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- 6. THE POLYMORPHISMS OF DOPAMINE RECEPTOR D4 AND THEIR EFFECT ON DOPAMINE REGULATION, IN THE MANIFESTATION OF ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) By Tammy Alsop Sheffield Hallam University
- 7. BACKGROUND AND DEFINITION • Aetiological factors include: Genetics/neurobiology, Environmental, Social and Psychological. • ADHD is defined by the American diagnostic and statistical manual of mental health as a persistent pattern of inattention and/or hyperactivity – impulsivity that interferes with functioning or development as characterised by the set criteria. • Subtypes Inattentive Hyperactive Combined type
- 8. PATHOPHYSIOLOGY RECEPTORS AND NEUROTRANSMITTERS • Noradrenaline/norepinephrine • Dopamine • DAT1 (Dopamine transporter) • DRD4 (Dopamine receptor)
- 10. SYMPTOMS AND DIAGNOSIS • Conditions with overlapping symptoms such as Autism or learning difficulties • ADHD presents with co-morbid conditions such as sensory processing disorder (SPD) • Ultimately the diagnosis is based on professional opinion of the attending paediatrician/psychiatrist • Symptomology is variable but must show at least 6 of 9 characteristics from either subtype.
- 11. TREATMENTS Medication • Medication in the UK is only given to severe ADHD cases. • There are 2 types of stimulants • There are also non stimulants such as Atomoxetine Behavioural and parental therapy • CBT • Parent coping courses • Occupational therapy • Education and learning programmes Alternative and Diet • Dietary modifications such as avoidance of sugar, caffeine and artificial additives • Dietary supplements to combat deficiencies such as zinc, magnesium and omega-3 commonly found in ADHD patients. • Meditation and mindfulness • Exercise
- 12. CONCLUSION • Scientific data and further research are a necessity. • Raising awareness of such a common but misunderstood unseen condition will be highly beneficial. Isn’t that the goal of Healthcare as a whole ?
Editor's Notes
- Im gna start with a question WHAT IS YOUR FIRST THOUGHT UPON SEEING THIS WORD ?
- Many of you will have misconceptions about the origins and treatments of ADHD without actually knowing any real scientific information. While the actual cause has not been pinpointed there is evidence to suggest a neurobiological/genetic basis.
- I started a poll over social media to engage those who live with ADHD daily, to find out what misconceptions exist. I got 3094 Replies with the main misconception being poor parenting.
- I got 3094 Replies with the main misconception being that ADHD is an excuse for poor parenting! The results are presented here in a graph.
- 33% of 3094 people were faced with the bad parenting misconception. I think more scientific research is necessary to alleviate the stereotypical view of ADHD and provide scientific evidence to support a neurobiological approach.
- So my literature review is focused on the polymorphisms of the dopamine receptor D4 and how this translates into the development of ADHD. I also chose this because my son has recently been diagnosed with a severe form of ADHD and I’m passionate about the role of genetics in the development of heterologous conditions as it influences individual treatment options which impact on quality of life. This is where my career focus is based and I would like to go on to sequence and identify genetic variants indicative of disease which ties into my project with Lucy crooks on bioinformatic sequencing.
- Adhd is a heterologous neurological condition with many causative factors to consider. Research has suggested that Genetics – neurobiology, Environmental, Social and Psychological Factors are all associated. Deficiencies such as zinc and magnesium have also been linked to ADHD. But This presentation will focus on the neurobiological/genetic aspect of the aetiology. In America the diagnostic and statistical manual of mental health defines ADHD as a persistent pattern of inattention and/or hyperactivity – impulsivity that interferes with functioning or development as characterised by the set criteria. In Britain however the WHO uses the ICD10, which stands for International Classification of Disease, to define and diagnose ADHD with slight differences to the diagnostic criteria. There are 3 main subtypes of ADHD Inattentive - predominantly diagnosed in females Hyperactive- impulsive Combined type
- The pathophysiology of ADHD is complex and involves specific neurotransmitters and Brain regions. Dopamine and Noradrenaline are the most common recognised deficits, causative of the symptomology seen in those with ADHD. Norepinephrine is associated with concentration and impulse control Dopamine is responsible for the pleasure and reward system and our motivational drive, So a dysregulation in the brain would result in issues with understanding consequence and motivation, poor impulse control and inattention. Typical features of those with ADHD. These neurotransmitters (or lack their of) directly correlate to the 3 main areas of difficulty identified in ADHD. *Inattention *Hyperactivity and *Impulsivity. Brain studies suggest that dysregulation occurs due to mutations in the dopamine receptor DRD4 and the overexpression of the dopamine transporter DAT1. This image highlights what is going on at the synaptic clefts between axon terminals in the brain. If DRD4 receptors (shown in pink) are mutated, this would lower the binding affinity of dopamine and result in ineffective dopaminergic neurotransmission. Furthermore overexpression of DAT1 transporters (shown in red) would reabsorb the dopamine (shown in blue) in the synaptic cleft, effectively limiting the interaction time between dopamine and the DRD4 receptors.
- MRI brain scanning has shown that people with ADHD have marked differences and structural abnormalities in specific brain regions. These include the cortical an subcortical regions in particular the prefrontal cortex ( controls self regulation, memory, planning and attention) and the basal ganglia (controls cognitive learning, habit formation, emotional control and coordination) respectively. The prefrontal cortex has been found to be smaller in adhd patients. The cerebellum is also affected ( controls coordination of movement and timing) The neuroactivity is disrupted, with underactivity being observed in the prefrontal region of those with ADHD as opposed to a control subject of the same age shown in this image on the left. Overall the total brain volume is alot less.
- Diagnosis is complex due to the amount of conditions with overlapping symptoms and also because often ADHD presents with co-morbid conditions such as sensory processing disorder (SPD) Diagnosis must follow specific criteria (DSM-V) but ultimately the diagnosis is based on professional opinion of the attending paediatrician/psychiatrist which leaves room for error and can often lead to misdiagnosis. Symptomology is variable as shown in the image there and not all those with ADHD will present with every symptom. However they must meet at least 6 of 9 characteristics in the diagnostic criteria, from either category of inattention or hyperactivity- impulsivity. If 6 characteristics are met from both categories then the person will be diagnosed with the 3rd subset ; combined type.
- 2 types of stimulants Equasym with the active ingredient being methylphenidate and (work by Adderall which is an amphetamine (work by There are also non stimulant medications such as atomoxetine (work by For mild to moderate cases therapies are tried first which address a variety of different issues such as movement, academia, parenting, understanding emotions and self esteem. If therapy is ineffective medication is used (last resort) Diet and lifestyle are often used to lessen ADHD symptoms in children whose parents do not want to medicate. Dietary modifications (caffeine, sugar) and supplementations such as omega-3, zinc and magnesium have no scientific evidence of benefit or risk however it has been shown that there is a higher prevalence of specific deficiencies seen in these patients.
- Ive illustrated the neurobiological basis of ADHD and I hope I have cleared up some of the misconceptions that people have. Scientific data and further research will help to improve our knowledge and understanding of this complex condition to aid the discovery of potential novel treatment paths. It will also raise awareness so people will seek out the necessary diagnosis and treatment without fear of the stigma attached, which may have a beneficial impact on the quality of the people who suffer at the hands of a debilitating unseen condition. Isnt that the aim of Healthcare research???