A family with troubles

This being notice of the book at reference 1, picked up from a chance encounter earlier in the month with the free part of a book review in the New York Times. The author is an established journalist, with a couple of other successful books to his name and with a great deal of work, over several years, with the Galvin family, their diaries and their records going into this one. A family sadly afflicted with a great deal of mental illness. A work loudly proclaimed as being a work of non-fiction despite the fact that many books of this sort do join up a lot of the dots. Lady protesting again, as in reference 11?

In the book, we have some introductory material followed by three parts made up of 45 generally short chapters, a number of which are digressions into the progress of research into and treatment of schizophrenia. Part one: chapters 1-17: from the beginning to the father’s retirement from public work after a stroke. Part two: chapters 18-40: to the mother’s death. Part three: chapters 41-45: aftermath.

An easy & interesting read, which could probably have been a lot shorter with tighter editing. The book is roughly chronological, but only roughly. The chapters generally focus on an individual or on a topic which means there is some jumping around. The book could have done with a pull-out diagram, time line across, family member down – the sort of pull out that you can read while keeping the book open at your place. And another one about the progress of relevant medical research. But I suppose you are not going to get that sort of thing in a small format, mass market paperback.

A book which attracted lots of media attention, which Bing or Google will turn up for the interested reader – and it was the ‘Daily Mail’ web site from which I have taken the illustration above, the occasion being the father finally getting his PhD in 1969, when he was 46 and I was an undergraduate.

For most of his working life, the father was in a non-airborne part of the USAF, having started in the Navy during the war and switched to the USAF in Colorado when this last was created in its present form after the second world war. He captained a landing craft during the closing stages of that war, there may have been some landing beach trauma and there were some mental health issues – although as it turns out, at the very end of the book, the gene which likely caused the problem came from the mother.

The family lived in a house in Hidden Valley Road, on a three acre plot to the north of Colorado Springs, a little to the south of the Air Force Academy. With Colorado Springs being on the right of the map, south of Denver and north of Pueblo, all visible if you click to enlarge. The area in general looks very hilly and this particular road looks very quiet, both by Surrey standards – and hilly by UK standards. I learn that the populous part of Colorado is to the east of the mountains and drained by the Arkansas River so well known to past-President Clinton. While the Colorado River rises to the west of the mountains before heading southwest, down to the Gulf of California, via the Grand Canyon. With Colorado Springs being close to being on the watershed between these two large systems.

The father was an enthusiastic falconer for many years, to the extent of claiming that he was responsible for the falcon being the emblem of the USAF. While I learn that the way to kick-start the training of a hawk is to sew its eyes shut for 48 hours or so. Not something that I can see the author of reference 3 going in for, noticed at reference 2. The family generally took advantage of the great outdoors and there was some skiing.

The couple clearly got along, having twelve children between about 1945 and 1965, ten boys followed by two girls. Morning sickness every time. Six of the boys went on to schizophrenia as young adults, with most of this six in and out of institutions all their lives – while most of the rest of them needed therapy of one sort or another for one reason or another – not least the challenges involved in living in such a family. Two of the normals – one of the boys and one of the girls – coped by getting away as soon as they could and largely staying away. While the other girl, the youngest, went through lots of therapy (which she paid for) but ended up being carer-in-chief for the family, shouldering her mother’s burden. Plus marrying and having children of her own, children of which she was, understandably, very protective.

Noticing along the way that a family friend paid for her to go to a private school in the very Lakeville, Connecticut where Simenon lived for while, at a place then called Shadow Rock Farm, noticed in the previous post.

One of the institutions was the mental hospital at Pueblo, a little to south. Once taking 6,000 patients, with the town of Pueblo being little more than an adjunct to its hospital – a size which makes the Exe Vale cluster which BH used to know at Exminster and the Epsom cluster we used to have here at Epsom seem quite modest. Now the Colorado Mental Health Institute at Pueblo and down to a very modest 450 in-patients. See references 4 and 5.

With an additional challenge for the family being abuse – which only saw the light of day many years later – by a priest, whom the mother, as a convert to Catholicism, was happy to have in her house.

Added to which, one or two of the sick boys abused the girls.

All in all, a grim story and one wonders how any of them made it, more or less in one piece.

The medical story

The medical part of the story makes an interesting and successful complement to the family history, spread over a dozen or so of the chapters. A few highlights follow, intended to illustrate the amount of time and effort which has been needed to make such progress as there has been.

Schizophrenia did seem to run in families and studies of families afflicted with a lot of schizophrenia wax and wane with academic and pharmacological fashion. One of the first such was the Genain family with its quadruplets, identical sisters, famous as babies for being identical quadruplets, thoroughly researched as schizophrenic adults and written up, for example, at reference 7. With a lot of interest arising from the four very different outcomes, despite starting out more or less identical, with one of them achieving a more or less normal life.

Up until the 1950’s the treatment for schizophrenics, at least during their florid phases, was usually committal to a mental hospital. Then the first generation anti-psychotics came along, and provided the schizophrenics took their tablets, they could often get on, after a fashion in the outside world. One problem was long-term side effects and another was not taking the tablets, apt to result in another florid phase and another admission to hospital. But at the time (as FIL remembered) these drugs were seen as a great leap forward, a leap which emptied some of the long-stay and sometimes deplorable wards of the mental hospitals – with many of them downsizing if not shutting.

This was about where things stood at the time the eldest Galvin boy was diagnosed in the mid 1960’s, and this boy was fed Thorazine (aka Laragactil), which did help control the symptoms but, as mentioned above, had unfortunate long term, physical side effects.

And despite this leap, schizophrenia remained an enigma. The experts were not even able to agree whether or not it was something which could properly be called a disease – as opposed to a miscellaneous collection of often difficult symptoms. With an introduction to this part of the story to be found at reference 8.

The psychoanalytic approach – the talking cure of Freud – epitomised by a famous clinic called Chestnut Lodge in Maryland – was generally regarded as having failed. Being expensive in both time and money and only really helping with maybe a third of the patients so treated.

In parallel, a dispute was going on between those who believed that schizophrenia was mainly down to nature, down to genes, and those who believed that it was mainly down to nurture, to the dynamics of the families concerned. Quite a lot of workers believed in the idea of a bad mother – an idea which generated much guilt in its time. But the nature team seemed to be gradually making ground. With some people attempting to strike a sensible compromise between the two camps: you needed problems with genes to make the disease possible, but you then needed problems with your life for that possibility to turn into disease, into schizophrenia.

In the background, no doubt because of the establishment’s rather mixed record in treating schizophrenia, various anti-psychiatry and anti-drug movements waxed and waned. One product of which was the famous film ‘One Flew Over the Cuckoo’s Nest’ of reference 9.

There were physical or neurological traits which seemed to be linked to schizophrenia. People with the disease had larger ventricles – fluid filled cavities – in the middle of the brain. They had smaller hippocampi, again in the middle of the brain. More promising, they seemed to fail something called the double click test.

This was in 1979. A Robert Freedman, now an eminence, had found that if you wired up a normal head and played two clicks close together, perhaps half a second apart, there was a large brain wave for the first click and a much smaller one for the second. The brain knew it did not need to bother with the second click. This did not happen with people with schizophrenia, the response to the second click was not being inhibited.

With this simple story being clouded by other studies which did not replicate this effect, at least not in a reliable way.

But he kept on, and twenty years later, in 1998, they found a receptor in the brain involved in this inhibition called the alpha-7 nicotinic receptor – and people with schizophrenia did not seem to have enough of them, maybe only half as many as was normal. With problems with this receptor being strongly implicated with schizophrenia. Problems which turned out to lie with a gene called CHRNA7.

At some point, he noticed that many schizophrenics were heavy smokers. They needed their shots of nicotine – the nicotine which seemed to prod the alpha-7 receptors that there were into activity. So Freedman now needed a drug which would pump nicotine into the body, and something called DMXBA seemed promising – but in the end the big drug companies backed off this one – with the Kolker story being that they did not go for a tablet which had to be taken two or more times a day.

Over the same period, the human genome project came to fruition and some people put their money on what were called GWAS – genome wide association studies. You just threw a big computer at the problem, that is to say a large sample of people with schizophrenia and a large sample of people without – and hunted down the gene variations, the mutations, which were associated with schizophrenia. With the result seeming to be that there were lots of them – one of them being the CHRNA7 already mentioned – each of which had a demonstrable but small effect, but with none of these effects being big enough to be worth targeting with drugs.

Another investigator, Lynn DeLisi, had a narrower focus and over the years she had assembled a big collection of samples from families with a lot of schizophrenia, the Galvins included. A collection which included groups of samples taken from closely related people, some of whom had or went on to have schizophrenia and some who did not. A collection which DeLisi was convinced must contain important pieces of the jigsaw but which was set aside for lack of funding.

But after a lull, DeLisi’s material was reactivated in 2009, and turned up a fault in a gene called SHANK2. There was also a SHANK1 and a SHANK3, seemingly implicated in mental disorders other than schizophrenia. And while this opened the door to some genetic counselling, there was no big therapeutic breakthrough here, just more work in progress.

Meanwhile, Freedman still kept on, and nearly another twenty years after the almost-breakthrough with nicotine, he worked on the idea of the brain being built in incremental stages, with the work of one stage depending in the work of previous stages, rather like incremental steps involved in starting up a large computer, with each step building on what has gone before. Which led to the further idea that a deficiency of something called choline in the very young brain was causing damage to some bit of the brain built early on, but only causing visible trouble many years down the line – a something which occurred naturally in lots of foods and you can (certainly now) buy the stuff in pill form in health food shops. This was what the faulty CHRNA7 needed to do its work. Which led in turn to the idea of dosing up pregnant women, known to be genetically vulnerable, with lots of choline. He was allowed to do a trial and the results – in terms of the performance of the resultant babies on the double click test – were promising. This being around 2015. A much longer haul trial, which will run over tens of years – is presently under way.

Is choline the magic bullet for schizophrenia that folic acid was for neural tube defects in unborn infants? A magic bullet which doesn’t stop then altogether, but is a big help.

Conclusions

Kolker makes good use of the tragic story of this family to tell us a lot about schizophrenia and what it is like to have to live with it in the family. Also about resilience; about how the more or less healthy half of this large family managed to cope with the other half.

A disorder which has been the subject of a huge amount of research over the years, which is slowly revealing its secrets, but which is still some way off being cured, never mind eradicated.

We are told something of the complexities of the academic and pharmacological worlds, in the first of which research can be expensive and in the second of which it is always expensive – and this money all has to come from somewhere. Not at all like some mathematical genius in the Soviet Union of old working it all out with blackboard and chalk. We are reminded that a drug company might make less money from a drug which cures a serious and widespread disease than from a drug which controls it. Market forces do not always force in the right direction.

PS: checking the USAF emblem suggests that this story might have got a bit overcooked. The mascot of the Air Force Academy is the falcon and their sports teams are collectively called the Falcons. But the bird on a lot of the USAF badges looks more like an eagle to me.

References

Reference 1: Hidden Valley Road - Robert Kolker – 2020. A recently published book, read in my case on my Kindle.

Reference 2: http://psmv2.blogspot.com/2014/12/goshawk-white.html.

Reference 3: H is for hawk – Helen Macdonald – 2014.

Reference 4: http://www.cmhipmuseum.org/history.html.

Reference 5: https://www.colorado.gov/pacific/cdhs/colorado-mental-health-institute-pueblo.

Reference 6: Memoirs of My Nervous Illness – Schreber – 1903. A read which is on its way to me, in translation from the German. One of the first, substantial, first person accounts of what it is like to be a schizophrenic.

Reference 7: Genain quadruplets – David Rosenthal – 1964. Far too expensive at Abebooks, so not on its way to me.

Reference 8: https://en.wikipedia.org/wiki/Diagnostic_and_Statistical_Manual_of_Mental_Disorders.

Reference 9: One Flew Over the Cuckoo’s Nest – Milos Forman, Jack Nicholson and others – 1975.

Reference 10: http://psmv4.blogspot.com/2020/04/choline.html. Choline got its own post.

Reference 11: https://psmv4.blogspot.com/2020/03/when-i-was-old.html.