Document Sample
wwwbergenclinicsnobk_archiveADHDHayBergen2010ppt.ppt Powered By Docstoc
					How genetic studies should
inform clinical practice in
  managing ADHD and
     substance abuse

         David A. Hay
        School of Psychology
       Curtin University, WA
Australia has
 The largest longitudinal twin study of
  childhood ADHD and comorbidities
 One of the largest twin studies of the
  genetics of substance abuse-run by
  Washington University, St Louis with
 How do we link these?
          ADHD Topics today-research
-genetic analysis means much more than just the
-why do some children “grow out” of behavioural
disorders and what predicts those who do not?
-can the same genes be expressed in different
disorders in childhood and adulthood?
can youth/adult problemssuch as SUD be the
consequence of a childhood behavioural problem?
Do the same genes contribute to the abuse of ALL
             ADHD Topics today-family

-how does ADHD impact upon siblings?

-how may parental behaviours impact on the ADHD
child, given the high genetic component to ADHD??

-what do we tell families when they ask about the
genetics, especially with the new field of gene-
environment interaction?
The key message –
now you can have a sleep

Think of the other disorders which may co-occur
  with ADHD and SUD
 prevalence-are you and your team assessing for
  these adequately
 causes-do they result from ADHD and SUD?
 consequences-what do they mean for
Suicidal Ideation on Brief
Symptom Inventory
  Male     Female    Male    Female
 Control   Control   ADHD    ADHD
  0.09      0.11     0.47     0.52
Number and % meeting criteria for
ADHD and depression
          No           Depression   Total

No ADHD   636 (93)     48 (7)       684 (93.6)

ADHD      37 (78.7)    10 (21.3)    47 (6.4)


No ADHD   777 (91.4)   73 (8.6)     850 (96.8)

ADHD      17 (60.7)    11 (39.3)    28 (3.2)
Previous Research ADHD & Depression

National Survey of Mental Health
and Well-Being
                                   Depression      ADHD
(Sawyer et al., 2000)                              8.3%
4500 children
4-17 years old
Adolescents with depression and               1.5%
ADHD had a poorer response to
antidepressants than those with
depression alone (Keller, 2001)
Frequency Statistics for
Adult AD/HD Subtypes

                          Drug Users       QIMR Participants

                       Frequency    %     Frequency     %

  No AD/HD                51       53.7     688        93.3

  Inattentive type        10       10.5      9         1.2

  Hyp-Impulsive type      9        9.5       24        3.3

  Combined type           25       26.3      16        2.2

  Total                   95       100      737        100
ADHD and substance abuse
 •In adolescent (12-15) substance experimentation, the
 relation is due to family environment

 •Adult substance abuse and ADHD share common

 •The link of ADHD to Substance abuse is NOT just
 mediated by CD or PTSD-work of Tara Yewers
  In a British court case in 2002, the Crown
  accepted a conviction of manslaughter rather
  than murder on the grounds of diminished
  responsibility of the defendant, due to childhood
  ADHD. The defendant, David Blackender, despite
  receiving a life sentence, was offered a minimum
  sentence of two years and four months, provided
  he co-operated with treatment including
  medication, and could demonstrate that he was
  not a risk to the public.
So there are many negative sides

   But can we identify the positive aspects of
    aetiology, treatment and prognosis for the
    clients and their families?
So ADHD is not due to bad
parenting or diet
   If that were the case, there would be a
    sizeable common family environmental
    effect as happens with Conduct Disorder
   The era has gone when we can even hope
to find “the” gene for any behavioural disorder
              In children or adults

       We need to change the mindset
        of professionals and families
 New developments in the last year

Jim Kennedy’s combination of MRI, molecular
 genetics and response to medication

ICASA initiative on genetics of ADHD and substance abuse-
Will we be able to predict which young people with ADHD
go on to develop substance use disorders?

Genetic information and DSM-V ADHD classification

   1/ Dopamine receptor/transporter variants and
    stimulant response
   2/ Serotonin transporter genes and
   3/ Polymorphisms and lithium response
   4/Alcohol treatment and naltrexone
   5/ Antipsychotic medication and
      Weight gain
      Tardive Dyskinesia
Does ADHD actually exist?
Reiger Prize of the American Academy, 1997

De Fries and Fulker

Multiple Regression Approach
• The basic question:
Is the heritability of the disorder the same as that
of    the     trait     (the    dichotomy-continuum

Heritability of the disorder is     0.91 (±0.12)
Heritability of the trait is        0.75 (± 0.21)
Are Inattention and Hyperactivity
genetically distinct?
OR How many types of ADHD will
DSM-V have

ADHD is defined by DSM-IV (1994) as
consisting of 2 dimensions: Inattention and
Hyperactivity-Impulsivity, compared with the
unitary DSM-III-R disorder.
Given the high heritability of ADHD, is this
change justifiable at the genetic level. Our data
on concordance for subtype
                 Continuum                         Heterogeneity

Two general models are shown illustrating how both continuum and multiple
heterogeneity genetic models can explain the distribution of symptoms for a
disorder in the general population. For the case of ADHD the axis might be
defined as Z=prevalence, X=inattentive symptoms, and
Y=hyperactive/impulsive symptoms. The continuum model resembles a lava
flow where there are smooth transitions in genetic risk to the extreme DSM-IV
subtypes (represented by the 3 darkly colored ends of the distributions). For
the heterogeneity model the same distribution resembles a piece of cloisonné
in which distinct genetic risk factors contribute to different parts of the
observed distribution of phenotypes. Todd, J Am Acad Child Adolesc
Psychiatry, 39:1571-1573 2000.
   Do genes contribute to
   developmental changes?
There are genes “switched off” at adolescence

Whether or not you grow out of your ADHD is
genetically programmed-twin data and father-son data

Other behaviours mediate-
Reading problems associated with Inattention
ODD and CD with Hyperactivity/Impulsivity
Genetics means the family

If children have a highly heritable behavioural
What is the rest of the family like?
What happens with children of adults with
ADHD, especially with substance abuse
ARE prenatal smoking and drinking
GENETIC not Environmental factors
 “Subgroups of children with ADHD might be
delineated on the basis of the disorder’s comorbidity
with other disorders. These subgroups may have
differing risk factors, clinical courses, and
pharmacological responses. Thus, their proper
identification may lead to refinements in preventative
and treatment strategies. Investigation of these issues
should help to clarify the etiology, course and
outcome of ADHD”

Biederman, Newcorn & Sprich, 1991, American
Journal of Psychiatry, 148: 564
Possible examples

ADHD+CD     more severe subtype in terms of genetic
loading and clinical severity. (Thapar)
ADHD and anxiety (Vance)
ADHD and reading (ATAP)
       Combined type with/without Reading problems
associated with different molecular markers

But how well do we understand the comorbid
Reading and ADHD share genes

Children with reading problems react by
 developing antisocial behaviours
Strategies for genetic analysis

 1) Conventional


 2) The Endophenotype


 3) The Bioinformatics

      Behaviour----Gene region(s)----Brain
    How wide is ADHD “behaviour”?
Same locus can affect several behavioural disorders
DRD4-ADHD and disorganisation in schizophrenia

16p3-ADHD and autism (Smalley et al, Am J Hum
Genet., 2002)

6p22-ADHD and reading disability (Willcutt et al, Am.
J. Med Genet., 2002)

        The Message

     Thinking comorbidities
         is best practice
in managing ADHD and Substance
The relevance to ADHD
 •Maternal (and paternal) smoking during pregnancy and
 the role of some genes-but do these genes just
 predispose to ADHD

•The genetic story is not going to be simple
•We are hampered by still not being sure how many
genetically distinct types there are of ADHD or CD, nor
the causal reasons for their relationship to substance
abuse and internalising disorders
•The growing acceptance of adult ADHD is helping to
give a better picture of differential diagnosis and
•Families need a realistic perspective of the potential for
genetics and how this pertains to THEIR family history
We still do not know enough about the relationship to a
wide range of more adult disorders
Antisocial and Borderline personality disorder
Bipolar disorder Paediatric Bipolar Disorder
                   Overlap of symptomatology
Schizophrenia “Old studies” on
      retrospective reporting of Inattentive ADHD
      rates of ADHD in high risk children-but is this
        “real” ADHD?
      Bellak’s ADD-psychosis
Baseline percent (n) of mania items
in bipolar versus ADHD group
                                          BP        ADHD
    Symptom area                        (n=60)      (n=60)
    Grandiosity                        85.0 (51)     6.7 (4)
    Elated mood                        86.7 (52)     5.0 (3)
    Daredevil acts                     70.0 (42)    13.3 (8)
    Uninhibited people seeking         68.3 (41)   21.7 (13)
    Silliness, laughing                65.0 (39)   21.7 (13)
    Flight of ideas                    66.7 (40)    10.0 (6)
    Racing thoughts                    48.3 (29)     0.0 (0)
    Hypersexuality                     45.0 (27)     8.3 (5)
    Decreased need for sleep           43.3 (26)     5.0 (3)
    Sharpened thinking                 51.7 (31)   23.3 (14)
    Increased goal-directed activity   51.7 (31)   21.7 (13)
    Increased productivity             36.7 (22)    15.0 (9)
    Irritable mood                     96.7 (58)   71.7 (43)
    Accelerated speech                 96.7 (58)   78.3 (47)
    Hyperenergetic                     96.7 (58)   91.7 (55)
    Distractibility                    91.7 (55)   95.0 (57)
 First question?
The rate of ADHD in Australian children is about 6%
and almost identical to the meta-analysis in 2007.
Yet no more than about 1.5% maximum are receiving any
(See Consult Winter, 2009 for references)

What are some of the barriers to more getting help?
Will this help reduce later substance abuse?
Who do we have to consider?
   Mothers and fathers
   GPs
   The child with ADHD
   Non-ADHD siblings
   Teachers
Next question?
   Mum wants a referral for her child for
    possible ADHD but Dad is adamant he‟s just
    an “active little sportsman and no child of
    mine is going to see a psychiatrist or
    behavioural paediatrician, far less be put on
   What to do?
   (Hint consider also the mother‟s wellbeing)
How train GPs and the referral
    The SWAN measure that is being recommended for GPs in
    the National Guidelines is less confrontational for them and
   The SWAN Rating Scale
Compared to other children, how does this child do the following:         far           slightly        slightly        far
                                                                          below        below       avg. above above above
                                                                           avg.          avg.            avg.           avg.
1. Give close attention to detail and avoid careless mistakes              __     __     __        __    __        __   __
2. Sustain attention on tasks or play activities                           __     __     __        __    __        __   __
3. Listen when spoken to directly                                          __     __     __        __    __        __   __
4. Follow through on instructions and finish school work or chores         __     __     __        __    __        __   __
5. Organize tasks and activities                                           __     __     __        __    __        __   __
6. Engage in tasks that require sustained mental effort                    __     __     __        __    __        __   __
7. Keep track of things necessary for activities                           __     __     __        __    __        __   __
8. Ignore extraneous stimuli                                               __     __     __        __    __        __   __
9. Remember daily activities                                               __     __     __        __    __        __   __
10. Sit still (control movement of hands or feet or control squirming)     __     __     __        __    __        __   __
11. Stay seated (when required by class rules or social conventions)       __     __     __        __    __        __   __
12. Modulate motor activity (inhibit inappropriate running or climbing)    __     __     __        __    __        __   __
13. Play quietly (keep noise level reasonable)                             __     __     __        __    __        __   __
14. Settle down and rest (control constant activity)                       __     __     __        __    __        __   __
15. Modulate verbal activity (control excess talking)                      __     __     __        __    __        __   __
16. Reflect on questions (control blurting out answers)                    __     __     __        __    __        __   __
17. Await turn (stand in line and take turns)                              __     __     __        __    __        __   __
18. Enter into conversations & games without interrupting or intruding     __     __     __        __    __        __   __
                       ADHD - Combined
                           SWAN SCORE
                           SNAP SCORE
                                                                   N = 847
                                                                   mean = .54, sd = .67, skew = 1.47





                    N = 656
                    mean = 2.13, sd = 1.46, skew = .01



               -3   -2.5    -2   -1.5    -1   -0.5     0     0.5      1     1.5    2    2.5    3
How do you work on the self-
esteem of the young person with

   Consider DARC and the areas where
   the child is failing
     DARC: Deficits of Attention,
      Reading and Coordination

              Neilson Martin, David Hay, Jan Piek,
                         Joe Sergeant

 Impulsive                 Inattentive          Combined

And what about adults with

 As well as their own needs, what about those
 of their children

Scores on the BSI
           Having a sibling
             with ADHD

David Hay, Megan McDougall, and Kellie Bennett

             School of Psychology
      Curtin University, Western Australia
 Family Functioning
• Co-twins of children with ADHD were more likely to report
significantly higher levels of family dysfunction compared to
                    10 0




                           Healthy Fam ily Functioning        Fam ily Dysfunction

                               Inattentive ADHD     Combined ADHD   Control

  Figure 1. Healthy family functioning and family dysfunction based on the report of
  co-twins in families with and without ADHD-PI and ADHD-C.
 ADHD-C Group

The majority of co-twins reported that they went to a different school than
their twin with ADHD-C (56%)
For those co-twins that did attend the same school as their twin many
were in different classes (38%)
 • Medication was an important issue for co-twins with a twin with
 • These co-twins recognised a shift in behaviour from when their
 twin was taking medication to when their twin had not taken

Experiences when twins were TAKING medication :

“…like polite, he’s more calm, he’s not really agitated or really like angry
 or anything, he’s just being calm and quiet and he’s happy and he’s in
                            control of himself.”
“he listens to what you say and even though sometimes he has a really
bad short-term memory so you tell him to do something or he’ll go to do
something but then he’ll forget, but when he’s on his tablets he’s better,
                 like he remembers things and stuff.”
How to handle a common
concern from parents at

Will he/she end-up in the Justice system?
Reactive and Proactive Aggression

“Reactive aggression involves angry
outbursts in response to
provocation...[while] proactive
aggression is goal-oriented requiring
neither provocation nor anger”

(Vitario et al., 1998; pp. 377).

ADHD                  CD

Reactive            Proactive
Aggression         Aggression
Are these genetic?
Different pathways during childhood-no
  common environment during adolescence
Different heritabilities
Different causal pathways with ADHD
Getting it right
Australia has several well-publicised examples where ADHD has
 been used inappropriately in criminal cases as varied as sexual
assault and fraud. This has led to antipathy by judges and juries over
the use of ADHD as a defence strategy.
The aim must be:
• Minimise the inappropriate use of the ADHD diagnosis
• Maximise an appreciation of the possible role of ADHD in genuine
cases in
        •Care in the prison system
Overseas studies

   One study estimated between 25% and 28% of adult
    prisoners in the United States have a diagnosis of
    ADHD. [Favarino, 1998 quoted in Collins and White,
   A study of 215 adult prisoners in maximum security
    prisons in the United States found an incidence of 38%
    for males and 41% for females for ADHD. [Minor SW,
   A German study of 129 male prisoners aged 19+/- 2.2
    years found an incidence of 45% for ADHD [Rosler et al,
Characteristics-Minor 2003

They display more:
 Physical aggression
 Verbal aggression
 Anger
 Hostility

And both in male and female prisoners
   A German study of young male delinquents in a juvenile
    offender facility found a prevalence of 21.7% [Retz et al,
   A Dutch study [Doreleijers et al,2000] found a
    prevalence of 28% of juvenile detainees with
    "hyperactivity", and 14% with ADHD as measured by
    DSM111 criteria.
   An Irish study of 129 juvenile offender detainees found
    10.71% were diagnosed with ADHD.[Hayes and O'Reilly,
Young Offenders-Australia
   A New South Wales study [Allerton et al, 2003] of
    802 juvenile offenders in custody found that the
    most frequently reported mental health diagnosis
    was ADHD at 19%.
   A South Australian study [Putnins ] of 524 youths in
    secure care found that the rate of prior diagnosis of
    ADHD was 28%.
   25.2% (n=520) of young offenders completing
    Community Service Orders in South Australia
    reported a prior diagnosis of ADHD.
   Rates of ADHD among female prisoners are
    elevated in comparison with the general population.
    While rates of crime among girls are lower than for
    boys, there is a trend in the United States for more
    girls to come into the juvenile justice system
    charged with more serious crimes.
   In a study of 40 female inmates aged 20-58 in a
    Californian federal correctional institution, 20% had
    diagnosable ADHD [Cholerton, 2000].
   In a study of 100 incarcerated female juveniles in
    Sydney aged 15-19, 13% had ADHD. [Dixon, Howie,
    Starling, 2005].
    Does treatment work?
   The question of whether treatment of ADHD in childhood can
    divert a child from later criminal activity, and if so, which
    treatment, is the subject of debate. One study concluded that
    they found " no intervention studies of grade school children at
    risk for delinquency, that have a beneficial effect on adult
    In the prison system there are many difficulties associated with
    assessment and treatment of individuals who may have ADHD.
    There is the difficulty of relying on self-reporting of symptoms.
    For those who may be diagnosed, the use of amphetamine
    medications is fraught with difficulties in a prison environment.
    Few prisons allow stimulants to be administered. Newer
    medications, such as atomoxetine may provide future
    opportunity for treatment of incarcerated individuals with ADHD.
Screening in the Justice System
       The SA Chief Clinical Psychologist has
       called for the routine screening of young
       offenders and has developed a screening
       tool for recidivism risk which rates
       "ADHD signs" as one of the best current
       predictors of offending risk. The best
       current predictors of offending risk among
       youths incarcerated in South Australia are-
        frequency of recent alcohol and inhalant
       use, current age, age at first proven offences,
       the ADHD signs scale, number of prior offences
Interviewing people with ADHD
   People with ADHD may be vulnerable in all
    stages of the justice system.
   Inattention and impulsiveness may hinder
    performance in a police interview.
   They may agree to an interview without waiting
    for a lawyer
   Juveniles may have parents with ADHD who are
    unable to provide adequate support and advice.
   Inattention in court could have implications for
    effective presentation, participation and
The FBI view
 The FBI suggests that interrogators who suspect that an
 interviewee may suffer from ADHD should ask nine questions
 to establish the likelihood. If the interrogators believe that the
 interviewee may have ADHD, they are advised to suggest that
 the person should have a pre-trial psychological or psychiatric
 assessment. Prosecutors and courts are similarly advised to
 seek assessment, diagnosis and treatment for people with
 ADHD who are charged with criminal offences. An individual
 with a diagnosis of ADHD is entitled to courtroom
 accommodations. These may include repetition of important
 information, additional time to reply to questions, and non-
 confrontational communication.
 (Goldstein S, 1997)
ADHD in Sentencing
 George Still‟s “Defective Moral Control”
 Low IQ
 Reactive vs proactive aggression-poor
  behavioral control vs premeditation
 Co-morbid ADHD and Substance Abuse
 Dysfunctional Family Environment
ADHD and Literacy
 „an average delay in reading attainment of 5 years
  and…48% of the sample had intellectual levels that
  were borderline and below in intellectual
  impairment….Young people in detention need to be
  given enriched and supportive opportunities to
  address their learning deficits since it is likely that
  their continued experience of inadequate skills will
  lock them into the cycle of delinquency and crime.'
Do we have a model or a muddle?
Challenges for the future
 Just what are the intervening variables,
  ODD, CD, Reading problems…. And how
  do we measure and model these?
 Ethnic group differences in association
 Cultural differences in substance
 Is genotype-environmental interaction real
So what we do-1

Implementing National Guidelines

Speak to your local politician-alert her/him to the issues

Challenge the fraudulent claims to “cure” ADHD
So what do we do-2
   Improving knowledge of the longterm outcomes
    of ADHD among those working with the young
   Identifying those young people most at risk of
    continuing with their ADHD and possibly
    developing SUD
   Improving knowledge of ADHD among ALL
    those working with adults including SUD
    agencies and the Justice System

Shared By:
lily cole lily cole