1. ADHD and autism Flashcards
ADHD?
Attention Deficit Hyperactivity disorder
What are the co-occuring disorders of ADHD?
Emotional and Behavioural disorders Learning difficulties: reading/writing disorder, asperger's Tourette’s Syndrome: Tic Sleep problems Oppositional defiant disorder (ODD) Developmental co-ordination disorder
What is ASD?
What is autism spectrum disorder
What defines ASD?
- Marked genetic predisposition, and a wide range of aetiologies
- Marked phenotypical heterogeneity
Co-occuring problems/disorders of ASD?
e.g. :-
•Learning Disability •Epilepsy
•ADHD (!)
•Sleep Disorders •Motor Difficulties •Sensory sensitivities
Definition of ADHD?
Developmentally inappropriate hyperactivity, Impulsivity, and/or inattention, leading to impairment in social, behavioural and/or academic function
Subtypes of ADHD
- Hyperactive/impulsive •Inattentive
* “Combined”
Classic inattention symptoms on ADHD
Does not attend Fails to finish tasks Can’t organise Avoids sustained effort Loses things, ‘forgetful’ Easily distracted
Classic hyperactivity symptoms on ADHD
Fidgets Leaves seat in class Runs/climbs excessively Cannot play/work quietly Always ‘on the go’
Classic inattention symptoms on impulsivity
Talks excessively Blurts out answers Cannot await turn Interrupts others Intrudes on others
What is meant by Tic disorder?
Tics are defined as repeated, sudden, rapid, nonrhythmic muscle movements including sounds or vocalizations. Tourette syndrome is diagnosed when people have had both motor and vocal tics for > 1 yr.
What is the course of ADHD in the psychosocial impairments?
Hint:
Symptoms domains + psychiatric comorbities -> Functional impairments (Self, school/work, home, social)
Symptom domains Inattention Hyperactivity Impulsivity \+ Psychiatric comorbidities Disruptive behavioural disorders (conduct disorder and oppositional defiant disorder) Anxiety and mood disorders
----> Functional impairments Self: Low self-esteem Accidents and injuries Smoking/ substance abuse Delinquency
School/ work:
Academic difficulties/
underachievement
Employment difficulties
Home:
Family stress
Parenting difficulties
Social:
Poor peer relationships
Socialisation deficit
Relationship difficulties
Prevalence of ADHD
•The Global prevalence is around 5%
•“Administrative prevalence” in Scotland average is 0.5% (i.e. Underdiagnosed * )
Of those diagnosed… Hyperactive/impulsive c. 15% of total
Inattentive c. 20-30%
“Severe-Combined” c.75%
Male/female ratio c. 3:1 in population studies and c. 10:1 in clinics!
•Increased prevalence is associated with lower socioeconomic status.
Genetic cause of ADHD?
Core symptoms are highly heritable. 75% mean heritability
(Evidence: from Family, adoption, twin studies.)
ADHD is associated with widely distributed markers e.g. at chromosomes 4, 5, 6, 8, 11, 16, and 17.
Analysis shows linkage with various dopamine receptor and transporter
genes, serotonin transport genes and others the role of which is unclear
Contribution factors to ADHD causation?
Anti/peri natal….
Postnatal…
Ante/peri-natal:-
•Pre-term delivery.
•Smoking
•Alcohol. (Note Fetal alcohol spectrum disorders and potential role of epigenetic
effects (**) plus the quantity, frequency, and timing of alcohol exposure) •Maternal stress
Intrapartum asphyxia
Postnatal:-
•Brain trauma
•Epilepsy •Deprivation/attachment
Pathophysiology of ADHD
at which structures of the anterior/posterior attentional pathways and in the cortex?
“Anterior attentional pathways” :
•Frontal Lobes
•Cingulate Gyrus
•Basal ganglia ( “Corpus striatum”, particularly the caudate nucleus)
“Posterior attentional pathways” :
•Locus Caeruleus
•Cerebellum
Cortex: Ventral prefrontal cortex Premotor cortex Anterior cingulate gyrus Dorsolateral prefrontal cortex (DLPFC) Orbitofrontal cortex (OFC)
What is the evidence based via imaging, neuropharmacology and neuropsychology to support disordered frontal lobe function and altered Dop and NA flux in ADHD?
IMAGING
•Volumetric CT and MRI studies – reduced volume of key structures
•Pet scanning, SPECT scanning Functional MRI – reduced activation of key brain areas,
particularly frontostriatal pathways
NEUROPHARMACOLOGY
•Improvement in core ADHD symptoms in response to medications which modify the release and reuptake of key neurotransmitters (Dopamine and Noradrenaline), which are region specific for key brain pathways concerned with self regulation and attention.
NEUROPSYCHOLOGY
•Identifiable alterations and deficiencies in frontal lobe mediated functions such as working memory, executive function, focus, distractibility.
Key structures of basal ganglia involved in ADHD?
Globus pallidus
Caudate nucleus
Putamen
What makes up the dopamine pathways relevant to ADHD?
- Reward system (mesolimbic pathway)
- From ventral tegmental area and nucleus accumbens - Control of cerebral motor output (nigostriatal pathways)
- From substantia nigra
- To the GP, Striatum (putamnen + caudate nucleus)
- To nucleus accumbens - Tuberoinfundibular
- Mesocortical pathways
o This tract is made up of dopaminergic neurons that project from the ventral tegmental area to the prefrontal cortex.
Relevant to the physiology of:
o Cognition and executive function @ dorsolateral prefrontal cortex
o Emotions and affect @ ventromedial prefrontal cortex
What are the NA pathways relevant to ADHD?
Release from the pons --> To cerebellum Thalamus Hippocampus Amygdala Hypothalamus Neocortex Spinal cord
Anterior cingulate gyrus links what structures…
Frontal cortex and amygdala
Which loop of the basal ganglia concerns ADHD?
Executive loop
i.e.
Dorsolateral prefrontal cortex --> Dorsolateral caudate nucleus -->GPi --> Medial dorsal and ventral anterior nuclei (then loops back to start)
• ADHD linked to malfunctioning _______ cortex
• Classic symptoms associated with specific prefrontal regions
– _______ = orbital frontal cortex
– Hyperactivity = prefrontal motor cortex
– Inattention = dorsal anterior _______ and dorsolateral prefrontal
• Specific regional cortico-striatal-______ circuit disruption contributes to specific ADHD symptoms
• ADHD linked to malfunctioning prefrontal cortex
• Classic symptoms associated with specific prefrontal regions
– Impulsivity = orbital frontal cortex
– Hyperactivity = prefrontal motor cortex
– Inattention = dorsal anterior cingulate and dorsolateral prefrontal
• Specific regional cortico-striatal-thalamic circuit disruption contributes to specific ADHD symptoms
Describe the neurochemistry and disturbed networks in ADHD patients?
Anterior attention system:
@ Prefrontal cortex **
@ Anterior cingulate gyrus
Dopamine selectively controls inputs to anterior attention system via D1 receptors inhibition of excitatory NMDA inputs
Posterior attention system: @ Posterior parietal cortex @ Pulvinar nucleus of thalamus @ Superior colliculus NA enhances the signal-to-noise ratio of target cells by inhibiting basal neuronal firing
Role of Dopamine and Norepinephrine (Noradrenaline) in Information Processing
- Optimum information processing requires distinguishing signals from noise
- DA and NE tune the prefrontal cortex to make information processing more efficient
- Too much DA or NE input can be as disruptive as too little input in regulating cortical information processing
Examples of how ADHD persists into adulthood
School failure, underachievement —> Job failure, under- employment
Multiple injuries —-> Fatal car wrecks, risk taking, accidental injuries
Definition of Autism spectrum disorders?
Highly variable and heterogeneous condition, with a wide range of aetiologies and phenotypes
What are the Triad of impairments of ASD?
- Social communication
- Social interaction
- Social “imagination”
What are the 3 social communication impairments of ASD?
- Difficulties in verbal and non verbal communication e.g appropriate use of…
- eye contact
- facial expression
- gesture
- prosody (rhythm and tone of speech) - Reciprocal aspects of communication e.g.
- initiating and turn taking in conversation
- negotiating a shared topics
- topic maintenance
- readily recognising what the listener knows. - Those with good language skills may interpret language in a literal manner, and may struggle to understand idiom, metaphor or sarcasm.
What are the 5 social “imagination” impairments of ASD?
1Difficulties with thinking and behaviour
- Poor imaginative skills may lead to restricted repetitive, stereotyped patterns of behaviour.
- Lack of a capacity to appreciate and integrate the “bigger picture” (central coherence).
- Interests tend to be circumscribed and intense, often not reflecting cultural norms.
- A preoccupation with routine and structure is also common.
What are the social interaction impairments of ASD?
- Social development is different, delayed or atypical with interaction difficulties
- Struggle with reciprocity, shown by lack of empathy or failure to adapt their behaviour according to others perspectives and social context.
Prevalence of ADS
At least 1% of children have ASD; some studies report a prevalence of around 2%.
•Around 50% or more children with ASD have an intellectual disability (Baird et al. 2006
Aetiology of ASD
Highly heritable
10% sibling recurrence
Twin studies show high concordance
Male:female 4:1
In a minority of cases (approximately 10%) ASD occurs in association with cytogenetically detectable chromosomal abnormalities and recognised genetic conditions, such as Fragile X Syndrome, Tuberous Sclerosis, Down’s syndrome, and Angelman’s Syndrome.
Clinical signs of ASD
Tuberous schlerosis
Brain tumours –> Seizures
Angelmans syndrome (maternal allele deletion)
Fragile X syndrome from males (big ears and testes*)
S/S of fragile x syndrome?
Long ears long face delayed speech large testes hyperactive tactile defensiveness gross motor delay austic-like behaviour
Clinically important other considerations in ASD
- Association with Childhood Onset Epilepsy *
- Brain disorder
- EEG is WILD - Prevalence of Sleep Disorders**
- 6/10 on spectrum don’t sleep
- Melatonin treatment - Altered Motor Function***
- Low tone
- Low co-ordination
- Repetitive action
- Ataxia - Altered Sensory Function**
- Hypo/hyper responsiveness
- Some stimuli can be upsetting
- Can affect vision, smell, taste, hearing, vestibular/ proprioceptive function and kinaesthetic sensitivity.
Pathophysiology of ASD
•Total brain volume enlarged in early infancy in 90% (subsequently slows) ALWAYS MEASURE HEAD SIZE
•Macrocephaly (Occiptofrontal circumference >97th centile) - 20% cases overall
•Histology – reduced size and distortion of neurones and intrinsic neuronal connectivity e.g. Purkinje cells of cerebellum, neurones in fusiform gyrus.
•Widespread reduction in white matter volume and connectivity, - demonstrated by MRI , Diffusion tensor imaging, Functional MRI, - described as “global extrinsic hypoconnectivity”
PUTATIVE LINKS BEWEEN BRAIN REGIONS AND ASD RELATED SEQUELAE?
In ASD for the following what is the dysfunction... Brain region: Frontal Putative area: Prefrontal Inferior frontal Primary motor Orbitofrontal
Dysfunction:
Prefrontal **: Executive function, attention, working memory
Inf frontal: Expressive language
Primary motor: Motor skills
Orbitotemporal: Repetitive ritualistic behaviours
In ASD for the following what is the dysfunction... Brain region: Temporal Putative area: Sup temporal Fusiform gyrus Hippocampus
Dysfunction…
Sup temporal: Auditory processing ; language comprehension
Fusiform gyrus: Facial recognition
Hippocampus: Short term memory ; verbal/spatial learning
In ASD for the following what is the dysfunction…
Brain region: Parietal
Putative area: Post-central gyrus
Dysfunction:
Somatosensory perception ; body image, spatial perception
In ASD for the following what is the dysfunction…Brain region: Insula
Putative area:
Insula cortex
Dysfunction: Pain, smell, taste and autonomic perceptions
In ASD for the following what is the dysfunction... Brain region: Limbic system Putative area: Cingulate gyrus Amygdala/hypothalamus
Dysfunction..
Cingulate gyrus: Emotion ; fear
Amygdala/hypothalamus: Affect ; aggression
In ASD for the following what is the dysfunction…
Brain region: Cerebellum
Putative area:
Vermis and hemispheres
Dysfunction…
Vermis: Balance, gait, motor co-ordination
Hemispheres: Learning, language, cognition
In ASD for the following what is the dysfunction..
Brain region: Occipital
Putative area: Visual cortex
Dysfunction in vision
However, A single “neurological” explanation
for the presenting signs of ASD is not yet possible.
Suggested deficits in psychological processing and function have included:-
1.Impairments in frontal lobe mediated “executive functioning” and working memory .
(difficulties with problem solving and forward planning in order to achieve a goal)
2.Deficiencies in “theory of mind”
(difficulties in the consideration of how other people might think and
react to a particular situation)
3.Problems in achieving “central coherence”
(the failure to integrate information into meaningful wholes)
ASD Postscript/Resume:
•_____ heritable and now well recognised neurodevelopmental disorder
•Brain abnormalities described but no unitary explanation for core symptoms
•Lifelong disability with prognosis dependant on coexisting ______ impairment
•Strong capacity to engender ______ and secondary psychiatric morbidity
•Wide variability in phenotypical _______
•Important associations with disorders including sleep disruption, epilepsy, motor and sensory problems
•ASD and ADHD used to be mutually exclusive diagnoses but it is now recognised you can have both!
ASD Postscript/Resume
•Highly heritable and now well recognised neurodevelopmental disorder
•Brain abnormalities described but no unitary explanation for core symptoms
•Lifelong disability with prognosis dependant on coexisting cognitive impairment
•Strong capacity to engender anxiety and secondary psychiatric morbidity
•Wide variability in phenotypical expression
•Important associations with disorders including sleep disruption, epilepsy, motor and sensory problems
•ASD and ADHD used to be mutually exclusive diagnoses but it is now recognised you can have both!
