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Summary Molecular Principles of Brain Disorders
Molecular Principles of Brain Disorders
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MPBD Thursday, 17 November 2022Neurodiversity for ASD & ADHD
The awareness of behavioural and personality traits and disorders exist along a spectrum.
Where lies the border between health and dysfunction or disorder
It is the question whether ADHD and ASD is a disorder or diversity. Is it a disability or a
difference?
So the first question that needs to be addressed is when a personality trait becomes a
psychiatric disorder. This is done via the DSM, the diagnostic and statistical manual of
mental disorders for classification and diagnosis.
DSM4 and DSM5 use a categorical diagnosis, so you either have it or not. Does this book
make us live an a disease-based society? For some diseases categorical diagnosis is logic
as the disease state is well separable from the state of being well (e.g. TB or leukaemia).
However, many psychiatric disorders might be better conceptualised as dimension or
spectrum-based instead of categorical.
In DSM5, Autism Spectrum Disorder (ASD) is finally approached in a spectrum/dimensional
way
The concept of neurodiversity came from a reaction of high functioning autistic people
(Asperger’s) in 1998.
‘There is a diversity among human brains regarding sociability, learning, attention,
impulsivity, mood and other important mental functions’. Maybe what we see as disorders
is not all disordered.
These individual saw themselves a neurodivergent, and the people without the disorder
neurotypical.
When embracing the concept of neurodiversity, the first obstacle to conquer is the stigma
on ADHD and ASD. Generally, ASD and ADHD are described in a negative way
ADHD : Overly active, low concentration, low impulse control, easily distracted
ASD : impaired social relationships, strange behaviours, narrow interests
However, emphasis can also be placed on the more positive aspects of both conditions
- ADHD : spontaneous, creative, divergent minds, vital, high-energy, fast-thinking
- ASD (level 1/Asperger’s) : strong persistent interests, attention to detail, unusual memory,
fascination with systems and patterns, and ability to concentrate for longer periods
Research with high functioning autistics showed that these individuals outperform
neurologically typical children and adults in a wide range of perception tasks. They are
better in visually/auditory spotting information in a distracting environment and
concentrating for a very long time
Personally, when you use the concept of neurodiversity, some things have to be taken into
account. First, you have to be aware of you mental condition (ASD, ADHD). After, you have
to determine your strong points and pitfalls. From here, you can adjust life and surroundings
to your unique qualities
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Niche construction : adjusting your life and surrounding based on your unique qualities
- In ADHD : Choosing jobs with creative and hand-working aspects and lots of travel or
moving around. Also use you smartphone for organising and managing daily schedule,
and use GPS tracking for keys and wallet (pitfall awareness). Also, behavioural theory
can be used to realise the cause of the symptoms you experience
- In ASD : choose job with solitary work in science of IT, often with large data sets
needing high concentration. The use of behavioural therapy to learn and understand
social relationships. Connection with like-minded people via internet is also important
for support and understanding
An important pitfall of neurodiversity is the romanticising of psychological and psychiatric
disorders, as the positive sides are lighted lots more.
However, these advantages are only significant in ADHD, bipolar disorder and high0-
functioning autists. Cases of severe depression, schizophrenia and severe autism/ADHD
almost have no advantages. In these cases there are severe brain disorders with negative
consequences for individuals and surroundings
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Schizophrenia
SYMPTOMS OF SCHIZOPHRENIA
Schizophrenia symptoms can be divided into 3 main categories
1. Positive symptoms = more present, excess of normal function. Includes psychosis,
agitation, disorganised speech and disorganised behaviour
2. Negative symptoms = less present, reduction in normal function
3. Cognitive symptoms
Positive symptoms
A big part of the psychotic character consists of delusions, which has different types
Delusion : misinterpretation of perception or experience
- Paranoid —> espionage, conspiracy
- Referential —> everything refers to the individual, in secret messages
- Grandiose (megalomania) —> the individual is a powerful person and can do anything
(overpowered)
- Scientific —> delusion has scientific theme, this is the solution to everything
- Religious —> one thinks they’re Jesus or another divine being
- Poison —> not only physical poisoning, also via mind control
- Sexual —> one is sexually irresistible (rarely in schizo due to decrease libido)
- Leaky mind —> thoughts leak from the brain and can be broadcasted
- Alienated —> thoughts are not ones own, but they are transplanted into the brain
Besides delusions, hallucinations are also important in psychosis
In schizophrenia, the hallucinations are mainly auditory in the form of voices. However, the
hallucination can also be visual, tactile, gustatory and olfactory (basically sensory).
Psychosis is such a convincible phenomenon that ones rational is sufficient anymore to
stay sane. This causes the individual to lose trust in their own brain whenever they get out
of a psychotic episode, as the brain cannot control itself anymore
Negative symptoms
Blunted affect : loss of emotional expression, feeling empty/blank
Dysfunctional motivation : poor personal hygiene, overlaps with MDD
Anhedonia : no pleasure capacity, main symptom of schizophrenia, overlaps MDD
A-sociality : little social motivation and sex drive, little socialisation
Cognitive symptoms
Cognitive symptoms mainly include problems with attention and executive function
Executive dysfunction : problems with planning, problem solving, and prioritizing
BRAIN CIRCUITS AND HYPOTHESES
The symptoms of schizophrenia are formed by a dysfunction of multiple brain circuits
- positive symptoms —> mesolimbic
- Negative symptoms —> mesocortical / prefrontal cortex
- Cognitive symtoms —> dorsolateral prefrontal cortex
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Dopamine hypothesis
Dopamine was one of the first compounds to had shown to play a prominent role in
schizophrenia. This was partly due to the fact that high doses of amphetamine and cocaine,
which release more dopamine in the synapse, could induce a drug-induced psychosis.
Therefore, the first antipsychotics were dopamine antagonists to prevent the large
dopamine release
Dopamine pathways in the brain lead from the midbrain (mesencephalon) into other areas,
and there are 4 different pathways
1. Mesolimbic : midbrain to nucleus accundens
2. Nigrostriatal : substantia nigra in midbrain to striatum
3. Mesocortical : midbrain to prefrontal cortex
4. Tuberofundibular : hypothalamus to pituitary
The positive symptoms of schizophrenia are mainly causes by a hyperactive mesolimbic
dopamine pathway. There is too many dopamine neurotransmitter release in this system.
The cognitive symptoms of schizophrenia are mainly caused by a hypoactive mesocortiyal
dopamine pathway. There is too little dopamine neurotransmitter release in the system.
The other dopamine pathways seem to work normal in schizophrenia
As mentioned before the classic antipsychotic is a dopamine antagonist. This prevents the
binding op dopamine, reducing its activity and normalising the activity of the mesolimbic
system. However, these antipsychotic also blocks the normal pathways as well, causing
o.a. too little dopamine in the striatum. This leads to EPS (Extra Pyramidal Symptoms),
which are Parkinson-like symptoms.
Glutamate hypothesis
The glutamate hypothesis is based on the hypofunction of the NMDA receptor. The NMDA
receptor can bind glutamate neurotransmitter for long term potentiation.
A common NDMA antagonist is ketamine, which can temporarily simulate the mind in a
schizophrenic-like state. Therefore, it is used as schizophrenia model and it induces all
symptom types. A ketamine-induced psychosis is however uncommon
There are 5 glutamate pathway
1. Cortico-brainstem
2. Cortico-striatal
3. Thalamo-cortical
4. Cortico-thalamic
5. Cortico-cortical
The NMDAr hypofunction is mainly seem in the cortico-brainstem projection. This projection
has a direct connection with the mesocortiyal dopamine circuit. The normal brain uses toxic
excitation to keep all circuits healthy. There is an extra excitation in the mesocortiyal
pathway coming from the cortico-brainstem projection. Glutamate binds in the brain stem
to the dopamine pathway for induction of action potential, increasing its fire rate
However, in schizophrenia, the NMDAr is hypo functional, causing the glutamate being
unable to bind. The excitation signal cannot release to the mesocortiyal pathway, causing
its hypofunction.
So, the problems in the dopamine pathway are caused by problems in the glutamate
pathway for schizophrenia
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