FASD: Attachment, Comorbidities and

Neurodevelopment

Dr Raja Mukherjee

Consultant Psychiatrist /

Lead Clinician FASD Behavioural Clinic

Surrey and Borders Partnership NHS trust

Honorary Reader University of Salford

Raja.mukherjee@sabp.nhs.uk

Countries where FASD has been assessed in literature:

And shows a similar profile

BRIEF Scores from UK and Canada (Mohamed et al 2018)

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85

90

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UK National FASD Clinic Rai et al. (2016)

Screening prevalence of ]

Fetal alcohol spectrum disorders (FASD) in a region of the

United Kingdom:

a population-based birth-cohort study

Dr Cheryl McQuire et al Population medicine 2018

Results – Clinical Characteristics

0

10

20

30

40

50

60

70

80

90

100

Growthdeficiency

Fullfacialphenotype

Partialfacialphenotype

CNSimpairment PAE

Proportionw

ithcharacteristic(%

)

NotFASD FASD

Method Total FASD prevalence

Single imputation 6.0%

Complete case 7.2%

Multiple imputation (MAIN

ESTIMATE)

17.0%

(sensitivity analyses 12.7% –

12.8%)

Results – FASD Screening Prevalence

Environment vs Biology

Parts involved

Environmental issues e.g. Attachment

Biological insults e.g. Genetic + prenatal /

postnatal causes

Observed Symptoms

Parts involved

Environmental issues e.g. Attachment

Biological insults e.g. Genetic + prenatal /

postnatal causes

Observed Symptoms

Parts involved

Environmental issues e.g. Attachment

Biological insults e.g. Genetic + prenatal /

postnatal causes

Observed Symptoms

Psychiatric onion! To coin a phrase!

Environmental Influences

Vulnerability from function

Neurodevelopmental

problems

Development of attachment (Schaffer and Emerson)

0 -6 weeks: Asocial; in both social and non social situations will make

responses

6 weeks – 7 months: Indiscriminate attachment; Begin to seek

social contact but from anyone. By 3 months a preference towards main carer is being

established

7-9 months: Specific attachment; preference for one person

established

10 months +: Multiple attachments: Babies begin to develop

attachments and can transfer security

Secure

Avoidant

Ambivalent

Disorganised

Reactive

Adjustment

Disorder

• Inhibited

• Disinhibited

Attachment styles

http://www.practicenotes.org/v19n3/identifying.htm

Attachment and PAE/ FASD , Wray, Palod, Mukherjee

7 Studies (2 FASD)

2 FASD ones showed no effect

Others with Prenatal alcohol exposure showed mixed findings on

attachment with most showing more insecure attachment

(disorganised type) irrespective of initial parenting

Some improvement with good consistent parenting

All had methodological issues

None stratified by intellectual level or level of exposure

Needs more research

Attachment and Autism /

ID research De Schippers 2006: Dutch Study of attachment behaviours

• Some attachment behaviour established

• Variations in the attachment behaviour seen

Schuengel 2007 attachment to parents with Child ID

• Attachment behaviour less clear

• Percentage children secure attachment lower

De Schippers 2008: Observation study Dutch Schools

• Secure attachment behaviour less characteristic.

• Higher the developmental age the more attachment behaviour

seen

Rutgers (2007) Attachment and parenting comparing ASD,

LD and normal controls,

• Parenting not found to be cause of attachment problems in ASD

group

Impact of Neglect and ACE Alcohol 2018

Mukherjee, Price, Norgate, Cook

Effects of neglect

Romanian study. Being adopted after 6 months

shows developmental delays. Even if some catch

up seen not as good as those adopted before 6

months. (Rutter et al 1998, Sonuga Barke2017)

Neglect associated with difficulties with behaviour

issues, emotional issues, cognitive problems,

medical sequelae which remain later in life. (Kauffmann

2009)

Overview Bellis 2005

• Romanian study showed significant neglect

• Tizzard and Hodges 74 and 77with lesser levels of neglect

showed improvement with no significant cognitive deficits

• PTSD common

• Effects on myelination and corpus collsum found but never

controlled alcohol.

Systematic review of Childhood Trauma and PAE (Price et al 2017)

5 Studies identified

Diverse studies with

heterogeneous methods

Where both, more likely to

present with more complex

communicatory, cognitive and

behavioural issues.

Limited by diverse and

sometime flawed methodology

More systematic evaluation

needed

Exploring the impact of Neglect and FASD

PAE Neglect Both

Outcomes

Exploring the impact of Neglect and FASD

PAE Neglect Both

Outcomes

Neurodevelopmental outcomes seen

( no significant difference between groups)

Neurodevelopmental outcome No neglect Some neglect

(up to 6

months)

Prolonged

neglect

Total

Autism spectrum disorder (ASD) or

social communication disorder (SCD)

No ASD/SCD 10 (34.5%) 5 (35.5%) 14 (26.6%) 29 (31.9%)

ASD/SCD 19 (65.5%) 8 (61.5%) 35 (71.4%) 62 (68.1%)

Total 29 13 49 91

Attention deficit hyperactivity disorder

(ADHD)

No ADHD 9 (28.1%) 3 (23.1%) 13 (25.0%) 25 (25.8%)

ADHD 23 (71.9%) 10 (76.9%) 39 (75.0%) 72 (74.2%)

Total 32 13 52 97

Findings Summary

Our findings suggest 2 broad

conclusions

• That Neurodevelopmental disorders

are seen independent of neglect

• Neglect does not appear to make

the neurodevelopmental

presentation any worse

Limitations

• Numbers not huge but does allow

analysis

• Does not have a group of neglect

alone

• Does not measure the psychological

impact and overlap

Exploring the impact of Neglect and FASD

PAE Neglect Both

Outcomes

Henry et al 2007

Specialist MDT assessment of

children

• PAE + Neglect

• Neglect alone

Both had been studied but not

together

Retrospective study 274

children 6-16 Michigan area

Comparing PAEwith Neglect to

neglect alone

• severe neurodevelopmental deficits

in language, memory, visual

processing, motor skills, and

attention greater oppositional/defiant

behaviour,

• inattention, hyperactivity, impulsivity

• social problem

Alan Price PhD ACE and FASD

Behavioural Emotional Social

Online survey advertised via social media

Completed by parents/cares of 253 children aged 4-16 with FASD

from 8 countries, but mostly from UK, USA and Canada

Adverse Childhood Experiences (ACE) questionnaire

• Abuse, neglect, witnessed domestic violence, lived with parent that

was an addict, mentally ill or imprisoned, experienced divorce

Griffith Empathy Measure

• Cognitive and affective empathy

Strengths and Difficulties Questionnaire

• Peer problems, conduct problems, hyperactivity, emotional problems,

prosocial behaviour

Adverse Childhood Experiences

• Sample of children with FASD scored significantly higher than population data on all ACE’s except for physical and sexual abuse.

• Physical abuse score was similar to population data and sexual abuse score was lower.

• However, these Figures probably underestimate the true scores.

• Survey was completed by (mostly adoptive) parents on behalf of their children and many reported being unsure of neglect or abuse.

Strengths and difficulties Questionnaire

• SDQ is standardised and gives a score of average, raised, high or very high

• Most children in general population will score average on every scale.

• Majority of FASD sample of children were very high on every scale. Prosocial is reverse scored so a high score indicates a lack of prosocial behaviour

• Overall, 82% of FASD children were in very high for overall behavioural difficulties.

• On empathy, FASD children in every age range had significantly lower empathy scores than normative data, with high effect sizes.

Relationship between ACEs

and behavioural/emotional/social functioning

No difference in empathy

or behavioural difficulties

related to maltreatment

No correlation between

ACE score and empathy

No, or weak impact of

trauma on

behavioural/social/emotion

al functioning in children

with FASD

Summary and conclusions

Children in this population with FASD had high levels of ACEs including

maltreatment

Low empathy, high levels of behavioural/emotional/social difficulties

Neurological and cognitive functioning was in normal range

Little or no impact of trauma on cognitive and behavioural

functioning identified in children with FASD

Impact on carers

Experiences of caregivers

12 interview with families of 17 of the FASD children

aged 8-14 from neurocognitive study

About half of those children had a history of

maltreatment

Questions on cognitive, daily living, behavioural, social

difficulties of children, and how these affected parents

and other family members

Thematic analysis identified 9 themes, which formed 2

overarching domains

The Child

The system

Experiences of caregivers - trauma

Parents of children with a history of maltreatment

described those events

Parents of children with and without maltreatment

contributed to all themes

Children with history of maltreatment qualified for

services designed for trauma/attachment

Children without maltreatment were also offered these

services

Nothing designed specifically for FASD

Themes found Carers Study ( Mukherjee et al 2015)

Different from other Children

Lack of information given

Lack of knowledge

• in professionals

• How to manage children

Have to fight for things

Misunderstood and blamed

Family stress and benefits of 1:1

Concerns future

Attachment Summary

Limited studies with FASD

Where have been done

• More likely to be disorganised

• Irrespective of parenting

Limitations by level of disability

Damaged underlying brain means

typical attachment not always seen

Biology appears to be influenced

prenatally and leads to vulnerability

that is impacted by experience

Not always the parents fault

How do I diagnose it And how do I make sure I don’t miss

it : Clinical pathways.

How it presents Mukherjee et al JRSM 2006

Gray and Mukherjee JMHLD 2007

Reasons for referral

Growth problems

Behavioural issues

Learning issues

Physical problems

Comorbidity of FASD Svetlana Popova PhD*1,2,3,4, Shannon Lange MPH1,4, Kevin

Shield MHSc1,4, Alanna Mihic MSc2, Albert E. Chudley MD 5,

Raja A. S. Mukherjee, PhD6, Dennis Bekmuradov BA7, and

Jürgen Rehm PhD1,2,4,8

The Lancet Jan 5 2016

Main findings

5068 studies identified of which

127 met criteria for inclusion

428 comorbid conditions linked

to FASD

From 18/22 chapters of ICD10

Important consideration clinically

and research

Co morbidity pooled estimates 1

Conduct disorder

Language disorders

Intellectual impairments

Other mental health disorders

Co morbidity pooled estimates 1

Visual impairments

Hearing issues

Surgical issues e.g. hernia

Other congenital abnormalties

Developmental Divergence by age

2 4 6 8 10 12 14 16 18

FASD

Non FASD

Neurodevelopmental findings Mukherjee, Mohamed, Carlisle 2018

Brain Structure

Alcohol and Myelin

• Clinically delayed myelination it has been observed

• Riikonen et al., 1999

• alcohol-induced delayed myelination are due to the delayed expression of myelin basic protein (MBP) and transferrin

• Ozer et al., 2000

• Effect is decreased speed of neural processing

2. Migration

Note that differentiation

is going on as neurons

migrate.

Courtesy of Diana S. Woodruff-Pak, Ph.D

Alcohol effects migration of cortical

neurons

Control Alcohol

Courtesy of MW Miller

CIFASD DTI studies

fMRI Controls ARND Dys PAE

(FAS)

Controls ARND Dys PAE

(FAS)

Left hand

response to

Same side

stimulation

(LS)

Right hand

response to

Same side

stimulation

(RS)

Slide courtesy of CIFASD and E Riley

Results: ‘Opposite’ Condition Controls ARND Dys PAE (FAS)

Controls ARND Dys PAE (FAS)

Left hand

response to

Opposite side

stimulation (LO)

Right hand

response to

Opposite side

stimulation (RO)

Significant difference between FAS and Control groups in

primary motor (arrows) and premotor areas

Significant difference between FAS and Control groups in premotor area

Slide courtesy

of CIFASD and

E Riley

FASD CONTROL FASD CONTROL

Response to CS at 250ms Response to US at 100ms

FASD fail to fully engage frontal and parietal cortex in the processing of CS+.

Enhanced activation to US reflects lack of prediction of the CS+/US relationship.

CS+

Paired

CS+

unpaired

CS-

never

paired

MEG Activation Patterns

The greater the demand the more the challenge

Cognitive flexibility is an issue

When combined with wider

executive deficits leads to

problems, e.g. holding and

manipulating information

Also affected by wider ability

Outcomes seen

Cause or Effect?

Top down or bottom up ?

Bottom Up: Aetiology

Top Down: Phemomenology

Cluster of Symptoms

Inattention

Hyperactivity

Poor social understanding

Impulsivity

obsessionality

Tics

Poor Planning

Cognitive flexibility problems

Working Memory deficits

Receptive language deficits

Expressive language deficits

Poor imagination

Cluster of Symptoms: ADHD

Poor social understanding

obsessionality

Tics Poor Planning

Cognitive flexibility problems

Working Memory deficits

Receptive language deficits

Expressive language deficits

Poor imagination

Inattention

Hyperactivity

Impulsivity

Cluster of Symptoms: ASD

Inattention

Hyperactivity

Poor social understanding

Impulsivity

obsessionality

Tics

Poor Planning

Cognitive flexibility problems

Working Memory deficits

Receptive language deficits

Expressive language deficits

Poor imagination

Cluster of Symptoms: ASD / ADHD

Inattention Hyperactivity

Poor social understanding

Impulsivity

obsessionality

Tics

Poor Planning

Cognitive flexibility problems

Working Memory deficits

Receptive language deficits

Expressive language deficits

Poor imagination

Cluster of Symptoms: FASD

Inattention Hyperactivity Poor social understanding

Impulsivity

obsessionality

Tics

Poor Planning

Cognitive flexibility problems

Working Memory deficits

Receptive language deficits

Expressive language deficits

Poor imagination

Relationship between disorders

(Chapter 13 FASD Inter professional perspectives Raja Mukherjee)

ASD Diagnoses by FASD category

FAS pFAS ARND Total

(%)

ASD

f84.0 6 19 63 88

(76.5)

Soc

Comm

f80.99

0 0 5 5

(4.3)

No

ASD 1 6 15 22

(19.1)

Total 7 25 83 115

(100)

88

5

22

115

76.5

4.3

19.1

100

0

20

40

60

80

100

120

140

ASD Soc Comm No ASD Total

Chart Title

Number Percent

SCQ scores as a screen for ASD

58.8% are above the internal

threshold for ASD

65.1% Score 13 or more

73.6% score 11 or more

Systematic review suggested

that based on pooled

prevalence (Lange et al 2017)

• ASD 2.6%

• ADHD 52.9%

28

9 7

41

21

106

26.4

8.5 6.6

38.7

19.8

100

26.4 34.9

41.5

80.2

100 100

0

20

40

60

80

100

120

0 to 10 11 + 12 13 + 14 15-21 22+ Total

Numbers Percentage Cumulative percentage

An example of complexity that needs to be

understood

S

o

c

i

a

b

i

l

i

t

y

High

Low

Angelmans

Runbenstein Taybi

Fragile X

Different types of social functioning

In people on the Autistic Spectrum

Oliver et al 2012 Cornelia de Lange

FASD

ADHD outcomes by FASD diagnosis

FAS pFAS ARND Total

(%)

ADHD

Combined 7 7 25 39 (30)

ADHD

Inattentive 2 14 42 58

(44.6)

ADHD

Hyperacti

ve/

Impulsive

1 1 1 3 (2.3)

No ADHD 0 7 23 30 (23.1)

Total 10 29 91 130

(100)

39

58

3

30

130

30

44.6

2.3

23.1

100

0

20

40

60

80

100

120

140

ADHD Diagnoses Percentage

76.9% will meet diagnostic criteria for

One forms of ADHD

Single item analysis of ADHD diagnostic criteria: inattentive symptoms

Percentage of Group meeting

Criteria (%) Total in group (130)

Not pay attention 77 (59.2)

Fail to stick at task 37 (28.5) Can stick to self directed

activity

Not listen when spoken to 77 (59.2)

Fail to Finish an instruction 100 (76.9)

Difficulties planning 113 (86.9)

Avoid areas find difficult 114 (87.7)

Loose things needed for task 101 (77.7)

Easily distracted 119 (91.5)

Forgetful 104 (80.0)

Single item analysis of ADHD diagnostic criteria: Hyperactive impulsive

criteria

Percentage of Group meeting

Criteria (%) Total in group (130)

Sits fidgeting 84 (64.6)

Gets up when should sit down 50 (38.5)

Not stay still / squirm 48 (36.9)

Cannot be quiet 57 (43.8)

Driven by a motor 38 (29.2)

Talk excessively 59 (45.4)

Blurt out answers 89 (68.5)

Difficulties waiting turn 82 (63.1)

Interrupts others 107 (82.3)

Comparison Between Cohort and Steinhaussen 2002

FAS Current

(n=21)

FAS *

(n= 38)

PWS *

(n=42)

FRAX *

(n=49)

Mean age (range) 9.9 (6.10- 16) 6.3 (4-12) 7.8 (3-16) 8.6(5.7-16.10)

Disruptive Subscale

Abusive 51.7(12) 57.9 (22) 25.6(10) 53.1(26)

Overexcited 85.7 (18) 65.8 (25) 46.2 (18) 71.4 (35)

Impulsive 100(21) 68.4(26) 46.2 (18) 79.6(39)

Irritable 80.9 (17) 57.9 (22) 25.6 (10) 59.2(29)

Jealous 85.7 (18) 63.2 (24) 30.8 (12) 55.1 (27)

Kicks hits others 71.4 (17) 73.7 (28) 25.6(10) 53.1 (26)

Mood changes rapidly 76.2 (16) 68.4 (26) 35.9 (29) 59.2(29)

Noisy or boisterous 90.4 (19) 78.9(30) 12.8(5) 57.1 (28)

Overly attention seeking 80.9(17) 78.9 (30) 38.5(15) 77.6(38)

Throws or breaks objects 66.7(14) 65.8(25) 12.8 (5) 49(24)

Manipulates or provokes others 66.7 (14) 63.2(24) 25.6(10) 40.8(20)

What happens if I miss it ?

It is everything getting on top on the person that leads to them kicking off!

Person with FASD

over aroused

Trauma

Auditory filtering

Executive deficits

Communication Sensation seeking

Social communication

difficulties

Cognitive flexibility problems

Vineland adaptive behaviour schedule: adaptive age scores

(n=51)

Domain Minimum Maximum Average

Age 6.10 16.00 9.93 (95%CI)

Receptive language 1.1 8.6 3.3 (2.8-3.6)

Expressive

language

2.9 13.0 5.4(4.9-5.9)

Written Language 4.5 14 8.1(7.4-8.8)

Personal Daily living

Skills

2.9 11.3 5.4(4.8-6.0)

Domestic Daily

living skills

1.0 20 6.2(5.3-7.1)

Community skills 2.5 16.3 6.9(6.2-7.6)

Interpersonal skills

0.9 13.6 4.3 (3.7-5.0)

Play/ leisure

socialisation

1.1 13.6 4.7(3.9-5.5)

Coping 1.1 12.6 4.4(3.8-5.1)

Behavioural Checklist (Sakano, Mukherjee, Turk 2018)

0

10

20

30

40

50

60

70

80

90

100

Disruptive Self Absorbed Communication Anxiety Social relating Total

Behaviour Checklist Percentile Ranks n=99

Parent Report Teacher Report

Secondary Disabilities

Disability %

Psychiatric problem 90

Disrupted School

experience

60

Trouble with the law 60

Confinement 50

Inappropriate sexual

behaviour

50

Alcohol /Drug

problems

30

Streissguth et al 1996, 2000

Ok So what difference does it make?

New publication on management Young et al 2016

Available on my research gate site

Intervention areas

Intervention areas

Red Flags

Rarely present as FASD but knowing FASD modifies

treatment response

• Complex NDD

• Non typical response to medication

• Hx of LAC / adoption and fostering

• Inattentive/ impulsive subtype with higher level of social

communication issues and sensory problems than typical ADHD

Treatment pathway

Principles

Try non pharmacological strategies first

Then if well try stimulant

• Principle of when needed and dose release

• Methylphenidate / dexamphetamine choice

If not working then re think and look if other things

affecting situation

Then change/ add

Additions if more complex presentation

FASD Clinic