Is psychosis an ‘immune disorder’?

A fascinating new study has just been published which found evidence for the immune system attacking a neuroreceptor in the brain in a small proportion of people with psychosis. It’s an interesting study that probably reflects what’s going to be a cultural tipping point for the idea of ‘immune system mental health problems’ or ‘madness as inflammation disorder’ but it’s worth being a little wary of the coming hype.

This new study, published in The Lancet Psychiatry, did blood tests on people who presented with their first episode of psychosis and looked for antibodies that attack specific receptors in the brain. Receptors are what receive neurotransmitters – the brain’s chemical signals – and allow information to be transferred around the nervous system, so disruption to these can cause brain disturbances.

The most scientifically interesting finding is that the research team found a type of antibody that attacks NMDA receptors in 7 patients (3%) out of 228, but zero controls.

The study found markers for other neuroreceptors that the immune system was attacking, but the reason the NMDA finding is so crucial is because it shows evidence of a condition called anti-NMDA receptor encephalitis which is known to cause episodes of psychosis that can be indistinguishable from ‘regular’ psychosis but for which the best treatment is dealing with the autoimmune problem.

It was only discovered in 2007 but there has been a long-running suspicion that it may be the best explanation for a small minority of cases of psychosis which can be easily misdiagnosed as schizophrenia.

Importantly, the findings from this research have been supported by another independent study that has just been published online. The two studies used different ranges for the concentration of NMDA antibodies they measured, but they came up with roughly the same figures.

It also chimes with a growing debate about the role of the immune system in mental health. A lot of this evidence is circumstantial but suggestive. For example, many of the genes associated (albeit weakly) with the diagnosis of schizophrenia are involved in the immune system – particularly in coding proteins for the major histocompatibility complex.

However, it’s worth being a little circumspect about this new enthusiasm for thinking of psychosis as an ‘immune disorder’.

Importantly, these new studies did blood tests, rather than checking cerebrospinal fluid – the fluid that your brain floats around in which lies on the other side of the blood-brain barrier, so we can’t be sure that these antibodies were actually affecting the brain in everyone found to have them. It’s likely, but not certain.

Also, we’re not sure to what extent anti-NMDA antibodies contribute to the chance of developing psychosis in everyone. Certainly there are some cases where it seems to be the main cause, but we’re not sure how that holds for all.

It’s also worth bearing in mind that the science over the role of the genes associated with the schizophrenia diagnosis in the immune system is certainly not settled. A recent large study compared the role of these genes in schizophrenia to known autoimmune disorders and concluded that the genes just don’t look like they’re actually impacting on the immune system.

There’s also a constant background of cultural enthusiasm in psychiatry to identify ‘biomarkers’ and anything that looks like a clear common biological pathway even for a small number of cases of ‘psychiatric’ problem gets a lot of airtime.

Curiously, in this case, Hollywood may also play a part.

A film called Brain On Fire has just been shown to film festivals and is being tested for a possible big release. It’s based on the (excellent) book of the same name by journalist Susannah Cahalan and describes her experience of developing psychosis only for it later to be discovered that she had anti-NMDA receptor encephalitis.

Hollywood has historically had a big effect on discussions about mental health and you can be sure that if the movie becomes a hit, popular media will be alive with discussions on ‘whether your mental health problems are really an immune problem’.

But taking a less glitzy view, in terms of these new studies, they probably reflect that a small percentage of people with psychosis, maybe 1-2%, have NMDA receptor-related immune problems that play an important role in the generation of their mental health difficulties.

It’s important not to underestimate the importance of these findings. It could potentially translate into more effective treatment for millions of people a year globally.

But in terms of psychosis as a whole, for which we know social adversity in its many forms plays a massive role, it’s just a small piece of the puzzle.
 

Link to locked Lancet Psychiatry study.

Hallucinating sleep researchers

I just stumbled across a fascinating 2002 paper where pioneering sleep researcher Allan Hobson describes the effect of a precisely located stroke he suffered. It affected the medulla in his brain stem, important for regulating sleep, and caused total insomnia and a suppression of dreaming.

In one fascinating section, Hobson describes the hallucinations he experienced, likely due to his inability to sleep or dream, which included disconnected body parts and a hallucinated Robert Stickgold – another well known sleep researcher.

Between Days 1 and 10 I could visually perceive a vault over my supine body immediately upon closing my eyes. The vault resembled the bottom of a swimming pool but the gunitelike surface of the vault could be not only aqua, but also white or beige and, more rarely, engraved obsidian or of a gauzelike nature mixed with ice or glass crystals.

There were three categories of formed imagery that appeared on these surfaces. In the first category of geologic forms the imagery tended to be protomorphic and crude but often gave way to the more elaborate structures of category two inanimate sculptural forms.

The most amusing of these (which occurred on the fourth night) were enormous lucite telephone/computers. But there were also tables and tableaux in which the geologic forms sometimes took unusual and bizarre shapes. One that I recall is a TV-set-like representation of a tropical landscape.

In category three, the most elaborate forms have human anatomical elements, including long swirling flesh, columns that metamorphosed into sphincters, nipples, and crotches, but these were never placed in real bodies.

In fact whole body forms almost never emerged. Instead I saw profiles of faces and profiles of bodies which were often inextricably mixed with penises, noses, lips, eyebrows; torsos arose out of the sculptural columns of flesh and sank back into them again.

The most fully realized human images include my wife, featuring her lower anatomy and (most amusingly) a Peter Pan-like Robert Stickgold and two fairies enjoying a bedtime story. While visual disturbances are quire common in Wallenberg’s syndrome, they have only been reported to occur in waking with eyes open.

Blurring of vision (which I had), and the tendency of objects to appear to move called oscillopsia (which I did not have), are attributed to the disturbed oculomotor and vestibular physiology.

 

Link to locked report of Hobson’s stroke.

a literary case of the exploding head

eOne of the most commented-upon posts on this blog is this from 2009, ‘Exploding head syndrome‘. The name stems from the 1920s, and describes an under-documented and mysterious condition in which the suffer experiences a viscerally loud explosion, as if occurring inside their own head.

I’m reading V.S.Naipaul’s “The Enigma of Arrival”, and the autobiographical main character experiences the same thing. Here we are on p93 of my edition of that novel:

In this dream there occurred always, at a critical moment in the dream narrative, what I can only describe as an explosion in my head. It was how every dream ended, with this explosion that threw me flat on my back, in the presence of people, in a street, a crowded room, or wherever, threw me into this degraded posture in the midst of standing people, threw me into the posture of sleep in which I found myself when I awakened. The explosion was so loud, so reverberating and slow in my head that I felt, with the part of my brain that miraculously could still think and draw conclusions, that I couldn’t possibly survive, that I was in fact dying, that the explosion this time, in this dream, regardless of the other dreams that had revealed themselves at the end as dreams, would kill, that I was consciously living through, or witnessing, my own death. And when I awoke my head felt queer, shaken up, exhausted; as though some discharge in my brain had in fact occurred.

The Enigma of Arrival on Goodreads
Vaughan’s 2009 post on Exploding Head Syndrome
Wikipedia: Exploding head syndrome

Reconstructing through altered states

Yesterday, I had the pleasure of doing a post-screening Q&A with the film-makers of an amazing documentary called My Beautiful Broken Brain.

One of the many remarkable things about the documentary is that one of the film-makers is also the subject, as she began making the film a few days after her life-threatening brain injury.

The documentary follows Lotje Sodderland who experienced a major brain haemorrhage at the age of 34.

She started filming herself a few days afterwards on her iPhone, initially to make sense of her suddenly fragmented life, but soon contacted film-maker Sophie Robinson to get an external perspective.

It’s interesting both as a record of an emotional journey through recovery, but also because Lotje spent a lot of time working with a special effects designer to capture her altered experience of the world and make it available to the audience.

I also really recommend a long-form article Lotje wrote about her experience of brain injury for The Guardian.

It’s notable because it’s written so beautifully. But Lotje told me she while she had regained the ability to write and type after her injury, she has been left unable to read. So the whole article was written through a process of typing text and getting Siri on her iPhone to read it back to her.

The documentary is available on Netflix.
 

Link to My Beautiful Broken Brain on Wikipedia.
Link to full documentary on Netflix.
Link to long-form article in The Guardian.

A brief hallucinatory twilight

CC Licensed Photo by Flickr user Risto Kuulasmaa. Click for source.I’ve got an article in The Atlantic on the hypnagogic state – the brief hallucinatory period between wakefulness and sleep – and how it is being increasingly used as a tool to make sense of consciousness.

There is a brief time, between waking and sleep, when reality begins to warp. Rigid conscious thought starts to dissolve into the gently lapping waves of early stage dreaming and the world becomes a little more hallucinatory, your thoughts a little more untethered. Known as the hypnagogic state, it has received only erratic attention from researchers over the years, but a recent series of studies have renewed interest in this twilight period, with the hope it can reveal something fundamental about consciousness itself.

The hypnagogic state has been better dealt with by artists and writers over the years – Colderidge’s poem Kubla Khan apparently emerged out of hypnagogic reverie – albeit fuelled by opium

It has received only occasional attention from scientists, however. More recently, a spate of studies has come out showing some genuine mainstream interest in understanding hypnagogia as an interesting source of information about how consciousness is deconstructed as we enter sleep.

 

Link to article in The Atlantic on the hypnagogic state.

The death of the soul has been greatly exaggerated

CC Licensed Image from Wikipedia. Click for source.I’ve got a piece in today’s Observer looking back on 20 years since novelist Tom Wolfe wrote a landmark article that threw open the doors on how the new science of cognitive neuroscience was challenging the notion of the self.

Exactly 20 years ago, Tom Wolfe wrote one of the most influential articles in neuroscience. Titled Sorry, But Your Soul Just Died, the 1996 article explores how ideas from brain science were beginning to transform our understanding of human nature and extend the horizons of our scientific imagination. It was published in a mainstream magazine, written by an outsider, and seemed to throw open the doors to an exhilarating revolution in science and self-understanding. Looking at the state of neuroscience and society two decades later, Wolfe turned out to be an insightful but uneven prophet to the brain’s future.

Wolfe’s article has been cited widely by both neuroscientists and the popular press.

It’s not entirely clear whether it shaped our popular understanding of brain science or whether it just predicted a future trend but it’s notable that before 1996 most press articles on fMRI were focused on technical details but subsequently they tended to be much more about ‘the brain reason for’ some aspect of human thought or behaviour.

Either way, it was clearly an important moment for neuroscience and my piece in The Observer looks back on Wolfe’s take on our changing view of human nature with the benefit of 20 years of brain science behind us.

And just to say, I occasionally have a bit of a grumble about the headlines written for my articles but hats off to however came up with “Neuroscience and the premature death of the soul” for this piece.
 

Link to ‘Neuroscience and the premature death of the soul’ in The Observer
Link to Tom Wolfe’s epic ‘Sorry, But Your Soul Just Died’.

Neuroimaging in 20 minutes

Neuroscientist Matt Wall did a fascinating talk on all things neuroimaging at a recent TEDx Vienna event. It’s a gently funny, engrossing talk that both introduces brain imaging and discuss some of the cutting-edge developments.

He particularly talks about some of the recent fMRI ‘mind reading’ studies – which are more complex, limited, and interesting than many people assume.

Recommended
 

Link to Matt Wall’s TEDx Vienna talk on neuroimaging.