is there a late onset form of adhd? · defining adult adhd (dsm-5) criteria a: 5 or more symptoms...

Philip Asherson MRCPsych, PhD

Professor of Molecular Psychiatry & Honorary

Consultant Psychiatrist,

MRC Social Genetic Developmental Psychiatry,

Institute of Psychiatry, UK

MRC Social Genetic and

Developmental Psychiatry

Is there a late onset form of ADHD?

Diagnostic criteria

What is ADHD

A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development

What is not ADHD

The symptoms are not solely a manifestation of oppositional behaviour, defiance, hostility, or failure to understand tasks of instructions

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, 2013

Criteria for Adult ADHD Diagnosis: DSM-5

Inattention Lack of attention to details, makes careless

mistakes

Difficulty sustaining attention

Does not listen when spoken to directly

Trouble completing or finishing job tasks

Problems organizing tasks and activities

Avoids or dislikes sustained mental effort

Loses and misplaces things

Easily distracted

Forgetful in daily activities

Hyperactivity Fidgetiness b(hands or feet) or squirming in

seat

Leaves seat when not supposed to

Restless or overactive

Difficulty engaging in leisure activities quietly

Always ‘on the go’

Talks excessively

Impulsivity

Blurts out answers before questions have been completed

Difficulty waiting in line or taking turns

Interrupts or intrudes on others when they are working or busy

American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition

2013

DSM-5: Age-appropriate descriptions of ADHD

Inattention

• Mind elsewhere in the absence of obvious distractions

• Starts tasks, quickly loses focus, easily side-tracked

• Fails to finish tasks in the workplace

• Reporting task unrelated thoughts (mind wandering)

• Problems returning calls, paying bills

• Poor time management, not meeting deadlines

Hyperactivity

• Feeling restless

• Feeling uncomfortable being sat in restaurants or meetings

Impulsivity

• Butting into conversations or activities

• Intrude into and take over what other people are doing

American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition 2013

Defining Adult ADHD (DSM-5)

● Criteria A: 5 or more symptoms of inattention or hyperactivity-impulsivity

● Criteria B: Several symptoms present by the age of 12

● Criteria C: Several symptoms present in two or more settings

● Criteria D: Symptoms interfere with or reduce quality of social, educational or occupational functioning

● Criteria E: Symptoms are not better explained by another condition, such as mood disorder

American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition 2013

6 6

1. *Work Functions 2. *Social relationships 3. *Coping with daily activities 4. Driving accidents (increased mortality) 5. *Behavioural problems 6. *Distress from the symptoms 7. *Low self-esteem 8. Emotional instability 9. Sleep problems 10. *Risk for comorbid disorders (substance abuse, anxiety, depression,

personality disorder) 11. Cognitive impairments, including general and specific learning

difficulties (dyslexia, dyspraxia, autism spectrum disorder)

Domains of ‘IMPAIRMENT’

NICE Clinical Guideline 72. 2008. http://guidance.nice.org.uk/cg72;

Asherson P, Expert Rev Neurotherapeutics. 2005 Jul;5(4):525-39.

Psychosocial

Psychiatric

Neurodevelopmental

(* NICE definition of impairment 2008)

Population prevalence rates

Polanczyk et al 2007

5.29%

Prevalence of ADHD in children

8.8

6.1

13.3

7.1

12.9

5.7 5.9

0

2

4

6

8

10

12

14

DSM_IV subtype Prevalence Male : Female

Combined 3.4 2.7 : 1

Inattentive 1.8 1.8 : 1

Hyper-imp 0.8 3.5 : 1

Willcutt Neurotherapeutics (2012) 9: 490-499

percent

Assuming 5% prevalence of ADHD during middle childhood and 50% decline every 5 years • Estimated prevalence age 20 = 0.84% • Estimated prevalence age 30 = 0.21% • Estimated prevalence age 50 = 0.01%

Hill and Schoener

Developmental delay

5 10 15

NORMAL

ADHD

AGE

ADHD symptoms

Developmental deficit

5 10 15

NORMAL

ADHD

AGE

ADHD symptoms

Does ADHD persist?

ADHD symptom scores at 7 and 17 years

0 0.2 0.4 0.6 0.8 1 1.2

Control

ADHD

Age 17 years

Age 7 years

Taylor et al. 1996 Scores from PACAS interview

The age-dependent decline and persistence of attention-

deficit/ hyperactivity disorder throughout the lifetime

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder

Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20

Estimates of adult ADHD prevalence based on longitudinal follow-up studies

Faraone meta-analysis 2006 • Full diagnosis of DSM-IV ADHD: 5% x 0.15 = 0.75%

• In partial remission: 5% x 0.65 = 3.3%

Prevalence of ADHD from US National Comorbidity Survey

Estimated prevalence of 4.4%

Kessler et al 2006, AmJPsych

• Six symptoms of either inattention or hyperactivity-impulsivity during last 6 months (A)

• Two or more symptoms before age 7 (B) • Some impairment in at least two areas of living during

the past 6 months (C) • Clinically significant impairment in at least one of these

areas (D).

Prevalence of adult ADHD

Fayyad et al., Br J Psychiatry. 2007 May;190:402-9.

4.1%

1.9%

7.3%

3.1%

2.8%

1.8%

1.9%

5%

1.2%

5.2%

3.4%

0 1 2 3 4 5 6 7 8

Belgium

Colombia

France

Germany

Italy

Lebanon

Mexico

Netherlands

Spain

USA

TOTAL

• Prevalence = 2.5% (95% CI: 2.1–3.1%)

Simon et al. Br J Psychiatry. 2009 Mar;194(3):204-11

Prevalence of adult ADHD

Estimates of adult ADHD prevalence based on longitudinal follow-up studies

Faraone meta-analysis 2006 • Full diagnosis of DSM-IV ADHD: 5% x 0.15 = 0.75%

• In partial remission: 5% x 0.65 = 3.3%

Potential problems with studies so far

• Child ADHD studies: clinical samples influenced by referral bias

• Adult ADHD studies: depend on retrospective recall

Dunedin Longitudinal Outcome Study

Child ADHD: follow-forward Adult ADHD: follow-back

Dunedin Child ADHD diagnosis n=61 (6% of sample)

• DSM-III diagnoses established in 1984 – 1988

• Assessments by child psychiatrists (age 11-13) and researchers (age 15) using DISC

• Parent/teacher ratings at ages 11, 13 and 15

• 8 or more symptoms rated by two sources (2/3 of cases) or one source (1/3 of cases)

• Onset before the age of 7 years

Dunedin Adult’ ADHD diagnosis n=31 (3% of the sample)

• Assessments in 2010-2012 aged 38

• Structured diagnostic interview with clinically trained research staff

• Based on behaviour/symptoms in last 12 months

• Blind to prior data

• DSM-5 criteria applied

• Included age adjustments (e.g. difficulty sitting through meetings, feeling restless)

• Informant ratings for childhood and adulthood

6% of the total sample met child ADHD diagnosis

5% met adult ADHD criteria

6% of the total sample met child ADHD diagnosis

5% met adult ADHD criteria

3% of the total sample met adult ADHD diagnosis

10% met child ADHD criteria

Child onset ADHD vs Adult onset ADHD

Child ADHD (n=61, 6%)

Adult ADHD (n=31, 3%)

% male 87.7% (p<.001) 61.3% (ns)

Cognitive impairments in childhood

YES (p<.001) NO (ns)

Cognitive impairments in adulthood

YES (p<.001) NO (ns)

Associated with ADHD genetic risk score

YES (p=.04) NO (ns)

Life impairment at the age of 38 Yes (p<.001) Yes (p<.001)

Questions

(1) Do children with ADHD grow out of the disorder by the age of 38 years?

(2) Does ADHD in adults reflect an adult onset condition that is distinct from childhood ADHD?

Questions

(1) Do children with ADHD grow out of the disorder by the age of 38 years?

(2) Does ADHD in adults reflect an adult onset condition that is distinct from childhood ADHD?

Child ADHD group

Adult ADHD group

INATTENTION

Number of ADHD symptoms reported by adults at age 38 years

Moffitt et al., 2015 Am J Psychiatry

Child ADHD group

Adult ADHD group

INATTENTION HYPER-IMPULSIVITY

Number of ADHD symptoms reported by adults at age 38 years

Moffitt et al., 2015 Am J Psychiatry

-0.2

0

0.2

0.4

0.6

0.8

1

Inattention

Hyperactivity-impulsivity

Controls Child ADHD Adult ADHD

Parent report for ADHD symptoms at the age of 38

Both p<.001

Moffitt et al., 2015 Am J Psychiatry

Do children with ADHD grow out of the disorder by adulthood?

NO

• Still cognitively impaired

• Still functionally impaired

• Still have high levels of ADHD symptoms according to parents

The only inconsistent finding are ADHD symptoms according to self-report

Moffitt et al., 2015 Am J Psychiatry

79

0

10

20

30

40

50

60

70

80

90

DSM-IV ADHD Combinedsubtype

Inattentivesubtype

Hyper-impsubtype

ResidualADHD

• Mean age at baseline assessment = 11.8 (SD=2.9; range = 6-17) • Mean age at follow-up assessment = 18.5 (SD=2.0; range = 12-26)

Percentage persistence of children/adolescents with DSM-IV ADHD: Follow-up period ~6.5 years

Cheung, Rijdijk, McLoughlin, Asherson, Kuntsi (2015) BJPsych, 2015

%

Du Rietz et al. 2016, J Psych Res

ADHD Persistent

(N)

ADHD Remittent

(N)

ADHD Persistence rate

Parent report

87 23 79%

Self report 48 60 44%

Self report leads to lower ADHD persistence rate than parent report

IQ

DSF

DSB

RTV

OE

CE

CNV

Cue-P3

Nogo-P3

Delta

Theta

Alpha

Beta

Movement intensity

Movement count

Parent Self

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✖

✖ ✔

✖ ✖

✖ ✖

✖ ✔

✖ ✖

✖ ✔

✖ ✖

Parent Self

✔ ✖

✖ ✖

✖ ✖

✔ ✔

✔ ✖

✖ ✖

✔ ✖

✖ ✖

✖ ✖

✔ ✖

✔ ✖

✖ ✖

✖ ✖

✔ ✖

✔ ✖

Cheung et al. (2015) British Journal of Psychiatry; Du Rietz et al. 2016, J Psych Res

Remittent vs Control Remitted vs Persistent

Remitted vs Persistent Remittent vs Control

IQ

DSF

DSB

RTV

OE

CE

CNV

Cue-P3

Nogo-P3

Delta

Theta

Alpha

Beta

Movement intensity

Movement count

Parent Self

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✔

✖ ✖

✖ ✔

✖ ✖

✖ ✖

✖ ✔

✖ ✖

✖ ✔

✖ ✖

Parent Self

✔ ✖

✖ ✖

✖ ✖

✔ ✔

✔ ✖

✖ ✖

✔ ✖

✖ ✖

✖ ✖

✔ ✖

✔ ✖

✖ ✖

✖ ✖

✔ ✖

✔ ✖

Cheung et al. (2015) British Journal of Psychiatry; Du Rietz et al. under review

Number of Neural and Cognitive markers showing significant group vs control differences

Parent rated ADHD status

Self rated ADHD status

Persistent vs remitted

8 1

Remitted vs controls

0 10

Dynamic switching between task positive and negative networks

Uddin L.Q. 2014, Nature Reviews Neuroscience

Default mode network Salience network Executive control

Faraone et al. 2000; Chen et al., NPG, 2008

Family studies

Risk to parents Risk to siblings

14.7

2.8

20

4.7

12.7

1.4

0

5

10

15

20

25

ADHD Control ADHD Control ADHD-CT Control

RR: 5.25 4.3 9.1

ADHD symptoms scores are

highly heritable

0 0.2 0.4 0.6 0.8 1

Willerman 1973

Matheny 1980

Goodman 1989

Gillis 1992

Edelbrock 1992

Stevenson 1992

Schmitz 1995

Thapar 1995

Gjone 1996

Silberg 1996

Sherman 1997

Levy 1997

Nadder 1998

Hudziak 2000

Willcutt 2000

Thapar 2000

Coolidge 2000

Kuntsi 2001

Martin 2002

Boomsma 2003

Heritability

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Co

rrela

tio

ns (r)

MZ twins DZ twins

Monozygotic/Dizygotic twins:

Correlations for Teacher ADHD rating scales

Identical twins (monozygotic): correlation ~ 76%

Non-identical twins (dizygotic): correlation ~ 35%

Asherson, unpublished data

DZ twins MZ twins

New ADHD meta-analysis 18,284 cases 33,836 controls

10 loci 8 look robust On the path!

Adult twin studies

1. Van Den Berg et al. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(1):55-60; 2. Boomsma et al. 2010; PLoS ONE 5(5): e10621. 3. Larsson et al, JAMA Psychiatry 2011

Phenotype Self-ratings Age Heritability

ADHD (study 1) Self 18-30 0.40

ADHD (study 2) Self 18+ 0.30

ADHD (study 3) Self 20-28 0.39

ADHD (study 3) Self 29-37 0.35

ADHD (study 3) Self 38-46 0.33

Heritability rates based on concordance rates for ADHD diagnosis on Swedish national medical records

Larsson et al., 2013, Psychological Medicine

0.88

0.72

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Heritability overall Heritability in adults

Heritability

Questions

(1) Do children with ADHD grow out of the disorder by the age of 38 years?

(2) Does ADHD in adults reflect an adult onset condition that is distinct from childhood ADHD?

Two other population studies UK study Brazil study

Age at ADHD 5 - 12 18 11 18-19

Number in sample 2232 4426

Prevalence of child ADHD 11% 8.9%

Prevalence of adult ADHD 7.4% 12.2%

% child ADHD with adult ADHD 21.9% 17.2%

% adult ADHD with child ADHD 67.5% 12.6%

ASSESSMENTS

Child assessment Parent or teacher reported ADHD

Parent rated SDQ

Adult assessment Participant interview Participant interview

Agnew-Blais, JAMA Psychiatry, 2016; Caye, JAMA Psychiatry, 2016

Is there an adult onset form of ADHD?

POSSIBLY but…..

- Rater effects: self-versus informant

- False positive paradox

- Neurodevelopmental origins - 1/3 had oppositional defiant, conduct disorder or school failure

- Subthreshold cases in childhood, with ADHD emerging later in life

Late onset and full ADHD had similar patterns of: - Impairment - Psychiatric comorbidities - Functional impairment - Familial risks

0%

10%

20%

30%

40%

50%

60%

70%

7-9 years 7-12 years > 12 years

Faraone et al., 2006, Am J Psych

SAIL Father SAIL Mother

Bimodal distribution for self-reported age of onset of

adult ADHD symptoms in a population sample

Howe-Forbes, PhD, KCL, 2004

Possible causes of late onset ADHD

• Scaffolding during childhood/adolescence - greater demands on ‘executive functioning’

• High IQ masking impairments

• Maturational delay/failure during adolescence (e.g. executive control)

• Head injury

• Sleep disorders

• Toxins or drugs

Default Mode Network

My mind is: Constantly daydreaming

In a fog A whirlwind of thoughts

Hamster on a wheel Jack in the box

Waves in a storm Flitting and jumping

Asherson, Expert Review, 2005

Words used to describe mind wandering by adults with ADHD

Mind Wandering in ADHD

“People with ADHD often struggle with filtering out”

Traffic noise Conversations Laughter

Is it my fault Can I do my job Do you still love me

Creativity Versatility Humour

Components of Excessive Mind Wandering in ADHD

• Thoughts on the go all the time

• Thoughts jumping of flitting from one topic to another

• Multiple lines of thoughts at the same time

Context regulation Sensitive to

reward

The decoupled brain: The brain does not detect sensory visual and other stimuli during periods of mind wandering

Baird et al., 2014, J Cog Neurosci.

Performing

tasks

Performing

tasks

Inattentive

behaviour

Performing

tasks

Sleep

problems

Inattentive

behaviour

Performing

tasks

Sleep

problems

Inattentive

behaviour

Self-

awareness

and control

of behaviour

Complete our online survey to help us understand the relationship between

Creativity, Occupation, Mind wandering, and Education (COME-on!!)

Everyone’s mind wanders, but we all do it to a different degree, so what is its impact?

tinyurl.com/mindwander

@FloMowlem

Contact: Florence Mowlem for more information E-mail: florence.d.mowlem@kcl.ac.uk