But they TOLD me I was Bipolar: It seems the twain CAN meet, Part II

Do you remember that I told you that bipolar disorder (BD) and schizophrenia have been considered completely different illnesses for. . .well, pretty much forever?

Until researchers started getting a look at people’s brains? And then it seemed possible–just possible–that these 2 illnesses might not be as fundamentally different as we’ve come to believe? (Hint: even if you don’t remember, you can just act like you do.)

So, look, I’d love to be able to explain exactly how researchers can actually prove the similarities between BD  and schizophrenia through their brain studies.  I really tried hard–and I’m going to give you as much as I’ve got. But at some point. . .all chaos breaks loose.

Let’s start simple.

Way back in 2005, one Dr. Arnsten at Yale Medical School discovered a “molecular trigger” that was one and the same for both BD and schizophrenia. Dr. Arnsten claimed that the trigger was stress (which would make these diseases just like so many, many others), which causes a brain protein called ‘protein kinase C’ (PKC) located in the prefrontal cortex (don’t panic–I’ll get back to this) to overactivate.

Increased PKC activity has been noted in the brains of those with BD and schizophrenia, leading to certain common symptoms in both disorders, such impulsivity, poor judgment, distractibility.  And–conveniently–antipsychotics, used to treat both disorders, often decrease PKC activity.

Okay–that had some brain structure talk in it, it’s true, but I think we did pretty well.  Let’s jump ahead a few years.

In 2009, a group of Swedish researchers ran the largest study ever on schizophrenia and bipolar within families. They analyzed information on (just imagine the poor researchers going through their paperwork) 9,009,202 individuals in over 2 million families between 1973 and 2004.

After sifting through all that data, the researchers found that if schizophrenia runs in a family, there’s a darn good chance BD does as well, and vice versa.

In fact, if a parent was schizophrenic, a child was 9.9 times more likely to be schizophrenic than in the “normal” population.  But. . .the child was also 5.2 times more likely to have BD than someone who didn’t have a schizophrenic parent.  Conversely, a child with at least one parent with BD was 6.4 times more likely to wind up bipolar–but that child’s chances increased as well for the other disease.  These children were 2.4 times more likely to have schizophrenia than children whose parents did not suffer from bipolar.

Other family members weren’t spared either.  If a sibling had schizophrenia, a full sibling was 9 times more likely than the general population to have schizophrenia and 4 times more likely to have BD.  Conversely, if a sib had BD, the other sibling was 8 times more likely to have BD and 4 times more likely to have schizophrenia.

Head researcher Lichtenstein asserts that his data clearly illustrates “the extent to which these two disorders are genetically related.”  He believes that “hundreds if not thousands of the genes are at the root of each disorder, about half of which may overlap;” in other words, he’s suggesting the two illnesses are caused by some–perhaps many–of the very same genes.


Okay–so far,  so good, right? Everyone with me? I’m pretty much with myself.  Let’s move on.

You might even remember this next step (I wrote about it as “One Big Not-So-Happy Family: Major Psychiatric Disorders Share a Common Genetic Link,” but it was all over the news in the middle of August).  Researchers finally determined what they had been coming to suspect for a while–that major psychiatric disorders shared genetic risk factors.

Truthfully, the illnesses didn’t all seem very similar–there was bipolar disorder, autism, major depression, ADHD, and schizophrenia. But if you would have pushed me to pick two that would be closely related, I would surely have gone for major depression and bipolar disorder.  Shows you what I know.

Bipolar and schizophrenia were the most strongly linked.

The National Institute of Mental Health put out a summary of the study (for which I am eternally grateful; reading the original was like reading Sanskrit).   Here’s the big news:  variation in the genes CACNA1C and CACNB2 linked all the disorders, but one region, called–obviously–the 3p21 turned out to be a clear connector and trouble-maker.  This region “which produced the strongest signal of illness association, harbors suspect variations identified in previous genome-wide studies of bipolar disorder and schizophrenia.” Aha!

Well. . .I’m not totally sure what it means–but I do see that BD and schizophrenia are not just linked statistically;  researchers are actually finding the sources of the linkages.

And then came a major paper, published in 2011, with clear evidence of brain similarities between the two illnesses.

Look–I have not given up on this paper–but when the title -just the title, this is before we get to the nitty-gritty–is “Common proteomic changes in the hippocampus in schizophrenia and bipolar disorder and particular evidence for involvement of cornu ammonis regions 2 and 3,”–and its authors get really excited when they find that their study “implicates the process of CME in psychotic disorders by showing altered expressions of proteins involved in or regulating this pathway, namely synaptotagmin, heat shock cognate 71-dKa protein, cathepsin D, dynactin subunit 2, ANXA6, PCMT1, and SPTAN1”–well, frankly, I’m in over my head. I’m accepting any offers of help.

There are a few things I can glean from this biochemical language, however.

First, this study, headed by Focking (unfortunate name, I know, but she’s done quite well for herself as a PhD in Ireland) was the first  to look at and compare sub-regions of the hippocampus  between a variety of groups.  Now, I struck gold when they mentioned the hippocampus, since I’ve: a) actually heard of it; and b)I know enough about it to have actually written a post on it (if you’d like to feel like more guilt about your failed exercise program, go ahead and read my  Of Bipolar Disorder, The Hippocampus, and The Return of the Exercise Fiend. Otherwise, if I don’t cover what you need here, there’s always Wikipedia.).

Briefly, the hippocampus is a major component of the brain’s limbic system (sited on top of the brainstem and just under the cortex, the brain’s outermost layer) which regulates emotion and memory. [Incidentally, in Alzheimer’s disease, it’s the hippocampus that suffers damage first.]

Abnormalities in the hippocampus are standard in both schizophrenia and bipolar–but that news is really old hat.  What Focking and her team did was to look at areas of the hippocampus called cornu ammonis regions 2 and 3.  Now, despite a number of Google, Scholar and PubMed searches, I still must confess myself still not intimately familiar with these particular areas of the brain–but I totally trust Focking and her team when she tells me they’re relevant to this discussion.

The researchers went ahead and collected brain tissue samples (this was postmortem, in case you were concerned) of 20 BD patients, 20 with schizophrenia, and 20 “mentally healthy individuals” (as if there really is any such thing left). What was strikingly clear was that in both schizophrenics and bipolar patients these cornu ammonis regions 2 and 3 were radically different from the healthy patients in the way their proteins. . . .well, do stuff. . . [if you’d like further explication, I encourage you to link to the article. Enjoy.].

Science Daily (acting as a translator), highlights that the differences that the researchers saw in these regions were “almost identical in both conditions.”

Then, just this past September 15, Sabin Khadka and colleagues published the results from a large project analyzing patients with both disorders, their healthy relatives, and healthy people who had no family history of any type of psychiatric disorder at all.

Sure enough, they found that both those with schizophrenia and bipolar had “disturbances in cortical circuit function.”  If differences emerged between the two groups, it was because schizophrenics tended to have more severe disturbances, with larger regions of the brain affected. Interestingly, the healthy people who were related to the mentally ill subjects had slight alterations–somewhere between the healthy and subject groups.

So there you have it–despite centuries of looking at the illnesses as if never the twain shall meet, suddenly researchers have started to be able to see the human brain, and lifetimes of common wisdom fall by the wayside. You just never know what people will find out once they have access to and can really fiddle around with those old cornu ammonis regions 2 and 3.




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