new free extensive online database of bipolar symptoms and DNA

Unfortunately, it’s not free to the public like the article implies; you have to be a “qualified investigator for research with legitimate scientific aims”.  (I think they just mean “not proprietary” by public.)

But still.  Huge online databases are some of the best new tools technology can give research.  I’m glad we’re seeing more and more.

And dammit, I want to poke around in the database.

back to circadian rhythms? treating bipolar depression with modafinil

Modafinil (more commonly known as Provigil), a drug approved for use in sleep apnea, narcolepsy, and shift work disorder, appears to be helpful with bipolar depression.

The article notes that the manufacturer supplied both the modafinil and the matching placebo.   I wonder how much placebo costs?  Are there places that manufacture brand-name placebo?  I mean, there must be, for researchers to run studies.

HealthCentral’s votes for best bipolar sites

Major health site HealthCentral has posted its list of picks for the highest-quality sites on bipolar disorder.  Via GJ of Living With A Purple Dog, who received one of the rewards.

bpII mixed states

 This article (abstract) compares “Mixed Depression” (major depression + some manic/hypomanic symptoms) with “Dysphoric/Mixed Hypomania” (major depression + full hypomania; as close as you can get to a DSM-defined mixed state (full mania + full depression) and still be bipolar-II.  They looked at a lot of bpII outpatients who presented for depression treatment, and also asked a separate bunch of bpII people who weren’t having symptoms at the time to remember what hypomania was like.  (Weird study design, but there’s probably a reason for it – maybe just that most people don’t come in complaining of regular hypomania.)

Seventeen percent of people had full-blown hypomania along with their depression, and 66% had mixed depression – that’s a *lot* of mixed states in people who are coming in for depression, not for mixed states.

More specifics at the link.  I’m at martial arts camp all this week, and am going to try very hard to keep up with regular content, but may have to just dump some links back in there.  After this week, I have no school or work for two weeks, and there will be extra-spiffy stuff then.

more crazy mice!

We had the manic mice; now, the schizophrenic mice!  Or, more accurately, the mouse model of mania and the mouse model of schizophrenia, since they’re unlikely to be exactly the same thing as what humans gets, just things that involve some of the same systems.  But even that will buy you a whole heck of a lot…

Coming soon: a mouse model of videogame addiction.  You give them a mini-Nintendo controller, and they punch the “A” key to get a pellet.  If you keep reinforcing them, they start punching it really fast.  (Maybe we should refer to the human model of mouse pellet addiction instead?)

sz mouse link via confused.

future potential bipolar treatment: dorky glasses?

Stabilizing circadian rhythms can be helpful with bipolar disorder, and there’s even one treatment called (straightforwardly) “dark therapy”, in which complete darkness is used to reset the circadian clock (there’s some limited data supporting this). Jim Phelps of bipolar site psycheducation.org has written about circadian rhythms and dark therapy, and now has a paper out looking to get around the issue where nobody actually wants to be in total darkness for long periods of time except maybe when they’re sleeping.

The paper doesn’t have a controlled trial, just a series of case studies where people with bipolar disorder were able to fall asleep faster when they were undergoing treatment involving amber-tinted safety goggles, which block some wavelengths of light that knock melatonin levels down (e.g., the goggles keep melatonin at night-time levels).

So, don’t go out and buy dorky goggles just yet, and maybe not at all depending on how the evidence turns out, but if you’re interested in the circadian-rhythm angle this might be something to keep an eye on.

Bipolar I longitudinal assessment: good and bad findings

Often studies only give you snapshots of a population – what one set of people looks like at hospitalization. What a different set looks like five years after hospitalization at a different hospital and in a different region. What fifty-year-olds look like right now, and what twenty-five-year-olds look like right now.

We often infer information about the course of a disorder based on who we can pick up at different points in life. But there’s no guarantee that the people we catch when they’re fifty were, at twenty-five, like the twenty-five-year-olds we’re catching now. We might have used recruiting techniques that caught (say) twenty-five-year-olds who are heavy drinkers, and fifty-year-olds who are drinkers now but were teetotalers at that age. There are a lot of ways these problems can come up, and researchers work diligently to do what they can with what is actually feasible to do, and we do our best to check on that knowledge in a variety of ways.

But it’s always good to have extensive longitudinal research to address questions about course of illness. Here’s an article (cite at bottom of entry) reporting on a large longitudinal study of people with bipolar I. I wanted to get ahold of the article to go into more depth, but my university doesn’t have it and it appears to be in either Portuguese or Italian, and since the closest thing I have is some Spanish my translation would be highly questionable.

This is from a decade-long project, the McLean-Harvard First Episode Project & International Consortium for Bipolar Disorder Research which followed people with bipolar disorder and psychotic disorders from their first hospitalization. This abstract only looked at data for bipolar I.

There are several findings I would prefer not to be true, but if we don’t consider the possibility, we can’t plan for them. People usually do not recover fully from their first episode, and they are very likely to have more episodes in the first two years (and to switch from depression to mania or vice versa),

Some conditionally good or bad stuff: Most people have the most problems early on with depression/dysphoria, and they tend to have a worse course. Initial mania or psychosis shows a better prognosis (interestingly enough). Very high rates of suicidal behavior accidents occurred early but not as much later on (this finding is pretty extensively reported). Early substance-use and anxiety go together. Prodromal symptoms (stuff indicating you’re about to have an episode) predicts bipolar disorder better than non-affective psychotic disorders (good for bipolar, bad for others).

Some good stuff: Most people didn’t cycle more and more over time (but if I’m reading the abstract right, they didn’t stick to a single steady cycle length, either). Also, how long people waited and how many episodes they’d had was unrelated to their response to mood stabilizers.

Salvatore, P., et al. (2007). Longitudinal research on bipolar disorders. Epidemiologia e psichiatria sociale, 16(2), 109-17.

 

Kindling: mood episodes get shorter and closer together – or do they?

If you stimulate rats’ brains once with a small electric shock, then they’ll be like “what the hell was that” and then go back to ratty things like munching on pellets.  If you keep doing that, eventually they’ll have a seizure in response to a shock. And if you keep that up, eventually they’ll start having seizures without you shocking them, and they’ll have them more and more easily in response to less and less provocation.  The original research was done by Dr. Graham Goddard in 1967, so this knowledge has been around a while. You can also do this to rats and humans with repeated exposures to some pesticides (says Wikipedia).

This is the idea behind “kindling” in both epilepsy and mood disorders.  I’m going to talk about mood disorders, and about research done surrounding kindling in mood disorders.  The Wikipedia article on epilepsy claims that role of kindling in human epilepsy is hotly debated.  I don’t know enough to follow up on that, but it might be interesting, given what we know about kindling in bipolar.

The idea in bipolar disorder is because of kindling that episodes become more frequent over time, with well periods between the episodes becoming shorter (this doesn’t include the episodes being more severe, which I had associated with the notion of kindling).  Kindling is often considered to be halted or reversed by medication, and efforts to communicate this to people has probably spared them and others a great deal of pain.  (Sadly, sometimes people are more responsive to the notion of potential brain damage than to the pain they’re causing in their lives and the lives of others.)

Now. It is absolutely true that untreated bipolar will fuck up your life (and other peoples’ lives – when someone decides not to take medication, they’re deciding that the people around them will continue to experience the consequence of their untreated disorder.  treatment is never a decision just about the individual).  And bipolar does rot your brain.

But it looks like the evidence for closer, more frequent episodes over time in all bipolars is limited and contradictory, as is the evidence that medication will help with it.  However (summary from Goodwin & Jamison; I looked through some primary source material and it wasn’t any more conclusive):

1) People have decreasing length of well intervals mostly for their first three episodes (Kessing et al 2004; Zis et al 1980; Angst & Selloro, 2000) up until one per year (Zis et al, 1980; another study they refer to as “Goodwin” but I can’t find in the text).  (The rapid-cycler in me says ha ha, one episode a year, let’s try one a week – and it is true that not everyone is well-represented by the average finding.)

2) Some but not all studies find that a subgroup of people with bipolar disorder (25-50%) have more frequent episodes over time (Goldberg and Harrow, 1994; Roy-Byrne et al, 1985, Kessing et al 1998).

3) Many studies find no evidence for shortening of well intervals over time (Winokur et al 1993, Turvey et al 1999, Tohen et al 2003).

4) Poor outcome was not found to be associated with shortening of well intervals over time, but with snapping directly from mania to depression or vice versa (Winokur et al 1993, Turvey et al 1999; Bratfos & Haug 1968; Angst et al 1973)
So: decreasing well intervals for the first three episodes up to about one episode per year.  And maybe a subgroup that has increasing frequency of episodes after that.

Goodwin and Jamison do note something I thought was really interesting: Post et al (1986, 1990), proposed the kindling hypothesis only for a subset of people with bipolar disorder: those who are unresponsive to lithium but respond to anticonvulsants (and have other non-classic-bpI-type symptoms).  Which makes the port of the concept over from epilepsy make more sense.  And Goodwin and Jamison say that *that* hypothesis is not inconsistent with the available literature.  (I’ll try to follow up on that later.)

As a moderator for a support forum heavily populated by people with bipolar disorder, I feel uncomfortable with this post.  I thought about it a lot before deciding to post it.  I don’t want to make getting adequate treatment less attractive.  On the good side, though, the research suggests that a lot of people are less likely to have have shorter well intervals with inadequate treatment or no treatment, and that’s a good thing for people with treatment-resistant bipolar and for people who won’t get treatment and the people who have to be around them.

But I’m posting it because it’s science and it’s relevant to what we know about what’s likely to happen to us.  And because it’s interesting.

I do want to say: No kindling doesn’t mean that untreated mood episodes won’t get worse…just that they won’t get closer together after the first few.  No kindling doesn’t mean no brain damage.  And no kindling doesn’t mean that no bipolar-aggravated life problems accumulating over time.  No kindling doesn’t mean that you’re not making other peoples’ lives miserable too.  And on and on…

mood swings can destroy gray matter in bipolar disorder

The more mood swings, the more deterioration.  They only looked at people with 1 to 6 swings over four years.  The news story doesn’t say whether they looked at frequency of mood episodes versus total number of days, so we don’t know whether someone with long, infrequent episodes would have the same damage as short, frequent ones (something of concern to people who rapid cycle). (I unfortunately don’t have access to this article.)

They did not find a decline in intelligence, although the article talks about declines that weren’t significant.  That just means the scientists want to say they found a decline, so they’re putting it forth even though the rules of science designed to keep that kind of thing under control say it isn’t sufficiently certain for people to count it as a finding.  (We have this kind of rule for a variety of good reasons, but mostly to keep people from overstating their findings.)

The lead author of the study says medication didn’t appear to be making the deterioration worse. He doesn’t say that helps, although both he and the writer of the news article hope that it does (as do I, and I hope someone follows up and tells us whether that’s the case).

What you can actually conclude from the news article is that people with infrequent episodes in bipolar disorder show gray matter loss in proportion to the number of episodes they have, and that we don’t have any evidence showing that this is harmful. My money is on yes, we will find it’s harmful, and maybe we’ll find that medication averts it (instead of, for example, finding that it’s related to the tendency to have more frequent episodes, rather than to the actual episodes).  But we don’t know that right now.  The news article (and possibly the lead researcher) are constructing a logical story around how things work, and telling that; and it makes sense.  But real life is often less intuitive than our stories.

On a related topic, I hope to post about kindling tomorrow.

Bipolar disorder: Not just circadian rhythms but social rhythms too

(And probably other kinds of rhythms, too.)

A long time before I was diagnosed with bipolar disorder I figured out that I felt a whole hell of a lot better if had a regular schedule. Not just sleep schedule, but work schedule, and regular doses of socialness instead of nothingnothingnothing and then hoursandhours of seeing other people.

Circadian rhythms are important in bipolar disorder; lithium is involved in helping reset circadian rhythms. But we have other rhythms, too. Social rhythm disruption often shows up in bipolar disorder, when people swing between the gregariousness and over-gregariousness of hypo/mania, and the withdrawal of depression. And externally regulated social rhythms (being around and not around people on a regular schedule) can help regulate bipolar disorder. (Not all on their own, duh, nor for everyone, but they can be helpful.)

Around The Clock is a blog written by a circadian rhythm and photoperiodism researcher (in case you were wondering, as I was, photoperiodism is “the physiological reaction of organisms to the length of day or night“). He has an entry with several short pieces on circadian rhythms, social rhythms, and bipolar that I recommend. I do want to say that he overstates the effect of social rhythm disruption on people with bipolar; it is not true that any new relationship, job, etc., will necessarily result in wild cycling. But don’t let that detract from the general interestingness of the post.