Disabilità intellettiva, relazionale e gravi problematiche di salute mentale nell’arco di vita di una persona: - Disabilità o disturbo? - Classificazione standard - Classificazione attuale - Diagnosi psichiatrica nella disabilità intellettiva - I gravi disturbi psichiatrici (Dr. Bertelli)

1. Sportello Unico Disabilità (SUD)
- 2 Classificazione e diagnosi dei disturbi dello
Sviluppo Intellettivo e Salute Mentale
(Dott. Marco Bertelli)

2. INTELLECTUAL DEVELOPMENTAL DISORDERS
AND MENTAL HEALTH:
CLASSIFICATION AND DIAGNOSTIC ISSUES
Marco Bertelli, MD, Psychiatrist, MISP
Presidente EAMH-ID - European Association on Mental Health in Intellectual Disability
Presidente WPA-SPID - World Psychiatric Association - Section Intellectual Disability
Segretario SIDiN – Società Italiana per i Disturbi del Neurosviluppo
Presidente Eletto AISQuV - Società Italiana per lo studio della Qualità di Vita
Direttore Scientifico CREA - Research and Clinical Centre of Fondazione San Sebastiano, Florence (Italy)
www.crea-sansebastiano.org
office: mbertelli@crea-sansebastiano.org
private: bertelli.fi@tiscali.it

5. WPA-SPID POSITION STATEMENT
 ID is a health condition
 ID is a meta-syndrome characterised by an
impairment in cognitive functioning prior to the
acquisition of skills through learning
 the intensity of the deficit is such to interfere in a
significant way with individual normal functioning as
expressed in limitations in activities and restriction in
participation (disabilities)
Salvador-Carulla L.. and Bertelli M. Intellectual Disability: A Hidden Mental Health Priority Area. Psychopathology, 2007

6. IDD DEFINITION
 A group of developmental conditions characterized by a significant
impairment of cognitive functions, which are associated with
limitations of learning, adaptive behavior and skills.
 IDD is a life span condition requiring consideration of
developmental stages and life transitions.
 Most individuals with IDD continue to acquire skills and
competencies, especially with optimal care, training, education and
opportunities for learning.
 However IDD is a vulnerable group associated with a higher rate
of mental and physical disorders and related unmet care needs as
well as an increased risk of abuse and neglect.
Salvador-Carulla L.. Reed G., Bertelli M. et al, World Psychiatry, in press

7. ID: DISABILITY OR DISORDER ?
?

8. ID: DISABILITY OR DISORDER ?
+

9. Is IQ reduction an useful criterion for ID?
1.Ardila A., (1999). A Neuropsychological Approach to Intelligence. Neuropsychology Review, Vol. 9, No. 3,1999; 45. 2.Salvador-Carulla L., Bertelli M.
(2007). Intellectual Disability: A Hidden Mental Health Priority Area. Psychopathology. 41:10-16. 3. Tiekstra M, Hessels MG, Minnaert AE. Learning
capacity in adolescents with mild intellectual disabilities. Psychol Rep. 2009 Dec;105(3 Pt 1):804-14; 35. 4.Torresan, P. (2006). Le intelligenze multiple.
Revista Conceptos, UMSA.

10. IQ AND COGNITIVE PROFILE IN GS
Syndrome
ID level
Down
Mild, moderate or severe
X Fragile
15% mild
49% moderate
26% severe
10% profound
Williams
7q delection
Mild or moderate
Smith-Magenis
(17p delection)
Specific Cognitive Dysfunction
Mild or moderate
Bertelli et al. (2011). PSICOGEN (PSIchyatric disorders and Cognition in GENetic syndromes).In submission.

11. IQ AND COGNITIVE PROFILE IN GS - 2
Syndrome
ID level
Warkany 2
(trisomy 8)
moderate or severe
Phenylketonuria
moderate or severe
Klinefelter
(47 XXY)
absent or borderline
Galctosemia
Specific Cognitive Dysfunction
absent or borderline
Bertelli et al. (2011). PSICOGEN (PSIchyatric disorders and Cognition in GENetic syndromes).In submission.

12. WAIS IV SUBTESTS AND SUBSCORES
Copyright © 2008 Pearson Education, Inc. or its affiliate(s). All rights reserved.

13. SCFs AND NOT IQ
FOR BIOLOGICAL SUBSTRATES
Findings of recent studies of genetics, neuroimaging and
neurophysiology identified more correlations with
cognitive functions (such as perceptual organization
deficit, poor working memory, lexical, visual-spatial and
phonological processing) than with IQ scores1,2,3,4,5,6
1. Steinlin M. (2008). Cerebellar disorders in childhood: cognitive problems. Cerebellum. 7:607-10; 2.Tavano A., Borgatti R. (2010). Evidence for a link among cognition,
language and emotion in cerebellar malformations. Cortex. 46:907-18; 3.Ardila A., Pineda D., Rosselli M. (2000). Correlation between intelligence test scores and executive
function measures. Archives of Clinical Neuropsychology. 15:31-6; 4.Friedman N.P., Miyake A., Corley R.P., Young S.E., Defries J.C., Hewitt J.K. (2006). Not all executive
functions are related to intelligence. Psychological Science. 17:172-9; 5.Johnson W., Jung R.E., Colom R., Haier R.J. (2008). Cognitive abilities independent of IQ correlate
with regional brain structure. Intelligence. 36:18-28; 6.Mackintosh NJ. (1999). IQ and Human Intelligence. Reviewed by Robert Plomin. The American Journal of Human
Genetics. 65:1476-1477.

14. 17,5 %
12,5 %
6%
2,5%
RM
FIL
NORMALE
ALTO
GENIO
Hassiotis A, Strydom A, Hall I, Ali A, Lawrence-Smith G, Meltzer H, Head J, Bebbington P. Psychiatric morbidity and social functioning
among adults with borderline intelligence living in private households. J Intellect Disabil Res. 2008 Feb;52(Pt 2):95-106.

15. BORDERLINE INTELLIGENCE
N = 8450 adults
 around 1/8 of the population has borderline intelligence
(12,3% of the sample)
 this people present higher rate of:
- neurotic disorders
- substance abuse
- personality disorders
- social disability
- psycho-pharmacological therapies, but not speech
therapies
- health service use, including emergency services
Hassiotis A. et al. J Intellect Disabil Res. 2008 Feb;52(Pt 2):95-106

16. Is the age limit of 18 an useful criterion for ID?
Although the specific age limit of 18 is clearly arbitrary,
WPA-SPID members expressed general agreement on the
importance to keep a distinction between a persistent
process that begins at birth and a change occurring after a
normal development.

17. INCREASE OF AUTISM AND ASDs
PREVALENCE RATE
■
Autism1
1. Newschaffer et al., 2007.
2. Lazoff et al., 2010; Baron-Cohen et al., 2009
■
ASD2

18. PREVALENCE RATE (%)
ASD AND ID
 PDD in ID = 30-40%1
 ID in autism = 25-80%2
 in ID around 50% of ASDs has been previously
diagnosed with schizophrenia3
 risk of underestimating ASD in ID in favour of
schizophrenia4
1. Kraijer 1997 (N=718); Morgan et al. 2002 (N=571); La Malfa et al., 2004 (N=166 adults); Cooper et al., 2007
2. Hoekstra et al., 2009 BJP; Centers for Disease Control and prevention USA, 2006; Edelson, 2006; Matson e Shoemaker, 2009;
Baird et al., 2006; Noterdaeme e Wriedt, 2010; Bryson and Smith, 1998
3. Bryson et al. Prevalence of autism among adolescents with intellectual disabilities. Canadian J of Psychiatry, 2008; 53(7): 449-59
4. Palucka et al., 2009; Savage et al., 2007

19. PREVALENCE RATE (%)
ASD AND SCHIZOPHRENIA
 21% of people with schizophrenia receive a
lifetime diagnosis of PDD-NOS1
 around 50 % of people with autismo also meets
criteria for schizophrenia disorganised-type2
 at least 1.5% of psychiatric outpatients don’t
receive the right diagnosis of ASD; 26% of these is
diagnosed with schizophrenia3
1. Sporn et al., 2004; Towbin et al., 2005
2. Konstantareas and Hewitt, 2001
3. Nylander and Gilberg, 2001

20. PREVALENCE RATE (%)
OF PSYCHIATRIC DISORDERS IN ID WITH AND WITHOUT AUTISM
Prevalence
Tool
with A
without A
Bradley & Bolton, 2006
SAPPA
Bradley et al., 2004
DASH
50
>50
16,7
25
50
67
58
8
8
8
25
8
Depression
Mania
Eating Disorders
Schizophrenia
Bradley E.A. and Bolton P. Episodic psychiatric disorders in teenagers with learning disabilities with and without autism. British Journal of
Psychiatry, 2006, 189: 361-366
Bradley E.A., Summers J.A., Wood H.L., Bryson S.E. Comparing rates of psychiatric and behavior disorders in adolescents and young adults
with severe intellectual disability with and without autism. J of Autism and Developmental Disorders, 2004; 34(2): 151-161

21. GENETIC OVERLAPPING BETWEEN AUTISM AND IDD
Gene:
Protein:
• FMR1 Xq27.32
• neuroligina3
• GRIK2 6q16.32
• neurexina3
• HOXA1 7p15.32
• SHANK-33
• PTCHD11
• CNTNAP24
• NLGN4 and IL1RAPL12
• PUM25 implications in mRNA
• RPL102
• CGG trinucleotide6
deletion
• 1q21.12
 LTD on mGluR7
• 15q13.32
• 16p11.22
1Noor A, Scherer SW. Disruption at the PTCHD1 locus on Xp22.11 in autism spectrum disorder and intellectual disability. Sci Transl Med. 2010 September 15; 2(49)
2Pinto D, Scherer SW. Functional Impact of Global Rare Copy Number Variation in Autism Spectrum Disorder Nature. 2010 July 15; 466(7304): 368–372. doi:10.1038/nature09146
3Bakkaloglu B, et al. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet. 2008 Jan;82(1):165-73.
4Alarcón M, et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet. 2008 Jan;82(1):150-9
5
Vessey J.P., Schoderboeck L., Gingl E., Luzi E, et al. Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function. PNAS ( Proceedings of the National Academy of
Sciences). Published online before print January 28, 2010
6
Gabis LV, Baruch YK, Jokel A, Raz R. Psychiatric and autistic comorbidity in fragile x syndrome across ages. J Child Neurol. 2011 Aug;26(8):940
7Lüscher C, Huber KM. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron. 2010 Feb 25;65(4):445-59

22. GENETIC OVERLAPPING
BETWEEN AUTISM AND SCHIZOPHRENIA
 Chromosome 1q21.1 deletion 1
Chromosome 15q13.3 deletion 1
Chromosome 3q29 and 22q11.21 deletion
Chromosome 16p11.2 duplication 1
exonic NRXN1 deletion 1
exonic VIPR2 and C16orf72 duplication 1
 Chromosome 16p11.22
 NRXN1 2p16.3 gene disrupted in ASD, MR, schizophrenia4
 16p13.11 deletion
 Deficits in RNA transcription without changes in DNA sequence5-6
1. Levinson DF, Gejman PV. Copy Number Variants in Schizophrenia: Confirmation of Five Previous Findings and New Evidence for 3q29 Microdeletions and VIPR2 Duplications. Am J
Psychiatry. 2011 Mar;168(3):302-16
2. McCarthy SE, Sebat J. Microduplications of 16p11.2 are associated with schizophrenia. 2009 Nov;41(11):1223-7
3. Akbarian S, Huang HS. Epigenetic regulation in human brain-focus on histone lysine methylation. Biol Psychiatry, 2009 Feb 1;65(3):198-203; Singh SM, O'Reilly R. (Epi)genomics and
neurodevelopment in schizophrenia: monozygotic twins discordant for schizophrenia augment the search for disease-related (epi)genomic alterations. Genome, 2009 Jan;52(1):8-19
4. Pinto D, Scherer SW. Functional Impact of Global Rare Copy Number Variation in Autism Spectrum Disorder Nature. 2010 July 15; 466(7304): 368–372. doi:10.1038/nature09146
5. Akbarian S, Huang HS. Epigenetic regulation in human brain-focus on histone lysine methylation. Biol Psychiatry, 2009 Feb 1;65(3):198-203
6. Singh SM, O'Reilly R. (Epi)genomics and neurodevelopment in schizophrenia: monozygotic twins discordant for schizophrenia augment the search for disease-related (epi)genomic
alterations. Genome, 2009 Jan;52(1):8-19

23. THE PROTEINS OF COGNITION
Pum 2 and elF4E and Scn1a
Neuroligina
SHANK-3
CNTNAP2
'cadherin' (Calcium
dependent adhesion
molecules) 10 and 9
Neurexine 1 (NRXN1)
N= 3540 under genomic comparative hybridization
NRXN1 mutation resulted to be associated with ASDs, IDD, and SLD
Ching MS, Shen Y, Tan WH, et al. Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am J Med Genet B
Neuropsychiatr Genet. 2010 Apr 7.

24. THE ROLE OF FMRP IN MAJOR MENTAL DISORDERS
 Fragile X Mental Retardation Protein is highly enriched in neurons and
binds to approximately 4% of mRNAs in mammalian brain
 FMRP loss is a hallmark of fragile X syndrome (FXS), the most common
inherited form of mental retardation
 reductions of FMRP in psychiatric disorders
•
autism
•
schizophrenia
•
bipolar disorder
•
major depressive disorder
Fatemi SH, Folsom TD. The role of fragile X mental retardation protein in major mental disorders. Neuropharmacology. 2011 Jun;60(7-8):1221-6. Epub 2010
Nov 22.

25. GENETICS OF NEURODEVELOPMENTAL DISORDERS
RELN
reelin
neuronal migration and synaptic function
Npas4G
Npas4
social and cognitive functions
1q21.1
CHD1, PBKAB2
chromatine and AMP kinase regulation
16p11.2
SEZ6L2
expressive language and socialisation
16p13.1
NDE1, NTAN1
synaptic plasticity, memory
GRIN2
NMDA rec
working memory and perceptual binding
TCF4
TCF4
memory and attention (N150)
NRXN1
neurexine
synaptic functions
CNTNAP2
contactin-L2
cell adhesion and receptors
SHANK 3
ProSAP2
synapse and dendritic spine formation
Ullman et al.,Human mutation, 2007; Folsom et al. Neuropharmacology, 2012; Coutallier et al. PLos One, 2012; Crespi et al. J Neurodev Disord, 2012; Endele et
al. Nat Genet, 2010 ; Hennekam et al. Dev Med Child Neurol, 2012

26. METACATEGORY
WPA-SPID proposed to include in a cluster of disorders
sharing salient cognitive symptoms and similarities on risk
factors, clinical factors, genetic phenotype, early onset, course,
and co-morbidity.
F7
Salvador-Carulla L.. Reed G., Bertelli M. et al, World Psychiatry, in press
F1

27. ICD-11-beta morbidity linearisation
and “impairment of behaviour”
• 05 Mental and behavioural disorders
NEURODEVELOPMENTAL DISORDERS
Disorders of Intellectual Development (DID)
5A00. Mild DID: IQ 50-69; in adults mental age (MA) 9 - <12 y
5A01. Moderate DID: IQ 35-49; in adults, MA 6 - <9 y
5A02. Severe DID: IQ 20 – 34; in adults, MA 3 - <6 y
5A13. Profound DID: IQ <20; in adults, MA <3 y
5A0Y. Other disorders of intellectual development
5A0Z. Disorders of intellectual development, unspecified
ICD-10 impairment of behaviour F7x. 1 “RETIRED”

28. DSM-5 ID/IDD Position
• disturbo con insorgenza nell’età evolutiva che include deficit
intellettivi e adattivi negli ambiti della concettualizzazione, della
socializzazione e delle capacità pratiche
• i livelli di gravità vengono definiti sulla base del funzionamento
adattivo e non sui punteggi di quoziente intellettivo (QI), poiché è
stato giudicato che sia il funzionamento adattivo, nelle aree della
concettualizzazione, della socializzazione e delle abilità pratiche, a
determinare il livello di supporto necessario a mantenere una
condizione di vita accettabile. In più, quando basse (inferiori a 60), le
misure di QI perdono di validità
• si continuano a distinguere 4 livelli di gravità (lieve, moderato, grave
e gravissimo), ma con criteri diversi dal DSM-IV e IV-TR.
APA. Diagnostic and Statistic Manual for Mental Disorders - %th edition, 2013

29. DSM-5 ID/IDD Position - 2
• il disturbo è stato collocato in un raggruppamento meta-sindromico, o
meta-strutturale, denominato ‘disturbi del neurosviluppo
• il gruppo include condizioni con insorgenza in età evolutiva, tipicamente
precoci, spesso precedenti l’ingresso a scuola e caratterizzate da deficit
di sviluppo che producono compromissioni del funzionamento personale,
sociale, scolastico o occupazionale
• il range di deficit spazia da limitazioni molto specifiche
dell’apprendimento e del controllo delle funzioni esecutive ad una
compromissione globale delle abilità sociali o dell’intelligenza
• i disturbi del neurosviluppo si presentano spesso insieme, per esempio
individui con autismo hanno spesso anche disabilità intellettiva (disturbo
dello sviluppo intellettivo) e molti bambini con disturbo da deficit
d’attenzione e iperattività hanno spesso anche un disturbo specifico
dell’apprendimento.
APA. Diagnostic and Statistic Manual for Mental Disorders - %th edition, 2013

30. DSM-5 ID/IDD Diagnostic Criteria
A. Deficit delle funzioni intellettive, come il ragionamento, la soluzione
di problemi, la pianificazione, il pensiero astratto, il giudizio,
l’apprendimento scolastico o l’apprendimento dall’esperienza,
confermato sia da valutazione clinica che da prove d’intelligenza
individualizzate e standardizzate.
B. Deficit del funzionamento adattivo che si manifesti col mancato
raggiungimento degli standard di sviluppo e socio-culturali per
l’indipendenza personale e la responsabilità sociale.
Senza supporto continuativo i deficit adattivi limitano il funzionamento
in una o più attività della vita quotidiana, quali la comunicazione, la
partecipazione sociale e la vita indipendente, in più ambiti diversi,
come la casa, la scuola, il lavoro e la comunità.
C. Insorgenza dei deficit intellettivi e adattivi nell’età evolutiva.
APA. Diagnostic and Statistic Manual for Mental Disorders - %th edition, 2013

31. PROPOSAL OF LINEAR STRUCTURE FOR ICD-11
F: MENTAL AND BEHAVIOURAL DISORDERS (meta-structure)
F1: NEURO-DEVELOPMENTAL DISORDERS (meta-category)
F1.Y PROBLEM BEHAVIOURS/BEHAVIOUR DISORDER (category)
F1.Y.1 Mild and infrequent
F1.Y.2 Mild and frequent
F1.Y.3 Severe and infrequent
F1.Y.4 Severe and frequent
F1.Y.5 External boundary prevents expression of behaviour
objects)
Self-injury
F1.Y.8 Unspecified
F1.Y.1-8.1 Physical aggression to others
F1.Y.1-8.2 Verbal aggression (e.g. screaming)
F1.Y.1-8.3 Destructive to property (e.g. throwing/pulling
F1.Y.1-8.4
F1.Y.1-8.5 Oppositional
F1.Y.1-8.6 Overly-demanding
F1.Y.1-8.7 Sexually inappropriate (e.g. repeated
stripping)
F1.Y.1-8.8 Other
Can multiple sub-sub categories be specified or not? – alternative descriptors if not
WHO WG on ID for ICD-11. Proceedings of the fourth meeting, Buenos Aires 2011.

32. LIFE EVENTS AND PSYCHIATRIC
DISORDERS IN PwID
 Association between recent life events and traumatic
experiences across the life span and psychiatric disorders
in PwID more than in general population
 Transition phases and PDs
 Though they have been less studied by the literature
regarding predictors of mental illness, traumatic
experiences seem to play a more important role in
psychopathology than life events1
Martorell A., et al., 2009

33. A NEW CULTURAL MODEL FOR
NEURODEVELOPMENTAL DISORDERS / CONDITIONS
PSYCHO-CHARACTERISATION
SPECIF COGNITIVE FUNCTIONS
INDIVIDUAL SKILLS
INDIVIDUAL ATTRIBUTION OF IMPORTANCE
OFFER OF A WIDE RANGE OF OPPORTUNITIES
IMPROVEMENT OF THE INDIVIDUAL IMPORTANCE/SATISFACTION
INDIVIDUAL QoL
Bertelli et al. Advances in Mental Health and Intellectual Disabilities, in press

34. MARCO BERTELLI
MD, Psychiatrist, Psychotherapist
CREA (AMG Research and Evolution Centre) Scientific Director
Via del Sansovino, 176 - 50142 Firenze (Italy)
www.wpanet.org/spid
www.crea-amg.org
bertelli.fi@tiscali.it
mbertelli@crea-amg.org