“Do you think studying monolayers of cells will tell you why you fall in love with a girl?”
The quote comes from Rudolf Hess, who won the Nobel Prize for physiology in 1949. His students remembered him as telling them never to study a neurotransmitter or even a cell without thinking about where this bit of the body comes from and what it is supposed to do.
This is one of two posts on boundaries – we want you to read this and Gateway to the Soul.
A boundary is the most basic, most primitive, essential to life. Something producing an inside that can be “defended” against an outside. Something creating an order that can be “stabilized” in the face of disorder.
Boundaries created life. The next step was boundary splitting to create more than one individual followed by boundary to boundary contact in order to pass on, reproduce, any secrets any individual has learnt. Sex has always been a boundary issue and boundaries were where it all happened long before we had brains.
You’d expect our most primitive chemical agents to be linked to boundaries. What you find on our boundary is lots of 5-hydroxytryptamine.
5-hydroxytryptamine was discovered in the gut – the gut is stuffed with it – and so it was first called enteramine.
Guts are buried deep in us – seemingly as far from our boundary as you can get in the human body. Not so. The gut is a hollow tube through us. What’s in our gut is outside us. Our skin and gut are continuous – and mark our boundary – a boundary that relatively speaking is bigger than the Great Wall of China and by far our biggest component, by definition, given that everything else has to fit inside it.
From the recent fuss about our microbiomes, you’d think we had millions of bugs living in our guts, all smarter than the average human, who essentially dictate out personalities, destinies, diseases and a lot more. There are also a ton of bugs on our skin, digging in and burrowing around but nobody ever figures these guys are all that bright and we’d rather not think about them.
In fact, the bright, intelligent thing is our boundary, whether the skin or gut wall. It’s much brighter and brainier than any bugs. The diversity of life on earth hinges on boundary adaptations – these give us the sexual plumage of birds, the hard skin of crocodiles which despite its hardness has built in vision sensors, the hooves of horses. All these shape shifts to our boundary make life on earth possible from ocean deep to mountain high, desert hot to polar chill. They are central to our vanity from the hair of women to the hair-loss of men.
The next place 5-hydroxytryptamine was found was in our blood, especially in platelets, leading to another name – serotonin. There isn’t any part of our boundary that isn’t supplied with blood the whole time. The heart is big and muscular, not to contain the soul, or to get blood to our brain, but to get blood cells out to our skin, where among other things when the boundary is punctured platelets release serotonin causing blood vessels to constrict so we don’t lose blood and triggering clots to stop any bleeding.
Our boundary is right in front of us the whole time. We delight in our children’s boundaries or the boundaries of our loved ones but yet we know less about these boundaries we see and touch every day than we know about the brain, which none of us ever gets to see or touch. Although it is right in front of us, or gurgles at inopportune moments, we know almost nothing more about our boundary that we knew a century ago.
Again and again when people with PSSD fill a RxISK report on the horrific effects an antidepressant has had on them, when asked what advice would they give to someone considering taking the drug, they typically reply on the lines of “You should not take these drugs without knowing the full effects they can have on your brain”.
There is almost no serotonin, 5-hydroxytryptamine, in our brains. But still most people with Post SSRI Sexual Dysfunction (PSSD), or enduring withdrawal problems from SSRIs, think they have damaged brains.
In the case of people who have an enduring sexual dysfunction syndrome very similar to PSSD, after Finasteride (Post Finasteride Syndrome) or after Isotretinoin (Post Retinoid Sexual Dysfunction) or in the case of people with what seems to be the mirror image condition – Persistent Genital Arousal Disorder (PGAD) – those affected don’t talk about brains as often. Those with PFS talk hormones. Those with PRSD looking through a glass darkly see a void where the culprit should be.
This turn to brains or hormones looks like the hand of pharmaceutical company marketing at work, directing people who have been on SSRIs to think their problem must lie in their brain, and people taking finasteride to think hormones.
We are not where we think we are
The root cause of the persisting sexual dysfunction problems that stem from the use of retinoids, finasteride and antidepressants may lie in our brains or hormones or, wherever it lies there may be knock-on effects on brains or hormones, but retinoids, finasteride and SSRIs also act on our boundaries.
Retinoids do so obviously – hence their use for acne. But almost as common is the effect they have on our gut from our lips to our anus causing what can be an intense and catastrophic drying.
We take finasteride to stimulate growth of our hair – a component of our skin.
The single commonest and most immediate effect of SSRIs is on genital skin sensitivity followed by the nauseating gut changes they trigger.
We also have a large number of reports to RxISK of hair changes – people finding that colour put into their hair doesn’t take or hair texture changes if they are on an antidepressant.
Four decades ago, in the relatively early days of neurotransmitter research, there was great excitement when an increasing number of gut peptides were found to be neurotransmitters and were also found to be present in the brain. There seemed to be little in the brain that wasn’t already in the gut.
The transmitters in our skin are still relatively unexplored compared to the gut. There is a must read book by David Linden, called Touch, which is a fascinating read but even it sticks primarily to describing the relatively well-known sensory receptors in skin – that deal with itch, vibration, temperature and pressure.
There are a host of other senses in skin. Our skins likely see – they contain a transmitter called neuropsin, which is closely related to the colour pigment, rhodopsin, in our eyes.
Our skins probably hear. Many people prefer live concerts or loud music to the radio or other means of listening to music. The experience is much richer, probably because the vibrations are part of their experience in addition to what we think of as hearing.
It seems highly likely that the keratinocytes in our skin respond to changes in atmospheric pressure and something else is what puts our “nerves” on edge if we live in any of the many places noted for having seasonal winds that can have dramatic effects on the population.
Skin and Mood
Our skin and gut, our boundaries, probably do more than our brains to determine our emotional state and our moods.
There is a nucleus in the brain, the locus coeruleus, the blue spot, that is stuffed full of catecholamines, the fight, flight or freeze hormones. This is critical to keeping us alive. Opioids turn the blue spot off and the resistance this nucleus puts up to being turned off is what creates opioid dependence and withdrawal.
Its job is to be vigilant. You might think evolution programmed this in to help our ancestors keep an eye out for the many animals on the savannah or in the jungle that could have wiped them out. You’d be wrong. Up to 90% of the inputs to the locus coeruleus come from our bladder (another boundary), bowel and skin – our boundaries – with only 10% devoted to the wider environment.
Our brains in other words are wired to monitor our boundaries.
There are lots of people with PSSD, PFS and PRSD who figure there is something slightly mad or quixotic about the RxISK focus on genital numbness as a cardinal feature of these problems. Many, in particular those on SSRIs, say their emotional numbness can be even more devastating and wonder why we don’t include this in our definition of PSSD.
There are a few answers to this. One is the very simple one that genital numbness is a much more clearcut phenomenon for researchers to get their teeth into. Especially as lidocaine produces an almost identical genital numbness. How exactly does this happen – well however it does, it’s a problem that looks a lot more soluble than establishing what is causing emotional numbness. But the reason to focus on genital numbness lies in the hope that nailing down what is happening in genital numbness will reveal what causes emotional numbness also.
There is no question that SSRIs can cause a devastating emotional numbness and for many that this may be worse than genital numbness.
But where does this emotional numbness come from? Our brains? What about from our skin or gut? Genital numbness happens too quickly after a first dose of an SSRI for there to be much of a brain effect and the same effect can be produced by rubbing things into the skin. Significant and enduring genital numbness, and the change in sexual function that goes with this, can in turn be expected to reduce libido – which happens weeks or months after the first genital numbing.
In the same way, the emotional numbing and depersonalization that is linked to SSRIs may stem from wider skin effects of these drugs. It may be a sensory numbness.
What wider skin effects? Well, all SSRI and most drugs that inhibit serotonin reuptake are derived from anti-histamines and have anti-histamine effects. As everyone with an allergic knows, they act on the skin around the body.
When we take an anti-histamine for itch or allergic skin responses, we don’t think its helping by acting on our brains.
These same antihistamines can cause akathisia (agitation), suicidality, sexual dysfunction and most of the problems we link to SSRI antidepressants. It’s the marketing that gets in the way of us thinking this is all happening in our skin rather than our brain.
What’s the brain got to do with it? Probably very little other than to interpret the threat that has been signalled from some part of our boundary. The brain is probably not where our soul is – it’s in our boundary.
Akathisia is one of the greatest threats any medicine can cause. It leads to suicide and homicide and intense restlessness. But no-one knows what akathisia is or how it happens. There is no akathisia centre in the brain.
What about in our skin, gut, bladder? Could it be boundary problem? A lot of the descriptions of this horrific state, talk about an almost indescribable inner itch that gives rise to fleeting disconnected “thoughts”, an emotional turmoil. This would map well onto the idea of a brain trying to make sense of the flood of inputs that are unfamiliar and wrong.
Skin drugs like Otezla, Siliq, Taltz and others along with Isotretinoin are among the drugs most likely to trigger an akathisia that leads on to a suicidal act.
Exploring the Boundary
Looking at PSSD, PRSD PFS and PGAD this way, we would see them as peripheral sensory disturbances.
Withdrawal from serotonin reuptake inhibiting may be the single commonest boundary problem – peripheral sensory disturbance syndrome – we have.
People finding it impossible to get off an SSRI, think brains because that’s where the key component of opioid dependence lies. Maybe we should be thinking skin, and gut, and bladder which is where the symptoms are.
As Willie Sutton might have said why look at skin – that’s where the symptoms are.
There are real cognitive problems on SSRIs and on stopping SSRIs but this doesn’t mean the problem is in the brain. None of the brain testing ever shows a cognitive problem there. But if our periphery is not working right, a normal brain will function abnormally.
Whether you agree PSSD, PGAD, PFS or PRSD or Antidepressant dependence and withdrawal have anything to do with our boundaries or not, it would be wonderful if some readers could start thinking about boundaries – without being too worried about current neuroscience orthodoxies. Having no background in these areas may make it easier to come up with just the kind of idea that are needed at the moment.
We need to come up with good descriptions of the sensory effects people may be having. We are so unused to thinking this way that we almost don’t have the words for it.
In an adjoining Gateway to the Soul post we ask you to improve on the questions we ask or to send us in comments or thoughts that might point to other questions we should be asking.