People in Glasgow are more likely than other UK citizens to die prematurely, even when socio-economic deprivation is taken into account. This excess mortality is largely due to problem substance use, suicide and violence: the 'Glasgow Effect'. There are compelling reasons to believe that experiences in utero and early childhood largely explain the Glasgow Effect through programming of the hypothalamo-pituitary-adrenal axis, through learned patterns of attachment to caregivers and through other learned behaviours. Several early indicators of vulnerability can now be identified and doctors should pay attention to them in the same way as they pay attention to blood pressure readings. Lecture given to the Glasgow Southern Medical Society on Thursday 8th November 2012 by Prof. Phil Wilson, Professor of Primary Care and Rural Health, University of Aberdeen. http://www.gsms.org.uk

1. How early childhood experience
determines our health
Phil Wilson
Centre for Rural Health
University of Aberdeen

2. Overview
• Childhood deprivation and health
• Adverse childhood experiences
• The “Glasgow effect”
• Some possible mechanisms
• Critical/sensitive periods
• HPA axis
• Parenting, social learning and attachment
• Early identification of vulnerability
• Glasgow maps
• Future plans

5. • Low childhood SES associated with increased
cortisol production regardless of current SES
• Genome-wide transcription profiling:
• Up-regulation of pro-inflammatory mechanisms
• Down-regulation of glucocorticoid receptor-related mechanisms
PNAS 2009, 106: 14716-21

6. 18
51
18 -18
20.0
30.0
40.0
50.0
60.0
70.0
80.0
90.0
55 53
18 -18
59 57
18 -18
63 61
18 -18
67 65
18 -18
71 69
18 -18
75 73
18 -18
Scotland
79 77
18 -18
83 81
18 -18
87 85
18 -18
91 89
18 -18
95 93
18 -18
99 97
19 -19
03 01
19 -19
07 05
19 -19
11 09
19 -19
15 13
19 -19
19 17
19 -19
23 21
Life expectancy trends
19 -19
27 25
19 -19
31 29
19 -19
35 33
19 -19
39 37
19 -19
43 41
19 -19
47 45
Source: Human Mortality Database
19 -19
51 49
19 -19
55 53
19 -19
59 57
19 -19
63 61
19 -19
67 65
Portugal
19 -19
71 69
19 -19
75 73
19 -19
79 77
Life expectancy: Scotland & other Western European Countries, 1851-2005
19 -19
83 81
19 -19
87 85
19 -19
91 89
19 -19
95 93
19 -19
99 97
20 -20
03 01
-2
00
5

8. Comparing health outcomes in Glasgow with those of
almost identically deprived cities Liverpool and
Manchester:
 premature deaths in Glasgow are over 30% higher,
 excess mortality found across men and women,
 all ages except the very young,
 both deprived and non-deprived neighbourhoods.

9. Standardised mortality rates by cause,
all ages: Glasgow relative to Liverpool
& Manchester
All ages, both sexes: cause-specific standardised mortality ratios 2003-07, Glasgow relative
to Liverpool & Manchester, standardised by age, sex and deprivation decile
Calculated from various sources
350
300
248.5
229.5
250
Standardised mortality ratio
200 168.0
150 131.7
126.7
112.2 111.9
100
50
0
All cancers Circulatory system Lung cancer External causes Suicide (inc. Alcohol Drugs-related
(malignant undetermined intent) poisonings
neoplasms)
Source: Walsh D, Bendel N., Jones R, Hanlon P. It’s not ‘just deprivation’: why do equally deprived UK cities experience different health outcomes? Public Health, 2010

10. UNICEF domains of child
wellbeing
• Material Deprivation – Relative Income, Households
without jobs
• Health & Safety – Infant Mortality, Immunisations
• Educational Well-being – School Achievement, Post-
15 Education
• Relationships – Family Structure, Peer Relationships
• Behaviours & Risks – Health Behaviours, Experience
of Violence
• Subjective Well-being – Self-assessed indicators.

11. UNICEF comparisons
Average Material Health & Educational Behaviours & Subjective
Ranking Deprivation Safety Well-Being Relationships Risks Well-being
Netherlands 4.2 10 2 6 3 3 1
Sweden 5.0 1 1 5 15 1 7
Denmark 7.2 4 4 8 9 6 12
Finland 7.5 3 3 4 17 7 11
Spain 8.0 12 6 15 8 5 2
Switzerland 8.3 5 9 14 4 12 6
Norway 8.7 2 8 11 10 13 8
Italy 10.0 14 5 20 1 10 10
Ireland 10.2 19 19 7 7 4 5
Belgium 10.7 7 16 1 5 19 16
Germany 11.2 13 11 10 13 11 9
Canada 11.8 6 13 2 18 17 15
Greece 11.8 15 18 16 11 8 3
Poland 12.3 21 15 3 14 2 19
Czech Republic 12.5 11 10 9 19 9 17
France 13.0 9 7 18 12 14 18
Portugal 13.7 16 14 21 2 15 14
Austria 13.8 8 20 19 16 16 4
Hungary 14.5 20 17 13 6 18 13
United States 18.0 17 21 12 20 20 N/A
UK 18.2 18 12 17 21 21 20

13. Adverse Childhood
Experiences study – 17,000
Kaiser Permanente patients
• Abuse
• emotional – recurrent threats, humiliation (11%)
• physical—beating, not spanking (28%)
• contact sexual abuse (28% women, 16% men; 22% overall)
• Household dysfunction
• mother treated violently (13%)
• household member was alcoholic or drug user (27%)
• household member was imprisoned (6%)
• household member was chronically depressed, suicidal, mentally ill, or
in psychiatric hospital (17%)
• not raised by both biological parents (23%)
• Neglect
• physical (10%)
• emotional (15%)

14. A C E S c o r e v s In t r a v e n o u s D r u g U s e
3 .5
3
% H a v e In je c te d D r u g s
2 .5
2
1 .5
1
0 .5
0
0 1 2 3 4 o r m o re
A C E S c o re
p < 0 .0 0 1
Felitti & Anda in: R. Lanius & E. Vermetten eds. 2010

15. Adverse childhood events and risk
of alcoholism
Hillis et al 2011

16. ACE and physical morbidity
The ACE Score and the Prevalence of Liver
Disease (Hepatitis/Jaundice)
A C E S c o re v s . C O P D
20
18
16
Percent (%)
14
P e r c e n t W ith P r o b le m
12
10
8
6
4
2
0
ACE Score COPD
Felitti & Anda in: R. Lanius & E. Vermetten eds. 2010

17. ACE and cardiovascular disease
A C E s In c r e a s e L ik e lih o o d o f H e a r t D is e a s e *
¥ E m o tio n a l a b u s e 1 .7 x
¥ P h y s ica l a b u s e 1 .5 x
¥ S ex u al a bu se 1 .4 x
¥ D o m e s tic v io le n c e 1 .4 x
¥ M e n t a l il ln e s s 1 .4 x
¥ S u b s ta n c e a b u s e 1 .3 x
¥ H o u s e h o ld c r i m i n a l 1 .7 x
¥ E m o tio n a l n e g le c t 1 .3 x
¥ P h y s ica l n eg lect 1 .4 x
• After correction for smoking, lipids, diabetes

18. Harsh parenting and
conduct disorder
• Strong association between erratic, coercive
or punitive parenting and conduct disorder
or other forms of aggression
• The earlier the exposure, the greater the risk
of CD
• CD much more common in boys
• Great variability between individuals in
response to harsh parenting

19. Harsh parenting and
conduct disorder
• Dunedin cohort study:
• MAO A gene – lower MAO
A activity shown in animal
studies to be linked to
aggression
• MAO A gene lies on X
chromosome
• Caspi et al (2002) looked
at the link between MAO A
genotypes and conduct
disorder
• High MAO A activity
protects against the
tendency of abuse to lead
to violence

20. Child psychopathology
and later health
• Few robust longitudinal studies
• Selective attrition of children with problems
• Lack of funding
• But good evidence of, for example:
• Strong associations between ADHD or conduct disorder and
problem substance use
• Strong associations between conduct disorder and later
psychopathology
• Substantial excess premature mortality with conduct disorder
(RR>9)

21. What happens during
early brain development?
• Physical growth
• Neuron numbers
• Basic structure: cell migration ends by sixth
month of gestation
• Synaptogenesis and myelination

22. What happens during
early brain development?
Reprinted with permission – Prof Peter Seeman

23. Critical and sensitive
periods
• The visual system
• Cataracts, hypermetropia and amblyopia
• Amblyopia represents the selective pruning of synapses in the visual
system as a result of lack of ‘through traffic’
• Partially preventable through patching
• Children under 4 need less patching than older children, and probably
pointless beyond age 7-8.
• Is emotional, social and cognitive
development like visual development?

24. Sensitive Periods in Early
Brain Development
High Pre-school years School years
Numbers
Peer social skills
Symbol Language
Habitual ways of responding
Emotional control
Vision
Hearing
Low
0 1 2 3 4 5 6 7
Years
Graph developed by Council for Early Child Development (ref: Nash, 1997; Early Years Study, 1999; Shonkoff, 2000.)

25. Early stress and
the HPA axis
Hunter, Minnis, Wilson. Altered stress responses in children exposed to early adversity: A systematic review of
salivary cortisol studies. Stress, 2011

26. Sandman et al. IJP 2011, # 837596.

27. Severe emotional deprivation
• Long term outcomes in
institutionalised
Romanian orphans:
• mild cognitive impairment
• Impulsivity
• Attention deficits
• Social deficits
• Abnormalities of HPA function

28. 00-046
The Founders’ Network
Evening Cortisol Levels Increase with
Months of Orphanage Rearing *
-0.2
-0.4
-0.6
-0.8
-1 *linear trendline
-1.2
0 10 20 30 40 50
Months of Orphanage Rearing

29. Severe emotional deprivation
• Chugani et al
(2001): ‘Glass
brain’
• 10 orphans
(mean age 9, in
orphanages from
5 weeks old for
mean 3 years)
and 24 controls
• PET scans

30. Epigenetic mechanisms

31. Early identification –
GUS*
• Looking for predictors of persisting conduct
problems at 3, 4 and 5 years
• Used Strengths & Difficulties Questionnaire
• 2070 children born in 2003 with SDQ data at all
time points
• Comparing:
• 90 children with conduct problems at all 3 times
• And 1557 who never had conduct problems
*Wilson, Bradshaw, Tipping, Henderson, Minnis, JECH 2012 in press

32. Early identification -
GUS
Adjusted odds, C.I. and P value
No. of natural parents in household
Two
One or none
2.10 (1.28, 3.44) <0.01
Child’s general health
Very good or good
Fair, bad or very bad
3.32 (1.35, 8.19) 0.01
Child had some difficulty being understood
No
Yes
1.93 (1.08, 3.44) 0.03
Maternal smoking during pregnancy
No
Yes
2.35 (1.32, 4.19) <0.01
Agree that smacking is sometimes the only thing that will work
No
Yes
2.07 (1.13, 3.79) 0.02
Frequency child taken to visit other people with children
Fortnightly or more often
Less often or never
2.16 (1.14, 4.09) 0.02
Frequency child is read to
Daily
Less often 1.86 (0.98, 3.52) 0.06

33. Early identification -
ALSPAC
• Avon Longitudinal Study of Parents and
Children – 14,000 pregnancies
• Videos (not very good!) of 10% sample of
children aged one year and their parents, in
1992/3
• Psychiatric assessment at age 7.5 years
(DAWBA)

34. Early identification -
ALSPAC
• 60 (6%) children had a psychiatric diagnosis:
• 27 Conduct/oppositional disorder (CD, ODD, DBD NOS)
• 6 Pervasive developmental disorder (autism)
• 16 ADHD
• 28 Emotional problems (anxiety, depression, phobias etc)
• 12 with more than one diagnosis
• Compared with 120 children with no diagnosis

35. ALSPAC findings so
far...
• (Specialist) clinicians failed to predict
psychopathology1
• Infant motor activity not associated with later
ADHD2
1
Allely et al , RIDD 2012 in press
2
Johnson et al, IJMPR 2012 in press

36. Motion tracking

37. ALSPAC findings so far...
• Increased infant vocalisation associated with later diagnosis of
disruptive behaviour disorders (ADHD/CD)
• MATERNAL hypoactivity is associated with later ADHD,
CD/ODD and anxiety disorders*
• Low levels of MATERNAL vocalisation are associated with later
ADHD and CD/ODD*
• Positive parenting behaviours associated with reduced risk of
conduct disorder
• Reduced mutual gaze and shared attention in conduct disorder
...even when adjusted for maternal depression
*Marwick et al 2012, RIDD, in press

38. The Glasgow parenting support
framework evaluation
• Three year project – 2011 to 2013
• Led by team at Glasgow University, in collaboration
with NHSGGC – Public Health Resource Unit
• Funded by Scottish Government and Fairer Scotland
Fund
• Multiple strands of data collection:
• Triple P monitoring data
• Population level data - assessing social, emotional and
behavioural problems at various stages
• Looking for population and individual changes
• Qualitative interviews with parents and practitioners

39. The Strengths and Difficulties
Questionnaire
(www.sdqinfo.org)
• A brief behavioural screening questionnaire for 3-16
year olds.
• 2 versions – 3-4 years, 4-16 years
• Can be teacher, parent or self-complete
• Used extensively as before- and after- measure for
range of parenting and family intervention studies as
well as a population measure of children’s wellbeing
e.g. GUS
• NOT a diagnostic tool

40. The Strengths and Difficulties
Questionnaire
• 25 questions in 5 domains:
• Emotional problems
• Conduct problems
• Inattention/hyperactivity problems
• Peer-relationship problems
• Prosocial behaviour
• First four domains summed to give total difficulties
score.

41. The SDQ in Glasgow

42. 30 month results
80% eligible children received visit
• ~20% had some language or
SDQ problem identified
• More than half the children with
likely SDQ or language
difficulties had been considered
to be at low risk
• 2/3 children with language delay
also had ‘abnormal’ SDQ score

43. Pre-school results
• Data from 2010-12
• About 10,500 children
• Linear mixed effects modelling
• Scores higher among boys, in looked-after
children and in areas of higher deprivation

44. Where are we now?

45. Where next?
• Analysis of local determinants of
social/emotional development problems
• Using data linkage to identify determinants of
‘good’ or ‘bad’ trajectories
• A new birth cohort?

46. Acknowledgements
• Carolyn Wilson and the SG Child and Maternal Health Division
• Lucy Thompson, Louise Marryat, Kim Jones, Kelly Chung, Elsa
Ekevall, Jane White
• Chris Gillberg, Christine Puckering, Helen Marwick, Clare Allely
• John Butcher, Amanda Kerr, Michele McClung, Morag Gunion
and City of Glasgow Education Services
• Margaret McGranachan and colleagues in PHRU
• Sarah Barry, Alex McConnachie, Paul Johnson
• Scottish Government produced the socio-economic data and
Scottish Neighbourhood Statistics provided the datazone
information.