQ, with
achievement in one of these areas at or below the 7th
percentile

16. Learning Disabilities
• With a more lax criterion, (e.g. achievement levels at
least two grades below current grade placement)
comorbidity estimates as high as 80% are found.
• Children with ADHD also show other types of
developmentally related difficulties that can impair
school functioning.
• Speech and language disorders which occur in as
many as 30 to 64 % of children diagnosed with ADHD.

17. Oppositional Defiant and Conduct
Disorder
• The finding of high levels of
comorbidity with oppositional
defiant disorder and conduct
disorder is very common
• Available data suggests as many as
50% of children with ADHD show
evidence of oppositional defiant
disorder
(Johnson, Alvarez & Johnson, 2009)

18. Oppositional Defiant & Conduct
Disorder
• 30 to 50 % of children with ADHD are consistent
with a clinical diagnosis of conduct disorder
(Johnson, et al, 2009)
• When ODD or CD occurs with ADHD the
clinical picture is one of increased severity
compared to children/ adolescents with ADHD
alone.

19. Oppositional Defiant & Conduct
Disorder
• Children with combined ADHD and ODD seem to
represent an intermediate group in terms of
symptom severity when compared to ADHD only
children, who show less severe problems, and
children with ADHD and CD, who show more
severe problems.
• Biederman et al have noted that “ ...children with
attention deficit hyperactivity disorder plus
conduct disorder appear to have a particularly
severe form of attention deficit hyperactivity
disorder.”

20. Oppositional Defiant & Conduct
Disorder
• These investigators indicate that “...
subgrouping based on comorbidity with conduct disorder
may be of potential value in determining which children with
attention deficit hyperactivity disorder have
More serious prognosis
 Different family-genetic risk factors
Require specialized comprehensive therapeutic
interventions.”
What are the pros and con’s of diagnostic subgrouping??

21. ANXIETY DISORDERS
• ADHD has not only been found to be
related to disruptive behavior disorders.
• It is related to internalizing problems
such as anxiety disorders and
depression.
• 25 and 30 % of children with ADHD
show evidence of some type of anxiety
disorder
(Johnson, et al, 2009).
• Rates between 23 and 58.8% have been
found in general population studies.

22. ANXIETY DISORDERS
• Here, children diagnosed attention deficit
disorder- primary inattentive type have been
found to show the highest degree of comorbidity
with regard to anxiety disorders.
• Comorbid anxiety may serve to reduce the
impulsiveness often associated with ADHD.

23. Mood Disorders
• The combination of the two disorders appears to
suggest a subgroup of children who show an especially
poor long term outcome.
• Comorbidity with bipolar disorder are somewhat more
controversial,
• The small number of studies in this area suggest that
the degree of overlap between ADHD and bipolar
disorder is in the range of 11 to 22 per-cent
(Johnson, et al , 2009)

24. Mood Disorders
• This apparent comorbidity may be partially an
artifact due to the fact that similar symptoms (e.g.,
attentional problems, poor judgment, high activity
level) are a diagnostic indicators of both disorders
• The relationship between ADHD and bipolar disorder
is unidirectional.
• That is, the presence of bipolar disorder seems to
suggest an increased risk for ADHD, while the
presence of ADHD does not seem to suggest an
increased risk of developing bipolar disorder.
(cite Katie’s dissertation research).

25. Mood Disorders
• Additional research is needed to
further investigate the precise
relationship between ADHD and
bipolar disorder.

26. Tourette’s Disorder
• Individuals with Tourette’s disorder, somewhere
between 40 and 50 % show features of ADHD .
• ADHD children who develop Tourette’s syndrome is
7%.
• Children displaying both disorders may be more likely
to be referred for assessment and/or treatment than
children who show either of the disorders alone.

27. Tourette’s Disorder
• Lower rate of ADHD diagnoses (12%) in children
with Tourette’s disorder.
• Additional studies in this area are necessary to more
carefully ascertain the degree of comorbidity and the
nature of the underlying relationships between
ADHD and Tourette’s Disorder.

28. Sleep Problems
• Children with ADHD have a higher sleep problems than
normals.
• As many as 56% of children with ADHD have problems falling
asleep (compared to 23% of normal children).
• Up to 39% of ADHD children show problems of night time
awakening.
• Resistance to going to bed and fewer total hours of sleep seem to
be a major problem with many children with ADHD (and likely
add to their difficulties in school functioning).
• Studies of sleep patterns do not, suggest specific difficulties
with the nature of sleep itself in these children

29. Speech Difficulties
• There is a tendency for children with ADHD to be
more delayed in talking than non ADHD children.
• Studies generally suggest that ADHD children are
likely to have problems with expressive language but
not receptive language.
• Here, anywhere from 10 to 54% of children have
speech/language problems compared from 2 to 25
percent of normal children.
• Often have problems on tasks of verbal fluency.

30. Motivational Deficits
• Children with ADHD are often characterized by their
apparent low level of sustained motivation.
• This is especially true on tasks that require repetitive
responding that involves little or no reinforcement.
• Multiple studies have documented an impairment in
persistence of effort in laboratory tasks in children
with ADHD.
• It is not clear whether this is due to the lack of
sensitivity of the ADHD child to reinforcement,
unless it is continuous, or due to some other type of
deficit

31. Motivational Deficits
• Barkley has suggested that the problem may relate to
the fact that, while normal children have the capacity to
bridge temporal delays across times when rewards are
sparse, children with ADHD are delayed in this ability.
• He suggests the problem is not that ADHD children are
not sensitive to reward or dominated by the tendency to
seek immediate rewards.
• Instead they have a diminished capacity to bridge
delays in reinforcement and permit the persistence of
goal directed acts (rule governed behavior?).

32. Types of Comorbidities in Children
with ADHD
*p<.05 for 2 test
aRelative risks were adjusted for child age, gender, race/ethnicity, parent education, household income, and family
structure
Larson et al. Pediatrics 2011;127(3):462-70
ARRa
5.12 7.79 12.58 7.45 8.04 4.42 8.72 2.77 3.93 1.47 10.7
ProportionofPatients(%)
*
*
*
*
* *
*
* * * *

33. ADHD Comorbidity: Relevance
• Comorbidity has important implications for the
understanding, assessment, and treatment of children
with ADHD.
• First, the findings reported here suggest that children
with ADHD frequently show evidence of significant
comorbidity.
• Indeed, many children with ADHD display Learning
Disabilities, ODD or CD, Anxiety Disorders, and
Depressive Disorders, while still others may show
evidence of co-occurring tic disorders and perhaps bi-
polar disorder.

34. Relevance of Comorbidity
• Some show multiple comorbid disorders.
• These patterns of comorbidity have been interpreted
by Biederman, et al as suggesting that “...attention
deficit hyperactivity disorder is most likely a group of
conditions with potentially different and modifying
risk factors and different outcomes rather than a
single homogeneous clinical entity.” (multiple
conditions or ADHD with multiple comorbidities???)
• The presence of comorbid conditions likely has
significant implications for long term outcome.

35. Relevance of Comorbidity
• Simply treating symptoms of ADHD is not enough!
•
• Appropriate case management involves addressing the
full range of clinical problems displayed.
• Effective treatments for children with ADHD and
comorbid conditions are likely to be multimodal and
multidisciplinary in nature and necessarily more
extensive and complex that treatments for children with
“uncomplicated” ADHD.

36. Treatment Of ADHD & CD
• Stimulant medication or ATX decrease :
- Physical aggression
-Verbal aggression
-Negative social interaction
• Antihypertensive , atypical AP for highly
aggressive , explosive cases
• Mood stabilizers are unhelpful
• Behavioural management techniques are
employed
Spencer T, et al Pediatr Clin North Am. 1999;46(5):915-927.

37. Treatment of ADHD & Anxiety
• Prioritize treatment
• Reduced response to stimulants
• Stimulants make anxiety worse ?
• Stimulants make some cognitive abilities worse in
combined cases
• ATX and GUANFACINE xr do not worsen anxiety
in comorbid cases
• SSRI may be effective for anxiety disorders
• Buspirone, high-potency benzodiazepines for
anxiety
Spencer T, et al. Pediatr Clin North Am. 1999;46(5):915-927.
Conners CK J Attn Disord. 2001;4(suppl 1):30.

38. Treatment ADHD& Depression
• Combination therapy often required
• Stimulants effective in treating ADHD but
not mood
• SSRIs may be effective in treating
depression but not ADHD
• Noradrenergic agents ATX may treat both
• Antihypertensive , Atypical AP and Mood
stabilizer are useful.
Spencer T, et al. Pediatr Clin North Am. 1999;46(5):915-927.

39. ADHD: Comorbid Depression
(cont.)
ADHD treatment
• Noradrenergic
antidepressants
• Stimulants
Depression
treatment
 SSRIs
 Bupropion
 Venlafaxine

40. Treatment ADHD& Bipolar
Disorder
• Juvenile mania is highly comorbid and
frequently mixed with depressive features,
ADHD, anxiety, and ODD/CD
• Prioritize treatment
• First treat mania or psychosis
• Mood stabilizers
• Atypical neuroleptic
• ADHD

41. Treatment of ADHD & Tourette's
Tics develop in 1-2% of ADHD receiving high
dose of Amphetamine but not Methylphenidate
• Stimulant medication is not contraindicated
• If unable to tolerate stimulants, consider
alternative ADHD medication (Atx or TCA)
• Adjunctive agents for tic control can be
successfully combined with stimulants (alpha
agonist, risperidone, pimozide)

42. Treatment Of ADHD & ASD
• 20- 25% of ADHD have ASD.
• 20- 5-% of ASD have ADHD.
• ADHD medication can be used to treat
ADHD symptoms effectively in context of
ASD

43. Treatment ofADHD& ODD
• Both stimulants and ATX reduce ODD with
ADHD but not ODD alone.
• Requires adjunctive parents training in
behavior management .
• Response is aged related:
-60-75% successful for children
-25-35% treatment response after 13 ys of
age .

44. TREATMENT Of ADHD &learning
Disorders
• Comorbid reading , spelling and math
disorder do not improve from stimulants
• Reading ability improve on ATX

45. ADHD: Alternative Therapies
Effective in ADHD children :
• Fish oil
• Lithium
• Zinc
Arnold LE. J Affn Disord. 1999;3(l):30.

46. ADHD: Alternative Therapies
Limited data Ineffective or dangerous
EPA Megavitamin therapy
Flax seed oil Megamineral therapy
Ginko preparation Caffeine
EEG biofeedback Primrose oil
L- carnitine DHA
Mg- VIT B6- VIT C
Arnold LE. J Attn Disord. 1999;3(1):30.

47. Summary: Treatment of ADHD
• In treatment planning targeting major areas of
impairment and comorbidities .
• Treatment may employ balance of behavioral and
medical intervention
• Stimulant medications are the gold standard for
medical intervention if no comorbidity is associated
• Apply Low- Slow- GO approach to titrating doses

51. • Hyperactivity, impulsivity and inattention are the final common
pathway of virtually all psychiatric disorders in childhood. The
specific constellation of symptoms and the course of a child's
difficulties distinguish one disorder from another. This brings up an
important point. An accurate diagnostic assessment does more than
determine the presence or absence of ADHD; it also assesses for the
presence, absence or co-occurence of other psychiatric and
developmental disorders. Approximately 2/3 of children with
ADHD have an additional diagnosis; approximately 20% have 2
diagnoses. About 50% of children with ADHD have a disruptive
behavioral disorder such as ODD or CD; 20-30% will have a
learning disability; 34% will have an Anxiety D/O; 6% will have a
depressive D/O. There's been a lot of press lately about the
association of ADHD and juvenile BPD. Two groups reported that
19% of Kids w/ ADHD also have BPD, and that nearly 90% of kids
w/ BPD meet criteria for ADHD @ some point in their clinical
course. Kids w/ ADHD are 2x more likely to develop a substance
abuse disorder as they get older, esp. if they also have CD or BPD.
An accurate assessment also includes a physical examination to rule
out medical disorders that can cause, or can mimic ADHD.
Ultimately, ADHD may prove to be a group of disorders with
different etiologies, risk factors and outcomes, rather than a single
entity.

52. ADHD: Childhood
Common Comorbid Diagnoses
Biederman J, et al. J Am Acad Child Adolesc Psychiatry. 1996;35(3):343-351.
Pllszka SR. J Clin Psychiatry. 1998;59(surppl 1,50-58.
Biederman J, at al. J Am Acad Child Adolesc Psychiatry. 1999;38(8):966-975.
Spencer T, et al. Pediatr Clin North Am. 1999;46(5):915-927.

53. Treatment Impact of anxiety
• Probe more for physical or sexual abuse or
bulling at school
• More responsive to behavioral therapy (
MTA)
• Better response to social skill training

68. Treatment ADHD & Depression
• Highly prevelant from 20 to 45%
• Severe explosive anger may be a sign of
either childhood severe mood dysregulation
(SMD) or Bipolar disorder