Understanding Schizophrenia

Psychosis gets nearly all the attention in schizophrenia, but that is not necessarily its most prominent feature, according to Cameron Carter of UC Davis (pictured here). Dr Carter keynoted the NAMI CA convention in Sacramento about two weeks ago. Rather, the big concern is cognitive disorganization. Cognitive deficits, he said, involve compromised ability to control our own thinking and behavior.

Thirty years ago, Dr Cameron related, a psychiatrist told him that schizophrenia was not a brain disorder. Rather, it was a psychosis (in the Freudian sense of the term) that could be treated with family therapy. Too bad no one got better.

The first indication that schizophrenia could in fact have something to do with the biology of the brain came more then three decades ago in the form of a breakthrough brain scan study by Johnstone and Crow. The scans, which compared the brains of those with schizophrenia to controls, revealed that those with schizophrenia possessed larger ventricles (open spaces) than the controls. Check out what looks like a butterfly silhouette in the two images below. Notice the decidedly more pronounced butterfly on the right.

Dr Carter recounted reading the Johnstone and Crow study back when it was first published in The Lancet in 1976. “Bollocks!” (a UK term of derision) someone had scribbled in his copy.

More sophisticated imaging studies over the years reveal losses in gray matter volume in different areas of the brain, but this is not the same as loss of brain cells as in Alzheimer's, Dr Carter was quick to point out. All the cells are there. What seems to be going on, among other things, is loss of connectivity (circuitry anomalies, especially in the dorsolateral prefrontal cortex) and neuronal oscillations (particularly in GABA cells). The different regions of the brain, in effect, are out of sync. Thinking gets disrupted.

Dr Carter gave the example of an American tourist in the UK having to negotiate crossing the street. Habitual responding won't do.

But cognitive challenges and psychosis are related, with the first anticipating the latter. Well before psychosis rears its head, it appears that first there are changes in the cortical areas. As these changes progress, this may lead to subcortical dopamine dysregulation and psychosis.

Then there is something called “psychosis risk syndrome.” Thirty to forty percent of those who experience attenuated psychosis features - ie not meeting DSM criteria - go on to develop schizophrenia or bipolar over two years.

So perhaps by improving function in the cortical areas prior to first psychosis, we can prevent psychosis.

This is one of the hot areas in schizophrenia right now. Dr Carter heads up the EDAPT program - Early Diagnosis and Preventive Treatment of Psychotic Illness - at UC Davis. Family involvement, Dr Carter, told us, is the most effective component. New developments include the likelihood of two or three new meds - not antipsychotics or dopamine blockers - that would target cortical areas to improve cognition. Also, cognitive training - pioneered by Sophia Vinogradov of UCSF - based on the “use it or lose it” principle is taking off. Another possibility is transcranial magnetic stimulation.

The brain science over the past five or six years has led to enormous advances in our understanding of schizophrenia. But will our knowledge lead to better treatments and possibly even prevention? Good question.

Rerun: Figuring Out Schizophrenia - Part II

Nothing like a three-part piece from March 2009 to rerun while I perform clean-up on the Augean Stables that is my website. Looking forward to being back live soon ...

Another full day at the International Congress on Schizophrenia Research, here in San Diego. To recap:

Breakfast: Beatriz Luna of the University of Pittsburgh tells me she isn't a schizophrenia researcher. Rather, she's into something called "development." I'm thinking development, as in a child psychologist.

No, she tells me. This is about brain development, as in the child brain maturing into the adult brain. She will be one of the speakers at a two-hour symposium later in the morning. (That's her in the photo.) Curious, I check it out:

Think of research into normal brain development shedding valuable light on schizophrenia, and, by extension, all of mental illness. The first speaker, Patricio O'Donnell of the University of Maryland, talks about cortical microcircuits and the balance between excitation and inhibition. Dopamine, he says, plays a large role in the modulation of circuits in the prefrontal cortex. During adolescence, he explains, these circuits experience dramatic connecting changes.

For instance, "phasic dopamine" (firing in bursts) gets dialed in, with improved signal to noise ratios.

But suppose the brain doesn't mature? Are we then looking at an approximation of schizophrenia?

David Lewis of the University of Pittsburgh shows slides that highlight the neuron's "dendritic spines." These spines play a major role in brain cells talking to one another. We know that people with schizophrenia are not favorably endowed in this category, but what does it mean?

In normal brain development, he explains, there is an early dramatic increase in spine density followed by a dropping off in adolescence and leveling out in adulthood. But are we talking about a drop-off in "functionally mature" or "functionally immature" connections? In other words, when the brain experiences structural changes, are the right chemical messages crossing the dendritic divide or the wrong ones?

Early intervention, he says, might be directed at enhancing the normal development of these synapses.

Dr Luna informs the audience that adolescence involves major risk of mental illness. As she explained to me over breakfast, this is when the brain changes gears. But what if something goes wrong in the transition? Might this underlie the pathology of mental illness?

During adolescence, the brain undergoes "synaptic pruning," along with axonal "myelination." In essence, brain function becomes more equally distributed, with less reliance on impulses from the basal ganglia and other more primitive regions of the brain.

But what if something goes wrong? Normal child brain function is suddenly not so normal, not in an adult brain anyway. You can kind of see this with the current economic meltdown, Dr Luna explains. It's a new world. AIG and GM and the rest can't behave the way they used to. The failure in executive behavior in this new context, she concludes, now becomes obvious.

Lunch time posters: This is where I get to ask all my stupid questions. For instance, over the past two days, the area of the brain I've been hearing most about is the dorsolateral prefrontal cortex, the brain function I've been hearing the most about is working memory, and the researcher I have been hearing most about is Joseph Callicot of the NIMH.

"Allelic Variation in KCNH2 is Associated with Dorsolateral Prefrontal Cortex Activation During Working Memory," reads the poster.

The name tag on the man standing in front of the poster reads Joseph Callicot.

Knock me over with a feather. Fire away with all your stupid questions, says the look on his face.

I love this job ...

Rerun: Reporting on Schizophrenia

Until I get my website overhauled (a mammoth undertaking), I will be posting reruns. This three-parter (from March, 2009) will get me through most of this week. Looking forward to being back live very soon ...

My annual conference season unexpectedly began three weeks early today, when I attended what I thought would be an afternoon local family forum on schizophrenia. I turned up at the Grand Hyatt on San Diego's waterfront only discover the forum was a satellite to a four-day major world conference: The International Conference on Schizophrenia Research, held every two years.

So that explained the star-studded list of speakers at our local family forum.

(Small sound-bite from that forum: According to John McGrath MD, PhD of the University of Queensland, hallucinations and delusions are "very very common" in the general population. Four percent of the US population hears voices.)

As soon as the forum ended, I headed over to the registration area of the main conference to secure media credentials. Mind you, here I was, a mental health journalist feeling obliged to explain why I knew nothing about a major world schizophrenia conference in my own backyard until today.

"Bipolar," I said to someone behind the desk, pointing to a copy of my book I happened to have in my bag, as if that explained everything. Another person was called over to assist.

"Tamminga," said the name on her tag.

She caught the look on my face. "It looks like you're familiar with the name," she said. "I'm her daughter." As in daughter of Carol Tamminga MD of the University of Texas Southwestern Medical Center, first rank researcher and one of the conference organizers. In addition, Dr Tamminga is very generous in giving her time to NAMI and other causes. (That's Dr Tamminga's photo on this blog post.)

Nearly two years ago I happened to sit next to Dr Tamminga over dinner in Pittsburgh at a closed function at the Seventh International Conference on Bipolar Disorder. (I was a special guest by virtue of a public service award I would receive two nights later.) Just to show you what a thoroughly gracious person Dr Tamminga is, our section of the table also included Thomas Insel MD, head of the NIMH, and Darrel Regier MD, co-chair of the DSM-V task force, but Dr Tamminga talked to me as if the other two weren't there.

"I was about to use your mother as a reference," I joked, then I briefly explained the connection.

Ten minutes later, I was at a patio table, poring over my conference materials. A brain scientist from Australia sat down, and for the next hour we talked about the brain, the metric system, politics, the environment, Einstein, and autism (she has a son with autism). Ninety percent of marriages involving an autistic child end in divorce, she informed me.

Tomorrow, I will be waking up before dawn to catch Dr Insel at a plenary session, then over to a morning symposium on "Dopamine Signaling in the Era of Molecular and Genetic Pathways." I'll hit the research poster sessions over lunch, then take in an afternoon of "Aberrant Functional Connectivity in Schizophrenia: Changes in Frequency, Symptoms, Drugs, and Genes."

Tuesday and Wednesday will be more of the same.

What is a depression and bipolar writer doing at a schizophrenia conference? From a recent blog post:

Back in 2003, I had one of those breakthrough moments, the type you associate with light bulbs switching on. I was at the American Psychiatric Association's annual meeting attending a symposium on genetics. Robert Freedman MD of the University of Colorado started explaining his research into schizophrenia.

"The DSM-IV was not designed with human gene function in mind and genes do not encode for psychopathology," he said. Instead, "genes encode simple molecules in cells that alter cell function and brain information processing."

I had kind of been aware of this, but this time I went, "Aha!" ... The upshot of my Aha! moment was the realization that to better understand my own illness (bipolar) I needed to research other illnesses as well, such as schizophrenia. The brain, after all, doesn't organize itself according to the DSM.

Listening to the schizophrenia people, in effect, gives me insights into my illness that I would never get from limiting my enquiry to the mood disorders experts. Take my word for it, I'm like a kid in a candy store at these events. The only thing about my job that I love more than listening to super-smart people who have dedicated their lives to improving yours and mine is writing about it.

Stay tuned ...

Rerun- Is Mental Illness an American Disease?

This from late January ...

An article by author Ethan Watters in the Jan 8 NY Times Magazine throws down the gauntlet:

For more than a generation now, we in the West have aggressively spread our modern knowledge of mental illness around the world. We have done this in the name of science, believing that our approaches reveal the biological basis of psychic suffering and dispel prescientific myths and harmful stigma. There is now good evidence to suggest that in the process of teaching the rest of the world to think like us, we’ve been exporting our Western “symptom repertoire” as well. ...

The article, "The Americanization of Mental Illness," is an adaptation from the just-released book, ‘‘Crazy Like Us: The Globalization of the American Psyche.” In the article, Mr Watters uses the example of a “culturally specific” form of anorexia documented by one researcher in Hong Kong during the 80s and 90s. Unlike Americans with anorexia, those in Hong Kong simply complained of bloated stomachs without dieting or expressing fear of becoming fat. The illness was rare.

Then, in 1994, in the wake of the death of a school girl, the local press attempted to explain the phenomenon using American diagnostic language. According to Watters, “the transfer of knowledge about the nature of anorexia (including how and why it was manifested and who was at risk) went only one way: from West to East.” Not surprisingly, there was an outbreak of “fat phobia.”

Says Watters:

In the end, what cross-cultural psychiatrists and anthropologists have to tell us is that all mental illnesses, including depression, P.T.S.D. and even schizophrenia, can be every bit as influenced by cultural beliefs and expectations today as hysterical-leg paralysis or the vapors or zar or any other mental illness ever experienced in the history of human madness.

This does not mean the illness or the pain is not real, Watters is quick to add. But an illness of the mind needs to be understood in its cultural context. Ironically, says Watters, the western notion (promoted by advocacy groups such as NAMI) that mental illness is a no-fault “brain disease” may have the opposite effect of increasing rather than reducing stigma. According to Watters, citing the research of Sheila Mehta of Auburn University:

The problem, it appears, is that the biomedical narrative about an illness like schizophrenia carries with it the subtle assumption that a brain made ill through biomedical or genetic abnormalities is more thoroughly broken and permanently abnormal than one made ill though life events.

The author cites a four-decades study that found a steady rise in the American public in their perceptions of schizophrenia as dangerous. Meanwhile, in Turkey, according to a study, “those who labeled schizophrenic behavior as akil hastaligi (illness of the brain or reasoning abilities) were more inclined to assert that schizophrenics were aggressive and should not live freely in the community than those who saw the disorder as ruhsal hastagi (a disorder of the spiritual or inner self).”

Most of us are aware of three WHO studies over the course of 30 years (starting in the 70s) that found that patients outside the US and Europe had significantly lower relapse rates (as much as two-thirds lower in one follow-up). Watters reports on anthropologist Juli McGruder from the University of Puget Sound who spent years in Zanzibar studying families of those with schizophrenia. There Muslim and spirit possession beliefs are incorporated into healing practices. Rather than spirits being “cast out,” they are “coaxed out” with acts of kindness.

Says Watters: “Since the illness was seen as the work of outside forces, it was understood as an affliction for the sufferer but not as an identity.”

The author adds:

The course of a metastasizing cancer is unlikely to be changed by how we talk about it. With schizophrenia, however, symptoms are inevitably entangled in a person’s complex interactions with those around him or her. In fact, researchers have long documented how certain emotional reactions from family members correlate with higher relapse rates for people who have a diagnosis of schizophrenia.

This negativity is referred to by experts as “high expressed emotion (high EE),” which include criticism, hostility and emotional overinvolvement (such as overprotectiveness). White American families caring for a family member with schizophrenia have notoriously high EE rates, with much lower EE rates among Mexican and other families.

It’s not that American families are unenlightened, says Watters. Rather, they “were simply expressing a particularly American view of the self,” and “applying the same assumptions about human nature that they applied to themselves.”

No one is seriously talking about withholding meds and other western treatments and therapies from individuals in need. But we do need to be mindful, says Watters, that even our best science is far from culturally neutral. Thus:

Offering the latest Western mental-health theories, treatments and categories in an attempt to ameliorate the psychological stress sparked by modernization and globalization is not a solution; it may be part of the problem.

Something to think about ...

My Totally Surreal Experience Lecturing on Problem Meds to Psychiatrists and Other Clinicians

In my two previous blog posts, I described my unequivocally frosty reception involving a grand rounds lecture I delivered on meds compliance two years back to a psychiatric facility in Princeton, NJ. My first section involved The Problem Patient, my last The Problem Clinician. Following is my version of the middle part of my talk, Problem Meds ...

Okay, maybe I went out of my way to piss off my audience. "Here's a question for you," I opened. "What is the one drug taken by 85 percent of those with schizophrenia and two in three with bipolar that they are 100 percent compliant with?"

They came up with nicotine right away.

We know that auditory gating is mediated by the alpha-7 nicotinic receptor. Those with schizophrenia have trouble filtering out background noise, thus have trouble concentrating. I recall Robert Freedman of the University of Colorado explaining this to a symposium of the American Psychiatric Association annual meeting a number of years before.

Dr Freedman and his colleagues noticed that those with schizophrenia seemed to experience a desperation that went way beyond normal cigarette cravings and decided to investigate. What they found was that in the brief time a cloud is in the patients' lungs, a cloud clears from the brain.

Mind you, this is hardly a long-term solution. But think about it. Nicotine works. With nicotine, some patients actually get their brains back - even if just for a precious few seconds. I don't know about you, but I don't take my brain for granted. Every precious second the reception comes in loud and clear is a gift to me.

Mind you, I'm not advocating cigarette use. But it appears that nicotine may be an effective drug for schizophrenia. Its major fault is the delivery system, but thanks to the research of Dr Freedman and others alpha-7 nicotinic agonists are in development.

"So, if you prescribe cigarettes," I joked, "you will get much better compliance than if you prescribe an atypical antipsychotic."

Zero degrees Kelvin frozen silence. It probably didn't help that earlier I had called out my audience for all the "No Smoking" signs on the grounds of the facility. (Mind you, perhaps thanks to the nicotine patch, patients and those who speak for them are putting up little resistance to hospital smoking bans.)

Now it was time to compare and contrast. Up on my PowerPoint went this slide from a 2007 editorial in the American Journal of Psychiatry:

Without adequate dopamine signaling, our patients do not feel ‘well.’ When dopamine systems are dysfunctional, patients seek a change. This may involve stopping a medication, such as antipsychotic drugs that block dopamine.

Rather than clearing the brain, these meds actually take major parts of the brain off-line. The major problem with schizophrenia is cognitive deficit. Up went a quote from leading schizophrenia researcher, John Krystal MD of Yale:

"Our medications are least effective for the most disabling symptoms of schizophrenia," namely, "the cognitive dysfunctions that seem to prevent people from performing in the workplace."

The pioneering diagnostician Emil Kraepelin, who "discovered" schizophrenia back in the early twentieth century, pointed to cognitive dysfunction as a core symptom, and we are also recognizing it looms large in bipolar.

I was just getting warmed up. "So, what's your answer?" I asked. "You give patients a drug that actually worsens the most pronounced feature of schizophrenia - and a significant feature of bipolar. Not only that, you're telling us we're going to have to take it the rest of our lives. Sure, it knocks out the psychosis, but so what?"

I could have gone on about the metabolic catastrophes from meds such as Zyprexa - surely the long-term risk to health was as bad as cigarettes - but I compassionately spared my audience. Instead, I simply drove home this point: 

"Far from lacking insight into their illness, even patients with schizophrenia have a much better understanding than the people charged with treating them. Far from refusing to put up with side effects, they are willing to put up with a drug with one of the worst side effects profiles in the world. Why? Because it works. It works where they want it to work."

"Let's face it," I concluded. "We've all been badly oversold on the new generation antipsychotics - you, me, family members. When all is said and done, these new generation atypicals are basically Thorazine with the tires rotated."

For some crazy reason, to my total amazement, they cracked up at that line. Then they went back to being bumps on a log.

"My question for you," I concluded in this part of my presentation, "is why did it take you so long to figure this out? The same info was in the journals you subscribe to, on the labeling of the meds you prescribe. More important, your patients have been telling you this for years. Why haven't you been paying attention?"

As I mentioned in previous blog pieces, my audience heard me out, then made for the exits the second my lips stopped moving.

Schizotypal: Deep into Creativity, Just Shy of Madness

In a March blog post, Madness and Creativity, I reported on how “latent inhibition” appears tied in to both psychosis and creativity. The piece drew heavily from a post on Psychiatry Today’s Beautiful Minds blog by Scott Barry Kaufman. As I reported:

What we seem to be looking at is that fine edge where productive novel thinking ventures close to the precipice of pathologically delusional thinking.

In his piece, Dr Kaufman talked about "latent inhibition" (LI), the brain's ability to unconsciously filter out information. High latent inhibition is conducive to rational thought. Low latent inhibition is associated with psychosis and schizophrenia.

But Dr Kaufman noted:

Recently researchers have wondered whether a reduced latent inhibition can actually be beneficial for creativity. After all, decreased LI may make an individual more likely to see connections that others may not notice.

In an ideal situation, a rational brain (the seat of executive function) processing novel information can produce astonishing insights that can pass for genius, creativity, or intuition. Dr Kaufman cited both his own research and the research of others in support of the proposition that those with a higher faith in their own intuition tested “high” for “low” LI.

People with schizophrenia, unfortunately, do not fare well with executive function. They get overwhelmed. Their low LI translates into psychosis. Sylvia Nasar, in her book “A Beautiful Mind,” recounts a colleague asking John Nash in 1959 how he could believe that extraterrestrials were sending him messages.

"Because," Nash replied, "the ideas that I had about supernatural beings came to me the same way that my mathematical ideas did. So I took them seriously."

In two blog pieces (on Nash and on Darwin) I speculated that Dr Nash may have been dealing with a form of “schizophrenia lite” (either under-the-radar “prodromal” symptoms or “schizotypy”) that allowed him to produce brilliant insights before the full force of the illness descended and robbed him of a quarter century of his life. What originally got me started on this line of thinking was a lecture I heard by Nancy Andreasen, who noted, among other things, that Einstein had a son who had schizophrenia and that he himself was an eccentric with “schizotypal” tendencies.

In his latest piece, Dr Kaufman dials in the “schizophrenia lite” connection. Schizotypy, he says, “is a watered-down version of schizophrenia” with a constellation of personality traits “that are evident in some degree in everyone.” He cites a recent study by Nelson and Rawlings in Schizophrenia Bulletin that suggests schizotypy “may be positively associated with the experience of creative flow.”

Dr Kaufman defines “flow as “the mental state of being completely present and fully immersed in a task.”

In addition: “When in flow, the creator and the universe become one, outside distractions recede from consciousness, and one's mind is fully open and attuned to the act of creating.”

As Susan Perry in “Writing in Flow” explains: “Looseness and the ability to cross mental boundaries are aspects of both schizophrenic thinking and creative thinking."

Dr Kaufman notes that this is an exciting time for research on the linkages between mental illness and creativity. The Nelson and Rawlings' study, he says, suggests that positive schizotypy, latent inhibition, and flow are intimately related, though a lot more research needs to be done.

Bring it on ...

Schizophrenia: In Their Own Voices

Last week I was at a one-day conference put on by NAMI San Diego and the Senior Mental Health Partnership. My good friend Sally Shepherd (pictured here) was one of the speakers. Just days before, she had been informed that a study she had played a major role in designing and implementing had been accepted by The Schizophrenia Bulletin. The study sheds important light on how those with schizophrenia see themselves. 

Sally and her fellow investigators interviewed 38 individuals with schizophrenia aged 50 and over, living in board and cares and unemployed. They asked six very basic questions, and essentially listened, just listened.

Significantly, only a quarter of the interviewees included relationships with family members in their criteria for "quality of life." Nearly half had never married. The remaining participants reported experiencing significant marital discord, including emotional abuse. Only two remained in long-term marriages.

In their own voices ...

Early Experience with Schizophrenia

But when you are labeled a schizophrenic or have psychosis and you don't understand it because you didn't learn about it prior to and you're like, all of a sudden you're in this nightmare, and with nobody to help you because nobody understands, nobody's in it with you. The whole world is dead; you're the only one alive in this big graveyard, which is the world. You have to survive with no money and no place to sleep and all these dead people trying to kill you or whatever, rob you of your sanity is more like it, same thing.

Personal Loss

It's not what I thought I'd have when I was younger. I thought I'd be doing something else. I didn't think I was going to be on Social Security when I was younger. I thought I was going to be a scientist.

Loss of Independence

In '98, I was sitting in the courtyard in the unit I was on. I was smoking my cigarette and went to find my [counselor]. I told her, "I don't want to die here, V. I don't want to die at [State Hospital]. V, what can I do?"

Self-Doubt

I asked her once, "Where did we go wrong? Why are we in these board and care homes?" I feel like we're here because people have given up on us or we've given up on ourselves.

Hopes and Dreams

I'm going to feel regretful because I never lived lived; I never had a chance to live. I never had a life. If I was just 21 and had accomplished my dream of a good job and my wife, my kids ...

Resignation

I have a roof over my head, I have food and clothing and my computer and my stereo, and if I compare my life with some of those starving in other countries, it's like I'm living in heaven compared to them.

My DSM-5 Report Card: Grading Bipolar - Part IV

Part I, Part II, and Part III to Grading Bipolar placed heavy emphasis on that largely unmapped middle ground where bipolar bleeds over into clinical depression. Why this is critically important is that clinical ignorance leads to misdiagnosis and wrong treatments, which translates into years and even decades of unnecessary suffering.

The current DSM abets numerous opportunities for bad psychiatric practice, which the DSM-5 was supposed to redress. Unfortunately, the Task Force and its various workgroups suffered an extreme outbreak of dereliction of duty.

So, can the DSM-5 do better where bipolar bleeds over in the other direction into schizophrenia? First a little background ...

Back in the early twentieth century, the pioneering diagnostician Emil Kraepelin separated out “manic depression” (bipolar and recurrent depression) from “dementia praecox” (schizophrenia). This distinction provided psychiatry with its first real navigational aid, which continues to guide diagnostic practice to this very day.

But Kraepelin also recognized the limits to making a clear categorical split, and recent genetic findings are backing his reservations. Virtually all the leading candidate genes for bipolar happen to be leading candidate genes for schizophrenia, as well.

The current DSM recognizes some of the crucial fine shadings. Thus we have “with psychotic features” as specifiers to both major depressive disorder and bipolar disorder. In addition, there exists the separate diagnosis of “schizoaffective disorder” that is widely interpreted as a hybrid between bipolar and schizophrenia.

The issue: Should those charged with the DSM-5 attempt to fix what doesn’t appear to be broken? Or is there considerable room for improvement?

On with the grading ...

Psychosis, a Clear Definition

The current DSM makes various references to psychotic features, but what precisely is “psychotic”? To find out, one needs to flip the pages to the rather obscure diagnosis of “brief psychotic disorder,” which mandates one or more of the following symptoms:

Delusions; hallucinations; disorganized speech; psychomotor symptoms, including catatonic behavior.

The DSM-5 would leave this unchanged.

Fine, that provides a breakdown of the component parts to psychosis, but what is psychosis? The glossary to the DSM-IV concedes that none of the historic definitions “has achieved universal acceptance.” Narrowly viewed, psychosis refers to hallucinations and delusions to which the patient lacks insight. A wider view would incorporate patient insight. Still wider are the symptoms listed for the positive symptoms of schizophrenia (same as for a brief psychotic episode) and wider still would incorporate “loss of ego boundaries or gross impairment in reality testing.”

The current DSM punted in coming up with an authoritative definition and set of distinctions. It appears the DSM-5 is similarly opting out.

Grade: F.

With Psychotic Features

Psychosis looms large in mania and less so in depression. The DSM-IV operative term is “with psychotic features,” which the DSM-5 would leave unchanged. Presumably, a “feature” is less intense than a “symptom,” but it would be helpful to see this spelled out. Is this asking too much? Apparently yes.

Grade: F.

Mood Congruent/Incongruent

When adding a “with psychotic features” specifier to depression or mania, the DSM-5 would mandate clinicians to differentiate “mood congruent” from “mood incongruent.” In a depression context, mood congruent psychosis might translate to, say, irrational feelings of deserved punishment. A manic context might involve delusions of a special relationship to a deity.

Mood incongruent, by contrast, involves no apparent linkage between mood and disordered thinking.

The current DSM buries this distinction way back in Appendix C. Moving this up front and center is a major step forward. But will clinicians have to flip to the back pages to find the definitions?

Grade: B.

How Psychotic is Psychotic?

We know we can have a mood disorder “with psychotic features.” What is unclear is whether we can have a mood disorder with full-blown psychosis. Or is that something else? Say schizophrenia or schizoaffective disorder?

Misinterpreting psychosis leaves no room for error, as a diagnosis of schizophrenia sends (very wrongly) a clear message to abandon all hope.

Grade: F.

Schizoaffective Disorder

The DSM-5 spells it out: “The current DSM-IV-TR diagnosis schizoaffective disorder is unreliable.”

To start, the current DSM classifies schizoaffective under “Schizophrenia and Other Psychotic Disorders,” but is this the right place to put it?

Too often, schizoaffective is employed as a glorified NOS diagnosis by clinicians who can’t decide whether their patient has bipolar or schizophrenia. As Goodwin and Jamison and others point out, the current DSM leaves wide room for mutually exclusive interpretations, such as:

A form of bipolar with psychosis, a form of schizophrenia with mood swings, co-occurring schizophrenia and bipolar, a separate illness, or a different phenomenon entirely occupying the psychosis spectrum.

Just to make things more confusing, a patient may appear to have schizophrenia during one phase of his or her life and bipolar in another.

So how would the DSM-5 fix a diagnosis it regards as “unreliable”?

“We recommend the following, minor change in the text ..."

A MINOR textual change? Is that it? Yes, apparently.

Grade: F-minus.

More to come ...

Tom Wootton - Visionary off the Edge

In three previous blog posts I created the impression that my friend Tom Wootton’s new book, Bipolar in Order, is a prime example why American civilization is in decline, which is true. I also made it clear that Tom is a visionary who got us thinking that we could lead better lives than the poor unfortunate souls operating within the “normal” emotional bandwidth.

In his 2007 book, The Depression Advantage, Tom represents himself as a person with “over 40 years of direct personal experience with bipolar symptoms” who, during one 15-year stretch “fluctuated between increasingly more extreme mania and depressions.”

But in January 2009, I played a video of a presentation he gave, in which Tom disclosed that, as well as manias and depressions, he had also experienced schizophrenia.

Schizophrenia? I got my first taste of trouble during this time when I asked Tom to write a guest blog for me. He suggested the preface to the new book he was working on. Fine, I said, so long as the preface works as a blog piece. Often they don’t. His draft repeated his assertion that he had experienced schizophrenia. I said he needed to delete the schizophrenia reference and replace it with psychosis.

Here is the email in full he sent back to me: “What is the difference between schizophrenia and psychosis?”

Suffice to say, our guest blog project never got off the ground.

Tom, in his new book, retreats from his claim of having experienced schizophrenia, instead referring to his delusions and hallucinations as “bipolar I schizoaffective.” Even the experts are confused about the schizoaffective diagnosis, but it’s safe to say that there is an overlap between bipolar and schizophrenia and that many individuals experience symptoms of both.

Nevertheless, in his book, Tom claims expertise in helping others gain control over the psychosis in schizophrenia, but he cites no case studies. His one and only example is John Nash in the movie version of “A Beautiful Mind.” John Nash is a real individual, but the movie treatment, especially in relation to his psychotic delusions, is fictional.

“In the beginning of the movie,” Tom writes, “his hallucinations helped him to see solutions to his mathematical problems. This ability earned him a Nobel Prize.” Imagine, Tom asks, if John Nash had been able to harness those abilities.

Sylvia Nasar’s book of the same name, upon which the movie is based, paints an entirely different picture, revealing an early John Nash as high functioning, though clearly a social oddball. The mathematical breakthroughs that led to his Nobel Prize occurred BEFORE his schizophrenia broke out. Once the delusions set in, by Nash’s own admission, he lost 25 years of his life to the illness.

Ms Nasar’s narrative suggests that Dr Nash may have been straddling a dangerous fault line where genius borders madness, but that is an entirely different discussion.

Since Tom gives workshops, it is reasonable to assume that he would have been anxious to document people he worked with, people he rescued from the hells of schizophrenia who went on to lead full lives. I would have loved to have read about this. Instead, all we get is a fictional example.

A fictional example.

This sort of thing goes over well in public speaking, where a skilled presenter can manipulate crowd emotions. At the NAMI CA conference last year, Tom actually drew applause from his fictional use of John Nash. But the left-brain world of the printed word demands substantial non-fiction documentation.

A personal example then? At both the conference and in his book, Tom describes experiencing the sensation of being crushed by a bus and finding himself inside his wife. Tom tells us this delusion is part of a pattern of similar ones that visit him. But instead of being freaked out, Tom tells us, or trying to put these delusions out of his mind, he incorporates these experiences as part of his own personal growth.

Had Tom restricted himself to his own experiences and built on them, he would have found many people who would have related. I, for one, have a creative and very quirky mind. Weird shit runs through it. And, like Tom, I too find myself contemplating my weird shit rather than ignoring it.

To be crushed by a bus. To be dead and in someone else’s body. Had this experience happened to me, automatically I’d be asking myself stuff like: What was it like to be dead? Is dead overrated? When is going into dead mode helpful to me?

Trust me, Stephen King turned this kind of thinking into a career. Tom is using it to seek greater insight and spiritual growth. Tom’s point is that it is not the psychosis that is bad - it’s how you react to the psychosis. Oddly enough, this is vintage Freud. The pre-brain science era DSM I of 1952 views mental illness as maladaptive reactions to one’s environment, including “schizophrenic reaction.”

There is some validity to rehabilitating this viewpoint, and the time is ripe for a full and spirited conversation. To a certain point, we all have the power to choose. But the kind of fleeting psychosis Tom experiences - or for that matter my own weird shit - is not schizophrenia, nor, for that matter, heavy duty psychosis. Being robbed of all power to reason is a whole different phenomenon.

There is a dangerous tendency to romanticize and trivialize schizophrenia, then morally judge those who fail to live up to our own often unrealistic expectations. Tom’s book is rife with this. Clearly, he has yet to spend a day negotiating rounds of transactions in public places dragging around someone with raving psychosis. Until he does, Tom needs to stick to his own experiences.

Reality is a treacherous place, where ivory tower ideas tend to founder. Tom compares himself to Columbus finding a new world. After reading Bipolar in Order, I see him more as a blind visionary who sailed off the edge.

This series of blog pieces sets the scene for future conversations. Stay tuned ...

Tom Wootton - A Visionary Overreaches

In two of my most recent blog posts - Bipolar in Flux and Visionary or Out of Touch - I made it clear that my friend Tom Wootton’s just-released “Bipolar in Order” is the worst piece of crap ever assembled between two covers. Besides the book being extremely badly-written and a blatant advertisement for his workshops, the author displays a complete ignorance of an illness he claims an affinity to.

But my first two pieces were actually highly-complimentary, focusing on Tom as a visionary who got us thinking that our manias and depressions, with mental discipline, could be turned to our advantage.

“Normal” people don’t have a chance against us, once we get our disorder “in order.”

Love him or hate him, you really have to admire Tom for putting that thought out there. Tom is by far the best public speaker I’ve ever come across in the field of mental health, and early last year I decided to view the master at work by checking out some videos of his talk segments. Here is what he said in his intro:

Some of you are going to think I’m crazy, which is true. I’ve got bipolar I, extreme manias, totally out of control, extreme depressions, and schizophrenia ...

Schizophrenia? My brain initially didn’t process the statement. It was only a day or two later that something went off in my head: “Did Tom actually say he had schizophrenia?” No, I thought. My mind is playing tricks on me. I actually went back and replayed the thing.

Yep, Tom actually said he had schizophrenia.

When we first met in the summer of 2006, Tom had been representing himself as someone with bipolar. His book from that year, "The Bipolar Advantage," focused exclusively on mania, with a work-in-progress on depression.

In the video I viewed, Tom referred to his own delusions and psychosis and paranoia, which I have no reason to doubt. After all, many depressions and manias come preloaded with these symptoms. But schizophrenia? There is a lot more to schizophrenia than psychosis and delusions and paranoia. Psychosis gets all the attention, but a major reason antipsychotic medications are not a magic bullet for schizophrenia is they fail to address the many cognitive dysfunctions associated with the illness, as well as the “flat affect” features.

Moreover, the DSM mandates a minimum time requirement of six months. This threshold is totally arbitrary. What is important is that the experts view schizophrenia as a long-term “chronic” illness, as opposed to the “episodic” nature of mood disorders. In other words, hallucinations and other psychotic features that occasionally come and go do not rate as schizophrenia, which is a good thing as otherwise four percent of the population would be walking around with a schizophrenia label instead of just one percent.

But if Tom truly had schizophrenia, why didn’t this come out in “The Bipolar Advantage,” which was largely autobiographical? Why didn’t this come out in the numerous conversations I had with him? More important, why didn’t it come out in a workshop I saw him present in Orange County in late 2006?

I had just moved to southern California. Tom was giving the talk under the auspices of a county mental health agency and here was the catch: He couldn’t just talk about the depression and bipolar advantage. It had to be something like the mental illness advantage. His talk had to include everyone.

The organizer of the workshop proved extremely efficient in busing in a large audience comprising those using county mental health services. This was not your typical DBSA segment that Tom was used to addressing, people with an “invisible” illness who do not stand out from a crowd. Far from it.

A number of individuals wheeled in grocery carts with their possessions. A good many looked lost and disoriented, some with thousand-mile stares in their eyes. The dress code was highly eclectic, featuring thrift shop specials, often randomly arranged. No doubt, individuals with depression and bipolar were well-represented, but it was clear Tom was addressing a large number with schizophrenia.

“Hey, I’m no different than you,” Tom could have told this group of people. He could have disclosed his struggles with schizophrenia and had everyone eating out of his hand. Instead, it was clear that there was a separation between speaker and audience. Tom gave a masterful presentation, of course, but afterward he admitted to me it was the toughest audience he had ever faced.

Naturally, I concurred. After all, what could he possibly know about schizophrenia? It turns out absolutely nothing.

More to come ...

Is Mental Illness an American Disease?

An article by author Ethan Watters in the Jan 8 NY Times Magazine throws down the gauntlet:

For more than a generation now, we in the West have aggressively spread our modern knowledge of mental illness around the world. We have done this in the name of science, believing that our approaches reveal the biological basis of psychic suffering and dispel prescientific myths and harmful stigma. There is now good evidence to suggest that in the process of teaching the rest of the world to think like us, we’ve been exporting our Western “symptom repertoire” as well. ...

The article, "The Americanization of Mental Illness," is an adaptation from the just-released book, ‘‘Crazy Like Us: The Globalization of the American Psyche.” In the article, Mr Watters uses the example of a “culturally specific” form of anorexia documented by one researcher in Hong Kong during the 80s and 90s. Unlike Americans with anorexia, those in Hong Kong simply complained of bloated stomachs without dieting or expressing fear of becoming fat. The illness was rare.

Then, in 1994, in the wake of the death of a school girl, the local press attempted to explain the phenomenon using American diagnostic language. According to Watters, “the transfer of knowledge about the nature of anorexia (including how and why it was manifested and who was at risk) went only one way: from West to East.” Not surprisingly, there was an outbreak of “fat phobia.”

Says Watters:

In the end, what cross-cultural psychiatrists and anthropologists have to tell us is that all mental illnesses, including depression, P.T.S.D. and even schizophrenia, can be every bit as influenced by cultural beliefs and expectations today as hysterical-leg paralysis or the vapors or zar or any other mental illness ever experienced in the history of human madness.

This does not mean the illness or the pain is not real, Watters is quick to add. But an illness of the mind needs to be understood in its cultural context. Ironically, says Watters, the western notion (promoted by advocacy groups such as NAMI) that mental illness is a no-fault “brain disease” may have the opposite effect of increasing rather than reducing stigma. According to Watters, citing the research of Sheila Mehta of Auburn University:

The problem, it appears, is that the biomedical narrative about an illness like schizophrenia carries with it the subtle assumption that a brain made ill through biomedical or genetic abnormalities is more thoroughly broken and permanently abnormal than one made ill though life events.

The author cites a four-decades study that found a steady rise in the American public in their perceptions of schizophrenia as dangerous. Meanwhile, in Turkey, according to a study, “those who labeled schizophrenic behavior as akil hastaligi (illness of the brain or reasoning abilities) were more inclined to assert that schizophrenics were aggressive and should not live freely in the community than those who saw the disorder as ruhsal hastagi (a disorder of the spiritual or inner self).”

Most of us are aware of three WHO studies over the course of 30 years (starting in the 70s) that found that patients outside the US and Europe had significantly lower relapse rates (as much as two-thirds lower in one follow-up). Watters reports on anthropologist Juli McGruder from the University of Puget Sound who spent years in Zanzibar studying families of those with schizophrenia. There Muslim and spirit possession beliefs are incorporated into healing practices. Rather than spirits being “cast out,” they are “coaxed out” with acts of kindness.

Says Watters: “Since the illness was seen as the work of outside forces, it was understood as an affliction for the sufferer but not as an identity.”

The author adds:

The course of a metastasizing cancer is unlikely to be changed by how we talk about it. With schizophrenia, however, symptoms are inevitably entangled in a person’s complex interactions with those around him or her. In fact, researchers have long documented how certain emotional reactions from family members correlate with higher relapse rates for people who have a diagnosis of schizophrenia.

This negativity is referred to by experts as “high expressed emotion (high EE),” which include criticism, hostility and emotional overinvolvement (such as overprotectiveness). White American families caring for a family member with schizophrenia have notoriously high EE rates, with much lower EE rates among Mexican and other families.

It’s not that American families are unenlightened, says Watters. Rather, they “were simply expressing a particularly American view of the self,” and “applying the same assumptions about human nature that they applied to themselves.”

No one is seriously talking about withholding meds and other western treatments and therapies from individuals in need. But we do need to be mindful, says Watters, that even our best science is far from culturally neutral. Thus:

Offering the latest Western mental-health theories, treatments and categories in an attempt to ameliorate the psychological stress sparked by modernization and globalization is not a solution; it may be part of the problem.

Something to think about ...

Ten Schizophrenia Myths Busted

Below is my Reader's Digest treatment from a very informative blog piece by Suzane Smith on X-Ray Technician Schools. Suzane dedicates her site to provide information to medical students. I strongly urge reading the full article. Now, to the myth-busting ...

1. Schizophrenia involves multiple personalities.


One of the most prevailing misconceptions regarding schizophrenia revolves around confusing it with Dissociative Identity Disorder (DID). DID requires the presence of at least two entirely unique personalities with easily distinguished behavior patterns, one of which must regularly assume control of the body over the other. 


Schizophrenia, by contrast, is classified under the psychotic disorder spectrum. It contains 5 different subtypes, each with varying symptoms and diagnostic requirements. Delusions, visual and/or auditory hallucinations, disorganized speech and thoughts, dramatically erratic or outright catatonic behavior patterns, avolition, alogia, and a deadening of emotional responses may all indicate the onset of a schizophrenic episode.

The confusion set in due to the Greek etymology of the word, which literally means “I split.”


2. Individuals with schizophrenia are inherently dangerous people.

In reality, those with schizophrenia and other psychotic disorders only comprise anywhere between 1% to 5% of violent crimes against other individuals. 10%, tragically, end up committing suicide – making those with schizophrenia more likely to stand as a danger to themselves rather than others. Many of them feel pushed to the brink of killing themselves due to extreme levels of marginalization and misunderstanding courtesy of mainstream society. In fact, people with schizophrenia are far more likely to end up as the victims of violent criminals rather than the perpetrators. 


3. There is no reason for individuals with schizophrenia to receive psychotherapeutic treatment – they’ll just keep relapsing.

Treatment for schizophrenia usually involves psychosocial therapy, cognitive behavioral therapy, self-help groups, family therapy, antipsychotic medications, or some combination thereof. By learning how to take control of their illness, people with schizophrenia may very well end up leading happy, productive lives once the proper blend of therapy and/or medication has been established. Unfortunately, due to stigmas regarding psychotherapy, many individuals suffering from schizophrenia shy away from pursuing it.

4. Individuals with schizophrenia are generally too far gone to work, and the ones who can rarely rise above the menial level.

In reality, those with schizophrenia run the gamut from a complete inability to work to highly functioning in an impressively accomplished career. Nobel Prize-winning mathematician John Forbes Nash, Jr. battles paranoid schizophrenia, as does bestselling author Robert M. Pirsig.

5. Schizophrenia is just a clinical term for a character defect.

Scientists have narrowed schizophrenia’s origins to genetics – possibly triggered by certain environmental factors – and a patient’s brain structure and chemical makeup.  Other research has revealed possible issues with the neurotransmitters glutamate and dopamine in addition to enlarged ventricles, irregular activity, cell distribution, and inadequate grey matter. 


6. Symptoms of schizophrenia are relatively homogeneous.

Because medical professionals recognize 5 different subtypes of the disorder (7 in Europe), the actual symptoms of schizophrenia remain far more diverse than many people think. All of them share at least 3 diagnostic criteria, with variances between the subtypes and some individuals. In order to be considered schizophrenic, a patient must display two or more of the following symptoms: auditory or visual hallucinations, delusions, a thought disorder, disorganized speech and behavior, catatonia, avolition, affective flattening, or alogia. He or she must also suffer from a social and/or career disruption, and all symptoms must persist for a minimum of 6 months.

7. Schizophrenia is an extremely rare disorder.

Approximately 1.1% of Americans over the age of 18 receive a diagnosis of schizophrenia every year. However, due to mainstream society shaming and stigmatizing the mentally ill and the psychotherapeutic avenues they need to get better, it is sadly possible that many more suffer from the disease and never seek out professional guidance. Symptoms generally begin their onset between the ages of 16 and 30, with males developing them earlier than females and delusions generally appearing first. Though rare, it is still possible for schizophrenia to manifest in a child.

8. The most defining characteristic of schizophrenia involves hearing voices in one’s head.


Not all cases of schizophrenia involve the clichéd voices in the head. Typically, those with paranoid schizophrenia suffer the most frequently and the most intensely from auditory hallucinations. Other types may experience them, though it is typically more sporadic and less severe. 

9. An individual with schizophrenia may only undergo rehabilitation upon attaining stability.


Once an individual has received a formal diagnosis of schizophrenia, rehabilitation must begin immediately in order to infuse him or her with all the tools necessary for the simultaneously most effective and swift method of treatment. Waiting too long for a patient to achieve stability prior to initiating the rehabilitation process may mean the difference between a recovery and merely doing better.

10. Individuals with schizophrenia have to be medicated the rest of their lives.


For schizophrenia patients who find a psychotherapy and medication regimen that efficiently quells their symptoms, the recovery rate remains startlingly high. Some professionals estimate between 25% and 50% of the schizophrenia population cease to display signs of the disorder upon responsible long-term cessation of their medications. However, whether or not they achieve a full recovery hinges on a number of different factors, such as a suitable combination of one or more types of therapy.

Full article ...

Also check out on Suzane's site:

Ten Common Myths About Suicide

Ten Myths About Domestic Violence

Is The Government Spying on Those with Schizophrenia Enough?

This from the Onion: The government needs to do more to help individuals with paranoid schizophrenia, such as implant devices in their heads so voices can tell them which bus drivers hate them and which manholes are covering up underground government prisons.

On a serious note, too many of us have bitter experiences of well-intentioned people charged with helping us doing the very opposite: Threatening restraints, not listening, telling us we will never work again, making us feel like outsiders ...

Have a good laugh, then when you're through laughing ...

Now Playing: The Soloist

On Friday, "The Soloist" went into general release. The movie, starring Jamie Foxx and Robert Downey Jr, is based on a book of the same name by LA Times columnist Steve Lopez. The book and movie chronicle the unlikely friendship forged on Skid Row between Lopez and Nathaniel Ayers, a gifted cellist who lost his mind to schizophrenia while attending Julliard.

I will be seeing "The Soloist" with a friend on Sunday, and plan to have a review here for Monday. In the meantime, here is a random sampling of newspaper reviews:

NY Times: The film is imperfect, periodically if unsurprisingly sentimental, overly tidy and often very moving. It works hard to make you feel good, as is to be expected, even as it maintains a strong sense of moral indignation that comes close to an assertion of real politics.

SF Chronicle: "The Soloist" finds success in one area, however, in director Joe Wright's subjective depiction of schizophrenia as experienced from inside an afflicted person's mind. In several memorable sequences, Wright creates a soundscape of imagined voices, all competing for attention, and through subtle, imaginative camera work, he conveys the dislocation of a person receiving reality through a distorted and frightening filter.

Chicago Tribune: We get only a drive-by sense of who Nathaniel Ayers, the former Juilliard music student plagued by undiagnosed schizophrenia, really is underneath the agonized surface. The film's poster lets you know who the movie's about: It's about the star Los Angeles Times writer Steve Lopez, played by Robert Downey Jr., whose influential columns on Ayers and his downtown L.A. skid row existence led to huge readership, political reform, a book deal and a movie sale.

Minneapolis Star Tribune: "The Soloist" is pitch-perfect, a sensitive rendering of challenging social and emotional themes. What could have been a maudlin exercise in sentimentality — the unlikely relationship between a homeless street musician and a Los Angeles Times metro columnist — becomes a soul-stirring tribute to the power of music and the importance of friendship.

***

When it comes to raising public awareness, Hollywood has no equal. For a short time at least, the general population will be receptive to our message and we're fools not to take advantage of it. So I urge you, please see the movie. Then tie in whatever pet beef you may have about living with your illness to the movie and start advocating. And then advocate some more ...

"The Soloist" trailer

Figuring Out Schizophrenia - Part III

Yesterday was the last day of the International Congress on Schizophrenia Research, held in San Diego. A brief recap of my third day there:

Early morning: My brain has clearly not booted up, not even after two coffees. I sleepwalk into the main hall for a lecture on "The Hidden Life of Genes: Endophenotyping Schizophrenia," by David Braff of UCSD, the year's recipient of the Congress' prestigious William Warren Award (that's Dr Braff pictured).

I've already given you a major hint into endophenotype: Me, with bipolar, with major difficulty regulating my sleep, which seriously interferes with my ability to function. The general population also experiences sleep disorders, but clearly sleep is tied into my illness.

Thus, rather than look for illness-specific genetic needles in haystacks, it may be more constructive to seek out more common and obvious bio-markers (such as sleep) and work one's way upstream or downstream from there.

Dr Braff was writing about endophenotypes back in the seventies, but it is only within the last five years or so that the topic has really taken off. For instance, Dr Braff explains, patients with schizophrenia experience major problems in sensory gating, ie screening out irrelevant stimuli (such as a noisy ventilation system) which plays havoc with their ability to focus on relevant stimuli (such as a conversation).

What we are finding, according to Dr Braff, is a clustering of patients around various different endophenotypes (eye movement - saccades - involving reaction time is another). Thus, one drug is not going to fit all. The next generation of meds, he says, need to be far more specific.

Schizophrenia, Dr Braff concluds, is a malignant terrible disease that is not going to give up its secrets readily. Instead, we "have to conquer schizophrenia gene by gene, step by step."

Late morning: "Optimizing Cognitive Training Approaches in Schizphrenia," reads the title to this two-hour symposium. Translation: The brain is plastic. As Michael Merzenich of UCLA describes it, "Basically, we create ourselves."

The brain is born stupid, then evolves and becomes "massively optimized to fit into your world."

In recognition of this, a relatively new field is opening up that involves drilling patients in cognitive tasks we tend to take for granted, such as holding a thought in our working memory long enough to lay down new neural roadwork or responding to stimuli in a timely fashion.

New computer programs are being developed and being tested on patients, Sophia Vinogradov of UCSF explains, and we are seeing enduring changes in the cognitive performance of patients six months later.

Afternoon: Today's poster presentation has a treatment theme, and here there is a clear disconnect from the rest of the conference and earlier poster presentations. Pharma is out in force, with products based on 50s technology. An example:

I stop at a J&J poster testing Invega on a schizo-affective population. No surprise, the antipsychotic knocks out the psychosis. Invega is son of Risperdal, which in turn is a descendant of Haldol.

See what I'm driving at? The emphasis of current schizophrenia research is on cognition and the underlying biology. Psychosis is what gets patients in trouble, but difficulties thinking is what keeps them from winning back their lives. Pharma has nothing in its current inventory for this, but they're still in a state of denial pretending that they are still relevant. (Think Detroit, only not nearly as smart.)

So here is J&J, pitching a med with roots in the 1950s, with a study designed for no other purpose than to milk its current patent. I ask some of the other researchers about this and get a lot of nodding heads and knowing looks.

If only these researchers were running Pharma, I can only think. The good news: Everywhere, Pharma is clearly losing both its influence and credibility. The bad news: In another year or two, we are going to know J&J as makers of baby powder and other fine consumer products. Same with the other drug companies.

Where, then, are the new smart meds going to come from?

Much more in future blog posts ...

Figuring Out Schizophrenia - Part II

Another full day at the International Congress on Schizophrenia Research, here in San Diego. To recap:

Breakfast: Beatriz Luna of the University of Pittsburgh tells me she isn't a schizophrenia researcher. Rather, she's into something called "development." I'm thinking development, as in a child psychologist.

No, she tells me. This is about brain development, as in the child brain maturing into the adult brain. She will be one of the speakers at a two-hour symposium later in the morning. (That's her in the photo.) Curious, I check it out:

Think of research into normal brain development shedding valuable light on schizophrenia, and, by extension, all of mental illness. The first speaker, Patricio O'Donnell of the University of Maryland, talks about cortical microcircuits and the balance between excitation and inhibition. Dopamine, he says, plays a large role in the modulation of circuits in the prefrontal cortex. During adolescence, he explains, these circuits experience dramatic connecting changes.

For instance, "phasic dopamine" (firing in bursts) gets dialed in, with improved signal to noise ratios.

But suppose the brain doesn't mature? Are we then looking at an approximation of schizophrenia?

David Lewis of the University of Pittsburgh shows slides that highlight the neuron's "dendritic spines." These spines play a major role in brain cells talking to one another. We know that people with schizophrenia are not favorably endowed in this category, but what does it mean?

In normal brain development, he explains, there is an early dramatic increase in spine density followed by a dropping off in adolescence and leveling out in adulthood. But are we talking about a drop-off in "functionally mature" or "functionally immature" connections? In other words, when the brain experiences structural changes, are the right chemical messages crossing the dendritic divide or the wrong ones?

Early intervention, he says, might be directed at enhancing the normal development of these synapses.

Dr Luna informs the audience that adolescence involves major risk of mental illness. As she explained to me over breakfast, this is when the brain changes gears. But what if something goes wrong in the transition? Might this underlie the pathology of mental illness?

During adolescence, the brain undergoes "synaptic pruning," along with axonal "myelination." In essence, brain function becomes more equally distributed, with less reliance on impulses from the basal ganglia and other more primitive regions of the brain.

But what if something goes wrong? Normal child brain function is suddenly not so normal, not in an adult brain anyway. You can kind of see this with the current economic meltdown, Dr Luna explains. It's a new world. AIG and GM and the rest can't behave the way they used to. The failure in executive behavior in this new context, she concludes, now becomes obvious.

Lunch time posters: This is where I get to ask all my stupid questions. For instance, over the past two days, the area of the brain I've been hearing most about is the dorsolateral prefrontal cortex, the brain function I've been hearing the most about is working memory, and the researcher I have been hearing most about is Joseph Callicot of the NIMH.

"Allelic Variation in KCNH2 is Associated with Dorsolateral Prefrontal Cortex Activation During Working Memory," reads the poster.

The name tag on the man standing in front of the poster reads Joseph Callicot.

Knock me over with a feather. Fire away with all your stupid questions, says the look on his face.

I love this job ...

Figuring Out Schizophrenia

I'm back home after an exhilarating and exhausting day at the International Congress on Schizophrenia Research in San Diego, 40 miles "down the hill" from where I live. To briefly recap:

Early morning: I'm up at 5 AM and out the door an hour later. Shortly after seven, I announce myself to a small breakfast gathering of brain researchers as, "The only C student at this table."

The line works so well I use it the rest of the day. It doesn't take me long to get into the spirit of the conference. I start referring to my coffee as my "neuro-cognitive starter." I find myself talking to a woman who is not a brain scientist. Her doctorate is in education, and she is involved in changing behavior in patients that just about everyone else has given up on.

"You can change the brain by changing behavior," she lets me know. Little steps at a time. You will probably hearing a lot more about her, if for no other reason than I plan to be writing more about her.

Late morning: I arrive at my appointed symposium for two hours of dopamine. These are brain scientists talking to brain scientists. To give you some perspective: When brain scientists talk to psychiatrists, they dumb down their talks. That way, I can almost understand their presentations.

Not the case here. Daniel Weinberger of the NIMH is one of the presenters. A couple of years ago, at the American Psychiatric Association annual meeting, I heard him explain to his audience the val-met COMT variation. Today, he just assumes that the people in the audience understood. Then he gets really technical.

Just over the aisle, in the same row where I am sitting is Arvid Carlsson, recipient of the 2000 Nobel Prize in Medicine (with Paul Greengard and Eric Kandel). Dr Carlsson received his Nobel for his work into dopamine. Let's put it this way: BC (Before Carlsson), dopamine had minor chemical status. Then Dr Carlsson started investigating and suddenly dopamine was a major neurotransmitter. (That's Dr Carlsson's photo to this blog post.)

In order to appreciate the environment Dr Carlsson was working in at the time, science only had theories about how brain cells communicated. Chemical? Electrical? Dr Carlsson and his contemporaries resolved that debate, but not without bucking a lot of the conventional wisdom of the day. In addition, Dr Carlsson connected dopamine deficiency to Parkinson's, which in turn led to L-DOPA for treating the illness, thus benefiting untold millions.

So here's Dr Carlsson listening to a younger generation of scientists carry on his work. Immediately after the session, I walk over and ask for his autograph. (I was a C student, remember? I can get away with this behavior.) He graciously signs the inside back cover of my conference booklet. My son-in-law is a neurosurgeon in New Zealand and a great guy. He's gonna be thrilled when this autograph arrives in the mail.

Don't tell - it's a surprise.

Early afternoon: Over lunch and at the poster session, I get to talk to the researchers one on one. First, let me make a confession - the technical stuff is way over my head. I'm here to simply get a feel for things, develop an appreciation. One of the things I notice is that the posters on the cognitive aspects of schizophrenia outnumber the psychosis side of the illness by a ratio of at least three to one.

Was it this way ten years ago? I wonder. I'll have to ask. Antipsychotics work very well against psychosis, but when your basic thinking is messed up - never mind the psychosis - your life is going to involve smoking cigarettes in front of TV in some dreary day room someplace.

No wonder the people I'm talking to are telling me that doctors and patients and family members got oversold on the new generation of antipsychotics. From what I can gather, certain systems in the brain go down. Systems we are only just finding out about. Systems we haven't even discovered yet. Systems all over the brain, interdependent, so when one system goes down, different parts of the brain all over fail to talk to one another.

Some of it is genetic. Some of the genetic mischief occurs during fetal development, other mischief further on in the life span. There may be direct genetic impact, or it may be like billiard balls caroming off one another. Or it may have something to do with a new area of gene research called epigenetics (which has something to do with why identical twins aren't really identical).

And forget about finding schizophrenia genes. These guys seem to be concentrating on "endophenotypes," symptoms common to the general population, as well, say, delayed reaction time to an event. If, say, we find a delayed reaction time gene and connect it to neurons and connect the neurons to brain systems and connect the brain systems to behavior, and connect the behavior to schizophrenia, maybe then we can really start connecting some dots.

Then there's environmental factors. The brain is shaped by literally everything, such as the way a mother holds her baby. African-Caribbean immigrants in the UK, for instance, have a nine-fold higher schizophrenia risk than the rest of the population there. What is going on?

Later afternoon: My brain is on overload. I leave the conference at four and am home at five. Twenty minutes later, I'm crashing in my own bed.

Evening: Dinner, chill time, and this blog post. Time to kick the cat off the prime spot on my bed. Up at five again tomorrow. I love my job ...

Reporting on Schizophrenia Research

My annual conference season unexpectedly began three weeks early today, when I attended what I thought would be an afternoon local family forum on schizophrenia. I turned up at the Grand Hyatt on San Diego's waterfront only discover the forum was a satellite to a four-day major world conference: The International Conference on Schizophrenia Research, held every two years.

So that explained the star-studded list of speakers at our local family forum.

(Small sound-bite from that forum: According to John McGrath MD, PhD of the University of Queensland, hallucinations and delusions are "very very common" in the general population. Four percent of the US population hears voices.)

As soon as the forum ended, I headed over to the registration area of the main conference to secure media credentials. Mind you, here I was, a mental health journalist feeling obliged to explain why I knew nothing about a major world schizophrenia conference in my own backyard until today.

"Bipolar," I said to someone behind the desk, pointing to a copy of my book I happened to have in my bag, as if that explained everything. Another person was called over to assist.

"Tamminga," said the name on her tag.

She caught the look on my face. "It looks like you're familiar with the name," she said. "I'm her daughter." As in daughter of Carol Tamminga MD of the University of Texas Southwestern Medical Center, first rank researcher and one of the conference organizers. In addition, Dr Tamminga is very generous in giving her time to NAMI and other causes. (That's Dr Tamminga's photo on this blog post.)

Nearly two years ago I happened to sit next to Dr Tamminga over dinner in Pittsburgh at a closed function at the Seventh International Conference on Bipolar Disorder. (I was a special guest by virtue of a public service award I would receive two nights later.) Just to show you what a thoroughly gracious person Dr Tamminga is, our section of the table also included Thomas Insel MD, head of the NIMH, and Darrel Regier MD, co-chair of the DSM-V task force, but Dr Tamminga talked to me as if the other two weren't there.

"I was about to use your mother as a reference," I joked, then I briefly explained the connection.

Ten minutes later, I was at a patio table, poring over my conference materials. A brain scientist from Australia sat down, and for the next hour we talked about the brain, the metric system, politics, the environment, Einstein, and autism (she has a son with autism). Ninety percent of marriages involving an autistic child end in divorce, she informed me.

Tomorrow, I will be waking up before dawn to catch Dr Insel at a plenary session, then over to a morning symposium on "Dopamine Signaling in the Era of Molecular and Genetic Pathways." I'll hit the research poster sessions over lunch, then take in an afternoon of "Aberrant Functional Connectivity in Schizophrenia: Changes in Frequency, Symptoms, Drugs, and Genes."

Tuesday and Wednesday will be more of the same.

What is a depression and bipolar writer doing at a schizophrenia conference? From a recent blog post:

Back in 2003, I had one of those breakthrough moments, the type you associate with light bulbs switching on. I was at the American Psychiatric Association's annual meeting attending a symposium on genetics. Robert Freedman MD of the University of Colorado started explaining his research into schizophrenia.

"The DSM-IV was not designed with human gene function in mind and genes do not encode for psychopathology," he said. Instead, "genes encode simple molecules in cells that alter cell function and brain information processing."

I had kind of been aware of this, but this time I went, "Aha!" ... The upshot of my Aha! moment was the realization that to better understand my own illness (bipolar) I needed to research other illnesses as well, such as schizophrenia. The brain, after all, doesn't organize itself according to the DSM.

Listening to the schizophrenia people, in effect, gives me insights into my illness that I would never get from limiting my enquiry to the mood disorders experts. Take my word for it, I'm like a kid in a candy store at these events. The only thing about my job that I love more than listening to super-smart people who have dedicated their lives to improving yours and mine is writing about it.

Stay tuned ...