EARLY ONSET NEURODEVELOPMENTAL DISORDERS
INTRODUCTION LECTURE – Corina Greven & Emma Sprooten
Educational aims
• Describe the clinical features of neurodevelopmental disorders such as ADHD, ASD and
intellectual disability and their comorbidity.
• Understand the neural correlates of early onset neurodevelopmental disorders.
• Understand the contribution of genetic and environmental factors to neurodevelopmental
disorders (at levels of molecular genetics, epigenetics, imaging genetics, early environmental risk
factors)
• Understand concepts and research literature on animal models on neurodevelopmental
disorders.
Overview course
• Final exam 80%
o Lecture contents are central
o Factsheet contains essential readings (exam questions can be based on them)
• Presentation 20%: 20 min + 10 min discussion in groups of ca 4-5 students
o Main message
o Formulate key TRUE/FALSE statement (not a simple fact, possible to argue pros and cons)
o Include 1-2 slides with a take-home message
o Structure as in a papier: background/intro, methods, results, discussion: limitations/future
directions, conclusions
Genetics
Heritability -> studying genetics can give us insights into biological mechanisms underlying individual
differences.
Neurodevelopmental disorders
• No universal definition, but broader definitions:
o Wide range of neurological and psychiatric problems… involving some form of disruption to
brain development
o Include rare genetics syndromes, schizophrenia, epilepsy, cerebral palsy, disruptive
behaviour disorders
• DSM-5 is a classification system that specifies which criteria apply to a particular
neurodevelopmental disorder, such as ADHD, ASD, intellectual disability, communication
disorders, specific learning disorders, motor disorders
• Defining characteristics (not universal or strict):
o Typical onset before puberty
o Clinical course steady in long term, rather than remitting/relapsing
o Early onset neurocognitive deficits
o More prevalent in males
o High heritability, aetiology multifactorial
o High level of overlap
Grouping of these disorders is clinically useful
• Symptoms and problems overlap
• Assessment and treatment require specialists from a range of disciplines
,• Children different care and expertise than adults (e.g. communication, legal issues, parents and
school involvement)
o Same experts can treat and care for children with different neurodevelopmental disorders
o Integration of care and knowledge across childcare and psychiatry is efficient
• Many NDDs have overlap in traits, for example:
o ADHD: Inattention, hyperactivity-impulsivity, sensory sensitivity
o Autism Spectrum Disorders (ASD): Social / communication problems, inattention,
hyperactivity-impulsivity, sensory sensitivity
o Intellectual ability (ID): IQ 2 SD below population mean, inattention, hyperactivity-
impulsivity
Heterogeneity
• Clinical heterogeneity: different patients with same disorder have different patterns and clusters
of symptoms
• Aetiological heterogeneity: different causes can be at play for different patients with the same
symptoms and/or disorder
• Treatment response is also heterogeneous
Lifelong course, a delta of trajectories
• Some symptoms decline intro adulthood
• Others more stable
• Different patients have different outcomes later in life
o Because of others are associated with new behavioural difficulties or
disorders
Comorbidity -> Co-occurrence
• Co-occurrence: the same patient has multiple disorders
o Within neurodevelopmental disorders and with other (later onset)
psychiatric disorders
• Co-occurrence: itself heterogeneous
o Different patients with the same disorder can have different co-occurring disorders
o Historically difficult for diagnosis, definitions of disorders (e.g. in DSM) difficult
▪ E.g. in DSM-IV, ADHD and ASD could not be diagnosed in the same person
-> considered mostly in isolation -> consequences for research, clinic
▪ E.g. ADHD: hyperactive-impulsive or inattentive symptom presentation
Dimensional traits vs categorical diagnoses
Dimensions Categories
NDDs are no diseases that you have or not, but You have a disease, or you don’t. For example,
there is more like a spectrum of traits. Traits are in the DSM5 a person must meet a specific
measured in terms of their intensity, rather than number of criteria for diagnosis with the
fitting into a strict category. You have mild, disorder.
moderate or severe levels of a disorder.
Advantages: Advantages:
• No artificial cut-off • Aids clinical decision making
• Better reflection of underlying biology • Includes impairment
, • Statistically more powerful • Access to treatment
• Similar prognostic, genetic & neuroimaging
correlates as diagnosis
Questionnaire must be suitable such that trait is
well distributed (normal) in general population.
No inclusion of impairment, or impact on daily
functioning.
Example question: The liability-threshold model is a threshold model of categorical outcomes in
which a large number of variables are summed to yield on overall liability score; the observed
outcome is determined by whether the latent score is smaller or larger than the threshold.
a) What is the main assumption made with regards to the genetic effect sizes involved in the
liability model of complex diseases? Individual (genetic) risk factors are of small effect (2 pt)
b) What makes an individual cross the threshold from non-affected and become affected?
Combination of risk factors small genetic effects (1pt) plus environmental exposures (1pt)
above a threshold (1pt) is necessary for disease manifestation (in a cumulative effect)
Neurodiversity
• Several meanings today:
o Differences between (typical) individuals in society
o Neurodiversity movement
o Neurodiversity paradigm: theoretical framework (similar to research paradigm)
→ Referring to all forms of natural diversity between people in a population
• Neurodiversity approache(s)
Medical model Social model
• Historically dominant view • Developed by physically disabled
• Disability is pathological by nature advocates
• Disability exists within the individual • Disability comes from society
• Goal to transform to treat and normalize E.g., inaccessibility is due to environment
the disabled person to be as typical as
possible
Criticism: Criticism:
• By disability communities • No efforts to prevent injury
• Might not want to/be able to become • Can still have barriers (autistic people can
neurotypical (‘masking’) have barriers even if social acceptance
• Strong negative effects when trying to and inclusion better)
camouflage/mask • Autistics with high support needs (need
for treatment, neurodiversity approaches
are for these with low support needs)
→ A middle ground approach between the two extremes medical model and social model
o Disability as interaction between individual and environment
▪ Difficult to separate challenges related to individual limitations and those due to social
barriers/discrimination
o Intervention at both individual level and/or changing environment
▪ Focusing on quality of life, not cause
• In research
o Study context and individuals: heritability but also environment
o Study strengths and weaknesses: not only focus on ‘dysfunctions’, weakness in one context
can be strength in another
, o Bias and subjectivity: researchers seem to see weakness in neurodivergent people when
there might not be a good reason to
o Incorporating neurodivergent ideas: should explore how these ideas could inform research
questions
o Community involvement: learn from each other
→ Neurodiversity is a broad, inclusive concept that encompasses the idea that neurological
differences are a normal part of human diversity. It focuses on the strengths and positive aspects of
neurological differences, advocating for a shift away from viewing these differences as purely
negative.
ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD) – Greven
Learning Goals
• Know the clinical and behavioural characteristics of ADHD: diagnostic criteria, symptoms and
demographics
• Understand some debated issues in relation to ADHD; and to gain insight into initiatives to
modernise the concept of ADHD
• Understand developmental course of ADHD
Clinical and behavioural characteristics - What is ADHD?
• According to the DMS-5 criteria -> two symptom dimensions:
o Inattentiveness: inattention to details; difficulty sustaining attention; seems not to listen;
fails to finish tasks; difficulty organizing; avoids tasks requiring sustained attention; loses
things; easily distracted; forgetful
o Hyperactivity-impulsivity: blurts out answer before question finished; difficulty awaiting
turn; interrupts or intrudes on other; fidgets; unable to stay seated; inappropriate
running/climbing (restlessness); difficulty in engaging in leisure activities quietly; ‘on the go’;
talks excessively
o At least ≥6 of 9 inattentive, or ≥6 of 9 hyperactive-impulsive symptoms (or both)
▪ These symptoms prevent for at least 6 months, developmentally inappropriate, cause
impairment, present in multiple settings, several symptoms present before age 12 years.
- The last one is on discussion. Some people experience ADHD symptoms for the first
time when they start living on their own, particularly when they go to university
▪ Adults (≥ 17 years): fewer symptoms required (≥ 5)
o ADHD presentations (not subtypes!)
▪ Continuous disorder in which different symptoms are possible
▪ People often shift between dimensions: hyperactivity early on, which diminish later
o Differential diagnosis: symptoms not better explained by another mental disorder (e.g.,
mood, anxiety, personality); do not happen during course of schizophrenia or another
psychotic disorder.
• If you have an ADHD diagnosis as child, is it most likely you have also another disorder: co-
occurrence.
o Learning disorders, sleep problems, motor problems, tics and OCD, bipolar disorder,
substance use / gambling obesity, autism, anxiety and depression, ODD and CD
• Prevalence of ADHD
o ~5% in children & adolescents and ~2,5% in adults
o Male preponderance (only in childhood & adolescence)
o Narrowing of male preponderance into adulthood
▪ Females diagnosed later -> insufficient attending to recognising ADHD in girls?
INTRODUCTION LECTURE – Corina Greven & Emma Sprooten
Educational aims
• Describe the clinical features of neurodevelopmental disorders such as ADHD, ASD and
intellectual disability and their comorbidity.
• Understand the neural correlates of early onset neurodevelopmental disorders.
• Understand the contribution of genetic and environmental factors to neurodevelopmental
disorders (at levels of molecular genetics, epigenetics, imaging genetics, early environmental risk
factors)
• Understand concepts and research literature on animal models on neurodevelopmental
disorders.
Overview course
• Final exam 80%
o Lecture contents are central
o Factsheet contains essential readings (exam questions can be based on them)
• Presentation 20%: 20 min + 10 min discussion in groups of ca 4-5 students
o Main message
o Formulate key TRUE/FALSE statement (not a simple fact, possible to argue pros and cons)
o Include 1-2 slides with a take-home message
o Structure as in a papier: background/intro, methods, results, discussion: limitations/future
directions, conclusions
Genetics
Heritability -> studying genetics can give us insights into biological mechanisms underlying individual
differences.
Neurodevelopmental disorders
• No universal definition, but broader definitions:
o Wide range of neurological and psychiatric problems… involving some form of disruption to
brain development
o Include rare genetics syndromes, schizophrenia, epilepsy, cerebral palsy, disruptive
behaviour disorders
• DSM-5 is a classification system that specifies which criteria apply to a particular
neurodevelopmental disorder, such as ADHD, ASD, intellectual disability, communication
disorders, specific learning disorders, motor disorders
• Defining characteristics (not universal or strict):
o Typical onset before puberty
o Clinical course steady in long term, rather than remitting/relapsing
o Early onset neurocognitive deficits
o More prevalent in males
o High heritability, aetiology multifactorial
o High level of overlap
Grouping of these disorders is clinically useful
• Symptoms and problems overlap
• Assessment and treatment require specialists from a range of disciplines
,• Children different care and expertise than adults (e.g. communication, legal issues, parents and
school involvement)
o Same experts can treat and care for children with different neurodevelopmental disorders
o Integration of care and knowledge across childcare and psychiatry is efficient
• Many NDDs have overlap in traits, for example:
o ADHD: Inattention, hyperactivity-impulsivity, sensory sensitivity
o Autism Spectrum Disorders (ASD): Social / communication problems, inattention,
hyperactivity-impulsivity, sensory sensitivity
o Intellectual ability (ID): IQ 2 SD below population mean, inattention, hyperactivity-
impulsivity
Heterogeneity
• Clinical heterogeneity: different patients with same disorder have different patterns and clusters
of symptoms
• Aetiological heterogeneity: different causes can be at play for different patients with the same
symptoms and/or disorder
• Treatment response is also heterogeneous
Lifelong course, a delta of trajectories
• Some symptoms decline intro adulthood
• Others more stable
• Different patients have different outcomes later in life
o Because of others are associated with new behavioural difficulties or
disorders
Comorbidity -> Co-occurrence
• Co-occurrence: the same patient has multiple disorders
o Within neurodevelopmental disorders and with other (later onset)
psychiatric disorders
• Co-occurrence: itself heterogeneous
o Different patients with the same disorder can have different co-occurring disorders
o Historically difficult for diagnosis, definitions of disorders (e.g. in DSM) difficult
▪ E.g. in DSM-IV, ADHD and ASD could not be diagnosed in the same person
-> considered mostly in isolation -> consequences for research, clinic
▪ E.g. ADHD: hyperactive-impulsive or inattentive symptom presentation
Dimensional traits vs categorical diagnoses
Dimensions Categories
NDDs are no diseases that you have or not, but You have a disease, or you don’t. For example,
there is more like a spectrum of traits. Traits are in the DSM5 a person must meet a specific
measured in terms of their intensity, rather than number of criteria for diagnosis with the
fitting into a strict category. You have mild, disorder.
moderate or severe levels of a disorder.
Advantages: Advantages:
• No artificial cut-off • Aids clinical decision making
• Better reflection of underlying biology • Includes impairment
, • Statistically more powerful • Access to treatment
• Similar prognostic, genetic & neuroimaging
correlates as diagnosis
Questionnaire must be suitable such that trait is
well distributed (normal) in general population.
No inclusion of impairment, or impact on daily
functioning.
Example question: The liability-threshold model is a threshold model of categorical outcomes in
which a large number of variables are summed to yield on overall liability score; the observed
outcome is determined by whether the latent score is smaller or larger than the threshold.
a) What is the main assumption made with regards to the genetic effect sizes involved in the
liability model of complex diseases? Individual (genetic) risk factors are of small effect (2 pt)
b) What makes an individual cross the threshold from non-affected and become affected?
Combination of risk factors small genetic effects (1pt) plus environmental exposures (1pt)
above a threshold (1pt) is necessary for disease manifestation (in a cumulative effect)
Neurodiversity
• Several meanings today:
o Differences between (typical) individuals in society
o Neurodiversity movement
o Neurodiversity paradigm: theoretical framework (similar to research paradigm)
→ Referring to all forms of natural diversity between people in a population
• Neurodiversity approache(s)
Medical model Social model
• Historically dominant view • Developed by physically disabled
• Disability is pathological by nature advocates
• Disability exists within the individual • Disability comes from society
• Goal to transform to treat and normalize E.g., inaccessibility is due to environment
the disabled person to be as typical as
possible
Criticism: Criticism:
• By disability communities • No efforts to prevent injury
• Might not want to/be able to become • Can still have barriers (autistic people can
neurotypical (‘masking’) have barriers even if social acceptance
• Strong negative effects when trying to and inclusion better)
camouflage/mask • Autistics with high support needs (need
for treatment, neurodiversity approaches
are for these with low support needs)
→ A middle ground approach between the two extremes medical model and social model
o Disability as interaction between individual and environment
▪ Difficult to separate challenges related to individual limitations and those due to social
barriers/discrimination
o Intervention at both individual level and/or changing environment
▪ Focusing on quality of life, not cause
• In research
o Study context and individuals: heritability but also environment
o Study strengths and weaknesses: not only focus on ‘dysfunctions’, weakness in one context
can be strength in another
, o Bias and subjectivity: researchers seem to see weakness in neurodivergent people when
there might not be a good reason to
o Incorporating neurodivergent ideas: should explore how these ideas could inform research
questions
o Community involvement: learn from each other
→ Neurodiversity is a broad, inclusive concept that encompasses the idea that neurological
differences are a normal part of human diversity. It focuses on the strengths and positive aspects of
neurological differences, advocating for a shift away from viewing these differences as purely
negative.
ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD) – Greven
Learning Goals
• Know the clinical and behavioural characteristics of ADHD: diagnostic criteria, symptoms and
demographics
• Understand some debated issues in relation to ADHD; and to gain insight into initiatives to
modernise the concept of ADHD
• Understand developmental course of ADHD
Clinical and behavioural characteristics - What is ADHD?
• According to the DMS-5 criteria -> two symptom dimensions:
o Inattentiveness: inattention to details; difficulty sustaining attention; seems not to listen;
fails to finish tasks; difficulty organizing; avoids tasks requiring sustained attention; loses
things; easily distracted; forgetful
o Hyperactivity-impulsivity: blurts out answer before question finished; difficulty awaiting
turn; interrupts or intrudes on other; fidgets; unable to stay seated; inappropriate
running/climbing (restlessness); difficulty in engaging in leisure activities quietly; ‘on the go’;
talks excessively
o At least ≥6 of 9 inattentive, or ≥6 of 9 hyperactive-impulsive symptoms (or both)
▪ These symptoms prevent for at least 6 months, developmentally inappropriate, cause
impairment, present in multiple settings, several symptoms present before age 12 years.
- The last one is on discussion. Some people experience ADHD symptoms for the first
time when they start living on their own, particularly when they go to university
▪ Adults (≥ 17 years): fewer symptoms required (≥ 5)
o ADHD presentations (not subtypes!)
▪ Continuous disorder in which different symptoms are possible
▪ People often shift between dimensions: hyperactivity early on, which diminish later
o Differential diagnosis: symptoms not better explained by another mental disorder (e.g.,
mood, anxiety, personality); do not happen during course of schizophrenia or another
psychotic disorder.
• If you have an ADHD diagnosis as child, is it most likely you have also another disorder: co-
occurrence.
o Learning disorders, sleep problems, motor problems, tics and OCD, bipolar disorder,
substance use / gambling obesity, autism, anxiety and depression, ODD and CD
• Prevalence of ADHD
o ~5% in children & adolescents and ~2,5% in adults
o Male preponderance (only in childhood & adolescence)
o Narrowing of male preponderance into adulthood
▪ Females diagnosed later -> insufficient attending to recognising ADHD in girls?
