Daily Archives: January 27, 2016

Scientists Move Closer to Understanding Schizophrenia’s Cause (Amazing research and information!)

SCHIZOPHRENIAThis is absolutely amazing! Scientists have found out that the cause of schizophrenia is too much synaptic pruning of neurons, “in which the brain sheds weak or redundant connections between neurons as it matures” in the prefrontal cortex. This begins in adolescence and the symptoms of schizophrenia also start in adolescence! “People who carry genes that accelerate or intensify that pruning are at higher risk of developing schizophrenia than those who do not, the new study suggests.”

They knew that the MHC locus was involved in schizophrenia, they pinpointed the exact gene that is involved, the C-4 gene, this is the gene that facilitates the aggressive tagging of connections, thereby accelerating pruning. Wow, this is so amazing! Here it is in a nutshell, why people get schizophrenia! I am totally floored! So floored, I almost forgot to put the reference, but here is is:


“Scientists reported on Wednesday that they had taken a significant step toward understanding the cause of schizophrenia, in a landmark study that provides the first rigorously tested insight into the biology behind any common psychiatric disorder.

More than two million Americans have a diagnosis of schizophrenia, which is characterized by delusional thinking and hallucinations. The drugs available to treat it blunt some of its symptoms but do not touch the underlying cause.

The finding, published in the journal Nature, will not lead to new treatments soon, experts said, nor to widely available testing for individual risk. But the results provide researchers with their first biological handle on an ancient disorder whose cause has confounded modern science for generations. The finding also helps explain some other mysteries, including why the disorder often begins in adolescence or young adulthood.

“They did a phenomenal job,” said David B. Goldstein, a professor of genetics at Columbia University who has been critical of previous large-scale projects focused on the genetics of psychiatric disorders. “This paper gives us a foothold, something we can work on, and that’s what we’ve been looking for now, for a long, long time.”

The researchers pieced together the steps by which genes can increase a person’s risk of developing schizophrenia. That risk, they found, is tied to a natural process called synaptic pruning, in which the brain sheds weak or redundant connections between neurons as it matures. During adolescence and early adulthood, this activity takes place primarily in the section of the brain where thinking and planning skills are centered, known as the prefrontal cortex. People who carry genes that accelerate or intensify that pruning are at higher risk of developing schizophrenia than those who do not, the new study suggests.

Some researchers had suspected that the pruning must somehow go awry in people with schizophrenia, because previous studies showed that their prefrontal areas tended to have a diminished number neural connections, compared with those of unaffected people. The new paper not only strongly supports that this is the case, but also describes how the pruning probably goes wrong and why, and identifies the genes responsible: People with schizophrenia have a gene variant that apparently facilitates aggressive “tagging” of connections for pruning, in effect accelerating the process.

Some scientists warned that the history of biological psychiatry stands as a caution against premature optimism. “This work is extremely persuasive,” said Dr. Samuel Barondes, a professor of psychiatry at the University of California, San Francisco, “but any step forward is not only rare and unusual, it’s just one step in a journey of a thousand miles” to improved treatments.

The study, by scientists from Harvard Medical School, Boston Children’s Hospital and the Broad Institute, a research center allied with Harvard and the Massachusetts Institute of Technology, provides a showcase of biomedical investigation at its highest level. The research team began by focusing on a location on the human genome, the MHC, which was most strongly associated with schizophrenia in previous genetic studies. On a bar graph — called a Manhattan plot because it looks like a cluster of skyscrapers — the MHC looms highest.


“The MHC is the Freedom Tower” of the Manhattan plot, said Eric S. Lander, the director of the Broad Institute. “The question was, what’s in there?”

The area is a notoriously dark warren in the genome known to contain genes that facilitate the body’s immune response, for example, by flagging invading bacteria to be destroyed. That property had given rise to speculation that schizophrenia might be a kind of autoimmune condition, in which the body attacked its own cells.

But the research team, led by Steven McCarroll, an associate professor of genetics at Harvard, and by Aswin Sekar, one of his graduate students, found something different. Using advanced statistical methods, the team found that the MHC locus contained four common variants of a gene called C4, and that those variants produced two kinds of proteins, C4-A and C4-B.

The team analyzed the genomes of more than 64,000 people and found that people with schizophrenia were more likely to have the over-active forms of C4-A than control subjects. “C4-A seemed to be the gene driving risk for schizophrenia,” Dr. McCarroll said, “but we had to be sure.”

The researchers turned to Beth Stevens, an assistant professor of neurology at Boston Children’s Hospital and Harvard, who in 2007 was an author of a study showing that the products of MHC genes were involved in synaptic pruning in normal developing brains. But how important was this C4 protein, exactly? Very important, it turned out: Mice bred without the genes that produce C4 showed clear signs that their synaptic pruning had gone awry, Dr. Stevens’s lab showed.

Taken together, Dr. Stevens said in an interview, “the evidence strongly suggested that too much C4-A leads to inappropriate pruning during this critical phase of development.”

In particular, the authors concluded, too much C4-A could mean too much pruning — which would explain not only the thinner prefrontal layers in schizophrenia, but also the reason that the disorder most often shows itself in people’s teenage years or early twenties. “The finding connects all these dots, all these disconnected observations about schizophrenia, and makes them make sense,” Dr. McCarroll said.

Carrying a gene variant that facilitates aggressive pruning is hardly enough to cause schizophrenia; far too many other factors are at work. Having such a variant, Dr. McCarroll estimates, would increase a person’s risk by about 25 percent over the 1 percent base rate of schizophrenia — that is, to 1.25 percent. That is not nearly enough to justify testing in the general population, even if further research confirms the new findings and clarifies the roles of other associated genes.

Yet the equation changes when it comes to young people who are at very high risk of developing the disorder, because they are showing early signs — a sudden slippage in mental acuity and memory, or even internal “voices” that seem oddly real. This ominous period may last a year or more, and often does not lead to to full-blown schizophrenia. The researchers hope that the at-risk genetic profile, once it has been fleshed out more completely, will lead to the discovery of biomarkers that could help clarify a prognosis in these people.

Developing a drug to slow or modulate pruning poses another kind of challenge. If the new study shows anything, it is that synaptic pruning is a delicate, exquisitely timed process, and that it is still poorly understood. The team does not yet know, for example, why C4-A leads to a different rate or kind of pruning than C4-B. Any medication that tampered with that system would be a risky proposition, the authors and outside experts agreed.

“We’re all very excited and proud of this work,” Dr. Lander said. “But I’m not ready to call it a victory until we have something that can help patients.”

Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study

This is exciting! Since responsiveness to Lithium runs in families, it seems logical to think that specific genes are involved that render a person treatable by lithium, a very fortunate person, I might add, as Lithium is the best treatment for bipolar disorder when it works, however it only works for 33% of bipolar people. (I am one of those 33%, and I consider myself very lucky!) Doing genome wide studies to see if there were any genes associated with being treated by lithium, four linked short pieces of DNA (SNP’s) on Chronosome 21 were found to be associated with lithium responsiveness. These 4 SNP’s are part of two genes which code for long non coding RNA sequences. These non coding sequences are important in gene regulation, particularly in the CNS! 


Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.

Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.

A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10−8; rs78015114, p=1·31 × 10−8; rs74795342, p=3·31 × 10−9; and rs75222709, p=3·50 × 10−9). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1–13·0).

The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.

Stable, Manic & Depressed Letters to the Editor – My Greatest Hits!

Suellene Petersen, Editor-in-Chief of the Press Banner Suellene joined the Press Banner staff last year and I’ve become a fan. One obvious reason is because Suellene liked my recent Letter to the Editor I sent her last week. (My letter appears at the end of this post.) I also love seeing a woman in this job … Continue reading Stable, Manic & Depressed Letters to the Editor – My Greatest Hits!


DId my yoga class again this morning. I feel sore while doing the poses and stretches, but it all goes away during the relaxing phase of the class. So I’m feeling pretty good right now.  Just waiting on laundry to dry.

I realized yesterday that I really am in a depressed mood right now.  I tried to start the exercise I’d been assigned for nonfiction class, and I could not come up with a positive take on the topic.  I kept wanting to wander down depressing paths.  WE were supposed to write about the concept of “home”, in whatever variation we wanted to on whatever home we wanted to talk about.   Like instead of talking about how much I enjoyed having my first apartment, what came to mind is the one time I regretted leaving home for it and that was when a pair of students were murdered in the town I was living in.  That kind of thing. I’m not sure what I’m going to do.

I just hope I make it through this depression with grace and a semblance of normalcy.  I don’t know how long it’s going to last or when I’ll come out of it.  Please pray for my new medicine to start working and bringing me out of it.



Bugged Out

Day two of feeling unsettled.  My skin is crawling with anxiety. I am trying to watch The Flash, normally a guilty pleasure I relish. The anxiety is so high today, I can’t even be distracted enough to enjoy one of my favorite shows. I have no explanation for the anxiety. The professionals always want a reason, want to know the trigger and some days…There’s neither. Every inch of my skin itches like I am on Fear Factor and in a tank with a million bugs crawling on me. It’s so disconcerting. Panxiety is settling in, and that is the cruelest insult of all. When I am robbed of the comfort of my safe bubble at home because whatever in my brain has decided to misfire and turn my nerve endings into a mosh pit from hell.

It was gray and hazy when I woke up. (Damn is it hard to get out of bed during the seasonal depression.) I stumbled through making my kid’s sack lunch, feeding the cats, doing a checklist to make sure she was wearing pants and didn’t have pudding smeared on her face. Got her to school but now I just sit and wait for them to call with some ailment de jour. Kid gets a hangnail and it’s a national tragedy and I blame my crazy ass mother for creating the medical drama llama child. If I hauled the kid to the doctor every time she cried “illness” I’d be up on charges for Munchausen by Proxy.

I am still irked from last night. I took my Restoril, then waited for it to kick in. Just as it started to…R invades, wanting me to find a pegacorn (part that’s not readily available) and it’s like, motherfucker, do you know how hard it is for me to get to sleep and now I gotta turn around and do it again? Polite people don’t call after ten p.m. R is not polite. Nothing exists outside his needs. So thanks to him it took me another hour to get back to sleep.

I guess if you want optimism, I took my lithium and haven’t started gagging yet. Yesterday I was not so lucky. It works like gangbusters on the bipolar but this “will I puke” lottery with the twice a day dose…Sucks.

And in another “Positive” topic…I mentioned how my cat Voodoo came back home after being gone for six months…So I wanted to show off my boy. He only has half a tail as he comes from the bobtail line. He loves to nose butt and head butt lovingly. Last week Spook gave him an award for winning the “butthead” contest. I laughed so hard I almost peed my pants and explained to her she kind of had it backwards….

Mr. Voodoo


I Forgot

Startled AwakeI forgot how hard this is.

Bipolar Disorder.

I forgot how it opens a plug and drains out all the color.

I forgot how it pours sludge into every thought.

I forgot how it grinds the gears of decision-making until they smoke and fail.

I forgot how much courage it takes to put on my coat.

I forgot how much the people who love me can’t stand it either:

I forgot how exhausting their good intentions can be.

I forgot how much I have to fight it.

I forgot how hard it is.

I Forgot

Startled AwakeI forgot how hard this is.

Bipolar Disorder.

I forgot how it opens a plug and drains out all the color.

I forgot how it pours sludge into every thought.

I forgot how it grinds the gears of decision-making until they smoke and fail.

I forgot how much courage it takes to put on my coat.

I forgot how much the people who love me can’t stand it either:

I forgot how exhausting their good intentions can be.

I forgot how much I have to fight it.

I forgot how hard it is.

The Bleedin’ Road Goes on Forever

Time is always running out: sometimes it's just more bleedin' obvious.

Time is always running out: sometimes it’s just more bleedin’ obvious.

Warnings for: swearing, self pity, & tears before breakfast

Life, as Tull so beautifully put it, is a long song. And sometimes that’s so Spockin’ annoying.

I’m part way through yet another of those holidays at home which are substitutes for time off sick. Nothing terribly specific this time, just a collection of personal shite, some of which has back stories which are so long, they could fill several shelves at my local library. With volumes that would make “War & Peace” and LOTR look like slim-line novellas.

Maybe I was a people pleaser before I started working in care. Maybe it’s me wanting to make up for all the emotional, financial, physical, & you-name-it havoc and chaos I created during the worst of my bipolar disorder. Maybe it’s a biological and/or conditioned part of being female.

These days, though, unless I’m in the absolute depths of despair, I feel that if I’m not making others happy as well, I’ve failed.

Pack horse as symbol of the human condition: Leeds, 2016

Pack horse as symbol of the human condition: Leeds, 2016

Meanwhile, I’m staring 60 down the barrel of a metaphorical gun that’s a few years away yet, and it’s not a pretty sight. If I were the victim of a tragic accident, I tell myself when I have too much time, gloom, and imagination at hand – and I always have the latter, and just now the former two as well – what would the headline say? Normally, for a woman of my age, “Mum of x” – where “x” represents number of children. Or even “Grandmother of x”.

But my “x” is an “0”, and my biological clock struck midnight years ago. And it’s probably as well I didn’t have kids, given the hell that was menopause.

Walk this way: Leeds, 2016

Walk this way: Leeds, 2016

Weirdly, I have just said that I have too much imagination, yet at the moment, I feel like I can’t write for toffee. (1) Or even tea and biscuits, which we actually have in the house.

What makes this particularly self pitying is that I have met loads of people with far worse metaphorical packs on their backs: bigger, heavier, messier. You name it.

I have to get a handle on this. Because I can’t face going back on meds (again) let alone back onto the wards (again). Because I don’t want to drag my husband or friends through the mud and gore of my particular brand of mental health hell.

I had a lovely time in Leeds yesterday, with my favourite person in the world. Took lots of photographs: even experimented with the black and white setting. Yet, when I tried earlier today to write something even mildly creative?


The best thing that could happen to me just now is probably getting stuck into a writing  project. But I’m creatively constipated, in part because I’m in despair. Which just leads to more despair.

Like a figure in an Escher drawing, stuck on the same damned stairwell, with a note in their back pocket reminding them that it doesn’t really matter, anyway.


2000-09-08 06.00.16

Here be dragons: Leeds market, 2016

(1) Near as I can trace it with a quick internet search, that’s part of a quote from the Regency period Blackadder.

The Bipolar Disorder Med-i-go-round

Originally posted on Our Lived Experience:
I wish I could tell you that this blog post was sponsored by a pharmaceutical company, but you know, the medical professionals get the perks, we just get an ever increasing array of horrible side effects and the vague hope of a little emotional stability somewhere along the way.…

The Bipolar Disorder Med-i-go-round

I wish I could tell you that this blog post was sponsored by a pharmaceutical company, but you know, the medical professionals get the perks, we just get an ever […]