Chemical Imbalances

[Christina]

(Warning - this OP is about brain chemistry. If you want to rant against psychiatrists go start your own topic :p )

Do any of you know very much about brain chemistry? I've been reading this (http://www.mental-health-matters.com/articles/article.php?artID=160) article and it's the only one that I've ever seen that reduces it down to a level that's understandable for someone without a science background, but I still have questions.

One of the most uncomfortable things for me is that there isn't a test that conclusively proves that someone has bipolar disorder or schizophrenia. Then I read this:
There are advanced imaging techniques such as Positron Emission Tomography (PET Scans) that are being utilized in research and in the development of medications that directly influence changes in specific neurotransmitters. Lacking a PET Scanner, most professionals evaluate neurotransmitter levels by looking for indicators in thought, behavior, mood, perception, and/or speech that are considered related to levels of certain neurotransmitters.
How do PET scans work and how do they test for neurotransmitter levels?

This section about dopamine was startling in how much it resembles what I went through a few years ago:
Moderately high Dopamine levels make us on-guard, suspicious, and prone to misinterpret experiences in the environment. Known as an "idea of reference" in psychiatry, we begin thinking unrelated experiences are suddenly directly related to us. People observed talking across the street are now talking about us. As Dopamine increases, it can become so intense that we feel the radio, television, and newspaper contain secret messages directed at us from Hollywood or elsewhere. It's as though we are attempting to incorporate/add everything we witness into our life.

But then it goes on with descriptions of symptoms that are far more like schizophrenia. My gut sense from talking to other people is that I have far more in common with schizophrenics than I do with people who have Bipolar II when it comes to the really extreme symptoms, but it stops short of hearing voices. How do they determine where the boundaries are between these different diagnosis are? Is it based on anything besides symptoms?

As Dopamine levels increase, the noises we heard loudly suddenly become auditory hallucinations. Our inner thoughts are now being heard outside our body. These "voices" begin talking to us, known to take different forms such as derogatory (putting you down), religious topics, command (telling you to do something), or sexual content. Hallucinations (experiencing something that is not truly there in reality) will soon develop in all our senses. We may begin seeing faces in clouds, carpets, or patterns. We may sense the touch of spirits or movements inside our body. We may experience unusual smells or tastes...Moderate to high levels of Dopamine, associated with severe psychiatric conditions such as Paranoia and Schizophrenia, are treated with medications that block or lower Dopamine in the brain. These medications, called antipsychotics, have been available for many years.
I had a few of these symptoms, most notably smelling horrible things that no one else could. It feels more like there is a continuum of symptoms than discrete conditions to me. I understand why I have to take an antipsychotic now, though.

This description of what it means to have not enough GABA is creepily familiar in terms of controlling brain speed. No wonder I go so fast that I go on tilt sometimes and when I take too much of the anti-convulsant I turn into a vegetable instead.
When GABA is in the normal range in the brain, we are not overly aroused or anxious. At the same time, we have appropriate reactions to situations in our environment. GABA is the communication speed controller, making sure all brain communications are operating at the right speed and with the correct intensity. Too little GABA in the brain, the communication becomes out of control, overstimulated, and chemically unstable. Too much GABA and we are overly relaxed and sedated, often to the point that normal reactions are impaired.

Low levels of GABA are associated with Bipolar Disorder, Mania. With GABA levels below average, the brain is too stimulated. We begin talking rapidly, staying up for days at a time, and develop wild and grandiose ideas. In a Manic state, we are so "high" and out of control that social problems are quick to develop, often due to hypersexuality, excessive spending, reckless decisions, risk-taking behavior, and grandiose ideas. We may feel so good that we think we are a heavenly spirit, an intellectual genius, or possessing extraordinary powers.

But then it goes on to say:
Low levels of GABA are also associated with epilepsy or seizure disorders. If we imagine a seizure as a type of electrical storm, the seizure begins at one location in the brain then rushes across and through the brain like a sudden storm. Low levels of GABA make it easy for the brain to develop seizures which is why seizures are part of the withdrawal syndrome for many substances that work with GABA such as alcohol and tranquilizers (benzodiazepines – Xanax, Ativan, Librium, Valium, etc.). Substances that artificially maintain a high level of GABA, when stopped, create a dramatic drop in GABA levels, thus creating the risk for withdrawal seizures due to the chemical instability that is created.
That explains why I take anti-convulsants and why I can't go off them abruptly without risking seizures. But are there conclusive tests for epilepsy that aren't just based on having seizures, and if there are, why can't they come up with a test for bipolar disorder too?

[Febble]

Well, this isn't my own area, but I'm married to someone whose area it is, so I'll have a go!

How do PET scans work and how do they test for neurotransmitter levels?

To have a PET scan you have to take in some kind of radioactive isotope. The simplest is a radioactive isotope of oxygen which you just breathe in, and it attaches itself to your haemoglobin in your blood-stream. The PET camera detects the pair of positrons that are emitted when the radioactive atom decays, and the computer constructs the position of the atom from those co-ordinates. That way you can get a picture of where the blood is going at any given time, and thus a picture of which parts of the brain are being used when (i.e. "functional" brain imaging).

But you can also use radioactive atoms in molecules called ligands (ie. "binding" molecules) that bind to neuroreceptors (receptor sites for neurotransmitters) so you can get a picture of the density of receptors in different parts of the brain.

Whoopsies, gotta run, be back in a bit.

[Christina]

[Right, now I know that edit button is lurking where the quote button used to be, I'll stop deleting posts accidentally - so sorry I deleted your post! - Febble]

[Febble]

Thanks, that made sense. It seems like no one knows why some of us have inadequate levels of some neurotransmitters. Is that what genetic research is trying to figure out, and do you know what other kinds of studies or tests can or are being done to find out more about what causes it?

Well, it's one of the things. One of the things about any medical research, though, and especially psychiatric research, is that diagnostic labels don't necessarily map on to causes all that well, or even to processes, or even to treatment! Which isn't that odd when you think about something like heart disease, which can be caused by bad diet, smoking, not enough exercise, genetic predisposition, etc, and which can be treated in various ways including changing life-style, surgery, blood-pressure lowering drugs, cholesterol lowering drugs etc. While knowing the cause might be useful in preventative medicine, it's not necessarily all that useful for selecting the right treatment. And the other classic example is TB which has a very clear cause (the TB bacillus) and treatment, but can manifest in all kinds of ways, depending on which parts of you it affects.

So to go back to a point in your original post:


But then it goes on with descriptions of symptoms that are far more like schizophrenia. My gut sense from talking to other people is that I have far more in common with schizophrenics than I do with people who have Bipolar II when it comes to the really extreme symptoms, but it stops short of hearing voices. How do they determine where the boundaries are between these different diagnosis are? Is it based on anything besides symptoms?
The short answer is "symptoms". I can't remember whether I recommended my husband's book ("Disordered Mind and Brain") but he took the approach of dealing with symptoms first, then mechanisms underlying symptoms, then disorders last, the disorders being, essentially, particular constellations of symptoms. And it's possible that people with schizophrenia may have the constellation of symptoms they do because of a particular causal pathways to those symptoms, although possibly not. He had at least on patient who seemed to develop schizophrenia following a head injury. So that is an unusual way to acquire the symptoms of schizophrenia, but those were what he had, so we have to assume that the accident damaged the bits of brain that are involved in schizophrenic symptoms.

And not all people with schizophrenia have auditory hallucinations, although it is the symptom most people think of in connection with schizophrenia. But for a while people have talked about the "positive" and "negative" symptoms of schizophrenia, the first being the florid "reality distortion" symptoms like hallucinations and delusions, and the negative symptoms being the psychomotor poverty - the anhedonia, lack of will to engage in action, or communication, also general cognitive slowing, which in some ways is what differentiates people with schizophrenia from people with bipolar and other conditions. He also identified a third group of symptoms, which he called the "disorganisation" syndrome - the fragmentation of thought, inappropriate affect (e.g laughing at things that are sad), word salad, general "derails"! His idea is that what these syndromes may have in common is a deficit in connectivity between brain regions, so one approach to a diagnostic test might be to find some way of measuring connectivity - the degree to which activity in one brain region is correlated with activity in another. Anyway, that's what he's working on right now.

But the big question really, is what would a test like that be actually used for? If you have a mental disorder - if your thoughts do strange and disruptive things - then that's what your brain is doing. You don't need a "test" for it, any more than you need a "test" to tell whether you have a headache or not. If you have a headache, you have a headache. And while it might help in treating the headache to know what caused it (migraine, say), it might not.

One incentive for getting a differential diagnostic test, though, is that the right treatment in adolescence might help prevent relapse. There's reasonable evidence to suggest that early intervention helps. And you don't want to weigh in with major anti-psychotics if a teenager is just going through a temporary daft spell. And also, some treatments do seem to work for specifically "labelled" conditions, e.g. lithium for bipolar.

But I suspect the genetic stuff won't help much with diagnosis, because what evidence we have suggests that the genes responsible may be non-specific (having genes associated with schizophrenia may predispose you to a range of psychiatric disorders, each of which might involve a different treatment, or none; one study at least found that "eccentricity" was more common in the relatives of people with schizophrenia, and there is no treatment for eccentricity, nor should there be! And at least one theory suggests that the genetics for schizophrenia are "the price we pay for language").

But the other thing to say (sorry this is a bit of a ramble) is that the brain, as you know, is very plastic. And every "thought" you have, including thoughts that are symptomatic of mental disorder, alters brain structure, and may predispose you to similar thoughts (that's the reasoning behind the early intervention story). So having too little of a neurotransmitter (or two few neuroreceptors for that neurotransmitter) or two much may tend to have a cascading effect - a kind of vicious circle. Being depressed makes you depressed, for example! Which is the rationale between hitting people with anti-depressants AND behavioural therapy, in the hope of breaking the cycle.

But perhaps it's time a proper psychiatrist weighed in here! I should try to recruit Constant Mews from IIDB (S/he never turned up at RnR as far as I know).

[Christina]

[Right, now I know that edit button is lurking where the quote button used to be, I'll stop deleting posts accidentally - so sorry I deleted your post! - Febble]

Now you're officially a mod :D

I did that so many time at HH because I only had mod rights in 2 forums. I did it to Raven the other day too, except that I just added to it. You get used to checking for the quote tag at the beginning after a while.

[Christina]

The short answer is "symptoms". I can't remember whether I recommended my husband's book ("Disordered Mind and Brain") but he took the approach of dealing with symptoms first, then mechanisms underlying symptoms, then disorders last, the disorders being, essentially, particular constellations of symptoms.
You did tell me about it but it sounded like it was going to be more scientific than I can probably follow with no background. Is it?

But the big question really, is what would a test like that be actually used for? If you have a mental disorder - if your thoughts do strange and disruptive things - then that's what your brain is doing. You don't need a "test" for it, any more than you need a "test" to tell whether you have a headache or not. If you have a headache, you have a headache. And while it might help in treating the headache to know what caused it (migraine, say), it might not.
I know that this sounds childish, but mainly I want one so that people stop saying that it isn't a real medical condition and that we could just drag ourselves out by our bootstraps if we really wanted to. I don't need a test to tell me that my symptoms match those described as Bipolar I but I wouldn't mind having one to shove in the face of a few people that I know so that I could tell them to shut up because they're wrong.

One incentive for getting a differential diagnostic test, though, is that the right treatment in adolescence might help prevent relapse. There's reasonable evidence to suggest that early intervention helps. And you don't want to weigh in with major anti-psychotics if a teenager is just going through a temporary daft spell.
Those are good reasons.

And at least one theory suggests that the genetics for schizophrenia are "the price we pay for language").
I'm not sure what you mean by this.

But the other thing to say (sorry this is a bit of a ramble) is that the brain, as you know, is very plastic. And every "thought" you have, including thoughts that are symptomatic of mental disorder, alters brain structure, and may predispose you to similar thoughts (that's the reasoning behind the early intervention story). So having too little of a neurotransmitter (or two few neuroreceptors for that neurotransmitter) or two much may tend to have a cascading effect - a kind of vicious circle.
One of the things that my psychiatrist says is that my tendency to let hypomania run a bit too long because it's fun is very dangerous, and that the more that I let my brain go down that path the more likely it is that I'll have more frequent and more serious episodes. That sounds like what you're saying. It's hard to get my brain around how thoughts are just chemicals doing their thing too even though I see the evidence of it all the time as meds change the contents of my thoughts and not just the speed of them.

But perhaps it's time a proper psychiatrist weighed in here! I should try to recruit Constant Mews from IIDB (S/he never turned up at RnR as far as I know).
I love when they join these discussions but they tend to be nervous that I and others with disorders will see it as giving inappropriate medical advice instead of providing only factual information. I wouldn't take personal advice from any psychiatrist unprofessional enough to give it out over the internet anyway. I'll publicly swear it if she'll come : )

[Febble]

You did tell me about it but it sounded like it was going to be more scientific than I can probably follow with no background. Is it?

Possibly, but you do have background! The first time I read it was before I got into the field myself (and it was being written) and I sort of managed to make sense of it. But mostly I was trying to describe his approach - to mechanisms behind groups of symptoms, regardless of what disorder they are part of. Offhand, I think they were: realitity distortion (delusions and hallucinations); psychomotor poverty/excitation (a bipolar syndrome, i.e. you can have one pole or the other, or flit between the two); disorganisation; depression/mania (another bipolar syndrome) and anxiety. I think anxiety was in there, but I'd have to check. His idea is that there are different mechanisms underlying each.

I know that this sounds childish, but mainly I want one so that people stop saying that it isn't a real medical condition and that we could just drag ourselves out by our bootstraps if we really wanted to. I don't need a test to tell me that my symptoms match those described as Bipolar I but I wouldn't mind having one to shove in the face of a few people that I know so that I could tell them to shut up because they're wrong.

I hear ya. I used to work in dyslexia, and the thing that struck me was how powerful the "diagnosis" was! People would leave with a spring in their step, saying "I'm not stupid! I've got dyslexia!" Having it on paper opened all kinds of doors too (even though I'm not an educational psychologist, so I can't "officially" diagnose it - I can do the "tests" though).

Yes, I think it's amazing how dualism lurks at the bottom of most people's thinking (at least, when I was a dualist, I knew it was there, and I explicitly excluded it from my thinking about the brain!) People think there's "brain disorder" and there's "someone doing stupid stuff" as though the brain was a separate thing from the someone. For me, the important question is not: "is it a disorder?" but "is it something that is going to recur regularly?" and, most importantly, "is it something we can do something to prevent recurring?"

I mean, I am not joking when I say I probably have ADHD. But no-one has ever diagnosed it (although I score high on screening tests when I do them myself), and the only independent assessment was by an educational psychologist who was hauled in when I was 11 to try and explain why I scored very high on tests of verbal cognition and very low on arithmetic. He decided there wasn't much wrong with me apart from being bad at addition. But thinking back, I think that was an important clue - I can't do addition because it requireds good working memory (and mine is crap) and ability to focus on one task without distraction (at which I am even crapper). But I was unusual enough, apparently, to trigger this investigation, even though, in 1963, people didn't know what to do with the answer. Just told me to try to not to be careless. Huh.

But whatever label I give it, it's me. Mostly I've figured out workarounds, but I do wonder whether methylphenidate might help. So when parents of the kids in our ADHD study (especially the control kids) ask "is it real, then, ADHD?" I have to say - well, it's as real as anything that we do is real. Kids not concentrating, day after day, are really kids not concentrating day after day. And methylphenidate seems to help. But even if it didn't, it would still be a disorder.

And at least one theory suggests that the genetics for schizophrenia are "the price we pay for language").
I'm not sure what you mean by this.

Well, I didn't explain! There is a theory that schizophrenia is to do with something going wrong with the way that the brain develops lateralization - how we develop handedness, how language gets established in the left hemisphere (for most of us). The idea is that the mutations that gave us the hemispheric specialization that allowed language to evolve also give rise to schizophrenia in adverse circumstances. However, I should say that this idea is probably wrong, although lateralization does seem to be important.

One of the things that my psychiatrist says is that my tendency to let hypomania run a bit too long because it's fun is very dangerous, and that the more that I let my brain go down that path the more likely it is that I'll have more frequent and more serious episodes. That sounds like what you're saying.

Yes. And this really true of epilepsy as well, which is why it is so important that fitting babies are treated rapidly. There is a mantra in neuroscience, attributed to Hebb, that goes "what fires together, wires together". The idea is that every time a neuron sends an impulse to another neuron, that connection is strengthened, physically. So any thought - a pattern of neural firing - is more likely be repeated once it has happened once. I think of it a bit like ripples in sand - once a ripple has got started, it makes it more likely that the next current will deposit more sand in the same place, and so the ripples keep growing. If you flatten it all, and start again, a different pattern of ripples will form, but once you have the start of the pattern, that pattern will tend to reinforce itself.

It's hard to get my brain around how thoughts are just chemicals doing their thing too even though I see the evidence of it all the time as meds change the contents of my thoughts and not just the speed of them.

Well I think "just chemicals" is a bit of a crude picture. Better to think of them as electrical signals, because that's what they are. But instead of tiny electrons carrying the current, it's carried by ions which are a lot bigger (so it's a lot slower than a man-made computer). And the ions are the "chemicals" (electrons aren't chemicals, of course, because they are sub-atomic). So it's not that thoughts are chemicals, any more than waves are water molecules, or that electrons are software. It's the pattern of electrical firing that constitutes the thought. When we try to make computer models of brain functions, we are making logic circuits - the brain just happens to make them out of chemicals.

I love when they join these discussions but they tend to be nervous that I and others with disorders will see it as giving inappropriate medical advice instead of providing only factual information. I wouldn't take personal advice from any psychiatrist unprofessional enough to give it out over the internet anyway. I'll publicly swear it if she'll come : )

Yeah. I'll PM her/him (never found out which, but my mental picture is a her). That means logging into IIDB....

[Christina]

Possibly, but you do have background!
I suppose I know the one part that psychiatrists and researchers can't know, which is what it really feels like to have things like racing thoughts that turn into unintelligible roaring noises or experience psychotic breaks where images smash apart in your mind. They can only know what it looks like and sounds like. It's fascinating for me to read their perspective though because it gives me a lot of insights into my own behavior. When it happens again it will be much less frightening now that I can attribute certain symptoms like suicidal impulses, hallucinations and loss of cognitive skills to specific chemical imbalances instead of a big huge "WTF is happening to me??!!".

But mostly I was trying to describe his approach - to mechanisms behind groups of symptoms, regardless of what disorder they are part of.
I remember talking to you about that when all of us in Mulysa were first discovering that we had a lot of symptoms in common in that 'how the world looks to me' thread on the Hub. It seemed like there were only so many ways for a brain to go off the deep end no matter how different the paths to get there were.

Offhand, I think they were: realitity distortion (delusions and hallucinations); psychomotor poverty/excitation (a bipolar syndrome, i.e. you can have one pole or the other, or flit between the two); disorganisation; depression/mania (another bipolar syndrome) and anxiety. I think anxiety was in there, but I'd have to check. His idea is that there are different mechanisms underlying each.
At one point or another I've experienced all of those except possibly psychomotor poverty/excitation since I have no idea how that differs from depresson/mania. It sounds like it has something to do with physical symptoms, but I've only gotten those from meds if that's what it refers to.

Having it on paper opened all kinds of doors too (even though I'm not an educational psychologist, so I can't "officially" diagnose it - I can do the "tests" though).
For me it changed the focus of what I had to work on. Instead of trying futilely to slow myself down as I had for years and years, now I focus on managing the inevitable instead of imagining that I can make it go away through sheer force of will. In a lot of ways it's a relief although of course I wish I had something that I could talk myself out of.

There is a mantra in neuroscience, attributed to Hebb, that goes "what fires together, wires together". The idea is that every time a neuron sends an impulse to another neuron, that connection is strengthened, physically.
That makes sense. I can feel my mind starting to go down those paths sometimes and I get really scared and yank it back. There's still something very seductive about following those paths, though.

*mentally slaps myself out of daydreaming about mania.

I'm not always sure that I know the difference between being manic and remembering how it feels to be manic, if that makes any sense to you. If I remember it, my brain starts doing it or it has to do it to remember it, or something like that. I'm sure that makes no sense if you can't feel what 'it' is.
Now I want to know how memory works : )

So it's not that thoughts are chemicals, any more than waves are water molecules, or that electrons are software. It's the pattern of electrical firing that constitutes the thought. When we try to make computer models of brain functions, we are making logic circuits - the brain just happens to make them out of chemicals.
That was what I more or less meant by 'doing their thing'. I'm exactly sure what that thing is, but I know it's not just a vat of chemicals percolating in my head : )