RANZCP Annual Congress,
14th May 2014, Perth WA
ADHD and Emotional
Dysregulation: Some
Current Topics
Wai Chen
PhD MPhil(Camb) BM DCH MRCP MRCPsych
Acknowledgement
Eric Taylor (DSM V),
Philip Asherson,
Anita Thapar,
Steve Faraone,
Richard Todd (DSM V),
Andrew Merwood.
Conflict of Interests
• Consultancy: national and international advisory boards
for Shire on LDX and Guanfacine; advisory board for
FlynPharma.
• Lecture fees from Shire, Lily, Jansen and FlynPharma.
• Research grant from Shire and NIMH.
• Conference attendance support from Shire, Jansen,
FlynPharma.
Narrative Review:
Share some findings
Limitations of current diagnostic
taxonomy
Think outside the box
Splitters’ vs ‘Lumpers’ vs
‘Diplomats’
Overview’
I.
Emotion Regulation or Dysregulation (ED)
In the context of ADHD
II. Clinical Considerations of ED:
•
.
Overview of 7 models of Emotion Regulation or Dysregulation
(ED):
Emotions
•
Emotion – ‘people’s valenced (positive or negative) reactions to
events that they perceive as relevant to their ongoing concerns
….multiple components that include specific thoughts, feelings,
physiological and behavioural responses (Koole 2011)
•
Evolutionarily adaptive  actions (survival and reproduction)
•
Supra-spinal, ‘sub-cortical’ ‘reflexes’
•
Fast (limbic) and slow (cortical) highways in ‘The Emotional Brain’
(JE LeDoux 1996)
Emotional Dysregulation
(Eisenberg & Fabes 1992, 1996):
Emotionality (E)
(automatic arousal; intensity experienced; negativity; frustration
intolerance; overwhelmed)
Emo Regulation
(capacity to self-regulate)
• Low E  predicts  high social competence
• high E with high Emo Reg  no risk
• high E with poor Emo Reg poor social functioning and
behavioural problems
Dysregulation:
Failure of automatic or effortful control
of immediate emotional reaction and
behaviours which are not compatible with
long term goals or advantages
(conflict with a temporal distant standard
– DLPFC, ACC)
Why Important?
Emotional lability (EL)
Excessive emotional reactions ,
frequent mood changes: Irritability,
Mood
instability
volatility, hot temper1
Emotional
dysregulation
Affective
lability
EL
60-70% heritable2
Emotional
impulsivity
Deficient
emotional self
regulation
1Skirrow
et al (2009); 2van Beijsterveldt et al (2004)
•Demands must be met immediately,
easily frustrated
•Cries often and easily
•Mood changes quickly
•Temper outbursts
Adult ADHD sample:
EL
•
most strongly predicted
by hyperactivity–
impulsivity rather than
subsyndromal comorbid
symptoms.
•
contributed independently
to impairment in family
life, life skills, selfconcept, social problems
and risks
The Experience sampling method
(ESM)
• Participant wears a watch
which vibrates at varying
intervals
• Then they fill out a
questionnaire on the PDA
• Responses collected 8
times a day for a working
week (mon-fri)
Anger ratings for individuals with ADHD and healthy
controls over the 5-day period (Skirrow & Asherson in press)
ADHD
n=35
Controls
N=44
Subjective
rating of angry
100
75
50
25
0
(Matched for age, IQ and years in education)
Impact of adult ADHD on
criminality
Proportion of Swedish adults with criminal convictions over a 4-year
period (Jan 1, 2006 to Dec 31, 2009)
Lichtenstein P, et al. N Engl J Med 2012;367:2006–14.
15
‘Emotional-Impulsivity’ (EI)
or ‘Deficient Emotion
Self Regulation’ (DESR)
(Barkley & Fischer 2010):
High rates of EI in ADHD cases persistent into
adulthood (from a FU study of ADHD childhood
cohort).
EI -after adjusting for Inatt & Ha/Imp - contributes to
impairments in:
•
•
•
•
•
•
occupational,
educational,
criminal,
driving,
financial,
social relationships.
16
Common mistaken diagnoses
Adults
Bipolar disorder
Personality disorder
Anxiety and depression
Children
Juvenile bipolar disorder
Severe mood dysregulation
Oppositional defiant disorder/conduct
disorder
Emotional disorders (anxiety/depression)
Childhood ADHD:
5 fold increase risk of
depression by age 18
(Chronis-Tuscano 2010).
Comorbid ADHD+
Depression cases are 3fold increase in complete
suicide than either
alone(James 2004).
Childhood ADHD:
5 fold increase risk of
depression by age 18
(Chronis-Tuscano 2010).
Comorbid ADHD+
Depression cases are 3fold increase in complete
suicide than either
alone(James 2004).
Childhood ADHD:
5 fold increase risk of
depression by age 18
(Chronis-Tuscano 2010).
Comorbid ADHD+
Depression cases are 3fold increase in complete
suicide than either
alone(James 2004).
Genetic Architecture: ADHD & Emotional Lability
in Manchester twins
Merwood & Chen, Thapar, Asherson et al. (JAACAP 2.2014)
• Sample:
– 1920 twin pairs from Greater Manchester Twin Register
– Mean age = 11.15 years (SD = 3.09, range = 5-18)
• Measures :
– 18 IA & HI items
– 4 EL items from Conner’s Abbreviated
Parent Questionnaire (APQ)
IA
HI
EL
1,920 twin pairs from Manchester Twin
Registry (mean age=11.2 (SD 3.1):
Phenotypic Correlations of HA. IA, EL
Summary
• IA & HI & EL = highly heritable and largely
influenced by a single liability
• This suggests EL likely a significant
component of ADHD at the genetic
(aetiological) level – potentially ‘third
dimension of ADHD’
• Univariate heritabilities (~70%) similar to previous
research (van Beijsterveldt et al, 2004)
• Caveat: family study showed ‘ADHD+ED’ cosegregation as ‘familial subtype’ (Surman et al.
2011).
Developmental Model of ADHD
(Halperin & Schultz (2006))
• ADHD is due to subcortical neural dysfunction
• These remains static throughout lifetime
• PFC circuitry is not linked to the cause of ADHD, but the
RECOVERY
• Age related remission of ADHD (mirror PFC/EF
maturity), compensating through ‘top down’ regulatory
control
Developmental Model of ADHD
(Halperin & Schultz (2006))
• ADHD is due to subcortical neural dysfunction
• These remains static throughout lifetime
• PFC circuitry is not linked to the cause of ADHD, but the
RECOVERY
• Age related remission of ADHD (mirror PFC/EF
maturity), compensating through ‘top down’ regulatory
control
Neuroscience-based Parenting Training (NBPT)Understanding Emotional Dysregulation
with 7 Models (Wai Chen 2014)
1.
2.
3.
4.
2-stage Model (Koole);
Process Model (Gross);
Neuroanatomical bottom-up and top-down model
Attachment Theory Model (Mikulincer & Shaver),
Compassion-Focused Therapy Model (Paul Gilbert);
5. Stress and Peer Victimisation Model (McLaughlin et
al.), Mediation to Depression Model (Seymour et al.),
Social Psychology and Group Identity Model (Amy
Cuddy); Neurobiology of abuse (Teicher)
6. SRS Depletion Model (Self-Regulatory Strength
System) (Baumeister)
7. Dynamic Network Connectivity (DNC) (Arnsten)
I: Two-stage Model
(Koole 2009)
Two-Stage Model of Emotional Reaction
(Koole 2009)
Two-Stage Model of Emotional Reaction
(Koole 2009)
Stage
 Stage 1 
Trigger, stress, habit, arousal
Entry gradient
 Stage 2

Appraisal, modulate arousal
Exit gradient
II. Process Model
Gross & Thompson (2007)
Process Model of Emotion Regulation
(Gross & Thompson 2007)
More Effective Upstream         Progressively Less Effective Downstream
III. Neuro-anatomical
Model
Reactive Bottom-up
Effortful Top-down
lobes of brain.gif
lobes of brain.gif
Neuro-anatomy of the emotional
brain:
‘Reactive’ Bottom-up System:
Limbic, amygdala, ventral striatum, vmPFC,
Insula, Orbitofrontal, Papez Circuit
‘Effortful’ Top-Down System:
Cingulate, Inferior PFC, DLPFC via OFPFC
Bottom-up System:
The Limbic System
Amygdala
Amygdala
Caudate
nucleus
Striatum
Lentiform
nucleus
Pallidum
Amygdala
Amygdala: 3 gp of nuclei
Central
nucleus
Basolateral
nuclei
Corticomedial
nuclei
Amygdala
EFFERENT
PATHWAY
OLFACTORY
AFFERENTS
(stria terminalis)
ISOCORTICAL AFFERENTS
Papez Circuit: CG  parahippo  hippocampus  amygdala
 fornix  Mamillary body (to HPA, brain stem, ANS, visceral)
 Th  back to Cortex
Cingulum bundle
Cingulate gyrus
Anterior
thalamus
Mamillothalamic
tract
Internal capsule
Mamillary body
(hypothalamus)
Fimbria / fornix
Hippocampus
Top-down System:
PCF:
Paralimbic : CgC
(1) Dorsal (DLPFC): cognitive; (2) Inferior PFC: Inhibition;
(3) Ventral and Ventral Medial: emotional/motivation.
DA/NE (dorsal) ------ 5HT (ventral) (Arnsten & Rubia 2012)
Cingulate Cortex
(transitional zone between archicortex and
isocortex)
Cingulate
gyrus
Isthmus
Cingulate
sulcus
OFC
Subgenual area
Parahippocampal gyrus
ACC
• Important in Error Detection
• ‘Reality mismatches Expectation’
• Alerting  Arousal
• Change ‘Reality’
• Change ‘Expectation’
• Dorsal ACC (cogntive) vs Rostral ACC
(emotional)
Subdivisions of Ant-CC:
•Dorsal (cognitive)
•Rostral
(affective/emotional)
Paul MacLean
The ‘triune brain’ model (1964)
Neuo-anatomy of the emotional brain
Bottom-up System (‘automatic’):
Top-Down System (‘effortful’):
:
Two-Stage Model of Emotional Reaction
(Koole 2009)
Reactive Limbic
Effortful OFC ACC (DLPCF)
IV. Stress Model:
Peer Victimization and
other abuse
Brain Structural Changes during Sensitive
Periods when Exposed to Sexual Abuse
(Andersen et al. 2008)
Brain Structural Changes during Sensitive
Periods when Exposed to Sexual Abuse
(Andersen et al. 2008)
-
Brain Structural Changes during Sensitive
Periods when Exposed to Sexual Abuse
(Andersen et al. 2008)
Source: Professor Martin Teicher
•
Blue indicates positive
correlation
•
Red indicates negative
correlation
Peer Verbal Bullying correlates with
psychiatric symptoms and brain changes
(Teicher et al. 2010)
707 young adults with no history of exposure to childhood sexual abuse, physical abuse,
witnessing domestic violence, peer physical bullying, harsh corporal punishment, or significant
parental verbal abuse; and 63 for neuorimaging.
ED as a mechanism linking stress and Internalising Symptoms:
Final Mediation Model of ED and Latent Variables predicting
Internalising Disorder (all paths shown p<0.05, except broken lines;
n=1,065, age 11-14) ( McLuaghlin, Hatzenbuehler & Hilt (2009)
ED increased IS over a
7 month period
Bullying increased ED
over a 4 month period
Stereotype Content Model (SCM)
(Amy Cuddy 2008)
In-group skills
(Social Identity Theory, Tajfel 1974)
• Prosocial
• Identify commonality
• Introduction and association by in-group
members
V. Attachment Model
Adult Attachment & Affect Regulation
(Mikulincer & Shaver 2008)
• Threats activate proximity and support seeking – especial from a
sympathetic figure
•
Internal attachment figure – supportive, soothing and available  reduce perceived threat, over-whelm,
 increase a sense of agency and coping
 impact ‘Appraisal’ & ‘Response’.
•
Internal speech – ‘super-ego’, ‘adult’ in TA, relational and reputational
self-concept
•
Bidirectional: Child is affected by, but also evokes environment.
Parents shape the child; but also react to child and to internal
attachment objects (trans-generational transmission). ADHD parents.
•
Oxytocin in father affect babies’ oxytocin (Feldman)
Trier Social Stress Test
Neural Bases of Threat Processing
(LeDoux, 1994)
Neural Bases of Threat Processing
(LeDoux, 1994)
Fright
Fight
Flight
Freeze
Overriding
circuit
What’s other major threat to human
beings?
Social threat
New-SCARF
SCARF (David Nock 2010)
Status
Certainty
Autonomy
Relatedness
Fairness
New-SCARF (Wai Chen)
Novelty
Types of Affect Systems
(Compassion Focused Therapy CFT (Paul Gilbert))
o.
Incentive/resource
focused
Affiliative focused
Seeking and
behaviour activating
Soothing/safeness
Opiates (?)
Dopamine (?)
Threat-focused
safety seeking
Activating/inhibiting
Serotonin (?)
Self-Critics & Shame
(‘Abuse by ‘self’)
• Shame (core self), self-criticisms, ruminations (past),
worries (future), frustrations (thwarted drives)  intensify
THREAT system.
• CBT challenges content (could increase threat).
• Drip-drip undermining; high Expressed Emotions.
Criticisms by parents more distressing.
• Highly critical internal dialogues.
• Inability to self soothe.
• Shame.
VI. Depletion Model:
Self-Regulatory Strength
(SRS)
(Bauer & Baumeister 2011)
SRS is a limited resource:
Self-control resemble a muscle
(Mauraven & Baumeister 2000, Baumeister et al. 2006)
•
SRS is limited
•
Various acts/tasks draw on the same and
limited resource
•
Repeated demands expend and deplete
 leading to self-control failure
•
Impairment and breakdown of self-control
following continuous challenges without
recovery breaks
•
ED is after-effects of stress, self-control,
dieting, ignoring distractions, suppression,
mood regulation, effort demands,
continuous performance, mental tasks,
resisting temptations
Boosting of SRS
(Bauer & Baumeister 2011)
• Glucose level dropped after self-control
exercise and restoring blood glucose boost SRS,
i.e. a glucose drink
• Positive mood induction
• Laughter/pleasure: watching a comedy
• Self-affirmation: being in touch with core values
• 3-10 minutes of relaxation
• Mindfulness training
• Regular physical exercise
• Practising self-control (SRS training)
consistently
VII. Dynamic Network
Connectivity (DNC)
(Arnsten)
Dynamic Network
Connectivity
The cellular architecture for executive
function and working memory has been
recently mapped
Working memory as ‘mental sketch pad’
differs from ‘short term and long term
memory’
Arnsten’s model for these functions,
called Dynamic Network Connectivity
(DNC) Model
Unstressed: Top-down control
(connectivity) of subcortical structures:
• Basal Ganglia (habits);
• Hypothalamus (drives – hunger,
sex, aggression);
• Amygdala (emo/fear)
Stressed: PFC ‘swtiched off’ 
connectivity lost  ‘Going to Hell in a
Handbasket’, ‘Meltdown’, ‘Lost it’.
Tonic vs Phasic DA Firing
Tonic vs Phasic DA
Tonic – good esp in PFC
Phasic – little is good in Nu Acc = motivated and rewarded
Phasic – excessive in sub-cortical regions leads to addiction/anxiety/noise
‘Dynamic Network Connectivity’ (DNC) model
involving Hyperpolarization-activated cyclic
nucleotide-gated (HCN channels)
(Arnsten, Wang, Paspalas 2012; Wang et al. 2007)
Prefrontal Network
Dynamic Network Connectivity
(Arnsten, Nat Rev NeuroSc 2009)
Balance between D1 and alpha
2A stimulation: Signal to Noise
(Arnsten & Rubia 2012; Arnsten
2009).
Optimal:
Moderate DA engagement of D1
increases cAMP, open HCN K+
channels.
NE engagement of alpha 2A
receptors inhibit cAMP close
HCN K+ channels
Under stress,
high levels of cAMP open HCN
channels,
When the Ca2+ waves invade
the
soma, Ca2+-activated K+
channels (SK channels) and
reduce
cell firing.
Balance between D1 and alpha
2A stimulation: Signal to Noise
(Arnsten & Rubia 2012; Arnsten
2009).
Optimal:
Moderate DA engagement of D1
increases cAMP, open HCN K+
channels.
NE engagement of alpha 2A
receptors inhibit cAMP close
HCN K+ channels
Under stress,
High levels of cAMP open HCN
channels
When the Ca2+ waves invade
the soma, Ca2+-activated K+
channels (SK channels) open
and reduce cell firing.
Dynamic Network Connectivity
(Arnsten, Nat Rev NeuroSc 2009)
Dynamic Network Connectivity
Exposure to even mild, uncontrollable stress causes a
rapid loss of PFC function.
Feedforward Ca2+-PKC and cAMP-PKA signaling rapidly
opens K+ channels to disconnect dlPFC networks and
reduce neuronal firing, i.e. Going To Hell In A Handbasket.
What do these all
mean?
Biological
(CUSHION)
Environment
(SCAFFOLD)
Self-control
(EFFORT)
JOSHUA
•
Adopted child – multiple high risk factors, low SES adopted parents
•
Crisis after crisis – exclusion by school (age 9); teachers scooped
him out under-table & attacked.
JOSHUA
•
Adopted child – multiple high risk factors, low SES adopted parents
•
Crisis after crisis – exclusion by school (age 9); teachers scooped
him out under-table & attacked.
•
Diagnoses: ADHD + ASD + EL + SLD
•
CUSHION: Medical (MPH/DEX) (+SSRI) (+AAP); parents find-dose
titration
•
SCAFFOLD: NBPT to parents/teachers (labelling, no mirroring)
JOSHUA
•
Adopted child – multiple high risk factors, low SES adopted parents
•
Crisis after crisis – exclusion by school (age 9); teachers scooped
him out under-table & attacked.
•
Diagnoses: ADHD + ASD + EL + SLD
•
CUSHION: Medical (MPH/DEX) (+SSRI) (+AAP); parents find-dose
titration
•
SCAFFOLD: NBPT to parents/teachers (labelling, no mirroring)
•
EFFORT: Child self-aware/applies efforts  change of internal
speech: ‘there are always solutions to most problems’ (age 14)
JOSHUA
•
Adopted child – multiple high risk factors, low SES adopted parents
•
Crisis after crisis – exclusion by school (age 9); teachers scooped
him out under-table & attacked.
•
Diagnoses: ADHD + ASD + EL + SLD
•
CUSHION: Medical (MPH/DEX) (+SSRI) (+AAP); parents find-dose
titration
•
SCAFFOLD: NBPT to parents/teachers (labelling, no mirroring)
•
EFFORT: Child self-aware/applies efforts  change of internal
speech: ‘there are always solutions to most problems’ (age 14)
Offered university place (age 17)
•
Happiness is not a destination.
It is a method of life.
Burton Hills
END
Thank you for your attention
•
EL were associated with altered amygdala–cortical intrinsic
functional connectivity (iFC).
EL scores:
•
greater positive iFC between the amygdala and rostral
anterior cingulate cortex I
•
Negatively associated with iFC between bilateral amygdala
and posterior insula/superior temporal gyrus.
Latent Class Analysis:
ADHD and Emotion Lability in
the IMAGE (International
Multicentre ADHD Genetic) Study
sample
LC
Latent Class Subtype
LC1
None or few
symptom
LC2
Mild Inattentive
LC3
Talkative/Impulsive
LC4
Moderate Combined
LC5
Mild
Hyperactive/Im
pulsive
LC6
Severe Combined
LC7
Severe Inattentive
LC8
Severe Hyperactive/
Impulsive
Emotional Lability problem (as rated by parents) is
strongly associated with any subtype of ADHD
Latent Classes.
EL is associated with LC7 (S Inatt) only in the presence
of ASD symptoms.
LC8 (S Ha-Imp) not driven by ASD
LC4 is as impaired as CT, IA and H/I LC subtypes
of ADHD, but is diagnostically ‘homeless’ –
replicating previous publications by his group
Take home messages:
1. Any form of ‘ADHD’ is associated with EL
2. ‘CT + EL’ & ‘Ha/Imp + EL’ driven by Imp.
3. ‘Inatt + EL’ indexes the presence of ASD
4. LC4 is a ‘lost tribe’ in DSM-IV and DSM-V
(6 or 6= disorder; but 3+3=no disorder)
Bifactor Model of ADHD
Three studies confirming the bifactor
model (Toplak et al. 2009; Martel &
Nigg 2010)
Replicated in IMAGE sample –
invariant across age and national
groupings (Toplak et al 2012)
ADHD and AU spectrum Disorders
(van de Meer 2013):
ADHD+(AU) highest EL; AU+(ADHD) high EL and highest
Perfectionism
_ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _
ADHD and AU spectrum Disorders
(van de Meer 2013):
ADHD+(AU) highest EL; AU+(ADHD) high EL and highest
Perfectionism
_ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _
In deep sleep, unconscious = the absence of acetylcholine stimulation of nic-α7R which
is permissive for NMDA actions.
When awake, cholinergic stimulation of nic-α7R allows networks to connect.
Moderate levels of NE (in response to interesting events) stimulates α2A-AR, which
strengthens preferred connections and promotes PFC cognitive abilities.
DA released to salient events, which gates out nonpreferred network inputs through
stimulation of D1R optimal for tasks requiring precise focus.
In contrast, high levels of norepinephrine and dopamine release during stress suppress
neuronal firing and impair prefrontal function through a α1R and D1R, respectively.
Dynamic Network
Connectivity
Emotional Dysregulation
(Lemerise & Arsenio 2011):
• Emotionality - increased
(drive/motivation/communicative)
• Emo Regulation – decreased
(within and in-between)
• Social Information Processing
(encode cues (internal/external)  interpret cues  goals
(pro-social, instrumental, homeostatic)  response
construction  response decision/evaluation/outcome
/cost-gain=self-efficacy)
SCM
Emotional Lability problem (as rated by parents) is
strongly associated with any subtype of ADHD
Latent Classes.
ADHD+EL Probands do not index higher ADHD recurrence
in siblings
ADHD+EL Probands do not index higher ADHD recurrence
in siblings
Partial ‘Breeding True’ of EL in LC6 (after accounting for the main effect of LC6) in
Familial Risk Analysis (n probands=997 and siblings=1112)
– partially consistent with ‘Deficient Emotional Self-Regulation (DESR) as familial subtype’ Surman,
Biederman, Spencer, Yorks, Miller Petty, Faraone June 2011 Am J Psych (n=83 probands and 128
siblings)
Autism Spectrum Disorder Symptoms (as rated by parents) is
strongly associated with ADHD LC4, 5, 6, & 7
EL is associated with LC7 (S Inatt) only in the presence
of ASD symptoms.
LC8 (S Ha-Imp) not driven by ASD
LC4 is as impaired as CT, IA and H/I LC subtypes
of ADHD, but is diagnostically ‘homeless’ –
replicating previous publications by his group
LC4 is as impaired as CT, IA and H/I LC subtypes
of ADHD, but is diagnostically ‘homeless’ –
replicating previous publications by his group
Acknowledgement and
Tribute to late Professor
Richard Todd (19512008), past member of
DSM-V workgroup:
Seminal works on LCA of
ADHD and
training/support during
the IMAGE LCA work
Bifactor Model of ADHD
Bifactor Model of ADHD
•
Two studies confirming the
bifactor model (Toplak et al.
2009; Martel & Nigg 2010)
•
Replicated in IMAGE sample –
invariant across age and
national groupings
(Toplak,.. Chen et al. in press)
•
External validation of Specific
Factors:
Specific inattention Factor:
associated with
depression/withdrawal, slower
cognitive task performance,
introversion, agreeableness, and
high reactive control;
specific hyperactivityimpulsivity Factors: associated
with rule-breaking/aggressive
behavior, social problems, errors
during set-shifting, extraversion,
isagreeableness, and low
reactive control.
Prefrontal Network
Prefrontal Network
Prefrontal Network
Mode of Action of Guanfacine
Stress and maternal separation
Rats exposed to stress  decreased dentritic spine density in anterior cingulate gyrus
and orbitofrontal cortext.
Prenatal exposure to stress hormone (animal studies)
•
increased adult Cortcotrophin-Releasing Hormone (CRH) in central nucleus of
amygdala, key region in regulating fear and anxiety
•
Learning impairments (hippocampal changes)
•
Enhanced sensitivity to drugs of abuse
•
Increased anxiety- and depression-related behaviours (CRH changes in amygdala
Natural experiments in children – exposure to maternal separation and nursury care,
effects of age (toddlers vs preschool aged) and duration)
•
•
Rise in glucocorticoid levels by late afternoon.
Less supportive care increased the rise and increases more emotionally negative and
disorangized behaviours.
•
In poor care – EARLY, LONGER – increased risk of behaviour problems in later
development
•
Parent-child interaction also modulate HPA axis