ali retweeted
Did you know that 84% to 98% of the common genetic variations that influence ADHD are also shared with other psychiatric and cognitive conditions?
The reason is that the exact same genetic variants perform multiple duties and influence entirely different clinical outcomes depending on how they interact with other factors.
Here’s an example: A child inherits multiple gene variants: a specific version of the DAT1 gene which means that their brain clears dopamine too quickly and a variation of SNAP25 which makes cellular communication sluggish.
On their own, these genes only slightly elevate risk.
Let’s also assume that the child is also born prematurely with a very low birth weight.
Now this creates an environment of physical stress that delays the maturation of the prefrontal cortex.
Because of the biological stress of early birth, certain chemical tags are placed on the child's DNA.
This causes the already vulnerable DAT1 and DRD4 genes to change their expression.
The combined force of weak dopamine pathways (genetics) and an altered prefrontal cortex timeline (environment) leads to the structural brain differences that manifest as ADHD.
Here’s another example.
In this case, the person does not have issues with how dopamine is pumped away, but rather how it is produced and how neurons physically shape themselves.
Let’s say for example that he has gene variants in tyrosine hydroxylase (TH) that is responsible for creating the enzyme that builds dopamine in the brain and in the FOXP2 which is involved in synaptic plasticity.
So these variants lead to low baseline dopamine levels and alter how neurons in the basal ganglia branch out and connect.
Now let’s say that as a toddler, the child lives in an older home with undetected lead dust from aging paint and old pipes.
The problem with ingesting even small amounts over time is that lead is a potent neurotoxin that specifically interferes with calcium signaling in the brain, which neurons rely on to pass messages and grow.
So the child’s brain is already struggling to produce enough dopamine (TH gene), is trying to build neural highways with a slightly flawed blueprint (FOXP2 gene) and when lead enters the system, it acts as a massive roadblock.
It disrupts the fragile calcium signaling exactly where the FOXP2 gene was already struggling to build strong synaptic connections.
Simultaneously, the toxic stress of the lead exposure triggers an epigenetic response, essentially "turning down the volume" on the TH gene even further.
At the end the structural networks connecting the basal ganglia to the prefrontal cortex fail to mature properly.
Because these circuits regulate motor inhibition and impulse control, the child develops the classic symptoms of ADHD combined type (more about the types of ADHD in a moment).
For more on the genetics and the environmental factors:
fitandball.gumroad.com/l/bra…
ali retweeted
"A reward is a reward dude, changing my lifestyle won't help my ADHD".
Nope.
Imagine that your brain has two main workers:
1. Dopamine
This is the chemical that makes you feel satisfied and motivated
2. Acetylcholine
This is the chemical that turns on when you focus and try hard
If someone gives you a piece of chocolate for doing nothing, you get a small, normal splash of dopamine.
If you have to walk 5 miles to get that exact same piece of chocolate, your brain turns on Acetylcholine because you are using effort.
When you finally get the chocolate, that Acetylcholine acts like a giant loudspeaker for your dopamine.
By giving you a bigger chemical reward for working hard, your brain literally teaches itself a lesson: "effort is worth it."
This is of vital importance if you have ADHD.
In an ADHD brain, the "loudspeaker" (Acetylcholine) doesn't always turn on properly when things get tough.
Without that loudspeaker, doing hard work feels incredibly draining, and the reward at the end feels small and disappointing.
This is why people with ADHD struggle so much to start difficult tasks, their brains are missing the chemical booster shot that makes effort feel good.
So while for a long time we thought that dopamine levels were entirely dictated by the firing of dopamine cell bodies located deep in the midbrain.
We now know that local interneurons in the nucleus accumbens release a rapid burst of acetylcholine when a task requires high effort.
This acetylcholine binds directly to nicotinic receptors on the nearby dopamine axon terminals.
It acts like a local amplifier, forcing a much larger hit of dopamine to spill out when the reward is achieved compared to when the exact same reward is given for free.
When researchers block this acetylcholine link, the subjects completely lost their drive to perform high-effort tasks, though they still happily ate "free" or low-effort rewards.
Now, to help your brain learn the "effort = worth it" loop, you need a dual strategy:
-Support acetylcholine (the amplifier) to make starting tasks easier
and
-Carefully manage artificial rewards (cheap dopamine) so they do not hijack your motivation system
fitandball.gumroad.com/l/bra…
ali retweeted
Neurotransmitters don't just affect your mood.
They affect everything from hormones all the way to gut health.
Serotonin for example initiates the peristaltic reflex (the wave-like muscle contractions that push food along the tract), triggers the secretion of water and electrolytes to lubricate the food bolus, signals visceral sensations, such as fullness or nausea, to the central nervous system via the vagus nerve and so on.
Acetylcholine acts directly on smooth muscle tissues, causing them to contract forcefully, increases the release of stomach acid, pancreatic enzymes, and digestive juices.
Norepineprhine and epinephrine act as the ultimate braking system for your digestion, slowing or completely freezing stomach emptying and intestinal muscle movement.
They also constrict blood vessels in the gut, shunting oxygen-rich blood away from the digestive tract and sending it out to your heart and skeletal muscles.
Dopamine relaxes the lower esophageal sphincter and suppresses upper GI movement.
In fact, did you know that many gram-negative bacteria commonly implicated in SIBO such as Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa possess specialized adrenergic receptors?
One example is the histidine kinase QseC, which functions as a bacterial adrenergic receptor/sensor for epinephrine/norepinephrine (and the bacterial autoinducer AI-3).
So when these bacteria sense norepinephrine, it triggers a quorum-sensing mechanism that increases their replication rate, motility, and attachment to host tissues.
Then norepinephrine for example strips iron away (*) from transferrin and lactoferrin and gives it directly to the bacteria.
(*) Norepinephrine possesses a catechol structure that has a natural, high binding affinity for ferric iron.
More: fitandball.gumroad.com/l/bra…
ali retweeted
The reason why stimulants and exercise improve sustained attention in ADHD might not be what you think.
There is an “energy deficit” or neuroenergetics hypothesis for ADHD.
It proposes that insufficient lactate supply from astrocytes to neurons (linked to catecholamine signaling and astrocyte glycogen/glucose metabolism) limits rapid ATP availability during high neural demand.
This can contribute to inconsistent performance, attention drift, and response variability.
In fact, hyperactivity has even been hypothesized in some models as a possible compensatory way to generate more muscle lactate for the brain.
Stimulant medications raise extracellular norepinephrine (and dopamine).
Norepinephrine acts on α1- and β-adrenoceptors on astrocytes to stimulate glycolysis and lactate production/release.
Then exercise raises catecholamines and can increase peripheral lactate.
Some animal-model work has suggested hyperactivity itself may upregulate monocarboxylate transporter 1 (MCT1) at the blood–brain barrier, potentially allowing more circulating lactate into the brain as a partial compensation for limited astrocytic supply.
But again, this is just a theory.
Direct evidence that people with ADHD have measurably reduced astrocytic lactate production or ANLS function is limited.
So it's brain candy.
The most effective strategies and underlying reasons are presented here: fitandball.gumroad.com/l/bra…
ali retweeted
Gut issues and ADHD create a vicious cycle.
Speaking of IBS for example, an overgrowth of bacteria like Prevotella copri and Ruminococcaceae, commonly associated with IBS, has been directly linked to a decreased expression of dopamine transporters (DAT) and D2 receptors (D2R) in the central nervous system.
And if you have ADHD this is the last thing you want.
fitandball.gumroad.com/l/bra…
Transferring gut microbiota from humans with ADHD not only gives mice ADHD but individuals with ADHD also have:
-Nearly 50% higher risk of overall gastrointestinal symptoms
-Are 63% more likely to suffer from IBS
"So there are shared biological root causes of ADHD and gastrointestinal issues?"
Yes, after all a single underlying genetic/physiological mechanism can cause completely different symptoms in different parts of the body.
Let's take dopamine as an example.
Because dopamine regulates both brain functions such as focus, drive etc but also gut motility, a disruption in your body's baseline dopamine system/metabolism/production hits both areas simultaneously.
Let me dumb it down even more (these are oversimplifications):
If dopamine is the "molecular handbrake" and coordinator for your intestines, dopamine "deficiency" as seen in ADHD, directly translates to a faulty, unpredictable brake system in your digestive tract.
In the digestive system, dopamine receptors act as regulators that tell your intestinal muscles when to relax and when to contract to push food through smoothly.
If your body has altered dopamine signaling or lower dopaminergic tone, that "handbrake" doesn't engage or disengage correctly.
Instead of a smooth, rhythmic wave moving food along, your peristalsis becomes erratic.
If the muscles stall completely, you get chronic constipation; if they contract chaotically, you experience the cramping, alternating cycles, and spasms characteristic of IBS.
Then without adequate local dopamine signaling, the intestinal barrier weakens, leading to increased gut permeability and painful issues like acid reflux or generalized indigestion.
Read more: fitandball.gumroad.com/l/bra…
ali retweeted
"Adderall makes me feel like i'm able to cure cancer".
Yeah no shit.
Dopamine helps our brains evaluate whether a reward is worth the energy required to get it.
When dopamine levels are depleted, the brain overestimates the "cost" of effort and underestimates the value of the reward, leading to low motivation.
Conversely, dopamine-enhancing drugs like amphetamines shift this calculation.
They increase a person's willingness to exert effort, even when the probability of a payoff is low or the task is tedious (cleaning a room etc).
fitandball.gumroad.com/l/bra…
He knows what he is talking about
A lot of the "nootropic" stacks that are recommended these days, add a tremendous load to brains that are already overloaded.
So stop trying to stimulate what's left in order to chase a sharper hour and start giving your brain what it needs.
Just start with your damn nutrition.
"So what are the most important nutrients then?"
Overall, any chronic nutrient deficiency can contribute to problems so for starters, it's a good idea to focus on consuming every single micronutrient and covering your baseline micronutrient needs.
For example, dietary biotin intake exhibited an approximately L-shaped nonlinear relationship with anxiety and depression risk, where risk decreased with increasing intake up to a moderate threshold (tap in the pics).
Now the main nutrients that seem to be able to impact the brain the most (so we are not saying that the rest are irrelevant) include:
-Zinc
-Magnesium
-Vitamin K
-Vitamin C
-Polyphenols
-Vitamin E
-B6
-B12
-B1
-B9
-Iron
-Choline
-O3
For example, without zinc, B6 and iron, neurons, astrocytes and oligodendrocytes flat out don't work.
Or, believe it or not, vitamin K was found to have a stronger diagnostic value for predicting suicide attempts than A LOT of other known biomarkers.
It had a diagnostic sensitivity of 84.2% and a specificity of 71.5%.
Or, in this mood disorder cohort, 35% had inadequate plasma vitamin C concentrations at baseline compared to 17% of the healthy control cohort.
Then:
Low B12:
-Reduces BH4
-Increases oxidative stress and homocysteine (which lead to all sorts of issues such as NMDA-mediated excitotoxicity, impaired hippocampal neurogenesis, blood–brain-barrier disruption, MMA-related demyelination etc)
-Lowers EGF
-Increases TNF-α
Low B9:
-Harms the production of every single neurotransmitter (folate is required to make SAMe (S-adenosylmethionine) low folate → low SAMe → increased risk of depression, anxiety, bipolar disorder, schizophrenia and cognitive decline).
-Harms monoamine synthesis (via BH4 regeneration).
-Harms the synthesis of melatonin, CoQ10, carnitine, creatine, phosphatidylcholine
And these are just the tip of the iceberg.
What's also important to note is that if you are on any medication, proven to cause a deficiency in a certain nutrient, you must focus on that as well.
CoQ10 is a good example of this.
Point being: Noticing, detaching and replacing dysfunctional thinking patterns is obviously helpful when it comes to winning the battle against depression.
But if you think that you can out-think your way out of chronic depression without working on your body, think again.
In MDD for example, studies show decreased expression of GAD67 and parvalbumin in prefrontal interneurons.
So the person's prefrontal regulation of limbic structures is impaired, making it very hard to escape negative thought loops.
This is why successful treatments often normalize cortical GABA levels/excitation/inhibition (E:I) balance in the prefrontal cortex.
"What does this have to do with nutrients".
Here are two basic examples:
-Vitamin B6 is the essential coenzyme that GAD67 requires to synthesize GABA.
So without adequate B6, GAD67 cannot function properly.
-Zinc enhances the presynaptic release of GABA and interacts with the GPR39 zinc receptor to help maintain homeostasis between excitatory and inhibitory systems overall.
For more about brain health and the impact of nutrients, go here:
fitandball.gumroad.com/l/bra…
ali retweeted
My roadmap for how markets trade in the rest of 2026. There's 2 big market drivers: (i) oil prices; and (ii) France. My base case is for oil prices to fall, as they now embed a huge risk premium, and for France to muddle along. Big winner is the S&P 500...
robinjbrooks.substack.com/p/…
ali retweeted
If depression is associated with lower ATP and disrupted phosphocreatine levels, then it makes obvious sense why T3 would be used, since it increases cellular ATP and helps normalize the ATP/PCr ratio.
On top, it also simultaneously increases beta-adrenergic receptor binding and alpha-2 autoreceptor binding.
Besides these noradrenergic effects, it acts at a nuclear level to decrease the transcription of 5HT1a and 5HT1b serotonin autoreceptors.
So it reduces feedback inhibition and boosts frontal cortex serotonin levels when paired with SSRIs.
It also downregulates or blunts presynaptic alpha-2 autoreceptors and stimulates gene expression of BDNF.
fitandball.gumroad.com/l/bra…
ali retweeted
Managed to nail the three previous tops in the US Dollar, which can be seen in previous posts, e.g. in the post linked below.
USD will go down much much further big picture, but right here, USD is at an inflection point.
If USD rolls over here, we could get one of my "everything but USD" up moves.
If USD continues up here, we might get an "everything but USD" down move.
Next Fed FOMC meeting might actually mean something this time around.
There are other charts that indicate what we will get, but let´s see.
Managed to nail the two previous tops in the US Dollar, so I of course have to try and do it this time around too.
So here it goes => now calling the USD top right here.
The Euro looks ready here now for putting in the weekly cycle low. And that means USD should be ready to top for the weekly cycle high. The Euro should push USD down as it moves up.
This major currency cycles turn should mean that we will get one of my "everything but USD & yields" upmoves, i.e. USD dropping should push up almost everything for a while. #joinus graddhy.com
ADHD could be nutritional deficiency
ADHD patients might have compromised or slowed B6-dependent enzymes.
The specific B6-dependent enzymes heavily implicated in ADHD include:
1. Dopa decarboxylase that converts L-DOPA into dopamine and 5-HTP into serotonin.
2. Glutamate decarboxylase (GAD) that converts glutamate into GABA.
3. Tryptophan metabolizing enzymes (think the kynurenine pathway)
"But i don't feel anything from B6".
A) Are you using P5P?
B) Do you have enough zinc, B2 and magnesium in your system?
"How do you have all these figured out?"
You should read this:
fitandball.gumroad.com/l/bra…
💰
BREAKING: Global physical gold-backed ETFs attracted +$30.7 billion in inflows in Q3 2026, their largest quarterly intake on record.
In September, inflows totaled +$10 billion, the 3rd-largest monthly inflow of 2026, following +$17.9 billion in August, the 2nd-largest monthly intake on record.
As a result, global gold ETF holdings rose +67 tonnes last month to a record 4,256 tonnes.
This surpasses the previous record of 4,176 tonnes set in February.
Year-to-date, global gold ETFs have seen +$38.5 billion in inflows, equivalent to an increase of +226 tonnes in gold holdings, with all regions recording positive demand.
UK-listed funds have attracted +$9.5 billion in inflows over the same period, overtaking China to become the largest source of country-level demand so far in 2026.
Demand for gold is extremely strong.
ali retweeted
"Gut health = mental health because most serotonin is produced in the gut".
Not exactly.
A) Serotonin in the brain is synthesized in neurons located in the raphe nuclei of the brain.
B) LPS lowers extracellular serotonin in the hippocampus since it increases histamine levels that bind to H3 heteroreceptors located on the terminals of serotonin neurons.
Activation of these inhibits serotonin release into the synapse → leading to lower extracellular serotonin levels in areas like the hippocampus.
Gut health = mental health for many other reasons, such as the composition and function of the gut microbiome strongly influencing adult neurogenesis through the microbiota-gut-brain axis.
Gut health = Mental health, also because it greatly influences the immune system.
So a dysfunctional gut = a dysfunctional immune system.
In the top right one for example (25K people) SLE was found to be independently associated with BD.
Also:
-A Danish study based on the records of 7,704 people, found that individuals with SCZ have a 50% lifetime prevalence of autoimmune disorders and that conversely, given a history of autoimmune disorders, the relative risk for SCZ increases by 45%
-A Swedish study reported an increased risk of affective, personality, and neurotic disorders among individuals hospitalized for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ankylosing spondylitis (AS)
-The kynurenine “shunt”.
When the gut is inflamed (due to dysbiosis or LPS), an enzyme called IDO is activated.
This leads to the overproduction of quinolinic acid, a neurotoxin that overstimulates NMDA receptors in the brain. This causes “excitotoxicity,” leading to anxiety, racing thoughts and so on.
-Ammonia and microbial metabolites.
Certain pathogenic bacteria and yeast (like Candida) produce byproducts like ammonia and acetaldehyde. If the gut barrier is permeable, these toxins enter the bloodstream and cross the blood-brain barrier.
This is of course, problematic since ammonia for example, interferes with astrocyte function.
This quite literally makes you feel dumber since it physically slows down neuronal signaling.
-Negative impacts on the vagus nerve.
The vagus nerve is the main physical connection between the gut and the brain.
Gut bacteria can release chemicals that stimulate this nerve to send “danger” or “distress” signals to the brain’s emotional centers, even if there is no external psychological stressor.
-The release of pro-inflammatory cytokines like IL-6 and TNF-α that can cross the blood-brain barrier (BBB).
Once in the brain, these inflammatory markers activate microglia (the brain’s immune cells), which can disrupt the growth of new brain cells and damage neural connections, a hallmark of major depressive disorder.
In animal models for example, candida-induced inflammation reduced cognitive clarity by 30%.
-Acetaldehyde release
Acetaldehyde can bind with dopamine in the brain to form substances called THIQs (tetrahydroisoquinolines), which are structurally similar to opiates.
Now to be more correct what happens is that when acetaldehyde reacts with dopamine, it forms compounds like salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) and THIQs are structurally similar to morphine-like alkaloids (opiates).
For instance, tetrahydropapaveroline (THP) is a THIQ precursor to morphine alkaloids.
fitandball.gumroad.com/l/bra…
ali retweeted
•Dopamine increases the release of inflammatory cytokine IL-6 in human macrophages
•IL-6 release is mediated by a rapid dysregulation of balanced mitochondrial function
•Dopamine-driven mitochondrial dysfunction increases glycolytic shift
sciencedirect.com/science/ar…
ali retweeted
The Brazilian Real is currently much stronger than it appears at first glance. That's because the Dollar is massively bid at the moment, so the fact that the Real has managed to strengthen - even as the rest of EM is tumbling - is a sign of real strength.
robinjbrooks.substack.com/p/…
Great thread
"I have become lazy and apathetic".
Just biohack your way out of it.
You can reprogram yourself to crave and enjoy "hard" things by default.
For example, when you cannot seem to start a task you have to do and procrastinate, it is usually caused by one of three things:
-A weak dopamine spike in response to normal cues.
-Your brain's calculator deciding the effort isn't worth the reward.
-The "indirect pathway" keeping the brakes slammed down
So what we call motivation is a cost-benefit calculation performed by dopamine circuits that connect your midbrain, prefrontal cortex, and basal ganglia.
If the pathways run smoothly and are supported, things don't feel like a constant drag and challenges can actually feel exciting.
If these pathways don't run smoothly, you feel lke you need to put in the effort of running an ultra marathon just to do the basic task.
The reward doesn't feel nearly that it justifies the amount of effort you need to put.
"Isn't this depression?".
Not exactly.
"Is a dopamine detox enough?"
It's usually unnecessary, and there are more effective measures you can take.
So here's the neuroscience of motivation and enjoyment.
Thread 🧵
