SIPNEI EARLY LIFE RASSEGNA N.1 DI GENNAIO 2020 della Commissione Nazionale Sipnei Early Life.

SIPNEI EARLY LIFE
Rassegna della ricerca scientifica internazionale sulle prime fasi della vita a cura
della Commissione Nazionale Sipnei Early Life.

RASSEGNA N.1 DI GENNAIO 2020

pag. 1 – Rassegna Gennaio 2020

Care colleghe e cari colleghi SIPNEI
Siamo un gruppo di socie, che vengono da percorsi differenti
ma accomunate dal desiderio
di conoscere e dalla volontà di apprendere e migliorarci ogni
giorno; curiose per natura, abbiamo nutrito questo progetto
perché diventasse uno stimolo per i professionisti Sipnei della
cura integrata, con l’intento di potenziare la prevenzione
nell’ infanzia in funzione di adulti più sani e resilienti.
Grazie al sostegno e allo stimolo del
Prof. Francesco Bottaccioli,
la rassegna vorrà essere uno strumento di approfondimento e
di studio per altri professionisti che condividono l’interesse
verso la Psiconeuroendocrinoimmunologia, con particolare
riferimento alle prime età della vita.

La rassegna, che arriverà al vostro indirizzo email alla fine di
ogni mese, sarà composta da tre articoli principali, ciascuno
dei quali è arricchito da tre articoli correlati.

Contributi a cura di:

Dott. Marilena Coniglio - psicologa psicoterapeuta
Dott. Vera Gandini - medico pediatria
Dott. Ornella Righi - medico pediatria
Dott. Emanuela Stoppele - psicologa psicoterapeuta

Rassegna a cura di:

Dott. Gloria Curati - fisioterapista osteopata

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ARTICOLO 1

Psiconeuroimmunologia dello stress nelle fasi precoci della vita: le
ferite nascoste del trauma infantile?
Danese A, Lewis S – Neuropsychopharmacology, Gennaio 2017
Neuropsychopharmacology. 2017 Jan;42(1):99-114. doi: 10.1038/npp.2016.198. Epub 2016 Sep
15.
ABSTRACT

Il cervello e il sistema immunitario non sono completamente formati alla nascita, ma
continuano a maturare in risposta all'ambiente post-natale. L'interazione bidirezionale tra il
cervello e il sistema immunitario permette agli stressors psicosociali dell’infanzia, di
influenzare lo sviluppo del sistema immunitario, che a sua volta può influenzare lo sviluppo
del cervello e il suo funzionamento a lungo termine. Basandosi su modelli animali
sperimentali e studi umani osservazionali, proponiamo che la psiconeuroimmunologia
dello stress precoce possa offrire un quadro innovativo per comprendere e trattare la
psicopatologia legata al trauma infantile. Lo stress precoce predice l'infiammazione tardiva
e ci sono sorprendenti analogie tra i correlati neurobiologici dello stress precoce e
dell'infiammazione. Inoltre, ci sono schemi trans-diagnostici sovrapposti di associazione
tra trauma infantile e infiammazione, con esiti clinici. Questi risultati suggeriscono nuove
strategie per rimediare agli effetti del trauma infantile prima della comparsa dei sintomi
clinici, come gli interventi antinfiammatori e il potenziamento dell'immunità adattativa.
Strategie simili potrebbero essere utilizzate per migliorare la risposta negativa al
trattamento descritta in pazienti psichiatrici con una storia di trauma infantile.

Psychoneuroimmunology of Early-Life Stress: The Hidden
Wounds of Childhood Trauma?
ABSTRACT
The brain and the immune system are not fully formed at birth, but rather continue to
mature in response to the postnatal environment. The two-way interaction between the
brain and the immune system makes it possible for childhood psychosocial stressors to
affect immune system development, which in turn can affect brain development and its
long-term functioning. Drawing from experimental animal models and observational human
studies, we propose that the psychoneuroimmunology of early-life stress can offer an
innovative framework to understand and treat psychopathology linked to childhood
trauma. Early-life stress predicts later inflammation, and there are striking analogies
between the neurobiological correlates of early-life stress and of inflammation.
Furthermore, there are overlapping trans-diagnostic patterns of association of childhood
trauma and inflammation with clinical outcomes. These findings suggest new strategies to
remediate the effect of childhood trauma before the onset of clinical symptoms, such as

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anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies
might be used to ameliorate the unfavorable treatment response described in psychiatric
patients with a history of childhood trauma.
COMMENTO
Il trauma infantile, così come situazioni stressanti per il bambino, costituiscono un fattore
di rischio per il suo sviluppo fisico e psichico.
Ancora poco si sa su come l'esposizione al trauma infantile si traduca in rischio biologico.
Studi osservazionali sull'uomo e modelli animali sperimentali, suggeriscono che
l'esposizione infantile allo stress può innescare una risposta infiammatoria sistemica e
duratura che influisce sui sistemi bio-fiosiologici e sul neurosviluppo.
Queste ferite determinate da eventi traumatici e/o stressanti in epoca infantile possono
influenzare lo sviluppo del cervello, tratti del comportamento, aspetti cognitivi, la reattività
ai fattori di stress successivi e costituire un rischio per una psicopatologia.
Di pari passo si è dimostrato chiaramente che maltrattamento, abuso e abbandono
dell'infanzia sono associati a malattie infiammatorie in età pediatrica quale asma,
dermatite atopica ecc. e a malattie più gravi in età adulta (per esempio cancro, malattie
cardiache, malattie autoimmuni) così come a una durata della vita ridotta.
I fattori di stress nelle prime fasi della vita interferiscono con quei meccanismi protettivi che
normalmente regolano e abbassano l’infiammazione che a lungo termine risulta
potenzialmente dannosa.
Rilevare e sanare queste ferite può aiutare a prevenire e curare sia la psicopatologia che
emerge dopo un trauma infantile che malattie fisiche croniche che possono insorgere già
in età pediatrica o adulta.

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ARTICOLO 2
Lancet Public Health. 2017 Aug;2(8):e356-e366. doi: 10.1016/S2468-2667(17)30118-4.
Epub 2017 Jul 31.

Gli effetti di ACE multipli sulla salute: una revisione sistemica
e una meta-analisi.
Hughes K1, Bellis MA2, Hardcastle KA3, Sethi D4, Butchart A5, Mikton C6, Jones L7,
Dunne MP8.
ABSTRACT
Un corpus crescente di ricerche identifica gli effetti dannosi che le esperienze avverse
dell'infanzia (ACE; che si verificano durante l'infanzia o l'adolescenza; ad esempio
maltrattamenti sui minori o esposizione alla violenza domestica) hanno sulla salute per
tutta la vita. Gli studi hanno quantificato tali effetti per i singoli ACE. Tuttavia, gli ACE
spesso si verificano e non e stata fatta alcuna sintesi dei risultati degli studi che misurano
l'effetto di più tipi di ACE.

METODI
In questa revisione sistematica e meta-analisi, abbiamo cercato cinque database
elettronici per studi trasversali, caso-controllo o di coorte pubblicati fino al 6 maggio 2016,
che riportano i rischi di esiti di salute, che consistono nell'uso di sostanze, salute sessuale,
salute mentale, peso ed esercizio fisico, violenza e stato e condizioni di salute fisica,
associati a più ACE. Abbiamo selezionato articoli che presentavano stime del rischio per
individui con almeno quattro ACE rispetto a quelli senza nessuno per i risultati con dati
sufficienti per la meta-analisi (almeno quattro popolazioni). Gli studi inclusi si sono
concentrati anche su adulti di almeno 18 anni con una dimensione del campione di almeno
100. Abbiamo escluso studi basati su popolazioni cliniche o ad alto rischio. Abbiamo
estratto i dati dai rapporti pubblicati. Abbiamo calcolato i rapporti di correlazione
utilizzando un modello a effetti casuali.

RISULTATI:
Dei 11621 riferimenti identificati dalla ricerca, 37 includevano studi che fornivano stime del
rischio per 23 esiti, per un totale di 253 719 partecipanti. Gli individui con almeno quattro
ACE erano ad aumentato rischio di tutti gli esiti di salute rispetto agli individui senza ACE.
Le associazioni erano deboli o modeste per inattività fisica, sovrappeso o obesità e
diabete (OR di meno di due) (OR significa ODDS RATIO, ovvero “rapporto di probabilità”
ndr), moderato per il fumo, consumo eccessivo di alcol, scarsa autovalutazione, cancro,
malattie cardiache e malattie respiratorie (OR da due a tre), forte per l'assunzione di rischi
sessuali, problemi di salute mentale e consumo problematico di alcol (OR di più di tre a
sei), e il più forte per l'uso problematico di droghe e la violenza interpersonale e auto-

pag. 5 – Rassegna Gennaio 2020

diretta (OR di più di sette). Abbiamo identificato una notevole eterogeneità (I²> 75%) tra le
stime per quasi la metà dei risultati.

INTERPRETAZIONE:
Avere più ACE è un importante fattore di rischio per molte condizioni di salute. I risultati
più fortemente associati a più ACE rappresentano i rischi ACE per la generazione futura
(ad esempio, violenza, malattie mentali e uso di sostanze). Per sostenere il miglioramento
della salute pubblica è necessario uno spostamento dell'attenzione per includere la
prevenzione degli ACE, la costruzione della resilienza e la fornitura di servizi informati
ACE. Gli obiettivi di sviluppo sostenibile forniscono una piattaforma globale per ridurre le
ACE e il loro effetto sul corso della vita sulla salute.

COMMENTO
L'infiammazione è stata oggetto di indagine per i ricercatori che cercano di comprendere le
variabili biologiche associate allo stress. Gran parte dei lavori si è basato sulla
misurazione dei livelli di CRP e IL-6 dimostrando significative associazioni tra ACE e i
livelli di questi 2 biomarcatori infiammatori. Questi tradizionali markers di infiammazione
sono correlati però a situazioni sia croniche che acute; CRP e IL-6 sono coinvolti nella
risposta in fase acuta di infiammazione. Il suPAR, recettore dell'attivatore del
plasminogeno di tipo urokinasi solubile è la forma solubile di uPAR che è un recettore
legato alla membrana per uPA, altrimenti noto come urokinasi è stato proposto come
marker di infiammazione cronica. Contrariamente a molti marker di infiammazione, che
sono labili, rapidamente sovraregolati e downregolati, il suPAR sembra essere più stabile
e meno sensibile alle influenze acute e non fluttua con il ritmo circadiano. Il suPAR elevato
in aggiunta a CRP e IL-6 è più fortemente associato all'esposizione a stress e violenza
durante l'infanzia e l'adolescenza rispetto a quella con CRP e IL-6. Questa scoperta
supporta la conclusione che l'aggiunta di suPAR alla misurazione di CRP e IL-6 può
migliorare la valutazione dell'infiammazione cronica associata allo stress nella prima
infanzia.

The effect of multiple adverse childhood experiences on
health: a systematic review and meta-analysis

Background

A growing body of research identifies the harmful effects that adverse childhood
experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or
exposure to domestic violence) have on health throughout life. Studies have quantified
such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of
findings from studies measuring the effect of multiple ACE types has been done.

pag. 6 – Rassegna Gennaio 2020

Methods

In this systematic review and meta-analysis, we searched five electronic databases for
cross-sectional, case-control, or cohort studies published up to May 6, 2016, reporting
risks of health outcomes, consisting of substance use, sexual health, mental health, weight
and physical exercise, violence, and physical health status and conditions,
associated with multiple ACEs. We selected articles that presented risk estimates for
individuals with at least four ACEs compared with those with none for outcomes with
sufficient data for meta-analysis (at least four populations).
Included studies also focused on adults aged at least 18 years with a sample size of at
least 100. We excluded studies based on high-risk or clinical populations. We extracted
data from published reports. We calculated pooled odds ratios (ORs) using a random-
effects model.

Findings

Of 11621 references identified by the search, 37 included studies provided risk estimates
for 23 outcomes, with a total of 253 719 participants. Individuals with at least four ACEs
were at increased risk of all health outcomes compared with individuals with no ACEs.
Associations were weak or modest for physical inactivity, overweight or
obesity, and diabetes (ORs of less than two); moderate for smoking, heavy alcohol use,
poor self-rated health, cancer, heart disease, and respiratory disease (ORs of two to
three), strong for sexual risk taking, mental ill health, and problematic alcohol use (ORs of
more than three to six), and strongest for problematic drug use and interpersonal and self-
directed violence (ORs of more than seven). We identified considerable heterogeneity (I²
of >75%) between estimates for almost half of the outcomes.

Interpretation

To have multiple ACEs is a major risk factor for many health conditions. The outcomes
most strongly associated with multiple ACEs represent ACE risks for the next generation
(eg, violence, mental illness, and substance use). To sustain improvements in public
health requires a shift in focus to include prevention of ACEs, resilience building, and ACE-
informed service provision. The Sustainable Development Goals provide a global platform
to reduce ACEs and their life-course effect on health.

Funding Public Health Wales.

pag. 7 – Rassegna Gennaio 2020

ARTICOLO 3
Una revisione sistematica di prove per migliorare i risultati dei
bambini associati alle esperienze avverse nell'infanzia

Am J Prev Med. 2019 May;56(5):756-764. doi: 10.1016/j.amepre.2018.11.030. Epub 2019 Mar 21.

Marie-Mitchell A 1 , Kostolansky R 2 .

Informazioni sull'autore
1
Dipartimenti di medicina preventiva e pediatria, Loma Linda University, Loma Linda, California.
Indirizzo elettronico: amariemitchell@llu.edu.

2 Claremont Graduate University, School of Community and Global Health, Claremont, California.

ABSTRACT
CONTESTO:
Lo scopo di questa revisione sistematica della letteratura era di riassumere le evidenze
attuali degli RCT (Randomized Control Trials) sull'efficacia degli interventi che coinvolgono
l'assistenza pediatrica per prevenire scarsi outcomes associati a esperienze avverse
dell'infanzia misurate durante l'infanzia (definite C- ACE).

ACQUISIZIONE EVIDENZE:
Il 18 gennaio 2018, i ricercatori hanno cercato su PubMed, PsycInfo, SocIndex, Web of
Science, Cochrane e liste di riferimento gli studi clinici controllati randomizzati (RCT) in
lingua inglese che coinvolgessero l'assistenza pediatrica e pubblicati tra il 1 gennaio 1990
e il 31 dicembre 2017. Gli studi sono stati inclusi se erano (1) un RCT, (2) su una
popolazione pediatrica e (3) reclutati o sottoposti a screening in base all'esposizione a
C-ACE. I ricercatori hanno estratto i dati relativi al campione di studio e alla strategia di
reclutamento, C- ACE, le condizioni di intervento e di controllo, gli esiti dei bambini e le
associazioni significative segnalate.

SINTESI DELLE EVIDENZE:
Sono stati inclusi un totale di 22 articoli che descrivono i risultati di 20 studi randomizzati.
La malattia mentale / depressione dei genitori era il C-ACE più comune rilevato, seguito da
abuso di alcol o droghe da parte dei genitori e violenza domestica. La maggior parte degli
interventi ha combinato l'educazione dei genitori, il riferimento ai servizi sociali e il
sostegno sociale per le famiglie di bambini di età compresa tra 0 e 5 anni. Cinque dei sei
studi che hanno coinvolto direttamente le cure primarie pediatriche hanno migliorato i
risultati, tra cui tre studi che hanno coinvolto lo screening per C- ACE. Otto dei 15 studi
che hanno misurato i risultati sulla salute dei bambini e 15 dei 17 studi che hanno valutato
la relazione genitore- figlio, hanno dimostrato un miglioramento.

CONCLUSIONI:
Interventi multidisciplinari che utilizzano professionisti per educazione parentale,
consulenza per la salute mentale, rinvio ai servizi sociali o sostegno sociale sono in grado
di ridurre l'impatto di C- ACE sul comportamento /problemi di salute mentale dei bambini

pag. 8 – Rassegna Gennaio 2020

e di migliorare il rapporto genitore-figlio per i bambini di età compresa tra 0-5 anni.

A Systematic Review of Trials to Improve Child Outcomes
Associated With Adverse Childhood Experiences
CONTEXT:
The purpose of this systematic literature review was to summarize current evidence from
RCTs for the efficacy of interventions involving pediatric health care to prevent poor
outcomes associated with adverse childhood experiences measured in childhood
(CACEs).

EVIDENCE ACQUISITION:
On January 18, 2018, investigators searched PubMed, PsycInfo, SocIndex, Web of
Science, Cochrane, and reference lists for English language RCTs involving pediatric
health care and published between January 1, 1990, and December 31, 2017. Studies
were included if they were (1) an RCT, (2) on a pediatric population, and (3) recruited or
screened based on exposure to C-ACEs. Investigators extracted data about the study
sample and recruitment strategy, C-ACEs, intervention and control conditions,
intermediate and child outcomes, and significant associations reported.

EVIDENCE SYNTHESIS:
A total of 22 articles describing results of 20 RCTs were included. Parent mental
illness/depression was the most common C-ACE measured, followed by parent alcohol or
drug abuse, and domestic violence. Most interventions combined parenting education,
social service referrals, and social support for families of children aged 0-5years. Five of
six studies that directly involved pediatric primary care practices improved outcomes,
including three trials that involved screening for C-ACEs. Eight of 15 studies that
measured child health outcomes, and 15 of 17 studies that assessed the parent-child
relationship, demonstrated improvement.

CONCLUSIONS:
Multicomponent interventions that utilize professionals to provide parenting education,
mental health counseling, social service referrals, or social support can reduce the impact
of C-ACEs on child behavioral/mental health problems and improve the parentchild
relationship for children aged 0-5years.

COMMENTO
L’articolo mi ha incuriosito perché cerca di rispondere alla domanda: può l’intervento del
pediatra migliorare gli esiti dei bambini esposti ad eventi avversi nell’infanzia (ACEs:
adverse childhood experiences, ndr). L’articolo evidenzia l’importanza di un intervento
multidisciplinare al fine di ridurre il rischio di esiti sulla salute psicologica e fisica dei
bambini soggetti ad eventi avversi. Viene inoltre ribadita la raccomandazione
fatta dall’Accademia americana di pediatria rispetto alla necessità che i pediatri attuino uno
screening per ACEs per identificare le famiglie a rischio e supportino i bambini esposti a
potenziali fattori stressanti (ad esempio nei pazienti che presentano epigastralgie o cefalee
frequenti pensare a violenze domestiche o genitorialità severa). La chiave per prevenire e
ridurre gli effetti degli eventi avversi è quella di migliorare il rapporto genitori-figli. Come
pediatra, ritengo che, anche nella nostra realtà italiana, potrebbe essere un’ottima
opportunità quella di identificare i soggetti a rischio durante le visite periodiche che
effettuiamo ai piccoli pazienti, come suggerisce anche lo studio correlato che allego.

pag. 9 – Rassegna Gennaio 2020

ARTICOLI CORRELATI
ARTICOLO 1

(A)
Childhood adversity and immune and inflammatory biomarkers
associated with cardiovascular risk in youth: A systematic review
Natalie Slopen, Karestan C. Koenen e Laura D. Kubzansky
Brain, Behavior, and Immunity, 2012-02-01, Fascicolo 26, Numero 2, Pagine 239-250, Copyright ©
2011 Elsevier Inc.

ABSTRACT
BACKGROUND:
Research suggests that adverse experiences in childhood affect the development of
cardiovascular disease (CVD), and immune and inflammation dysregulation has been
postulated to play role. However, it is unclear whether the effects of social adversity on
immune-related biomarkers are evident in early life, and if these biomarkers may provide
an early risk marker for targeting prevention and intervention. The purpose of this review is
to evaluate research on the relationship between adversity and CVD-relevant immune
biomarkers in youth, assess the consistency of the findings, and consider what additional
research is needed.
METHODS:
PubMed and PsycINFO searches were conducted through September 2011. Studies were
selected using criteria related to the childhood exposure, biomarker outcome, age range,
and sample selection. Twenty articles were identified, examining associations between
childhood adversity and immune biomarkers (assessed during childhood) that are potential
risk markers for CVD later in life.

RESULTS:
Although childhood adversity was not consistently related to youth levels of inflammatory
and other immune markers relevant to CVD, a trend toward positive findings was
observed. No detectable patterns were evident based on measure of adversity, biomarker,
study design, or sample size.
CONCLUSIONS:
Overall, our findings suggest this avenue of research is worth continued investigation. We
offer recommendations for future research related to (1) study design and sample, (2)
definition and measurement of adversity, (3) statistical analysis, and (4) outcomes that will
help distinguish whether there are immunologic alterations related to adversity and
subsequent CVD risk that can be reliably detected in childhood.

pag. 10 – Rassegna Gennaio 2020

(B)
Early childhood family instability and immune
system dysregulation in adolescence.
Schmeer KK1, Ford JL2, Browning CR3.

ABSTRACT

Exposure to stress is one way in which social disadvantages during childhood may alter
biological and psychological systems with long-term consequences. Family social and
economic conditions are critical for early childhood development and exposure to difficult
family conditions may have lasting physiological effects. However, there is little research
linking early childhood conditions with physiological indicators
of stress and system dysregulation in adolescence. In this study, we assess how family
social and economic instability that occurred in early childhood (birth to age 5) is
associated with immune system dysregulation in adolescence, as indicated by DNA
shedding of the Epstein-Barr virus (EBV). We utilize a biomarker of EBV obtained through
saliva, a non-invasive method of collecting immune-system biomarkers, in 674
adolescents 11-17 years old. Multivariable regression results indicated that experiences of
moving into a new parent/caregiver household or moving in with a grandparent
during early childhood was associated with an estimated 100% increase in EBV DNA
shedding among prior EBV-infected adolescents. Other measures of early childhood family
instability, total number of family structure changes and economic insecurity, were
marginally significant. Contemporaneous family conditions were not associated with
adolescents' EBV DNA shedding.

(C)
Proinflammatory T Cell Status Associated
with Early Life Adversity.
Elwenspoek MMC1,2, Hengesch X3, Leenen FAD1,2, Schritz A4, Sias K1, Schaan
VK5, Mériaux SB1, Schmitz S1, Bonnemberger F1, Schächinger H3, Vögele C5, Turner
JD6, Muller CP1,2.

ABSTRACT
Early life adversity (ELA) has been associated with an increased risk for diseases in which
the immune system plays a critical role. The ELA immune phenotype is characterized by
inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-
specific immune effects are largely absent. Additionally, stress systems and health

pag. 11 – Rassegna Gennaio 2020

behaviors are altered in ELA, which may contribute to the generation of the
ELA immune phenotype. The present investigation tested cell-specific immune differences
in relationship to the ELA immune phenotype, altered stress parameters, and health
behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n =
73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of
monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow
cytometry. ELA was associated with significantly reduced numbers of CD69+CD8+ T cells
(p = 0.022), increased numbers of HLA-DR+ CD4 and HLA-DR+ CD8 T cells (p < 0.001),
as well as increased numbers of CD25+CD8+ T cells (p = 0.036). ELA also showed a trend
toward higher numbers of CCR4+CXCR3-CCR6+ CD4 T cells. Taken together, our data
suggest an elevated state of immune activation in ELA, in which particularly T cells are
affected. Although several aspects of the ELA immune phenotype were related to
increased activation markers, neither stress nor health-risk behaviors explained the
observed group differences. Thus, the state of immune activation in ELA does not seem to
be secondary to alterations in the stresssystem or health-risk behaviors, but rather a
primary effect of early life programming on immune cells.

pag. 12 – Rassegna Gennaio 2020

ARTICOLO 2

(A)
2017 Dec 1;171(12):1168-1175. doi: 10.1001/jamapediatrics.2017.3009.

Association Between Early Life Adversity and Risk for Poor
Emotional and Physical Health in Adolescence: A Putative
Mechanistic Neurodevelopmental Pathway.
Luby JL1, Barch D1,2, Whalen D1, Tillman R1, Belden A1.
ABSTRACT
IMPORTANCE:
Adverse childhood experiences (ACEs) have been associated with poor mental and
physical health outcomes. However, the mechanism of this effect, critical to enhancing
public health, remains poorly understood.
OBJECTIVE:
To investigate the neurodevelopmental trajectory of the association between early ACEs
and adolescent general and emotional health outcomes.
DESIGN, SETTING, AND PARTICIPANTS:
A prospective longitudinal study that began when patients were aged 3 to 6 years who
underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health
outcomes were observed at ages 9 to 15 years. Sequential mediation models were used
to investigate associations between early ACEs and brain structure, emotion development,
and health outcomes longitudinally. Children were recruited from an academic medical
center research unit.
EXPOSURE:
Early life adversity.
MAIN OUTCOMES AND MEASURES:
Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex,
the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness,
depression severity, and general health outcomes in children and adolescents aged 9 to
15 years.
RESULTS:
The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean
(SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61
(1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global
physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively.
Sequential mediation in the association between high early ACEs and emotional and
physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor
emotional awareness sequentially mediated the association between early ACEs and poor

pag. 13 – Rassegna Gennaio 2020

general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher
depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in
adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25%
increases in depression severity and physical health problems, respectively.
CONCLUSIONS AND RELEVANCE:
Study findings highlight 1 putative neurodevelopmental mechanism by which the
association between early ACEs and later poor mental and physical health outcomes may
operate. This identified risk trajectory may be useful to target preventive interventions.

(B)
Acad. Pediatr. 2016 Apr;16(3 Suppl):S30-6. doi: 10.1016/j.acap.2016.01.010.

Poverty, Stress, and Brain Development: New Directions for
Prevention and Intervention.
Blair C1, Raver CC2.
ABSTRACT
We review some of the growing evidence of the costs of poverty to children's
neuroendocrine function, early brain development, and cognitive ability. We underscore
the importance of addressing the negative consequences of poverty-related adversity early
in children's lives, given evidence supporting the plasticity of executive functions and
associated physiologic processes in response to early intervention and the importance of
higher order cognitive functions for success in school and in life. Finally, we highlight some
new directions for prevention and intervention that are rapidly emerging at the intersection
of developmental science, pediatrics, child psychology and psychiatry, and public policy.
KEYWORDS:
brain development; early childhood; executive function; infancy; parenting; poverty; stress

(C)
Annu Rev Clin Psychol. 2016;12:331-57. doi: 10.1146/annurev-clinpsy-032814-112855.
Epub 2015 Dec 7.

The Neurobiology of Intervention and Prevention in Early
Adversity.
Fisher PA1, Beauchamp KG1, Roos LE1, Noll LK1, Flannery J1, Delker BC1.
ABSTRACT
Early adverse experiences are well understood to affect development and well-being,
placing individuals at risk for negative physical and mental health outcomes. A growing
literature documents the effects of adversity on developing neurobiological systems. Fewer

pag. 14 – Rassegna Gennaio 2020

studies have examined stress neurobiology to understand how to mitigate the effects of
early adversity. This review summarizes the research on three neurobiological systems
relevant to interventions for populations experiencing high levels of early adversity: the
hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive
functioning, and the system involved in threat detection and response, particularly the
amygdala. Also discussed is the emerging field of epigenetics and related interventions to
mitigate early adversity. Further emphasized is the need for intervention research to
integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use,
alcohol exposure) and early adversity. The review concludes with a discussion of the
implications of this research topic for clinical psychology practice and public policy.
KEYWORDS:
HPA axis; adversity; amygdala; epigenetics; intervention; prefrontal cortex

pag. 15 – Rassegna Gennaio 2020

ARTICOLO 3

(A)
Glob Pediatr Health. 2019 Jul 4;6:2333794X19862093. doi: 10.1177/2333794X19862093.
eCollection 2019.
Implementation of the Whole Child Assessment to Screen for
Adverse Childhood Experiences
Marie-Mitchell A1, Lee J1, Siplon C1, Chan F1, Riesen S1, Vercio C1.
Author information
1 Loma Linda University, Loma Linda, CA, USA.

ABSTRACT
Pediatricians are encouraged to screen for adverse childhood experiences (ACEs). The
current study developed and implemented a tool to screen for Child-ACEs at a pediatric
resident clinic in San Bernardino, California. Development of the tool, named the
Whole Child Assessment (WCA), was based on an iterative process that incorporated
triangulation of references, patient data, and physician feedback. Implementation of the
WCA occurred over the course of 6 improvement cycles that involved obtaining and
responding to stakeholder feedback, streamlining paperwork and workflow, and providing
physician education. Over the course of our study, we reviewed 1100 charts from well-
child visits. We demonstrated that use of the WCA increased identification of multiple
Child-ACEs compared with no screening and that reports of multiple Child-ACEs increased
with age. These results suggest that use of the WCA provides an acceptable and feasible
way to screen for Child-ACEs during routine pediatric practice.
KEYWORDS:
adverse childhood experiences; pediatrics; prevention; preventive health services; quality improvement

(B)
JAMA Pediatr. 2019 Sep 9:e193007. doi: 10.1001/jamapediatrics.2019.3007. [Epub ahead
of print]

Positive Childhood Experiences and Adult Mental and
Relational Health in a Statewide Sample: Associations Across
Adverse Childhood Experiences Levels

Bethell C1, Jones J2, Gombojav N1, Linkenbach J3, Sege R4.

Author information
1 Johns Hopkins Bloomberg School of Public Health and Child and Adolescent Health
Measurement Initiative, Baltimore, Maryland.
2 Alliance for Strong Families and Communities, Milwaukee, Wisconsin.
3 The Montana Institute, Bozeman, Montana.
pag. 16 – Rassegna Gennaio 2020

4 Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston,
Massachusetts.

ABSTRACT

IMPORTANCE:
Associations between adverse childhood experiences (ACEs) and risks for adult
depression, poor mental health, and insufficient social and emotional support have been
documented. Less is known about how positive childhood experiences (PCEs) co-occur
with and may modulate the effect of ACEs on adult mental and relational health.

OBJECTIVE:
To evaluate associations between adult-reported PCEs and (1) adult depression and/or
poor mental health (D/PMH) and (2) adultreported social and emotional support (ARSES)
across ACEs exposure levels.

DESIGN, SETTING, AND PARTICIPANTS:
Data were from the cross-sectional 2015 Wisconsin Behavioral Risk Factor Survey, a
random digit-dial telephone survey of noninstitutionalized Wisconsin adults 18 years and
older (n = 6188). Data were weighted to be representative of the entire population
of Wisconsin adults in 2015. Data were analyzed between September 2016 and January
2019.

MAIN OUTCOMES AND MEASURES:
The definition of D/PMH includes adults with a depression diagnosis (ever) and/or 14 or
more poor mental health days in the past month. The definition of PCEs includes 7 positive
interpersonal experiences with family, friends, and in school/the community.
Standard Behavioral Risk Factor Survey ACEs and ARSES variables were used.

RESULTS:
In the 2015 Wisconsin Behavioral Risk Factor Survey sample of adults (50.7% women;
84.9% white), the adjusted odds of D/PMH were 72% lower (OR, 0.28; 95% CI, 0.21-0.39)
for adults reporting 6 to 7 vs 0 to 2 PCEs (12.6% vs 48.2%). Odds were 50% lower (OR,
0.50; 95% CI, 0.36-0.69) for those reporting 3 to 5 vs 0 to 2 PCEs (25.1% vs 48.2%).
Associations were similar in magnitude for adults reporting 1, 2 to 3, or 4 to 8 ACEs. The
adjusted odds that adults reported "always" on the ARSES variable were 3.53 times (95%
CI, 2.60-4.80) greater for adults with 6 to 7 vs 0 to 2 PCEs. Associations for 3 to 5 PCEs
were not significant. The PCE associations with D/PMH remained stable across each
ACEs exposure level when controlling for ARSES.

CONCLUSIONS AND RELEVANCE:
Positive childhood experiences show dose-response associations with D/PMH and
ARSES after accounting for exposure to ACEs.
The proactive promotion of PCEs for children may reduce risk for adult D/PMH and
promote adult relational health. Joint assessment of PCEs and ACEs may better target
needs and interventions and enable a focus on building strengths to promote well-being.
Findings support prioritizing possibilities to foster safe, stable nurturing relationships for
children that consider the health outcomes of positive experiences.

pag. 17 – Rassegna Gennaio 2020