In terms of asking patients who have had mania whether they’ve also had depression, it makes intuitive sense to me that we should be looking for pretty severe depressive episodes, especially ones with suicidality or profound decrease in daily functioning. Im less concerned about mild depressive episodes given the difficulty in distinguishing them from responses to adverse life events or other “non-clinical” ways of being unhappy. It’s also more difficult to forget being suicidally depressed and not getting out of bed for weeks vs. forgetting a mild depressive episode.
Anyway, I’m inclined to think unipolar mania could be real. I’ve met a few women in their 50s-60s who seemed to be having their first manic episode (full blown mania, usually with psychosis) and confidently reporting never being severely depressed. If anything, they seemed to have a hypomanic temperament generally. And even if we’re unclear whether this was their first manic episode, or if there had been earlier ones that went unnoticed and were self medicated, the denial of a history of depression counts for something.
Either mania due to a secondary (medical) cause, which I presume was excluded with your patients, or alternatively just a different type of bipolar illness than the one that presents in adolescence / early adulthood. There doesn’t have to be a unitary pathological process, right?
I agree there doesn’t have to be only one pathological process. The interesting thing about the cases I’m thinking of is that they had all the classic features of bipolar disorder with the exception of age of onset. At least two had the manic episode start within a few weeks of their first trying an SSRI. If we want to be parsimonious, the most likely explanation is that these patients had unreported manic episodes earlier and I just didn’t catch it. But it’s also possible that somewhat different processes (early vs late onset) result in indistinguishable presentations. My point in bringing them up is that since I haven’t followed someone with bipolar disorder for their whole life, these late-onset mania examples are the closest I can get to a mania-only syndrome.
Out of ignorance... If there's a possibility of substance induced bipolar (SSRI) while admittedly more likely in bipolar 1, I tend to think of it as a different beast to pure bipolar (BP1) and would think of it as "substance induced" and that as the explanation for the unipolar mania, but substance induced doesn't rank as an explanation for the apparent unipolar mania, to you? I would not expect a history of depression in substance (including medication) induced mania.
I think some would categorise hypomanic episodes which are only induced by SSRIs as a separate class of bipolar disorder.
I would definitely regard drugs as being a potential cause of unipolar mania but would probably regard this separately from unipolar mania not triggered by substances
The physics side of me will always be interested in symmetry-breaking phenomena. Whether or not unipolar mania exists, would you be able to point me towards any literature with theories as to why bipolar almost always has both manic and depressive components?
And I guess the contrasting question is, why are there so many cases of depression without a mania aspect? Why is depression symmetry-breaking?
A little little little bit more than all the DSM 1-5 taken together. Read his classification of psychoses. Was his assistent for the last 10 years and was allowed to conduct annual follow-up examinations of the Berlin patients.
Those with bipolar 2 that display the same qualities during hypomanic episodes as those you described having bipolar 1 (in short: no euphoria, increased motor activity but in a very ego dystonic manner, with socio economics wrecks at the end) are much more reliable when it comes to diagnostic than those who don't
I know I'm very worry about those little hypomanic bursts that usually occur during early spring for instance, a pattern I see much more in those "frank" bipolar 2 patients than those I consider on the "mood disorder spectrum"
I am a highly educated, “high functioning” 40yo with a 20yo bipolar ii diagnosis that was re-endorsed via extensive psychological testing in the last 5 years. I’m in a relationship with someone with a similar background and illness history. I take no mood stabilizers. My partner takes lamotrigine (what I used to take until about 35). We both live in Minneapolis, which has a bipolar climate lol.
The seasonality of hypomania is NEVER discussed and it’s totally a thing. My wife notices that my depression hits a nadir around March. Then, as soon as the snow melts, it’s a slow climb to a hypomanic peak around mid June. Then, I level out around the 4th of July.
In that hypomanic peak, I’m more likely to interact with new clinicians (because I’m more motivated to get stuff done - my seasonal depression and hypomania interact with my executive function quite a bit), who tend to undervalue the seasonality and read me initially as much more disordered than I actually am, which they figure out once they meet me in subsequent appointments.
So much of my spring and early summer is working with my therapist to “land the hypomanic plane” without incident. It’s complicated because hypomania feels fucking great, and it’s such a change from the wintry stuck-in-the-mud feeling.
I kind of hate when clinicians over pathologize my well-managed seasonal hypomania in a way they don’t pathologist seasonal depression. Pretty much all humans are a little hypomanic in the spring. Animals are, too. It seems like an adaptive trait of sorts to ensure we can get through the survival and reproduction labor of spring time. My response is just a little outsized.
At this point, seasonal depression and seasonal hypomania are the only bipolar states I experience at this point.
I agree this topic is under-researched, I came across one systematic review which might be of interest - Seasonality and bipolar disorder: a systematic review, from admission rates to seasonality of symptoms https://pubmed.ncbi.nlm.nih.gov/25063960/
A slightly adjacent question is the effect of changing timezones (through long-haul travel) on bipolar relapse - this is well recognised clinically, but I'm not aware of good quality research
I wish this information was more diffuse among practitioners. I can much more easily manage my bipolar without medication when I can anticipate states.
Moreover, there are external/environmental choices that I’ve made that support better functioning across seasons. One major change was getting out of the academic calendar. As both a student and a university employee, I found the artificial deluges of work right before the holidays and in late spring made my subsequent seasonal depression and hypomania worse. The fall deluge made it so I couldn’t fully enjoy the holidays (stressed at Thanksgiving, exhausted and likely sick over Christmas), which resulted in early winter being much more difficult to endure. Spending mid-late spring indoors and working long hours facilitated more hypomania, which was easier to indulge as a hedonistic post-semester bacchanalia. This environment disrupted my ability to develop year-over-year adjustments to soften the peaks/valleys. I also find that the academic calendar disrupts my ability to fully engage with seasonality in the way that humanity has adapted. It’s easier and more sustainable for me to indulge moderately over a long period than to have a binge/purge cycle.
Another thing that helped me realize the seasonality of my mental illness was not restricting my sleep. I started setting an alarm less and less during my first non-academic white collar job, but really letting go of a bedtime schedule (I go to bed when I’m tired and wake up when I’m rested most days) helped show me how much I respond to natural light, both its excesses and its dearth. In fact, the regimented rituals/routine commonly prescribed for people with depression actually makes my mental health stuff worse. Letting go of “diligent” regimentation helped me and manage my mental health symptoms better.
"I can’t think of any cases in which it looked enjoyable. These aren’t pleasurable ‘highs’. They are the kind of episodes that leave you at risk of financial and reputational ruin."
You're the expert, but my limited personal impression is that manic episodes can be both pleasurable and disastrous? I've had passing encounters with people who were having manic episodes, and they seemed to be ecstatic (although also combative and paranoid).
Believing you're God or communicating with God, about to start the world's best company, can't lose at blackjack—doesn't that sometimes feel pretty awesome for people? Curious to hear your thoughts!
I guess most of the patients I have seen are having these experiences while at the same time having their liberty restricted by mental health services, usually for good reasons
No no this : But at what point should you intervene at all? When they’re taking Prozac and Vyvanse and feel mania out of a long depression? Mania is relative to many things affectively. That’s what makes it not BI polar - but multi-polar. Mania also affects executive function and who’s to say what level of executive function is necessarily maladaptive or not.
Is it teleologically going to affect the involuntary inpatient’s life decisions when it comes to forensic recidivism for choosing to “party” too much? necessary in patient
At what point is mania a necessary disorder? It should be examined more thoroughly what the limits and … yet that neuroscience is not generalizable enough to assume a biomarker will effectively be useful diagnostically - especially when clinical psych disorders are so vague from the start.
This article feels like a way to enforce your political opinion that a person has a “higher order” choice that they can override mania with some kind of Victorian moral code of appropriate behaviour.
Try a psychedelic brother.
Roll 💊 👁️
Just chew gum and stay hydrated.
Euphoria can be a beautiful virtue and necessary to love and appreciate yourself - I contend at least. Don’t glue the word mania or euphoria to a bullshit disorder just cuz ur friends lose money on a dumb stock trade and their wife left them for following Andrew Tate and spending money on his dumb schemes to get rich quick by eating the liver of your best friend to become the alpha 😘
While mania’s teleological consequences may be associated w psychiatry’s golden rule of “if the patient is distressed to affect adaptive behaviour” (to which adapted behaviour is and always will be a humanistic phenomenological term that which you can never deny anyone’s experience - prescriptively adaptive or not) it should not - by deontological standards imo - extend beyond forensic decision making.
Should the bipolar schizoaffective murderer be forced to take lithium because they killed someone in a manic state? Is mania responsible for the death?
No, they're quite distinguishable. The list of features you've described, though, is rather imprecise if they are just read out of a book. How many people would confuse thought alienation with the perplexed, dreamlike state seen in some cycloid psychoses? Thought disorganisation is completely transdiagnostic and appears across a wide range of conditions. Negative symptoms and autism in schizophrenia are easily mistaken for stuporous or catatonic states to the untrained eye.
Unipolar mania and schizophrenia feel completely different in real life, but on paper the terms are very imprecise. With proper pattern recognition people can learn to tell the difference but it seems obvious to me a great many cases are indeed misdiagnosed.
Don't get me wrong though, I'm not saying they're all mood disorders, rather that they are biphasic, cyclic and periodic diseases that alterate between excitement and inhibition, which may or may not include mood, and are quite separate from classic schizophrenia. Maybe they represent channelopathies given their courses.
Well, I’m not a doctor so I might be using the term ignorantly, but when I look at the bipolar literature as a whole—and especially now that you’ve told me Ian Brockington self-published (which makes sense, because I had in the back of my head that he’d written books, but I could never work out why I was never able to access them)—I start to see a broader picture emerge.
Like, take Kraepelin—he was monitoring rapid cycling patients for signs of silent seizures, following Fahlret and others’ theories of larval epilepsy. Or Kahlbaum’s periodic catatonia. And perhaps most importantly, Wernicke’s periodic and cycloid syndromes, which included many periodic disorders of movement. These weren’t just vague ideas—they were trying to map recurring psychiatric states onto neurological rhythms.
And then, later on, we discovered things like episodic ataxia, Dravet syndrome, and hypokalemic periodic paralysis, which are channelopathies. So it’s like they were intuiting something about a class of diseases with this type of rhythm without having the means to explain it. Then fast forward to the early lithium research, and the first idea from Schou and Coppen was that lithium competes with sodium in the ion transport system. Coppen in particular was looking at electrolytes. I’m not entirely sure why that line of thinking was abandoned—maybe because no other pharmacological probes could replicate the effect—so Coppen dropped it, though I don’t think Schou ever completely let it go. I'm sure you'll remember from medical training just how tightly the body controls the homeostasis of electrolytes, it’s this system rigidity that I think made Coppen have doubts, if bipolar is a problem with ion transport where are all the autonomic diseases and the heart attacks? Well... what’s up with all those borderline women nowadays who have POTS?
I also remember a case report—though I could be completely misremembering this—but I think it was from the ’40s: a cycloid psychosis, and they put the woman on either a salt-restricted or salt-loading diet and she had a marked improvement. That might be a total mash-up of a dozen case reports, because I’ve never been able to find it again. But it left an impression. I came across it when I was doing research on the ketogenic diet which has diuretic effect.
Then we get into second messenger theories, which also point toward ion transport, but my understanding is that second messenger issues are not called channelopathies or are they?
But what really got me thinking was going back through the GWAS studies with all of this in mind—especially looking at them through the lens of subtypes, something I took from Tom Ban and Ian Brockington’s refusal to abandon subtyping.
Instead of seeing the results as support for polygenicity, I started to think: what if we’ve simply front-loaded the data with a heterogeneous mix of subtypes? What if some of these are monogenic—or at least oligogenic—subtypes buried in the noise?
With all that in mind, the overall impression I get from GWAS is of a family of channelopathic diseases that cause psychiatric symptoms. I might just be pointing out the obvious and reframing existing ideas, but it makes sense to me—especially when you compare the course of these illnesses with other known channelopathies. It also accounts for pretty much every drug used in bipolar disorder—all of which, in one way or another, affect some part of the ion transport system. It even opens the door to an osmotic explanation for why antidepressants sometimes worsen the condition.
There’s more. I’ve been hearing a few anecdotes—nothing systematic yet—that those with ANK3 variants might correspond to the mixed cycling subtype. The fabled antidepressant switchers. If anyone else has heard similar rumours or has seen this kind of thing, I’d really like to hear about it.
Most recently I've become fascinated by keto, anecdotal reports of dramatic remission and anecdotal reports of dramatic worsening. I can't help but notice the dramatic worsening and manic episodes are often reported to occur during the "keto flu" phase when the body dumps electrolytes. Why Coppen never got anything crazy to happen from pumping people with Gatorade is a mystery, but then no one ever seems to be able to get keto to do anything in the clinic either, so maybe the subtype that is sensitive to electrolyte and osmotic shifts is not the subtype being picked for study.
Anyway, I'm a layperson, so I've probably butchered all that and engaged terrible biobabble. I would love to better understand what I'm talking about.
Are you thinking that patients with a 'true' diagnosis of schizophrenia (prototypical symptoms, thought alienation, thought disorganisation, negative syndrome) may be classified (?misdiagnosed) as unipolar mania, or that these are true cases of unipolar mania (psychotic symptoms are all mood congruent) that have been misdiagnosed with schizophrenia?
Or do you think the distinction between episodes of unipolar mania and schizophrenia are not distinguishable?
In terms of asking patients who have had mania whether they’ve also had depression, it makes intuitive sense to me that we should be looking for pretty severe depressive episodes, especially ones with suicidality or profound decrease in daily functioning. Im less concerned about mild depressive episodes given the difficulty in distinguishing them from responses to adverse life events or other “non-clinical” ways of being unhappy. It’s also more difficult to forget being suicidally depressed and not getting out of bed for weeks vs. forgetting a mild depressive episode.
Anyway, I’m inclined to think unipolar mania could be real. I’ve met a few women in their 50s-60s who seemed to be having their first manic episode (full blown mania, usually with psychosis) and confidently reporting never being severely depressed. If anything, they seemed to have a hypomanic temperament generally. And even if we’re unclear whether this was their first manic episode, or if there had been earlier ones that went unnoticed and were self medicated, the denial of a history of depression counts for something.
I wonder if later first presentation might represent something different going on
But if it’s mania then it’s mania, right? What kind of something different did you have in mind?
Either mania due to a secondary (medical) cause, which I presume was excluded with your patients, or alternatively just a different type of bipolar illness than the one that presents in adolescence / early adulthood. There doesn’t have to be a unitary pathological process, right?
I agree there doesn’t have to be only one pathological process. The interesting thing about the cases I’m thinking of is that they had all the classic features of bipolar disorder with the exception of age of onset. At least two had the manic episode start within a few weeks of their first trying an SSRI. If we want to be parsimonious, the most likely explanation is that these patients had unreported manic episodes earlier and I just didn’t catch it. But it’s also possible that somewhat different processes (early vs late onset) result in indistinguishable presentations. My point in bringing them up is that since I haven’t followed someone with bipolar disorder for their whole life, these late-onset mania examples are the closest I can get to a mania-only syndrome.
Would be interesting to follow their subsequent illness course!
Out of ignorance... If there's a possibility of substance induced bipolar (SSRI) while admittedly more likely in bipolar 1, I tend to think of it as a different beast to pure bipolar (BP1) and would think of it as "substance induced" and that as the explanation for the unipolar mania, but substance induced doesn't rank as an explanation for the apparent unipolar mania, to you? I would not expect a history of depression in substance (including medication) induced mania.
I think some would categorise hypomanic episodes which are only induced by SSRIs as a separate class of bipolar disorder.
I would definitely regard drugs as being a potential cause of unipolar mania but would probably regard this separately from unipolar mania not triggered by substances
The physics side of me will always be interested in symmetry-breaking phenomena. Whether or not unipolar mania exists, would you be able to point me towards any literature with theories as to why bipolar almost always has both manic and depressive components?
And I guess the contrasting question is, why are there so many cases of depression without a mania aspect? Why is depression symmetry-breaking?
Interesting stuff as always Thomas!
Good question - I’m not sure if we have a theoretical explanation!
Have you read Karl Leonhard?
No I hadn't but he sounds very relevant, thanks for sharing.
A little little little bit more than all the DSM 1-5 taken together. Read his classification of psychoses. Was his assistent for the last 10 years and was allowed to conduct annual follow-up examinations of the Berlin patients.
Here's my take:
Those with bipolar 2 that display the same qualities during hypomanic episodes as those you described having bipolar 1 (in short: no euphoria, increased motor activity but in a very ego dystonic manner, with socio economics wrecks at the end) are much more reliable when it comes to diagnostic than those who don't
I know I'm very worry about those little hypomanic bursts that usually occur during early spring for instance, a pattern I see much more in those "frank" bipolar 2 patients than those I consider on the "mood disorder spectrum"
That's a study that could easily be done
I am a highly educated, “high functioning” 40yo with a 20yo bipolar ii diagnosis that was re-endorsed via extensive psychological testing in the last 5 years. I’m in a relationship with someone with a similar background and illness history. I take no mood stabilizers. My partner takes lamotrigine (what I used to take until about 35). We both live in Minneapolis, which has a bipolar climate lol.
The seasonality of hypomania is NEVER discussed and it’s totally a thing. My wife notices that my depression hits a nadir around March. Then, as soon as the snow melts, it’s a slow climb to a hypomanic peak around mid June. Then, I level out around the 4th of July.
In that hypomanic peak, I’m more likely to interact with new clinicians (because I’m more motivated to get stuff done - my seasonal depression and hypomania interact with my executive function quite a bit), who tend to undervalue the seasonality and read me initially as much more disordered than I actually am, which they figure out once they meet me in subsequent appointments.
So much of my spring and early summer is working with my therapist to “land the hypomanic plane” without incident. It’s complicated because hypomania feels fucking great, and it’s such a change from the wintry stuck-in-the-mud feeling.
I kind of hate when clinicians over pathologize my well-managed seasonal hypomania in a way they don’t pathologist seasonal depression. Pretty much all humans are a little hypomanic in the spring. Animals are, too. It seems like an adaptive trait of sorts to ensure we can get through the survival and reproduction labor of spring time. My response is just a little outsized.
At this point, seasonal depression and seasonal hypomania are the only bipolar states I experience at this point.
Thank you for sharing your personal experience!
I agree this topic is under-researched, I came across one systematic review which might be of interest - Seasonality and bipolar disorder: a systematic review, from admission rates to seasonality of symptoms https://pubmed.ncbi.nlm.nih.gov/25063960/
A slightly adjacent question is the effect of changing timezones (through long-haul travel) on bipolar relapse - this is well recognised clinically, but I'm not aware of good quality research
I wish this information was more diffuse among practitioners. I can much more easily manage my bipolar without medication when I can anticipate states.
Moreover, there are external/environmental choices that I’ve made that support better functioning across seasons. One major change was getting out of the academic calendar. As both a student and a university employee, I found the artificial deluges of work right before the holidays and in late spring made my subsequent seasonal depression and hypomania worse. The fall deluge made it so I couldn’t fully enjoy the holidays (stressed at Thanksgiving, exhausted and likely sick over Christmas), which resulted in early winter being much more difficult to endure. Spending mid-late spring indoors and working long hours facilitated more hypomania, which was easier to indulge as a hedonistic post-semester bacchanalia. This environment disrupted my ability to develop year-over-year adjustments to soften the peaks/valleys. I also find that the academic calendar disrupts my ability to fully engage with seasonality in the way that humanity has adapted. It’s easier and more sustainable for me to indulge moderately over a long period than to have a binge/purge cycle.
Another thing that helped me realize the seasonality of my mental illness was not restricting my sleep. I started setting an alarm less and less during my first non-academic white collar job, but really letting go of a bedtime schedule (I go to bed when I’m tired and wake up when I’m rested most days) helped show me how much I respond to natural light, both its excesses and its dearth. In fact, the regimented rituals/routine commonly prescribed for people with depression actually makes my mental health stuff worse. Letting go of “diligent” regimentation helped me and manage my mental health symptoms better.
Good point. I'm sure there are subtleties in psychopathology that we often gloss over.
Seasonality in bipolar is another super-interesting topic!
"I can’t think of any cases in which it looked enjoyable. These aren’t pleasurable ‘highs’. They are the kind of episodes that leave you at risk of financial and reputational ruin."
You're the expert, but my limited personal impression is that manic episodes can be both pleasurable and disastrous? I've had passing encounters with people who were having manic episodes, and they seemed to be ecstatic (although also combative and paranoid).
Believing you're God or communicating with God, about to start the world's best company, can't lose at blackjack—doesn't that sometimes feel pretty awesome for people? Curious to hear your thoughts!
I take your point!
I guess most of the patients I have seen are having these experiences while at the same time having their liberty restricted by mental health services, usually for good reasons
No no this : But at what point should you intervene at all? When they’re taking Prozac and Vyvanse and feel mania out of a long depression? Mania is relative to many things affectively. That’s what makes it not BI polar - but multi-polar. Mania also affects executive function and who’s to say what level of executive function is necessarily maladaptive or not.
Is it teleologically going to affect the involuntary inpatient’s life decisions when it comes to forensic recidivism for choosing to “party” too much? necessary in patient
At what point is mania a necessary disorder? It should be examined more thoroughly what the limits and … yet that neuroscience is not generalizable enough to assume a biomarker will effectively be useful diagnostically - especially when clinical psych disorders are so vague from the start.
This article feels like a way to enforce your political opinion that a person has a “higher order” choice that they can override mania with some kind of Victorian moral code of appropriate behaviour.
Try a psychedelic brother.
Roll 💊 👁️
Just chew gum and stay hydrated.
Euphoria can be a beautiful virtue and necessary to love and appreciate yourself - I contend at least. Don’t glue the word mania or euphoria to a bullshit disorder just cuz ur friends lose money on a dumb stock trade and their wife left them for following Andrew Tate and spending money on his dumb schemes to get rich quick by eating the liver of your best friend to become the alpha 😘
While mania’s teleological consequences may be associated w psychiatry’s golden rule of “if the patient is distressed to affect adaptive behaviour” (to which adapted behaviour is and always will be a humanistic phenomenological term that which you can never deny anyone’s experience - prescriptively adaptive or not) it should not - by deontological standards imo - extend beyond forensic decision making.
Should the bipolar schizoaffective murderer be forced to take lithium because they killed someone in a manic state? Is mania responsible for the death?
Anyways…
Thanks for taking the time to comment!
No, they're quite distinguishable. The list of features you've described, though, is rather imprecise if they are just read out of a book. How many people would confuse thought alienation with the perplexed, dreamlike state seen in some cycloid psychoses? Thought disorganisation is completely transdiagnostic and appears across a wide range of conditions. Negative symptoms and autism in schizophrenia are easily mistaken for stuporous or catatonic states to the untrained eye.
Unipolar mania and schizophrenia feel completely different in real life, but on paper the terms are very imprecise. With proper pattern recognition people can learn to tell the difference but it seems obvious to me a great many cases are indeed misdiagnosed.
Don't get me wrong though, I'm not saying they're all mood disorders, rather that they are biphasic, cyclic and periodic diseases that alterate between excitement and inhibition, which may or may not include mood, and are quite separate from classic schizophrenia. Maybe they represent channelopathies given their courses.
What do you think?
I hadn’t come across that hypothesis, but sounds interesting!
What hypothesis, channelopathy?
Yes!
Well, I’m not a doctor so I might be using the term ignorantly, but when I look at the bipolar literature as a whole—and especially now that you’ve told me Ian Brockington self-published (which makes sense, because I had in the back of my head that he’d written books, but I could never work out why I was never able to access them)—I start to see a broader picture emerge.
Like, take Kraepelin—he was monitoring rapid cycling patients for signs of silent seizures, following Fahlret and others’ theories of larval epilepsy. Or Kahlbaum’s periodic catatonia. And perhaps most importantly, Wernicke’s periodic and cycloid syndromes, which included many periodic disorders of movement. These weren’t just vague ideas—they were trying to map recurring psychiatric states onto neurological rhythms.
And then, later on, we discovered things like episodic ataxia, Dravet syndrome, and hypokalemic periodic paralysis, which are channelopathies. So it’s like they were intuiting something about a class of diseases with this type of rhythm without having the means to explain it. Then fast forward to the early lithium research, and the first idea from Schou and Coppen was that lithium competes with sodium in the ion transport system. Coppen in particular was looking at electrolytes. I’m not entirely sure why that line of thinking was abandoned—maybe because no other pharmacological probes could replicate the effect—so Coppen dropped it, though I don’t think Schou ever completely let it go. I'm sure you'll remember from medical training just how tightly the body controls the homeostasis of electrolytes, it’s this system rigidity that I think made Coppen have doubts, if bipolar is a problem with ion transport where are all the autonomic diseases and the heart attacks? Well... what’s up with all those borderline women nowadays who have POTS?
I also remember a case report—though I could be completely misremembering this—but I think it was from the ’40s: a cycloid psychosis, and they put the woman on either a salt-restricted or salt-loading diet and she had a marked improvement. That might be a total mash-up of a dozen case reports, because I’ve never been able to find it again. But it left an impression. I came across it when I was doing research on the ketogenic diet which has diuretic effect.
Then we get into second messenger theories, which also point toward ion transport, but my understanding is that second messenger issues are not called channelopathies or are they?
But what really got me thinking was going back through the GWAS studies with all of this in mind—especially looking at them through the lens of subtypes, something I took from Tom Ban and Ian Brockington’s refusal to abandon subtyping.
Instead of seeing the results as support for polygenicity, I started to think: what if we’ve simply front-loaded the data with a heterogeneous mix of subtypes? What if some of these are monogenic—or at least oligogenic—subtypes buried in the noise?
With all that in mind, the overall impression I get from GWAS is of a family of channelopathic diseases that cause psychiatric symptoms. I might just be pointing out the obvious and reframing existing ideas, but it makes sense to me—especially when you compare the course of these illnesses with other known channelopathies. It also accounts for pretty much every drug used in bipolar disorder—all of which, in one way or another, affect some part of the ion transport system. It even opens the door to an osmotic explanation for why antidepressants sometimes worsen the condition.
There’s more. I’ve been hearing a few anecdotes—nothing systematic yet—that those with ANK3 variants might correspond to the mixed cycling subtype. The fabled antidepressant switchers. If anyone else has heard similar rumours or has seen this kind of thing, I’d really like to hear about it.
Most recently I've become fascinated by keto, anecdotal reports of dramatic remission and anecdotal reports of dramatic worsening. I can't help but notice the dramatic worsening and manic episodes are often reported to occur during the "keto flu" phase when the body dumps electrolytes. Why Coppen never got anything crazy to happen from pumping people with Gatorade is a mystery, but then no one ever seems to be able to get keto to do anything in the clinic either, so maybe the subtype that is sensitive to electrolyte and osmotic shifts is not the subtype being picked for study.
Anyway, I'm a layperson, so I've probably butchered all that and engaged terrible biobabble. I would love to better understand what I'm talking about.
Don't you think a good chunk of schizophrenia diagnoses with a waxing and waning course are candidates for unipolar mania?
Are you thinking that patients with a 'true' diagnosis of schizophrenia (prototypical symptoms, thought alienation, thought disorganisation, negative syndrome) may be classified (?misdiagnosed) as unipolar mania, or that these are true cases of unipolar mania (psychotic symptoms are all mood congruent) that have been misdiagnosed with schizophrenia?
Or do you think the distinction between episodes of unipolar mania and schizophrenia are not distinguishable?