Contemporany Treatment In Autism Spectrum Disorder

MINISTRY OF HEALTH OF THE REPUBLIC OF MOLDOVA

STATE MEDICAL AND PHARMACEUTICAL UNIVERSITY

“NIVOLAE TESTEMITANU”

FACULTY OF MEDICINE NR. II

Department of Psychiatry

Chief of the Department: Anatolie Nacu, MD, PhD, Professor

License Thesis

CONTEMPORANY TREATMENT IN AUTISM SPECTRUM DISORDER (review and analyses)

Scientific coordinator:

Jana CHIHAI, MD, PhD, associate professor

Abu Rumi Rani (Gr.M 1041)

Chisinau 2016

Verified:

Data__________________

Scientific Coordinator: dr. Chihai Jana, PhD, associate prof.

Semnătura ____________

“Recommended for approval”

At meeting od Psychiatry, Narcology, Medical Psychology Department

Protocol nr.____________from________________

Head of the Department prof. Anatol Nacu

ABSTRACT

The AUTISM is a concept describes impairments in social interaction and different kind and way of communication, restricted interests and repetitive behaviours, during the hall life. Around 70% of people with autism have a second diagnostic for at least one other psychiatric disorder that further impairs psychosocial functioning, like, attention deficit hyperactivity disorder (ADHD) or anxiety disorders. Intellectual disability
(IQ below 70) coexists in approximately 50% of children and young people with autism. Recent reviews estimate a global median prevalence of 62/10 000: one child in 160 has an ASD and subsequent disability.The treatment for ASD is very difficult and disputable. Psychosocial interventions are very effective, reduce core symptoms and improving adaptive skills and functioning are available, but all these intervention are very expensive and intensive. Increased evidence on affordable service delivery models and effective and scalable capacity building approaches are required. Young children receiving high-intensity applied behavior analysis (ABA)-based interventions over extended timeframes displayed improvement in cognitive functioning and language skills relative to community controls. Among the potential modifiers or moderators of early intensive ABA-based interventions, younger age at intake was associated with better outcomes for children in a limited number of studies. Evidence consistently showed that SGAs resulted in greater symptom improvement and a poorer safety profile than placebo. Evidence was sparse for several patient important outcomes, such as health-related quality of life, involvement with the legal system, and school performance. However, interventions mediated by parents and other non-specialist providers have the potential to significantly increase access to care

CONTENTS

ABSTRACT 3

INTRODUCTION 5

CHAPTER I. AUTISM SPECTRUM DISRDER: a literature review 9

1.1 Burden of mental health diseases in childhood and adolescent 9

1.2. Context and introduction and AUTISM SPECTRUM DISORDERS 12

1.3 Classification of Autism Spectrum Disorders: ICD-10 and DSM-IV-TR criteria 18

1.4 Evidence statements – risk factors of autism 25

1.5 Clinical signs and symptoms of autism according the age: warning signs. 26

CHAPTER II. STUDY DESIGN AND RESULTS 30

2.1. Methodology of the study 30

2.2. Procedure and instruments. 30

2.3. Study review 1: Therapies for Children With Autism Spectrum Disorder: Behavioral Interventions Update 32

2.4. Study review 2: Studies about early intensive behavioral and developmental interventions to people with ASD. 33

2.5. Study review 3: Studies that provide information about social skills of ASD people 34

2.6. Study review 4: Studies about Play-/Interaction-Focused intervention in ASD. 35

2.7. Study review 5: Studies of Interventions Targeting Conditions Commonly Associated With ASD 35

2.8. Conclusions for studies 1-5: 36

2.9. Study review 6: Use of first- (FGA) and second-generation antipsychotics (SGA) for children and young adults 37

GENERAL CONCLUSION AND RECOMANDATION: 40

REFERENCES 42

V. Annexes 45

INTRODUCTION

The magnitude of the burden of disease related to child and adolescent mental disorders is understood by clinicians and parents,
but has until recently been difficult to quantify. Now, with world-wide crises involving
children impacted by war, exploited for labor and sex, orphaned by AIDS, and forced
to migrate for economic and political reasons the dimensions of the burden of com-
promised mental health and mental disorders are increasingly evident and quantifiable. Pervasive (Autism) Development Disorder: Low incidence with high morbidity and need for intensive rehabilitative efforts involving many sectors including education, rehabilitation and social services. Poor occupational attainment has a great cost to families and societies dependent on cultural setting and community acceptance. Milder cases may first present as learning delays and less with problems in socialization. 


The term autism describes qualitative differences and impairments in reciprocal social interaction and social communication, combined with restricted interests and rigid and repetitive behaviours, often with a lifelong impact. In addition to these features, children and young people with autism frequently experience a range of cognitive, learning, language, medical, emotional and behavioural problems, including: a need for routine; difficulty in understanding other people, including their intentions, feelings and perspectives; sleeping and eating disturbances; and mental health problems such as anxiety, depression, problems with attention, self-injurious behaviour and other challenging, sometimes aggressive behaviour. These features may substantially impact on the quality of life of the individual, and their family or carer, and lead to social vulnerability. Autism spectrum disorders are diagnosed in children, young people and adults if these behaviours meet the criteria defined in the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) and have a significant impact on function.

Around 70% of people with autism also meet diagnostic criteria for at least one other (often unrecognised) psychiatric disorder that further impairs psychosocial functioning, for example, attention deficit hyperactivity disorder (ADHD) or anxiety disorders. Intellectual disability
(IQ below 70) coexists in approximately 50% of children and young people with autism. Recent reviews estimate a global median prevalence of 62/10 000: one child in 160 has an ASD and subsequent disability. This estimate represents an average figure, and reported prevalence varies substantially across studies.

Psycho-educational, developmental and behavioural interventions are the first interventions used for deficits in communication, social behaviour in ASDs, and nether less they provedsucces, they are very resource, financial and work intensive. However, emerging evidence shows that non-specialist providers in school and community settings can effectively deliver psychosocial interventions, including behaviour modification approaches and parent-mediated interventions, to children with ASDs and intellectual disability. Research understands the effective elements of interventions and allow the development of evidence-based, lower-cost treatments for people with ASDs. Innovative intervention processes in this field focus on changes to the person’s environment, schools, to enable functional or participation-based outcomes.

The goal and objectives of the study (systematical review)

This clinical review will focus in analyzing the different sources about types of approach in Autism Spectrum Disorders, especially in identification of the evidence-based treatment approach for Autism.

Objectives:

Literature review about child mental health problems and burden of mental illnesses in childhood worldwide;

To identify the risck fators and determinants leading ASD;

Identify different types of intervention: Pharmacological and non-pharmacological approach for ASD.

The study consists of review and study of different kind of sources, including Guidelines and research and study from medical sites. In review we included: 4 researches, 1 guidelines and 1 books.

In order to accomplish the goals and the objectives of the study, the following research methods and types of analysis were used:

Historical – review of the literature and theoretical synthesis;

Observation;

Empirical – research based on experience;

Sociological – questionnaire, survey and observation;

Comparison – comparison of data received from the research with previous studies in our country and abroad.

The stages of the study:

I stage:

September – October 2014 – review of the literature child mental health problems and burden of mental illnesses in childhood worldwide;

October -November 2014 – elaboration the concept and design of the study;

II stage:

January – September 2015 – Analysis of child mental health problems and burden of mental illnesses in childhood;

September – October 2015 – Selection of scientific methods of review;

November 2015- January 2016 – Identifying the medical sites and relevant researches, books and guidelines for review;

February – April 2016 – Processing the results obtained and drawing conclusions and recommendations.

The study consists of review of relevant sources from National Institute for Care and Excellence, PubMed.

Criteria for selection of respondents were:

Validated studies from PubMed.

The importance of the work is that causality of ASD, social, cultural and family risk factors and the importance of stress, poverty and urbanization was approached, as well as the social vices involved in the development of ASD.

Key words: autism, Autism Spectrum Disorders, developmental and behavioural interventions.

CHAPTER I. AUTISM SPECTRUM DISRDER: a literature review

1.1 Burden of mental health diseases in childhood and adolescent

The magnitude of the burden of disease related to child and adolescent mental disorders is understood by clinicians and parents,
but has until recently been difficult to quantify. Now, with world-wide crises involving
children impacted by war, exploited for labor and sex, orphaned by AIDS, and forced
to migrate for economic and political reasons the dimensions of the burden of com-
promised mental health and mental disorders are increasingly evident and quantifiable. It is estimated that in 26 African countries the number of children orphaned for
any reason will more than double by 2010
and 68% of these will be as a result of AIDS.
40 million children in 23 developing countries will lose one or both parents by 2010 (Foster, 2002).

Absence from education, underachievement leading to dependency, involvement in criminal activity, the use of illicit drugs, the inability to benefit from rehabilitation, co- morbid medical conditions are but some of the very many impacts that have an associated cost. The DALY calculation underrepresents disability caused by mental disorders in children and adolescents because childhood psychiatric disorders such as ADHD, conduct disorder, learning disorder, mood disorders, autism developmental disorders and mental retardation, among others, were not included (Fayyad, 2001).

Some highlights about ASD: in global context up to 20% of children and adolescents suffer from mental disabilities (WHR, 2000); suicide is the 3rd leading cause of death among adolescents (WHR 2001); Major depressive disorder often has an onset in adolescence, and is associated with substantial psycho- social impairment and risk of suicide (Weissman, 1999)

Some authors in researches demonstrated that the poor outcome of adolescent onset major depressive disorder. There was continuity and specificity related to the adolescent onset which continued into adulthood and was associated with high rates of suicide and suicide attempts, increased rates of psychiatric and medical hospitalizations, psychosocial impairment and lower educational achievement. An other research reported that children with early major depressive disorder had higher rates than a normal comparison group of bi-polar disorder, major depressive disorder, substance use disorders and suicidality.

Early childhood

• Learning disorders: high incidence and prevalence, with serious implications for future productivity. Treatment is limited and focused on education and school; the goal of treatment is to obtain occupational useful and authnomy. They may be associated with hyperkinetic disorders.

• Hyperkinetic disorders (ADHD): high incidence, greatly influenced by pharmaceutical awareness campaigns. Treatable at relatively low cost when the diagnosis is appropriately made. Long-term consequences relate to reports of poorer occupational attainment, and in- creased co-morbid psychiatric illness and substance use disorders.

Middle childhood

• Tics (Tourette’s syndrome). More recently diagnosed with an incidence and prevalence not previously appreciated. The disorder now appears to be treatable without highly specialized interventions. Untreated, this disorder has high degree of stigmatization, and social isolation.

Adolescence

• Depression and suicide. Depression is now recognized as a diagnosable disorder in children and adolescents. The magnitude of the association of depression and aggression with suicide open to confirmation on a general population but nevertheless have important clinical problems.

• Psychosis: early identification of psychotic conditions is important for good and effective interventions in First Psychotic episode. Psychoses can transform in a host of maladaptive behaviors.

In addition to the above noted disorders categorized by age, which could be appropriately managed at the PHC level, the following disorders should be considered for treatment at higher levels of complexity:

Autism Development Disorder has low incidence with high morbidity and need intensive rehabilitation involved a lot of domains such as education, rehabilitation and social services. Poor occupational therapies have a good cost to families and societies and depend on services and public acceptance. Milder cases may first present as learning delays and less with problems in socialization. 


Attachment disorders: big issue of infancy and have a major long-term impact, but appear can be modifiable with common early intervention programs. 


1.2. Context and introduction and AUTISM SPECTRUM DISORDERS

The term autism describes qualitative differences and impairments in reciprocal social interaction and social communication, combined with restricted interests and rigid and repetitive behaviours, often with a lifelong impact. In addition to these features, children and young people with autism frequently experience a range of cognitive, learning, language, medical, emotional and behavioural problems, including: a need for routine; difficulty in understanding other people, including their intentions, feelings and perspectives; sleeping and eating disturbances; and mental health problems such as anxiety, depression, problems with attention, self-injurious behaviour and other challenging, sometimes aggressive behaviour. These features may substantially impact on the quality of life of the individual, and their family or carer, and lead to social vulnerability.

The clinical picture of autism is variable and the differences depends of autism’s severity, the presence of coexisting conditions and levels of cognitive ability, from severe intellectual disability in some case to medium and light intelligence indicators (IQ) in others.

Autism spectrum disorders are diagnosed in:

children,

young people and

adults

Children with autism may have the following characteristics:

not respond to requests or adult's name (unless you "want " ) and apparently did not hear or understand what is required ;

Do not look where he looks and does not look at adult if he wants something from him ,

although it can tolerate other children around him , and can even be glad of their presence does not interact effectively with children

protest when asking him something and insist on receiving a response ;

The game is marked by a stereotyped character ( using objects or toys always the same, ie they close / open , knocking objects in certain places, we spins etc )

do not use objects in their usual order ( lick them , shake them , walk you fill bottles and empties them etc ) ;

sensory disturbances manifested sometimes shows the need to touch anything, to lick , to touch, and other times by refusing to come into contact with certain textures , sample some food

• may have stereotyped behaviors : strings and align objects, spinning or waving your hands or small objects etc ..

may have trouble eating and sleeping problems ;

• unwilling or unable to use words meaningful communication ;

goes peaks , often has bizarre movements have hands and body ;

ecolalia (repeat the sounds and words etc).

Children with autism introduced a program of intensive therapy before the age of three years has a good chance to recover delays in development and to form skills, social behaviors.

Research has shown that up to 49 % of children enrolled in early intervention and intensive programs ( between 15 and 40 hours per week ) get to be independent and make remarkable progress.

The ADS diagnostics can be establish in case their behaviours meet the criteria defined in the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) and have a significant impact on function. Both these diagnostic classification systems use the term 'pervasive developmental disorder', which encompasses autism, Asperger's syndrome and atypical autism (or 'pervasive developmental disorder not otherwise specified'). For a diagnosis of autism to be made, there must be impairments present and an impact on the person's adaptive function. Both classification systems are undergoing revision and have announced that the term 'autism spectrum disorder' will be used in future editions.

Although autism was once thought to be an uncommon developmental disorder, recent studies have reported prevalence rates of at least 1% in children and young people. Autism is diagnosed more frequently in boys. The core autism behaviours are typically present in early childhood, although some features may not manifest until a change of situation, for example, the start of nursery or school or, less commonly, the transition to secondary school. Regression or stasis of language and social behaviour is reported for at least a third of children with autism. This usually, but not exclusively, occurs between the ages of 1 and 2 years, and the reasons for regression and stasis are unknown. The way in which autism is expressed will differ across different ages and therefore for any individual may change over time as they mature, in response to environmental demands, in response to interventions, and in the context of coexisting conditions.

Around 70% of people with autism also meet diagnostic criteria for at least one other (often unrecognised) psychiatric disorder that further impairs psychosocial functioning, for example, attention deficit hyperactivity disorder (ADHD) or anxiety disorders. Intellectual disability
(IQ below 70) coexists in approximately 50% of children and young people with autism.

There are many claims of a 'cure' for autism, all of which are without foundation. However, there are interventions that can help some of the core features of autism, some of the symptoms, behaviours and problems commonly associated with autism, and support families and carers. There is also evidence for treatment strategies to reduce behaviour that challenges. NICE guideline will summarise the different ways that health and social care professionals can provide support, treatment and help for children and young people with autism, and their families and carers, from the early years through to their transition into young adult life.

I authorize international sources a global prevalence is 62/10 000: one child in 160 has an ASD and subsequent disability. This estimate represents an average figure, and reported prevalence varies substantially across studies. Some well-controlled studies have, however, reported rates that are substantially higher.

Autism is a profound pervasive developmental disorder which etiology is still unknown. Autism symptoms become apparent in the first 3 years of children`s life and has different clinical aspects.

It affects the normal evolution of the child, mostly three areas of child development which are:

• Social communication: verbal and non-verbal communication difficulties.

• Social interaction: difficulties in establishing relationships with peers. Children seem indifferent to others, they prefer to isolate themselves from others, because they do not know how to communicate with them.

• Restrictive, repetitive and stereotyped behavior, interests and activities: poor imagination referring to symbolic games and restricted repertoire of interests and behaviors

People with autism may present a series of behavioral symptoms including hyperactivity, hyper- or hiposensibility to sounds, light, pain, touches, smells, as well as a reduced attention. Often children with autism have different behaviors in excess such as: autostimulation, self-harming, aggression, hyperkinetism, obsessive and stereotyped behavior.

Many children with autism have abnormal eating behavior (a selective diet or consumption of inedible products), sleeping disorders, abnormalities of mood or emotional ones (laughing or crying without an obvious reason).

Autism doesn`t mean:

• a mental illness

• a contagious disease

• a refusal to communicate

• a consequence of education

• curable in any way

Autism represents:

• a developmental disorder that affects three areas: communication, socialization and imagination

• a lifelong disorder

Information about ASD needs and services are rarely collected correctly at a country level, hampering efforts to describe the quality and equity of available care; monitor changes in the health status of populations and groups; evaluate the impact of social policies; and establish approaches to quality improvement. Without such information it is all too easy for the health needs of people with developmental disorders and their families to be ignored. The WHO Executive Board resolution on Comprehensive and coordinated efforts for the management of ASD, the WHO World Health Assembly Resolution on The global burden of mental disorders and the need for a comprehensive, coordinated response from health and social sectors at the country level, and the WHO European Declaration and Action Plan on the Health of children and young people with intellectual disabilities and their families all urge countries to improve surveillance frameworks and information systems to better capture data on ASDs, intellectual disability (ID) and other developmental disorders.

Psycho-educational, developmental and behavioural interventions are the primary interventions used to address the core deficits in communication, social behaviour and behavioural flexibility in ASDs, and while they have demonstrated efficacy, they are very resource and labour intensive. However, emerging evidence shows that non-specialist providers in school and community settings can effectively deliver psychosocial interventions, including behaviour modification approaches and parent-mediated interventions, to children with ASDs and intellectual disability. Research that enables a better understanding of the effective elements of interventions may allow for the development of evidence-based, lower-cost treatments for people with ASDs. Innovative intervention processes are beginning to emerge in this field that focus on making changes to the person’s environment, including schools, (rather than changing the person’s abilities) to enable functional or participation-based outcomes.

Inadequate availability and/or inequity in distribution of mental health and child health specialists and their insufficient knowledge and skills to manage ASDs and developmental disorders in general, are recognized among the major barriers to improving access to care in high-income as well as low- and middle-income countries. However, evaluation of training approaches and e-health and m-health approaches have received little attention in autism research. Furthermore, much of the research on ASDs and developmental disorders focuses on children and it will be important to adopt a research agenda that takes a full life-course perspective and is inclusive of both adults with developmental disorders and caregivers/families.

Increasing efforts are being made to facilitate the production of policy-relevant evidence and its uptake by policy-makers and advocates. With the expansion of research in low-resource settings, it is crucial that such research is locally relevant, and that local communities are actively engaged, including people with ASDs and their families. Models of co-research now exist that enable the active participation of people with autism and other mental disorders in the research process and dissemination of findings.

1.3 Classification of Autism Spectrum Disorders: ICD-10 and DSM-IV-TR criteria

The autism spectrum describes a pattern of behaviour characterised by qualitative differences and impairments in social interaction and communication, together with restricted interests and rigid/repetitive behaviours in children, young people and adults. This is a lifelong condition that can have a profound impact on the child or young person and their family. Co-occurrence with other conditions is common, causing variable impact on the individual across time and in different contexts and an adverse impact on adaptive function. The word „spectrum‟ implies a range of behaviours manifest in various combinations and levels of severity.

Diagnosis is the decision-making process that determines if an individual has a disorder or not. ‟Disorder„ is not an exact term, but it is used here (as in the International Statistical Classification of Diseases and Related Health Problems [ICD-10]) to imply the existence of a clinically recognizable set of symptoms or behaviours associated with distress and with interference with personal functions. Any clinical diagnosis is based on internationally accepted diagnostic criteria described in ICD-10 and the Diagnostic and Statistical Manual of Mental Disorders DSM-IV Fourth Edition (Text Revision) (DSM-IV-TR). Both of these publications use the category „pervasive developmental disorder (PDD)‟ to group together diagnoses relating to conditions of the autism spectrum. The terms pervasive developmental disorder and autism spectrum disorder are regarded as conveying the same meaning.

In ICD-10 we have next diagnostics:

childhood autism

atypical autism
Asperger‟s syndrome


other childhood disintegrative disorder
overactive disorder associated with mental retardation and stereotyped movements other pervasive mental disorders and pervasive developmental disorder,

unspecified Rett syndrome.

In DSM-IV-TR we have next diagnostics:

autistic disorder

Asperger's disorder
pervasive developmental disorder not otherwise specified (including atypical autism)

childhood disintegrative disorder


Rett disorder.

When autism is diagnosed, families and careers live terrible emotions, shock, sadness and concern about the implications of diagnosis for the future, as well a profound sense of relief that others agree with their observations and concerns. At best, diagnosis and the assessment of needs can offer an understanding of why a child or young person is different from their peers. It can open doors to support and services in education, health services and social care, and a route into voluntary organisations and contact with other children and families with similar life experiences.

The following characteristics can be specific to a child with autism:

• lack of response to adult requests or calls (except the case the child with autism wants it)

• also there is an image of not hearing or understanding what is required to the child;

• lack of visual contact when it is shown something to the child or when the child is asking the adult for something,

• the interaction with peers is not effective although the child with autism can tolerate thei presence near him or even be glad they are nearby,

• protests occuring when being asked to do something or one insist on receiving a response from him/her;

• the game presents a stereotyped character (using objects or toys always the same way, for example: closes / opens them, knocks the objects in certain places, spins them, etc.), or is not attracted by the toys rather likes to play with empty bottles, strings, plastic bags etc.;

• the objects are not used in their usual way (they are licked, shaken, fill and empty bottles, etc.);

• presence of sensory disturbances sometimes manifested by the need to achieve anything, to lick, to touch, or refusing to come into contact with certain textures, to taste certain food, etc.;

• presence of stereotyped behaviors: puts in series and align objects, spinning or waving hands or small objects, etc.

• trouble eating and sleeping problems;

• refusal or incapacity of using words for communication purpose;

• “toe” walk, or bizarre movements of the body or hands;

• Echolalia (endlessly repeat sounds, words, commercials, etc.).

An autistic child involved into an intensive therapy program before the age of 3 has a very good chance to catch up in development and build his/her social skills and appropriate behavior.

ABA (applied behavioral therapy) is proven to be the most effective in the recovery of children with autism.

Research has shown that up to 49% of children enrolled in early and intensive intervention programs and intensive (15 – 40 hours weekly) have the chance to become independent and make good progress.

The causes of autism

Autism has no single, known cause. Given the complexity of the condition, and the fact that symptoms and severity vary, there are probably many causes. Both genetics and environment may play a role. There is no evidence that autism is caused by a child’s upbringing or social circumstances.

Sometimes we observe:

Autism linked to vaccines

Genetic causes

Environmental causes

Autism and vaccines: No proven link between vaccines and autism:

One of the greatest controversies in autism is centered on whether a link exists between autism and certain childhood vaccines, particularly the measles-mumps-rubella (MMR) vaccine. Despite extensive research, no reliable study has shown a link between autism and the MMR vaccine

Genetic factors: Several genes appear to be involved in autism. Some may make a child more susceptible to the condition. Others affect brain development or the way that brain cells communicate. Still others may determine the severity of symptoms. Each problem in genes may account for a small number of cases, but taken together, the influence of genes is likely substantial. Some genetic problems seem to be inherited, while others happen spontaneously.

Environmental factors: Researchers are currently exploring whether such factors as viral infections, complications during pregnancy and air pollutants play a role in triggering autism.

A number of medical conditions are associated with increased risk of autism. Autism is strongly associated with a number of coexisting conditions which have an impact on the wellbeing of the child or young person and their family. Recent studies have shown that approximately 70% of individuals with autism also meet diagnostic criteria for at least one other (often unrecognised) mental and behavioural disorder that is further impairing psychosocial functioning. Intellectual disability (intelligence quotient [IQ] less than 70) co-occurs in approximately 50% of young people with autism.

Manifestations of autism are due to both delay in and disorder of typical development and the presence of unusual features of development affecting behaviours in the following areas:

social and communicative reciprocity – in both initiation of and responsiveness to interpersonal verbal and non-verbal communication and social interaction

the ability to infer what another person is intending, experiencing or thinking creative, imaginative social play and thinking
cognitive and behavioural flexibility
the range and intensity of interests and activities

sensory interests and sensitivities
emotional reactions to the environment
self absorption in repetitive behaviours and stereotyped mannerisms motor coordination competences.

The autism spectrum is a range of behaviours that are heterogeneous both in causation and manifestation. Once thought of as a categorical disorder, so that an individual either definitely did or did not have autism, the concept of continuously distributed traits with no clear diagnostic boundary is a challenge when it comes to deciding the „threshold‟ for a definite disorder and hence the diagnosis of a disorder. Strengths and weaknesses in the core autistic behaviours of reciprocal social communication skills and rigidity of thinking are now thought to be distributed throughout the general population as traits and found in approximately 5% of the population. Intellectual disability, severe language impairments and stereotypes are absent and although features of the broader autism phenotype are evident in early childhood, any impairment may become more manifest over time. Thus, during diagnostic assessment, an individual may be found to have qualitatively similar traits to those of autism but be below the threshold („subthreshold‟) for a diagnosis of disorder. In such cases, the individual and/or family may still find the information about autism helpful. That individual may or may not have „needs‟ which will be identified during the „profiling assessment‟ and support similar to that provided for autism may be helpful.

Evidence statement: stability of ICD-10 and DSM-IV-TR criteria

The evidence for all age groups was very low quality.

Children aged under 24 months at first diagnostic assessment using ICD-10/DSM-IV-TR

All children, except a single case (1%), diagnosed as having autism based on ICD-10/DSM-IV-TR retained that initial diagnosis at the second assessment at least 12 months later.

All children diagnosed as having another ASD based on ICD-10/DSM-IV-TR retained that initial diagnosis at the second assessment at least 12 months later.

However, of children under 24 months who were thought not to have any ASD, 41% were found to have an ASD at the second assessment at least 12 months later.

Children aged 25 to 36 months at first diagnostic assessment using ICD-10/DSM-IV-TR

The majority of children (95%) diagnosed as having autism based on ICD-10/DSM-IV-TR retained that initial diagnosis at the second assessment at least 12 months later.

The majority of children (84%) diagnosed as having another ASD based on ICD-10/DSM-IV-TR retained that initial diagnosis at the second assessment at least 12 months later.

No child thought not to have an ASD was found to have ASD at the second assessment at least 12 months later.

Children aged 37 to 48 months at first diagnostic assessment using ICD-10/DSM-IV-TR

No studies were identified for this analysis.

Children aged 49 to 60 months at first diagnostic assessment using ICD-10/DSM-IV-TR

No studies were identified for this analysis.

1.4 Evidence statements – risk factors of autism

Low quality evidence demonstrated the following risk factors for autism or ASD to be clinically and statistically important:

sibling history of autism


sibling history of another ASD


parental history of schizophrenia-like

psychosis
parental history of affective disorder


parental history of another mental and behavioural disorders

maternal age older than 40 years


paternal age between 40 and 49 years (ASD)


paternal age older than 40 years (autism)


birthweight less than 2500 g


prematurity under 35 weeks
admission to a neonatal intensive care

unit
presence of birth defects
presence of multiple birth defects
male gender
threatened abortion at less than 20 weeks
residing in a capital city
residing in suburb of a capital city.

Overview of the evidence: conditions with an increase risk of ASD

The GDG selected the following conditions they considered in clinical practice to have a higher than normal prevalence of ASD and these conditions were included in the review.

intellectual disability,


fragile X


tuberous

sclerosis
neonatal encephalopathy / epileptic encephalopathy (including infantile spasms)

cerebral palsy

Down‟s syndrome

muscular dystrophy neurofibromatosis


fetal alcohol syndrome.

1.5 Clinical signs and symptoms of autism according the age: warning signs.

Child behaviors are those that announce the presence of the disease and parents are usually the ones who experiences anything unusual . In some cases , the baby seems different from birth , does not observe those around them, focus on an object for a long time , it is very quiet and very plaintive .

Signs that occur in a first year :

• does not return when he hears his mother's voice

• has low visual contact

• no finger-pointing

• does not smile

Signs appear at the age of two years :

• not say a word up to 16 months

• knows how to play with toys

• do not combine words until age 2

loses language skills

• it is not interesting when adults them pointing objects

Signs appearing to 3 years:

Has repetitive activities / stereotypical ( repeated opening and closing doors , rotating on its axis , waving hands and watching etc. )

Avoid touching and eye contact

repeat words or phrases

attaches a particular toy or object

goes peaks

Poor coordination

Pre-school (5 years or under)

Of all the signs and/or symptoms examined for this age group, only the combination of „declarative pointing, gaze monitoring, pretend play‟ met the pre-defined levels of diagnostic. The evidence was of very low quality.

Primary school (6–11 years)

Of all the signs and/or symptoms examined for this age group, only „no social play‟ and „doesn’t sustain conversation with others‟ met the pre-defined levels of diagnostic accuracy. The evidence was of very low quality.

ASD children and adolescents in school (primary or secondary school)

Of all the signs and/or symptoms examined for this age group, only „repetitive talk about one topic‟ met the pre-defined levels of diagnostic accuracy. The evidence was of very low quality.

Social interaction and reciprocal communication behaviours:

Spoken language: In thus field we have some language trouble; unused or less use of speech. Unusual spoken language may include vocalizations without speech, odd or flat intonation, frequent repetition of set words and phrases ('echolalia'), reference to self by name or 'you' or 'she/he' beyond 3 years, use only single words although able to speak in sentences like communication.

Interaction’s field: difficulties in personal space, namely when people pas they space; social interest are reducing or absent, they don’t have any relations with children of his/her own age; aggressive or disruptive emotions; dicreas imitation of others' actions; the child plays independently, they don’t initiate the social play with others; they don’t enjoy the situations that most children like, for example, birthday parties; they don’t share the pleasures.

Gesture, eye contact and others: Reduced or absent use of gestures and facial expressions to communicate (although may place adult's hand on objects), reduction of gestures and facial expressions poor integration, body orientation , eye contact.

When we discus about “Ideas and imagination” this is about reduce or luck of imagination.

The children are unusual or restricted interests and/or rigid and repetitive behaviours: they have repetitive 'stereotypical' movements – hand flapping, body rocking while standing, spinning, finger flicking, they do the repetitive and stereotyped play, for example opening and closing doors, they have unusual interests to different objects and situations, excessive insistence on following own agenda, they do an emotional reactivity to change or new situations, insistence on things being 'the same'. The children with ASD have over or under reaction to sensory stimuli, for example textures, sounds, smells.

Spoken language: may be unusual in several ways:
limited use language, monotonous tone, repetitive speech, frequent use of stereotyped (learnt) phrases, content dominated by excessive information on topics of own interest, talking at others rather than sharing a two-way conversation, responses to others can seem rude or inappropriate.

The of responding to others are: reduced or absent response to other people's facial expression or feelings; diminished or luck of response to name being called, despite normal hearing; subtle difficulties in understanding other's intentions; may take things literally and misunderstand sarcasm or metaphor; negative response to the requests of others.

Interacting with others: the children are reducing or absent of awareness of personal space, or unusually intolerant of people entering their personal space. The don’t have or have a reduced social interest in people, especially about children of his/her own age – may reject others. If the children are interested in others, they may approach others inappropriately, seeming to be aggressive or disruptive.

CHAPTER II. STUDY DESIGN AND RESULTS

2.1. Methodology of the study

The goal and objectives of the study

This clinical review will focus in analyzing the different sources about types of approach in Autism Spectrum Disorders, especially in identification of the evidence-based treatment approach for Autism.

Objectives:

Literature review about child mental health problems and burden of mental illnesses in childhood worldwide;

To identify the risck fators and determinants leading ASD;

Identify different types of intervention: Pharmacological and non-pharmacological approach for ASD.

The study consists of review and study of different kind of sources, including Guidelines and research and study from medical sites. In review we included: 4 researches, 1 guidelines and 1 books.

2.2. Procedure and instruments.

In order to accomplish the goals and the objectives of the study, the following research methods and types of analysis were used:

Historical – review of the literature and theoretical synthesis;

Observation;

Empirical – research based on experience;

Sociological – questionnaire, survey and observation;

Comparison – comparison of data received from the research with previous studies in our country and abroad.

The stages of the study:

I stage:

September – October 2014 – review of the literature child mental health problems and burden of mental illnesses in childhood worldwide;

October -November 2014 – elaboration the concept and design of the study;

II stage:

January – September 2015 – Analysis of child mental health problems and burden of mental illnesses in childhood;

September – October 2015 – Selection of scientific methods of review;

November 2015- January 2016 – Identifying the medical sites and relevant researches, books and guidelines for review;

February – April 2016 – Processing the results obtained and drawing conclusions and recommendations.

The study consists of review of relevant sources from National Institute for Care and Excellence, pubmed.

Criteria for selection of respondents were:

Validated studies from pubmed.

The importance of the work is that causality of ASD, social, cultural and family risk factors and the importance of stress, poverty and urbanization was approached, as well as the social vices involved in the development of ASD.

2.3. Study review 1: Therapies for Children With Autism Spectrum Disorder: Behavioral Interventions Update

In this research, namely systematic review, highlight behavioral intervention and generally multitude of therapies for children with ASD published in 2011. Categories of interventions in ASD to overlap substantially, and this imposes difficulties in identification , namely the category should be placed intervention. Ultimately, we defined behavioral interventions to include early intensive behavioral and developmental interventions, social skills interventions, play/interaction-focused approaches, interventions targeting symptoms commonly associated with ASD, and other general psychosocial approaches. All this behavioral interventions do not include primarily medical interventions, complementary and alternative interventions, allied health interventions, or educationally focused interventions unless a behavioral intervention representative of the operationalization above was included within the study design.

At the time of the 2011 review, the results and strength of the evidence is considered low for the effectiveness of early intensive behavioral and developmental interventions. Positive outcomes from an early and intensive behavioral and developmental intervention were noted in the next performances: cognitive field, language skills, adaptive behavior. All these performances was delivered over substantial intervals of time (i.e., 1–2 years). Variability in response to such approaches was tremendous, with subgroups of children who demonstrated a more modest response. The ability to describe and predict these subgroups was limited.

Some other behavioral interventions with different scope, target, and intensity had demonstrated effects, but the lack of consistent data limited understanding of whether these interventions were linked to specific clinically changes in functioning. Information was about lacking on modifiers of effectiveness, generalization of effects, treatment context, components of multicomponent therapies that do the effectiveness, and predictors of treatment success.

2.4. Study review 2: Studies about early intensive behavioral and developmental interventions to people with ASD.

In this subchapter I tried to find the systematical review about early behavior interventions and we found one paper that list 37 papers that comprise 25 studies about early intensive behavioral and developmental interventions. The studies included: 5 Randomized Control Trials with very good quality, six of fair quality, and one of poor quality. Individual studies that were put on the paper were: University of California, Los Angeles (UCLA)/Lovaas-based interventions, the Early Start Denver Model (ESDM), the Learning Experiences and Alternate Program for Preschoolers and their Parents (LEAP) program, and eclectic variants reported improvements in outcomes for young children. In all studies were described about improvements in cognitive abilities and language acquisition, with less robust and consistent improvements seen in adaptive skills, core ASD symptom severity, and social functioning.

Young children receiving high-intensity applied behavior analysis (ABA)-based interventions – 8 months–2 years, displayed improvement in cognitive functioning and language skills relative to community controls. Nevertheless, the importance of effects varied across studies. This variation may reflect subgroups showing differential responses to particular interventions. Intervention response is likely moderated by both treatment and child factors, but exactly how these moderators function is not clear. Despite multiple studies of early intensive treatments, intervention approaches are vary substantially, which makes it difficult to tease apart what these unique treatment and child factors may be.

2.5. Study review 3: Studies that provide information about social skills of ASD people

13 studies addressing interventions targeting social skills, including 11 RCTs. The overall quality of studies improved in comparison with the previous review, with 2 good-quality and 10 fair-quality studies. Social skills interventions varied widely in terms of scope and intensity. Other studies incorporated peer-mediated and/or group-based approaches, and still others described interventions that focused on emotion identification and Theory of Mind training. The studies also varied in intensity, with most interventions consisting of 1–2 hour sessions/week lasting approximately 4–5 weeks. However, some of the group-based approaches lasted 15–16 weeks.

Most studies reported short-term gains in either parent-rated social skills or directly tested emotion recognition. However, our confidence (strength of evidence) in that effect is low. Although we now have higher quality studies of social skills interventions that demonstrate positive effects, our ability to determine effectiveness continues to be limited by the diversity of the intervention protocols and measurement tools. Studies also included only participants considered “high functioning” and/or with IQ test scores >70, thus limiting generalization of results to children with more significant impairments. Maintenance and generalization of these skills beyond the intervention setting are also inconsistent, with parent and clinician raters noting variability in performance across environments.

2.6. Study review 4: Studies about Play-/Interaction-Focused intervention in ASD.

We found different papers about studies of well-controlled joint attention interventions across a range of intervention settings. This showed evidence base includes 11 Randomized Control Trials of good and fair quality and suggests that joint attention interventions may be associated with positive outcomes for toddler and preschool children with ASD, particularly when targeting joint attention skills themselves as well as related social communication and language skills.

Specific training that used naturalistic approaches to promote imitation (e.g., Reciprocal Imitation Training) was associated with some improvements, not only in imitation skills, but also potentially in other social communication skills (such as joint attention). Additionally, parent training in a variety of play-based interventions was associated with enhanced early social communication skills (e.g., joint attention, engagement, play interactions), play skills, and early language skills.

2.7. Study review 5: Studies of Interventions Targeting Conditions Commonly Associated With ASD

For this study review we found six Randomized Clinical Trials of interventions about conditions associated with ASD identified for the current update measured anxiety symptoms as a primary outcome. Five of these studies reported significant and good improvements in anxiety symptoms in the intervention group. Two found positive effects of cognitive behavioral therapy (CBT) on the core ASD symptom of socialization, and one reported improvements in executive function in the treatment group. The one RCT that did not find a significant benefit of CBT compared it with social recreational therapy rather than with treatment as usual or a wait-listed control group.

Studies have shown the effects of CBT on anxiety and methodologies applied. Six studies provided data tracking treatment effects. On the strength of the nature of CBT, which is often language intensive and requires a certain level of thinking skills to make abstract connections between concepts, most studies included only children with IQs more than 70. These studies report positive results regarding the use of CBT to treat anxiety in children with ASD.

Additional data in the current review relate to training and information, namely parent training to address challenging behavior. In one study we sow the combination of a parent-training approach with risperidone. This combination significantly reduced irritability, stereotypical behaviors, and hyperactivity, and improved socialization and communication skills. However, these effects were not maintained at 1 year after treatment.

2.8. Conclusions for studies 1-5:

A. Different Modifiers of Treatment outcomes

Among the potential modifiers in ABA intervention is intensive early start, younger age at admission, but in a limited number of studies. Good cognitive skills and higher adaptive behavior scores were associated with better results across behavioral interventions, but, these associations were not important very well. In general, children with lower symptom severity or less severe diagnoses improved more than participants with greater impairments.

B. Treatment effects that predict long-term results

We didn’t find a lot of studies that assess end-of-treatment effects that may predict results. Several early intensive behavioral and developmental interventions are associated with changes in outcome measures over the course of very lengthy treatments, but such outcomes usually have not been assessed beyond treatment.

C. Uniqueness of treatment results

The majority of the social skills and behavioral intervention studies show us the association’s conditions to collect results based on parent, self, teacher, and peer report of targeted symptoms (e.g., anxiety, externalizing behaviors, social skills, peer relations) at home, at school, and in the community.

D. Treatment approaches for children till age 2 with risk for diagnosis of ASD

In the studies that discus about interventions for younger children, children who received behavioral interventions seemed to improve regardless of intervention type. None of the fair- or good-quality studies compared treatment groups with a no-treatment control group. Potential modifiers of treatment efficacy include baseline levels of object interest. Most measures of results of adaptive functioning were based on parent report.

2.9. Study review 6: Use of first- (FGA) and second-generation antipsychotics (SGA) for children and young adults

Eleven RCTs and one retrospective cohort study examined the effectiveness of FGAs and SGAs in treating patients with pervasive developmental disorders. The majority of the studies reported both symptom improvement and other short- and long-term outcomes, with four exceptions: three RCTs reported only symptom improvement, and one retrospective cohort study reported only other outcomes. The studies are grouped according to the drug class comparisons. Studies that include both head-to-head and placebo comparisons are listed under the head-to-head category.

The overall of the average age of respondents was 8.3 years. Patients were in majority male (79 %). A diagnosis of pervasive developmental disorder was based on the Diagnostic and Statistical Manual of Mental Disorders. All studies included patients with autistic disorder. In five studies we find the patients with different ASD, including Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified.

Three studies provided evidence for comparisons of a FGA (haloperidol) with SGAs (olanzapine and risperidone). One Randomized Clinical Trial compared the effectiveness of continuous versus discontinuous administration of haloperidol. Most of the studies compared a SGA, usually risperidone, with placebo.

Haloperidoli versus risperidoni (one RCT): Patients on risperidone had a significantly greater reduction in the Aberrant Behavior Checklist (ABC) at 12 weeks and greater improvement on the Clinical Global Impressions (CGI) scale and language at 24 weeks than patients on haloperidol.

Haloperidoli –continuous versus discontinuous (5 days on haloperidol with 2 days on placebo): There was no significant difference in Clinical Global Impressions of Improvement (CGI–I) between the administration schedules.

Aripiprazole – dosing (one RCT): High-dose (15 mg/day) aripiprazole resulted in significantly greater improvement in the ABC lethargy/social withdrawal subscale than medium-dose (10 mg/day) aripiprazole.

An other study was about FGAs sersus SGAs. We found two randomized clinical trials about haloperidol versus olanzapine. First study: A 6-week RCT compared haloperidoli (about 1,5 mg) with olanzapine (about 8 mg) in children ages 5 to 17 years. Patients on olanzapine showed significantly greater improvement on the Children's Psychiatric Rating Scale (CPRS) anger and hyperactivity subscales. Clinical Global Impressions of Severity (CGI–S) and other CPRS subscales did not significantly differ between groups.

Second study: Haloperidol Versus Risperidone A 12-week RCT with a 12-week extension assessed the comparative effectiveness of haloperidoli (2,6 mg/day) and risperidone (3 mg/day) in children ages 8 to 18 years. Risperidone led to significantly greater improvement in ABC scores at 12 weeks, CGI scores at 24 weeks, and the language subscale of the Ritvo -Freeman Real Life Rating Score at 24 weeks.

GENERAL CONCLUSION AND RECOMANDATION:

Much of the knowledge on ASDs and other developmental disorders is based on research conducted in high- income countries.

An important source of information in countries is represented by surveillance systems and information systems. They should capture data on ASDs and other developmental disorders.

Psychosocial interventions that are effective in reducing core symptoms and improving adaptive skills and functioning are available, but they are very resource intensive.

Interventions mediated by parents and other non-specialist providers have the potential to significantly increase access to care.

Local communities, including people with developmental disorders and their families, should take active roles in the research process and dissemination of findings.

A growing evidence base suggests that behavioral interventions can be associated with positive outcomes for children with ASD.

Young children receiving high-intensity applied behavior analysis (ABA)-based interventions over extended timeframes (i.e., 8 months–2 years) displayed improvement in cognitive functioning and language skills relative to community controls.

The efficacy and safety of FGAs and SGAs have been studied in children, adolescents, and young adults for the following conditions: pervasive developmental disorders, ADHD and disruptive behavior disorders, bipolar disorder, schizophrenia, Tourette syndrome, and behavioral problems. Overall, data for head-to-head comparisons (FGAs vs. SGAs, FGAs vs. FGAs, and SGAs vs. SGAs) were generally of low strength of evidence; therefore, few conclusions regarding the relative efficacy and safety of antipsychotics could be drawn.

However, evidence consistently showed that SGAs resulted in greater symptom improvement and a poorer safety profile than placebo.

Children with autism introduced a program of intensive therapy before the age of three years has a good chance to recover delays in development and to form skills, social behaviors.

Up to 49 % of children enrolled in early intervention and intensive programs ( between 15 and 40 hours per week ) get to be independent and make remarkable progress.

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V. Annexes

Annex nr. 1:

TOOLS used in ASD – Sensitivity and specificity of tools to identify an increased likelihood of ASD

Autism – Tics, ADHD and other coexisting conditions (ATAC)


Baby and Infant Screen for Children with Autism Traits (BISCUIT)


Brief Infant-Toddler Social and Emotional Assessment (BITSEA)


Childhood Asperger Syndrome Test (CAST)


Children‟s Communication Checklist (CCC)


Infant/Toddler Checklist of Communication and Language Development (CHECKLIST)

Child Symptom Inventory – 4 (CSI-4)


Early Childhood Inventory – 4 (ECI-4)


Early Screening of Autistic Traits (ESAT)

questionnaire
Early Social Communication Scale (ESCS)


Gilliam Asperger‟s Disorder Scale (GADS)


Infant/Toddlers Checklist (ITC)


Krug Asperger‟s Disorder Index (KADI)


MacArthur Communicative Development Inventories (MCDI)


Parental Concerns Questionnaire (PCQ)


Scale of Pervasive Developmental Disorder in Mentally Retarded Persons (PDD-MRS)

Pervasive Developmental Disorder Rating Scale (PDDRS)


Pervasive Developmental Disorder Screening Test (PDDST)


Repetitive Behavior Scale (RBS)


Screen for Social Intervention (SSI)


Strengths and Difficulties Questionnaire (SDQ)


Social Responsiveness Scale (SRS)


Screening Tool for Autism in Two-year-olds (STAT)


Young Autism and other developmental disorders Checkup Tool (YACHT-18).

Declaration

I hereby declare that the diploma paper entitled ” CONTEMPORANY TREATMENT IN AUTISM SPECTRUM DISORDER (systematical review)” It is written by me and never ever submitted to another university or higher education institution in the country or abroad. Also that all sources used, including those on the Internet, they are stated in the paper with the rules to avoid plagiarism:

all text fragments reproduced exactly, even in his own translation of other languages are in quotation marks and have detailed reference source ; 


reformulation of texts written in their own words by other authors hold detailed reference;


summarizing the ideas of other authors hold detailed reference to the original. 


Data

Student: ABU RUMI RANI ________________ (signature)