It has come to light (by 2007ish) that drug companies have been less than
fully honest about the scientific basis for various claims about drugs intended
for the treatment of depression and bipolar disorder.
There is also criticism of the
widely-reported, but poorly supported by scientific studies, theory that
depression is linked to
levels of the neurochemical serotonin. I have a
particular interest in this, as I was treated (successfully and without any
unwelcome side-effects) for clinical depression in the course of 1993; a
hypothesis based around serotonin was my doctor's stated rationale for the
choice of drug used to treat my condition.
I was ill, was told a particular explanation of my illness, was treated in a manner based on the hypothesis behind that explanation and subsequently got better. None of that is proof that the hypothesis was in fact correct – it's merely data which fails to contradict the hypothesis. Nor is it proof that the treatment caused me to get well; that might have happened for some other reason. Even if the treatment did cure me, this doesn't prove the hypothesis that prompted giving me that treatment; the medication might have worked for some quite different reason. All the same, both the hypothesis and the treatment can claim it as supporting (mild) evidence: a prediction was made and tested by an experiment which didn't contradict it. At the very least, my experience is evidence that there is a form of depression which can be cured by the combination of my doctor's explanation, my understanding of it (and trust in him) and the medication I was given; some of those ingredients may be irrelevant, but something there worked. Furthermore, my subsequent history bears testimony to something significant having definitely changed, since this cure and unexpectedly, in the way my brain works.
I shall begin my story in the middle, since what I've learned since sheds light on what I experienced before. I can no longer describe my prior life as I perceived it at the time, because that light illuminates details I never could have recognised at the time.
I had gone to my doctor to ask for a psychiatric referral, as I was finding life hard to cope with. His response was to invite me to talk about it, just as a psychiatrist surely would have done. I duly told him my tale of woe and he listened intently, asking questions from time to time. In due course he was persuaded that I was suffering from a neurochemical disorder he believed could be cured by feeding me the right tablets for a while. He had, previously, found me an articulate and scientifically-educated patient, so took the time to explain to me a moderate amount of the details of what was wrong and how the treatment might remedy it. I have had more than two decades in which to forget the details; and scientific understanding of the subject matter has moved on significantly in the interval; so I give here an account of what I remember (with minor corrections where I now know better) and remind you, dear reader, not to be too hasty to believe it too certainly.
Serotonin is a neurochemical heavily implicated in our emotions; it
encourages the brain to establish or strengthen neural connections. Like many
regulatory and messaging systems in the body, it is a chemical released by some
parts and responded to by others (in the case of serotonin, mere millimetres
away, if I remember correctly: other chemicals travel comparatively tiny or huge
distances, but have similar mechanisms). For such systems to work, it is
necessary to mop up the chemical once it has done its job; otherwise, it'll
trigger responses where it shouldn't and a background concentration of it shall
build up and make new activations hard to notice. So there is an accompanying
chemical, present as part of the background chemistry of the brain, whose job is
to mop up serotonin; I'm not sure what the right term for it is, so I'll stick
mop, if only for brevity's sake. Now, the mop needs to be present
at the right concentration: if there is too much, serotonin gets
away before it can do its job; if too little, the general problems that make
mops necessary begin to manifest. Most people's brains manage to keep that
concentration right by noticing what's responding to serotonin and adjusting
dynamically. However, the mop is produced only slowly and is, likewise, only
removed slowly, by the body's steady draining away of internal fluids via the
lymphatic system. The brain can be slow to respond; but, when all is working
well, it generally manages to keep to a comfortable stable state in which
serotonin can do its job and the brain can recognise small perturbations away
from proper functioning so as to respond to these by tweaking mop production to
As it happens (albeit, please do remember, this is a very imprecise account
of the matter) there is a moderately well-known condition in which the patient's
brain's regulation of serotonin's mop fails to keep to that happy medium; it
spends periods over-producing the mop, hence suppressing serotonin activity; and
it spends periods under-producing, causing extraneous serotonin activity, over
and above what's actually helpful. The former state tends to leave patients
depressed and the latter tends to bring out rather more enthusiasm for life;
this rather over-simplistic characterisation of the two states leads to the
old-fashioned name for the condition,
manic-depressive, but the reality
is far more complex than I shall try to express here. The term
is now more usually used, to address the fact that there are two states that the
patient flips between, without going into over-simplistic characterisations of
In, I suppose, the late '80s or early '90s, drugs were developed that were
touted as helping to stabilise the bipolar condition. To the surprise of
everyone involved, some patients weren't simply stabilised: they got better. In
due course, it emerged that there was a class of patients who were (sometimes)
being mis-diagnosed as bipolar but actually had a rather different condition, in
which the mop is over-produced all the time and the brain, for whatever reason,
mistakes the total absence of serotonin's effects as a reason to produce more
(where it should be recognising this as a reason to produce less). Patients
(such as me) with this condition respond to the relevant drugs by pausing
mop-production; after some months, mop concentrations drop down to a healthy
level and the
usual regulatory mechanism is able to keep the patient
stable without further pharmacological assistance.
Now, as it happens, I am a mathematician with moderately
well-informed intuitions about dynamical systems, which I naturally model as
systems of differential equations. In the absence of any reason to suppose
otherwise, it is reasonable to expect such systems to be non-linear,
multidimensional and (to use less technical terms) downright messy. As my
doctor was describing this to me, I was picturing a dynamical system which, with
one set of underlying control parameters, has two stable points but which, when
perturbed, loses those stable points in favour of a pair of
attractors, regions that the system tends to hang around near for sometimes
long periods before drifting away. Given a system with a known stable point and
the information that a perturbation of its control parameters can turn it into a
system with two strange attractors, it struck my intuitions as entirely
unsurprising (albeit by no means guaranteed) that there is a second stable state
in the unperturbed system. All this ran around in the back of my head while I
was listening to my doctor explain my situation.
Note, by the way, that my doctor wasn't saying the problem was high or
serotonin levels: unless I've wildly misunderstood, serotonin is
produced in bursts, in response to suitable situations, to promote the formation
of particular kinds of neural links, so the level of it in the brain would be
affected by how much relevant neural activity was triggering transient
production. That signal would be scaled up or down by the concentration of the
mop, but it's levels of the mop that the given hypothesis claims are
significant, not levels of serotonin per se.
The doctor described my condition as
clinical depression; this was
indeed a fair description of the last three years of my third decade. I am
fairly certain, all the same, that I endured the underlying condition for the
whole of my first thirty years, except possibly for some early part of childhood
(that I can't remember). I routinely had to fight off despair; but I could, so
I did. I found many social situations terrifying; but I managed somehow to keep
that to myself. I was unaware that there was anything wrong with me, so
supposed everyone else lived with similar and was coping, so I should do the
same; and, for the most part, I was successful in this. My doctor did mention
that, once my condition had come to the attention of the medical profession, it
turned out to be rather more common than doctors expected: it is possible for a
patient to endure a living nightmare for long periods without bringing it to
anyone else's attention. I shall not be surprised if many with this condition
have succeeded in holding back despair so well that they're unaware there's
My doctor remarked that, given my condition, I was
Mayhap he just wanted to reassure me that I had no need of the psychiatric
referral I'd asked for, but I chose to take it as a testament to something in my
head being robust against a rather major difficulty. In any case, I knew that I
was hearing good news and welcomed it.
As I was leaving my doctor's surgery, on my way to the chemist's shop (which
some dialects call a pharmacy) I remember experiencing great relief. The vast
weight of despair that had crushed me for three years began to evaporate, in
large part because what I had just learned broke a feed-back cycle in that
despair, where the
knowledge that I would live out my life always with
despair was one of tha major unwelcome truths of my life, that inclined me
towards despair. Consequently, the possibility that a placebo cure might
actually work did cross my mind. None the less, I chose to trust my doctor and
believe what he had told me (if only to make the placebo work). I took the
tablets for a bit over half a year, during the course of which my thirtieth
birthday came and went, I visited Katmandu with a friend of a friend, I got a
job back in Cambridge after a few years away and I never once had to fight off
I was living with a very different brain, after that. It had a whole new class of possibilities open to it and it began working out how to use them. I was only dimly aware of change, which I certainly couldn't have characterised at the time, but I was aware that something was changing. Since it wasn't a permanent nightmare, I wasn't too worried about that. With hind-sight, I now believe that I had belatedly begun the emotional development that most folk go through as part of growing up; but the first clue to this that I noticed came about seven years in, so I had plenty of time to wonder around in a daze.
When my peers had been growing up, in all respects, I had missed out on the emotional development that they got as part of the deal. I still got a pile of dumb hormones, instincts and general bodily development to live through; and my intellect was steadilly learning more about the world as I went along. I'll return to what that experience was like, but crucially there were things I didn't learn while growing up because, quite simply, I lacked the mental machinery to make sense of much of the social dynamics going on around me. The social dynamics of kids and teens growing up includes a fair bit of emotional rough-and-tumble, with which I was not equiped to cope, and is the arena in which most folk learn about their emotions, learn to recognise similar in others and learn to understand the effects of their actions on one another. They may well learn a great deal more that builds on those lessons; but these basic lessons are the prerequisites of even recognising the phenomena from which such other lessons are learned – and I missed out on the basics.
I lived through my (belated) emotional development amid the relatively sedate social dynamics of adult professionals, who generally keep their emotions to themselves and try not to disturb one another emotionally; so the world around me offered few opportunities to learn the lessons I'd missed. Even after I noticed that I was experiencing my emotional development, this didn't occur to me: it has taken me more than two decades to recognise that there are lessons I never learned, that those about me mostly learned while growing up and take for granted. I did, all the same, learn a little along the way; and now that I know what I missed, I can see the need to pay attention so that I may learn more. My ability to learn is not so good as a child's – there are pieces of neurochemistry, to facilitate creating new neural pathways faster and making them stronger, that go away after puberty; serotonin never got to help me create new pathways until those were long gone. so I lay down new pathways slower and do not make them as strong as I would have, had I done so while growing up – but I can at least still learn, albeit slowly and with effort.
My personal relationships remained clumsy through my thirties, thankfully without any major disasters to upset those around me. A decade after being cured, with emotions presumably somewhat akin to those of a teen-ager, I did have the good fortune to meet and fall in love with a woman who coped with my strangeness for a decade. I do not entertain the delusion that I was an ideal boyfriend; certainly, there were things she wanted that I failed to understand, much less give her. I have much to learn yet, before I can suppose courtship a sensible use of my time; but I live and learn – and one thing I have learned is that I can find solace in solitude.
To this day (in my fifties) I remain poor at recognising details of the emotional terrain around me – especially at seeing any sense in which I might be important to others. I have no idea why anyone likes me and am often surprised at how many clearly do. When I do recognise that someone likes me, I have little idea of how relevant I am to them; indeed, I have a painful habit of assuming myself incidental to the lives of others, even when faced with clear evidence of friendliness. This surely makes me difficult for others to deal with, if only because most take for granted that those they meet know what they and those around them learned while growing up, that I am barely beginning to learn. If someone fond of me is less than direct about letting me know it, I am apt to fail to notice subtler messages, which may lead to me appearing to rebuff them, when in fact I've simply missed a message that would have been amply clear for most others. Underestimating my significance to others does also manifest as shyness: perhaps they would be glad of my company, but I fear I am intruding, so leave them be.
I was, in many regards, very fortunate in the circumstances of my birth and growing up. I come from a well-educated and prosperous family; my parents took great care over our upgringing and particularly our education; and my material needs were well provided for. Even a massive neurochemical flaw does not negate those things; I was given a good start in life.
All the same, the kid who has trouble learning to control his emotions is, it would seem, a fun target for those who want some practice at upsetting others or making them angry. Worse, even when I was not being picked on, I had little grasp of the subtleties of social situations. That, on its own was enough to ensure that I perceived much of the social interaction of my peers as plain meanness; and, when misunderstanding situations lead me to respond in ways those about me didn't like, I was apt to be on the receiving end of deliberate meanness.
The emotional rough-and-tumble of the games kids play is moderated by empathy and peer pressure; if you treat me in ways our peers doubt they would be able to cope with, they shall shun you and treat you unkindly; so you learn not to treat me more unkindly than you would be able to cope with yourself. That works adequately well to keep the game educational without getting hurtful; but empathy relies on the premise that I'm like you, so can cope with the same kinds of unkindness you can. As my emotional development was (at least) behind my peers', that premise failed and I was routinely treated more unpleasantly than I could cope with. I consequently learned significantly different lessons from these games than my peers did.
I cannot remember being similarly horrible to my peers; but my impression is that no adult remembers having been so when we were kids; yet we all remember how mean everyone else was. So I shall not trust that memory to mean I wasn't as horrible to my peers as they were to me. All the same, my abiding memories of childhood and my early teens are full of endless nastiness; I certainly would not describe my first two decades as the happiest days of my life. My fifth decade now holds that title quite unequivocally.
Fortunately, I am not entirely stupid. Though I missed many subtleties of the social dynamics going on around me, I did learn from what I could witness; I could see quite a lot of what can upset, annoy or distress people; and I have come away from it all knowing how to avoid the more obvious of those. (No doubt, as a child, I also learned how to deliberately do them, too; but I'm fairly sure I was less competent at it than my peers.) On the other hand, I have rather less understanding of what can brighten the lives of others; and failure to do those things can also upset those who see quite plainly that I like them.
I have fallen in love more often than I can enumerate. I have also had a moderate number of girlfriends. Sad to say, (up past age fifty) the overlap is only one; all I can say in my defense is that, even when I met her, I wasn't yet emotionally adult; before her I was crashing around in an adult body, with (mostly) adult hormones and instincts, but with emotions closer to those of a child. I must thus entertain the possibility that I have broken more hearts than I have any inkling of; and I have inklings of several.
More painfully, since the inklings I have do include them, there were also some near misses. More than once it has happened that: I loved her dearly and might well have been her boyfriend had I but recognised that she loved me too. Two of those I have never stopped regretting, despite knowing full well that regret does no good and despite the glib answer I could so easily give – that it was all my neurochemistry's fault. In each case, I believe I hurt her by failing to follow my own heart. In the first, I was terrified of being too forward; but writing to her when she moved to another school could surely not have been described thus. Dancing with her at a friend's birthday party should have come naturally; instead, a little boy huddled in terror and refused to listen to his friends telling him to do what his own heart begged him to do. When I think back to the other, I cannot comprehend how I managed the mental convolutions that left me still thinking her attached to her prior boyfriend; and asking her if she was would have been simple, reasonable and natural. Yet instead I managed a mistake that ended in divorce (from someone else) four years later.
My remorse at recognising what I had done is what finally put an end to my on-going fight against the despair that had all too often loomed at the back of my consciousness. After holding it off (with a minor lapse or three) for more than a quarter century, I allowed that despair to claim me – and plunged headlong into three years of curling up in a little ball of tears and wishing I had never been. A stubborn part of my head insisted on dragging me to what was needful – bed, work, shops, cooking and all – and had to talk the rest of me into letting it do so – Why bother, life is pointless ? It would likely be worse if jobless and soon after homeless – until one day it dragged me to the doctor. Thus, perversely, it was my grief at the enormity of the harm I had done that finally lead me to the doctor's door and my eventual cure.
I have enumerated two, yet mentioned there were more than I can enumerate (several dozen, roughly speaking). I was at one point in love with half a dozen women; yet had no clue how to even approach the possibility of courtship. I would visit and chat; but to ask more seemed too forward. I could not assess her interest in me sufficiently to persuade myself she would be glad of my company; so I fretted about whether I visited too often. I assumed she would not have much interest in me and so failed to give her any reason to take much interest in me. Asking her out might have discovered what she did feel for me, for better or for worse, yet I was terrified of offending, so did not ask.
The serotonin lapse may have contributed to some of these difficulties; but I fear there is a good deal more to it than that. I do now find myself able to believe that a woman might love me; and I notice some clues, though doubt does hold me back. I think there is now some hope that I may try, should I find myself in love with one who seems interested – yet I have a great deal to learn.
My doctor never told me I had missed out on emotional development, nor that I could expect to live through significant changes in how I experience emotions and social interactions. (It is entirely possible that the medical profession only knew about the depression that they know how to recognise. The agonising shyness is, after all, not that rare – hopefully, not everyone that shy is so because their neurochemistry is broken – so can't be regarded as a symptom by which to diagnose.) So it's hard to see how the emotional changes I've lived through could be a placebo effect. They look like a real effect of a real cure for whatever was, in fact, wrong with me – and there was more to that than just the depression that served as obvious symptom to bring it to my doctor's attention.
Even so, reading the after-effects as consequences of a real cure for a real condition, my doctor's hypothesis about my condition is just a hypothesis; and a placebo that did cure the real condition might indeed (as a consequence) trigger the after-effects. The doctor, after all, took no samples of my cerebral fluid, to measure the concentration of serotonin's mop. So my case is no proof that the medication cured me, or that my condition was as described to me, though it is (mild) evidence that may fairly be cited as supporting both. All the same, I'm fairly sure something was wrong with my brain for thirty years; and I definitely like life better since it got mended. The difficulties I'm left with are consistent with a failure to establish, while growing up, the neural infrastructure to support believing myself important to others; which is indeed something my cursory understanding of serotonin's rôle suggets would be a natural result of growing up with serotonin activity suppressed.
As it happens, just a few months before my doctor diagnosed what was wrong with me, I'd decided to take a break from shaving. This was partly prompted by curiosity to see what scraggly mess my facial hair would produce but mostly arose from seeing no sense in going to all the effort of shaving when nothing mattered anyway – least of all my appearance. As a result, I grew a whispy thin strand from my chin, reminiscent of portrayals common in Chinese art of old sages in rural settings (the photograph here, at left, was taken in spring, I believe; as summer progressed, only the centre-thread of beard got appreciably longer). Later in the year, I allowed some good folk raising funds for charity to shave my head and beard; after that, I let the hair grow back (while looking after it significantly better than I had previously) but resumed shaving my face.
Twenty-three years later, for approximately the same reasons, I embarked on a repeat of this experiment. I was mildly surprised to find myself with a somewhat more substantial beard (albeit nothing to write home about – I have yet to decide, ten months in, whether to keep it; but I let it grow enough to give a fair comparison picture here). I am, indeed, generally hairier than I used to be (albeit by no means hirsute).
Of course, the changed facial hair might just be a normal part of aging, but my capacity for confirmation bias definitely has an excuse for reading it as confirming my suspicion that the emotional transformation I'd gone through in the interval might have opened the door to some hormonal changes to catch up (and instincts to materialise) that hadn't made themselves felt before.
One after-effect of all of the above is that I can fully sympathise with the
view Martin Luther King Jr., at the end
Remaining awake through a revolution, quoted from
Negro slave preacher who didn't quite have his grammar right:
Lord, we ain't what we oughta be;
We ain't what we wanna be;
We ain't what we're gonna be;
But thank God we ain't what we was !
I'm not sure how orthodox or
accurate the inner mammal
institute is, but what
Dr. Breuning says about
the primary neurochemicals related to emotions (paraphrasing the rôle of
each) – dopamine (motivation towards near-term goals), endorphin (enduring
short-term hardship), serotonin (confidence of social importance) and oxytocin
(trust in and comfort with social context) – makes for interesting reading
(and these are the neurochemicals I've heard others mention in this
context). I was unaware of the rôle of myelin (which helps establish
strong neural pathways in childhood; but is gone by the time we reach
adolescence); this would indeed limit my delayed emotional development, as
serotonin got to join the party long after myelin left. The link between
serotonin and social
dominance (Dr. Breuning's phrasing; I've
importance) fits with: my tendency to think of myself as
unimportant to others; the trouble I have making any sense of it when I seem not
entirely irrelevant to others; and my tendency to underestimate my relevance
even in so far as I notice I have any.
Here's a relevant quote from an article about psychoactive drugs:
Written by Eddy.
How exactly, for example, do serotonin reuptake inhibitors help some patients with depression? We don’t actually know. Nor do we know why they don’t help some patients much at all, et cetera.