More on How Lousy Psychiatrists are at Determining Prognosis

A few days ago I put up my post on the Clinical Psychiatry News website on Rethinking Bipolarity.  I talked about how we've expanded the diagnosis so that now it captures so many problems as to make the diagnosis imprecise and I talked about how we really can't predict prognosis.  In the same vein, the front page of the New York Times has an article about people with schizophrenia who do better if they keep busy with busy careers, even if they are very stressful.  In a High Profile Executive Job as Defense Against Mental Illness, Benedict Carey writes:

Now, a group of people with the diagnosis is showing researchers a previously hidden dimension of the story: how the disorder can be managed while people build full, successful lives. The continuing study — a joint project of the University of California, Los Angeles; the University of Southern California; and the Department of Veterans Affairs — follows a group of 20 people with the diagnosis, including two doctors, a lawyer and a chief executive, Ms. Myrick.


The study has already forced its authors to discard some of their assumptions about living with schizophrenia. “It’s just embarrassing,” said Dr. Stephen R. Marder, director of the psychosis section at U.C.L.A.’s Semel Institute for Neuroscience and Human Behavior, a psychiatrist with the V.A. Greater Los Angeles Healthcare System and one of the authors of the study. “For years, we as psychiatrists have been telling people with a diagnosis what to expect; we’ve been telling them who they are, how to change their lives — and it was bad information” for many people. 

It's a good article, but I have one gripe with it (...ah, for me to have only one gripe with an article by Mr. Carey is close to amazing).  He makes it sound like people with schizophrenia have chosen less stressful jobs because that's what doctors recommend.  I think some people with schizophrenia lose their motivation to work at any job because it's one symptom of the illness.  Like bipolar disorder,  schizophrenia and schizoaffective illness seem to play out differently in different individuals.  As a field, our crystal balls don't seem to work very well. 

Henry's Demons: A Father-Son Memoir of Schizophrenia

My mother and father and the dreaded psychiatrist definitely believe I am schizophrenic.
---Henry Cockburn


Now here's a Shrinky book I haven't read. Or at least not yet?

In yesterday's New York Times Book Review, Darin Strauss reviews a father-son memoir by Patrick Cockburn and Henry Cockburn. Henry's Demon's is the story of Henry's battle with schizophrenia.

Did Strauss like the book? I couldn't say. He spent a fair amount of time picking apart the writing of the father/war correspondent. I think he wished the son of a novelist had become schizophrenic for the sake of fewer cliches.

What about Amazon, how do it's reviewers feel? No reviews yet. If you read this book, by all means, tell me what you think! Here's the father-son dual on the Diane Rehm Show if you'd like to listen to their tale.

Did Your Cat Cause Your Schizophrenia?

From the front page of today's Baltimore Sun: Researchers Explore Link Between Schizophrenia, Cat Parasite.

Frank D. Roylance writes:
Johns Hopkins University scientists trying to determine why people develop serious mental illness are focusing on an unlikely factor: a common parasite spread by cats. The researchers say the microbes, called Toxoplasma gondii, invade the human brain and appear to upset its chemistry — creating, in some people, the psychotic behaviors recognized as schizophrenia. If tackling the parasite can help solve the mystery of schizophrenia, "it's a pretty good opportunity … to relieve a pretty large burden of disease," said Dr. Robert H. Yolken, director of developmental neurobiology at the Johns Hopkins Children's Center.

Roylance continues:
A University of Maryland study last year found that people with mood disorders who attempt suicide had higher levels of T. gondii antibodies than those who don't try to take their own lives. Still, the links between schizophrenia and toxoplasmosis are not simple. For example, most people infected with T. gondii never become schizophrenic. And not all schizophrenics have been exposed to toxoplasma. Yolken believes additional factors, such as an unlucky combination of genes, are probably needed to produce schizophrenia among Toxoplasma-infected people. The parasite's DNA may also be important, since some strains are known to cause more disease.

Meow?

Schizophrenia, Still Figuring it Out

New York Times reporter Benedict Carey likes to write about mental health issues. Today, he talks about the diverse presentation of schizophrenia, as well as variations patients have with regard to treatment response. Carey writes:

The findings confirmed in a rigorous way what psychiatrists who work in the trenches know from experience: Many patients bounce from medication to medication for years. Some find a drug they can live with; others do not and choose not to take drugs at all.

Psychosis can be miserable — and it says something when people prefer its twisted torments to being on a medication.

The shortcomings of the drugs, in turn, cast doubt on one working theory of the biology behind schizophrenia. The drugs act on the brain by numbing cells to a brain chemical called dopamine, which was thought to be overactive for some reason in people with schizophrenia. Most researchers now regard this so-called “dopamine hypothesis” as simplistic at best.

He goes on to say that, according to European studies,with the right support, there are patients with schizophrenia who can be maintained for years without medications. Wouldn't it be nice if we knew exactly which patients they were?

Latest Genetic News in Schizophrenia

Schizophrenia has been long thought to be a heterogeneous disease, with many different pathways all leading to an illness with similar symptoms among its affected ranks. It is believed to be caused by a combination of genetic and environmental triggers, as there is a 50% chance of getting it if your identical twin does and a 10-15% chance if your parent or sibling does. Various environmental triggers appear to increase the risk of getting it, such as in utero infections, being born in the winter, and growing up in a family where there is a lot of yelling and emotional expressiveness. About one percent of the population has schizophrenia.

A recent study in Science of whole genome DNA in hundreds of people with and without schizophrenia finds that rare DNA mutations may more of a role to play than previously thought. From Scientific American: "In this study, researchers combed the genomes of 150 schizophrenia sufferers and 268 healthy individuals for never-before-seen copy number variations (CNVs)—mutations that result in large swaths of DNA encompassing multiple genes either being deleted or duplicated. Some such mutations have been found to be benign, but others have been implicated in ailments such as autism and cancer. The team of scientists, from research facilities across the U.S., found novel gene alterations in 5 percent of the healthy volunteers and 15 percent of the schizophrenia patients; new CNVs showed up in 20 percent of those subjects who developed symptoms at or before the age of 18."

53 different mutations were found in these patients. As more of these studies look at whole genomes from families with a high number of affected individuals (like mine, with 7 or 8 people with schizophrenia spectrum diagnoses), we will learn more about what goes wrong in these illnesses and how to better treat them.

Hollywood, Schizophrenia

I'm watching the Academy Awards. I'm betting on Atonement. You heard it hear first. I also loved Juno. We were going to do a podcast today, but Clink went to the opera. Roy and I and our beloved non-shrink proles went to see Vantage Point. Not shrinky, I leave it to Roy to find a way to blog about it.

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You can read about a new Schizophrenia medication in development in the New York Times business section: "Daring to Think Differently About Schizophrenia." LY2140023 works on glutamate receptors, a new approach but the article mentions that preliminary testing shows it to be slightly less effective than Zyprexa.

CANVAS (The Movie): This is Mental Illness Awareness Week

(from NAMI): Help CANVAS Fight Stigma This Week
Movie about a boy whose mother has schizophrenia — Spread the word about the movie, no matter where you live.

View the Trailer

Just in time for Mental Illness Awareness Week (October 7-13), the movie CANVAS is being released in Chicago and New York on Friday, to be followed by three other cities next week. If Friday and Saturday ticket sales run high in these five cities, the release may expand to 200 cities nationwide.

Starring Emmy Award-winner Joe Pantoliano and Academy Award-winner Marcia Gay Harden, CANVAS is the story of a family's struggle with schizophrenia. It educates as well as entertains. It will build awareness about mental illness and strike a blow against stigma--but only if enough people see it. In order for the movie to reach a nationwide audience, please take action to help:

• Spread the word! Please spread the word now with a personal message to family and friends in the cities below—and friends elsewhere.
• Buy tickets on-line early each week. You don't even have to live in the opening cities. Tickets make great gifts or donations. Use the links below to purchase tickets online.
• If you live in one of the five cities, go see the movie on a Friday or Saturday. Take a friend. Go in a group. Hold a discussion afterwards.

Starting October 12...
• In Chicago, AMC Loews 600 North Michigan 9, 600 N. Michigan Ave. 60611
• In New York, Regal Union Square Stadium 14, 850 Broadway, 10003

Starting October 19...
• In Los Angeles, Laemmie Sunset 5, 8000 Sunset Boulevard, 90046
• In Phoenix, Harkins Shea 14, 7354 E. Shea Blvd, (Scottsdale) 85260
• In Fort Lauderdale, check local listings as the date approaches.

Molecular Psychiatry: Schizophrenia Mouse Model

Here's another interesting knockout mouse model for schizophrenia. This was in the July 31 issue of Molecular Psychiatry, "Phospholipase C-1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration," by McOmish et al., in Australia.

"Phospholipase C-1 (PLC-1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenia-like symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene–environment interactions."

PLC-1 is one of those proteins involved in processing the signal after the receptor is activated. Think of the ignition in your car. If the key is the neurotransmitter, like serotonin (or medication, like Prozac) and the lock (or keyhole) is the receptor, then PLC-1 is one of the wires that connects the lock on the steering column to the starter, which gets the engine going. We are all so used to thinking that what is important is the action at the receptor, but it is easy to forget that there is this whole other layer of machinery that gets engaged once the receptor is activated.

These so-called second messenger systems use a cascade of Rube Goldberg connectors to make things happen. Just like a genetic error can cause a receptor to malfunction, so can errors in this second messenger cascade.

This particular enzyme is involved in the growth and connectivity of brain cells. The researchers show that mice who are engineered to not produce PLC-ß-1 develop cognitive problems which have similarities to those seen in humans with schizophrenia. Changes in the environment can minimize these problems, suggesting that this animal model could be used to test other treatments -- including medications that work very differently from what is out there now -- for potential use in this neurodevelopmental illness.