Major Psychiatric Disorders Share a Common Genetic Link

I’m a recipient of a Google Alert on Bipolar Disorder.  This just means that Google automatically notifies me when there’s new news (as opposed to the old kind, I guess) on the web on BD. It can be from news sources, blogs, videos—you name it.

Some days, 5 out of 6 of the news stories will be about Catherine Zeta Jones.  I don’t usually feel I’m getting my money’s worth on those days.

I also have to overlook the fact that on any given day, the majority of the news stories cover the same topic. Let’s take yesterday.  There were 9 news alerts, which made it a pretty big news day in Google land—and 8 of them covered breaking news—I mean, the same piece of breaking news, but it’s nice to have “new news” nonetheless.

The last one was on a topic we’ve known for years now, but it keeps re-appearing in my alerts, making me wonder if there’s a secret lithium lobby.  Every every time there’s a moment of quiet, they push to get this factoid back into the public’s consciousness: “Lithium can reduce suicide risk in bipolar disorder.” (It’s true—you can click on it and check it out—over and over again.)

In an effort not to be outdone by yesterday, today’s Google Alert again covered the story—as if it was brand new—but perhaps they realized they couldn’t ride the coattails of this self-same story forever, for out of 10 stories, 7 addressed the genetic overlap I’m about to explain, but 3 spread out in other directions—addressing sleep and BD, asking “What is depression?” (leading me to ask, Why is this in my Bipolar Disorder Alert?), and, finally, ending with a big finale, important to scholars, researchers, and patients alike, as you can tell from the title which reads, “North Carolina man who killed a Montgomery man because God told him to will enter secure mental facility.”

For years scientists and researchers have viewed most mental illnesses as distinct diseases, leading to different treatments and dissimilar public understanding of the illnesses.  And I say “understanding” with a grain of salt: frankly, no one has a clue as to the causes of psychiatric illnesses. Psychiatrists have long used symptoms to diagnose illnesses, but, look, we all know that’s far from perfect. Recently research has pointed up genetics as playing a major role, which gives diagnosticians something to hang their hats on.

And so they were super-excited (you know, in the way scientists get so worked up) to find that 5 of the major psychiatric illnesses are genetically connected in a big way. The hope—although it’s a long way off, I don’t expect to be getting a Google Alert that it’s happened too soon—is that doctors can soon make diagnoses based on the genetic aberrations underlying the diseases.


This past week researchers partially funded by the National Institutes of Health published evidence of  “substantial overlap for genetic risk factors” shared between bipolar disorder, major depressive disorder, schizophrenia, attention deficit-hyperactivity disorder (ADHD), and autism.

Interestingly enough, the overlap was highest between bipolar disorder and schizophrenia; was only moderate for bipolar disorder and depression [which is where I would have put my chips, had anyone asked me], moderate for ADHD and depression—and low between schizophrenia and autism.

In total, common genetic variation accounted for 17-28 percent of risk for the illnesses.

If you want to find out more, this will be published as “Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, August 11, 2013.”  Or, you could simply do a web search—it will come up all over.

Alternatively, you can hurry up and sign yourself up for a Google Alert on Bipolar Disorder.  You’ve probably missed the days when the this topic will make up 7 out of 9 headlines, but it’s sure to linger on, unwilling to give up its moment in the sun, just like lithium with its anti-suicidal properties, and—goodness knows—just like Catherine Zeta Jones.


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National Minority Mental Health Awareness Month

Yup it’s still Minority Mental Health Awareness Month.

In fact, I stand corrected. It is the Bebe Moore Campbell National Minority Mental Health Awareness Month.

And I have a sneaking suspicion that you’ve forgotten that–that to you it’s Cord Blood Awareness Blog Month, or International Group B Strep Awareness Month–or even Eye Injury Prevention Month–but within all those months you’ve forgotten about Minority Mental Health’s existence.

Which is just par for the course.

But it’s a deadly serious issue–and maybe if we all knew a little bit more about it, we’d be able to keep it in our heads just a wee bit longer.

It’s hard to know where to start.

Maybe with this treasure: According to the American Psychiatric Association, one out of every three African-Americans who needs mental health care actually receives it.

And, apparently once they’ve gotten it, they’re not that thrilled with what they’ve got.  The APA also found that, compared to the general population, African-Americans tend to stop treatment early.

Switching sources, the CDC created a chart comparing suicide rates from 2005-2009 among those 10 and older by race/ethnicity and sex.

The grand winner is pretty shocking–and is consistent among gender.

The highest suicide rates were among American Indian/Alaskan Native males–they had 27.61 suicides per 100,000.  But their women, too, suicided the more than any other ethnicity, as well, at the rate of 7.87  suicides per 100,000.

[Just as an aside, you may be surprised to learn that non-Hispanic White males 65 and older top the list, with a shocking 32.37 suicides per 100,000.  But they’re not the target demographic of this awareness month, so ‘nuf said.]

Moving sources again: The U.S. Department of Health and Human Services Agency for Healthcare Research and Quality (AHRQ) took a look at the percent of adults (meaning those 18 and older–we can dispute that later if we’d like) who received prescription meds for mental health care OR just received counseling in 2008.  Comparing  Hispanics and Non-Hispanic Whites, the table below looks at the number of individuals per 100 who received mental health care.



Non-Hispanic White

Hispanic/ Non-Hispanic White Ratio













Source:  2010 National Healthcare Disparities Report. Table 17_3_3.2b

I say a lot–but in this case I think the table speaks for itself.

Now–back to those African-Americans, those who weren’t going and getting the mental health care they needed.  I found out some discouraging information about what goes on even when they do make the effort to get themselves the care they need.

Psychiatrists have been treating schizophrenia, mania, and sometimes even depression with a new type of antipsychotic medication, called ‘second-generation’ antipsychotics, since these meds arrival in the 1990s.  These drugs don’t have some of the scarier side effects of the ‘first-generation’ antipsychotics, particularly a side effect called tardive dyskinesia, where the body makes uncontrolled, repetitive, involuntary, purposeless movements. Really, it’s hard to find a doctor’s office today that uses the old meds.

That’s why I was totally shocked to learn that Herbeck et al wrote in  2004, in”Variations in use of second-generation antipsychotic medication by race among adult psychiatric patients,” over a decade after the original second-generation drug appeared, found that African-American patients were “less likely than white patients to receive second-generation antipsychotic medications.”  Standard of care today really is these first-generation antipsychotics–it’s just so hard to imagine doctors offering anything else.  But there it is again, two years later–things had apparently not improved. Mallinger et al summarizes his research: “In this sample, blacks were less likely than whites to receive second-generation antipsychotics, demonstrating a persistent gap in the quality of care for patients with schizophrenia.” Quite a gap, indeed.

“But wait, there’s more!” Back to the AHRQ for a few good reasons why we just might badly need this minority month–and just might need to pay it more mind. For example:
  • Among adolescents, whites are much more likely than blacks or Hispanics to use antidepressants. In fact, whites are more than twice as likely as Hispanic adolescents to use them–and nearly five times as likely as black adolescents. While it is always possible that minorities may have an overall more negative view of adolescent antidepressant use, the facts also tell us that family income, levels of education, and–the kicker in my book–health insurance play into this discrepancy.
  • Blacks and Hispanics are less likely than whites to seek treatment for mental health problems. This seems a tricky one to prove but researchers combed through 2001-2004 Medical Expenditure Panel Survey data to try to figure out why minorities do, indeed, seek out mental health services less frequently than whites.
    The authors of the study (Zuvekas & Fleisman 2008) determined that this discrepancy arose due to “different propensities to interpret emotional symptoms as reflecting one’s mental health and then to seek professional intervention for emotional problems.” This sounded to me as if, in short, whites were kvetches who  rushed themselves to the psychotherapists or psychiatrists the minute they felt overwhelmed, but apparently the authors firmly believe that the data reflect underuse by minorities rather than overuse by whites.

In the study we find that Asian Americans might resist using standard Western mental health services for any number of reasons–stigma, lack of belief in the power of psychotherapy to heal at all, fear of being hospitalized. Truthfully, they sound like the same reasons we’re all afraid of using mental health services. But their fear really keeps them away.

Until it’s too late.  Those Asian Americans who do, finally, seek care are the most severely mentally ill. This study by Shin (2009) was done in New York (where, believe me, they’re intimately familiar with mental illness, as it resides on the streets and in the alleyways of the city, seemingly everywhere you look), where he found that the most common disorder among American Asians [remember: these are the ones he sees, the ones who are too sick to stay away anymore] was schizophrenia–a higher number than any other group.  Additionally, these Asian schizophrenics spent longer in the hospital than other patients.

It’s a sticky problem. If the minorities who might need the care are reluctant to seek it out, we have a choice problem on top of an availability one.  This means that Minority Awareness Month has, like Ben Bernanke, a dual mandate. We need more awareness within the minority community of the benefits of mental health treatment. And we need awareness among the political and economic movers and shakers. In other words, let’s hope this Awareness Month promotes both education and advocacy.

ECT–The Less Than Shocking Story, Part I

Why write about ECT today? Isn’t it yesterday’s news? Actually, in the words of health writer Melissa Dahl (, 8.6.2008), “the practice has been making a quiet comeback.”

“One Flew Over the Cuckoo’s Next” did nothing to help make ECT fashionable. In fact, according to the 2003 Sixth Edition of The Columbia Electronic Encyclopedia, it is the “most controversial treatment in psychiatry.” Commonly referred to by the forbidding name “shock treatment,” ECT stands for electroconvulsive therapy, in which electric current is administered through the skull to the brain in order to induce a seizure. The patient–under anesthesia–experiences a 20-second grand mal seizure.

Of course the treatment didn’t start out in a manner meant to win friends and influence people. In its earliest days, ECT occurred before anesthesia and muscle relaxants, and patients underwent such violent seizures that it was possible for them to break bones. Doctors and nurses physically restrained patients–and the image  that didn’t played well to the masses. Patients had up to 100 treatments. Today, a typical protocol is 6-12 treatments over a 2-3 week period.

What is ECT used for? It’s most well-known as a treatment for depression, particularly treatment-resistent depression, but it also is used–although less commonly–in bipolar disorder and schizophrenia.

The idea of using seizures to treat depression was introduced by one Ugo Cerletti, an Italian psychiatrist, in 1938.  Less than a  year later the New York State Psychiatric Institute introduced ECT as a treatment into the U.S.  By the 1960s around 300,00 patients a year were treated with ECT.  No one knows exactly how it works, although Andy Berhman, author of Electroboy: A Memoir of Mania, has collected some theories (see his blog).

ECT’s usage dropped sharply in the U.S. when psychiatric medications became available to treat depression in the 50s. Around the 80s the number of patients seeking ECT stabilized at an estimated  100,000 patients per year in the US,  and approximately 1-2 million individuals undergoing ECT worldwide.

Sadly, anti-depressant medications don’t work at all for all patients, which makes many of them desperate for relief. According to the American Psychiatric Association,  the success rate with medication is 50-60%. Even amongst those who have success with medications, the healing process is slow, often requiring several different trials, each of which may have  side-effects. The deeper and more chronic the depression, the more challenging the treatment.

Despite its past (and even current) bad press, ECT remains a treatment that people turn to because it works. In cases of debilitating depression, ECT has a greater success rate than any other treatment, according to Dr. Demitri Papolos, associate professor of psychiatry at the Albert Einstein College of Medicine in New York City, where he is the co-director of the Program in Behavioral Genetics, and author of Overcoming Depression: The Definitive Resource for Patients and Families Who Live with Depression and Manic-Depression.

In England,  Professor John Geddes and his colleagues at Oxford University looked at over 73 ECT treatment outcomes over the past 40 years. Sure enough they discovered that ECT was more efficacious than dummy electroconvulsive therapy, and  more effective at treating depression than medication. They wrote in The Lancet, “the randomised evidence consistently shows that in the short-term, ECT is an effective treatment for adult patients with depressive disorders.” Speaking to the BBC News Online, Professor Geddes said of the study that “[W]e found that in the short-term ECT reduces depressive symptoms and that it may be a bit better than drugs.”

As an added boon, it usually yields fairly quick results, unlike antidepressant medicines which can take weeks to yield any form of relief. The well-known Dr. Harold Sackeim, famous American psychologist, Chief of the Department of Biological Psychiatry at New York State Psychiatric Institute and Professor of Clinical Psychology at Columbia University (and author of over 200 ECT-related papers), has run several studies on the efficacy of ECT. He found in one study that the response rate was 65 percent for low-dose bilateral therapy and 63 percent for high-dose bilateral therapy. Sackeim concludes that ECT is the most effective treatment for treatment-resistant depression.

Not all is golden, however, so please read Part II.

Three Biggest Pharmaceutical Lawsuits of 2012: Psychiatric Drugs Focus of All Three

“A billion here, a billion there, sooner or later it adds up to real money.” ~ Everett Dirksen, Congressman

What Senator Dirksen knew about government spending is these days being applied to drug company fines. And it seems these penalties are, indeed, finally adding up to some ‘real money.’ 2012 saw three of the biggest lawsuits against pharmaceutical companies–and the billions are coming in.

2012 wasn’t a good year for the makers of certain psychiatric drugs.

After making millions, if not billions, on a mood stabilizer, an antipsychotic, and two antidepressants, with misguided promises of the wonders they could work, the truth–and the government–caught up with three major pharmaceutical companies, and took their practices surrounding their psych meds down a steep peg.

Landmark lawsuits against Johnson and Johnson and its subsidiary Janssen Pharmaceutica, Abbott Laboratories Inc, and the largest settlement ever against GlaxoSmithKline found the states and federal government cracking down on illegal practices surrounding and misrepresentation of of psychotropic medications.

After years of drug-makers successfully–and profitably–promoting off-label uses of drugs, exaggerating medications’ effectiveness, and often hiding safety data, the gold mine appears to be shutting down.

Johnson and Johnson

This is “a big win for Arkansas,” said Arkansas Attorney General Dustin McDaniel. “These two companies [Johnson and Johnson and subsidiary Janssen] put profits before people, and they are rightfully being held responsible for their actions.”

In one of the largest penalties ever for a state fraud case involving a drug company, Johnson and Johnson (J&J) got slapped with over $1.1 billion in fines by an Arkansas judge in April for marketing that violated Medicare fraud laws and Arkansas deceptive trade practice statutes.

J&J was accused of promoting its antipsychotic drug Risperdal for unapproved uses, and of misrepresenting the safety and relative effectiveness of the drug.

Risperdal is approved by the FDA to treat schizophrenia and bipolar disorder, as well as behavior problems in teenagers and children with autism.

However, argued the state, J&J marketed the medicine ” for “unapproved uses, including various symptoms in children and the elderly,” despite being warned by the government to stop.

But J&J’s underhandedness didn’t end there. There are risks associated with the drug, risks J&J was accused of hiding. Weight gain, increased likelihood of diabetes, and increased risk of stroke in the elderly are all possible adverse side effects of Risperdal.

Additionally, asserted persecutors, J&J claimed Risperdal was a superior drug and worth its hefty price tag, when in reality it was not better than the cheaper generic alternatives.

As a result, the state said, public funds were improperly used to pay for Risperdal through programs like Medicaid.

It wasn’t as if J&J hadn’t been warned. Three separate times, in 1994, 1999 and once again in 2004, the FDA ordered Janssen to stop making false and misleading claims about the superiority of Risperdal.

The 12-person jury deliberated for only three hours before deciding in favor of the state.

The jury found J&J and its Janssen unit guilty of “false or deceptive acts,” and in particular pointed to letter J&J sent to over 6000 doctors in 2003 asserting Risperdal was safer than other drugs.

Then the judge stepped in and found J&J had committed more than 238,000 violations of the state’s Medicaid fraud laws by illegally marketing Risperdal starting in 2002. Each violation carries a $5,000 fine, pushing the total to more than $1.1 billion. He also fined the company another $11 million for violations of the state’s deceptive practices act.

This was hardly the beginning of trouble for J&J, the second-biggest maker of health products, and its Rispderdal. It was just January of this year when Texas settled a similar case with Janssen for $158 million, in 2011 a South Carolina judge penalized it to the tune of $327 million, and in 2010 a Louisiana jury close to $258 million in damages.

This is already the fifth state jury trial over claims that J&J hid Risperdal’s diabetes risks and tricked Medicaid regulators into paying millions of dollars more than they should have, for equally effective and less dangerous medicines.

Even worse for J&J, numerous other states have lawsuits filed against it, awaiting hearings.


Just this past week J&J announced that it had an “agreement in principle” with the US Department of Justice to pay close to $2.2 billion in fines for its mis-marketing of medications, mainly Risperdal but also antipsychotic Invega and cardiovascular drug Natrecor. That sum would include

and would help the company avoid a felony charge.

If the details of the deal can be hammered out, other lawsuits and state investigations–including an investigation into whether J&J paid Omnicare to buy its drugs and then sell them to nursing homes–will be wrapped up on the agreement.

However, despite J&J’s optimism about the agreement, it is not at all clear that the fines will satisfy state attorneys general who have cases pending against the company.


Monday, May 7, 2012:
Abbott Labs to Pay $1.5 Billion to Resolve Criminal & Civil Investigations of Off-label Promotion of Depakote (Company Maintained Specialized Sales Force to Market Drug for Off Label Purposes; Targeted Elderly Dementia Patients in Nursing Homes)

. . . Abbott Laboratories Inc. has pleaded guilty and agreed to pay $1.5 billion to resolve its criminal and civil liability. . . The resolution – the second largest payment by a drug company – includes a criminal fine and forfeiture. . .” [emphasis mine]

Two of Depakote’s FDA-approved uses are well-known to those familiar with them medication: as an anti-seizure medication, and as a mood stabilizer. In fact, it is often the second-line mood stabilizer treatment for bipolar disorder after an initial trial of lithium, the old standard. It is additionally approved for treatment of migraines.

The above approvals glaringly do not include use in Alzheimer’s patients for controlling behavioral disturbances in dementia patients.

It’s not because Abbott didn’t try to get such approval. Hoping for just such a nod from the FDA, they ran clinical trials using Depakote to manage dementia, but in 1999 they had to discontinue a trial of Depakote for dementia due to adverse effects in the elderly subjects, ranging from sleepiness to dehydration to anorexia. The drug wasn’t safe enough to even continue to test in that population.

But that didn’t stop Abbott from aggressively marketing just such off-label uses of its drug for dementia patients.

Acting Associate Attorney General Tony West asserted, “Not only did Abbott engage in off-label promotion, but it targeted elderly dementia patients and downplayed the risks apparent from its own clinical studies. As this criminal and civil resolution demonstrates, those who put profits ahead of patients will pay a hefty price.”

However, Abbott wasn’t done with its off-label promotion (see the legal document “Agreement of Facts“). They marketed Depakote as a schizophrenia drug–again, not approved–from 2001-2006. Although they could never show a significantly different outcome between antipsychotic drugs used alone and those used in combination with Depakote, it took Abbott researchers almost two years to publish the results indicating the lack of effectiveness, during which time the company continued promoting the drug for schizophrenia.

Abbott will pay back big time. They pleaded guilty to a criminal misdemeanor for mis-marketing Depakote. Under the plea deal they will have to:

1. pay a criminal fine of $500 million,
2. forfeit assets of $198.5 million,
3. submit to a term of probation for five years,
4. pay $1.5 million to the Virginia Medicaid Fraud Control Unit,
5. agree that during probation they won’t pay sales representatives for off-label sales, and
6. design policies to ensure that clinical trials are “approved by the company’s medical or scientific organizations and published in a consistent and transparent manner.”

It’s not a pretty picture for Abbott, but the situation is, if anything, worse for GlaxoSmithKline.


“Today, I am pleased to announce that the Justice Department and our law enforcement partners have reached an historic $3 billion resolution with the pharmaceutical manufacturer GlaxoSmithKline, LLC, to resolve multiple investigations into the company’s sales, marketing, and pricing practices. This action constitutes the largest health care fraud settlement in United States history.” ~ Deputy Attorney General James M. Cole (emphasis mine)

Along with Johnson and Johnson for its Risperdal and Abbott for its Depakote, GlaxoSmithKline (GSK) got in trouble for practices surrounding its own psychiatric drugs–and for a diabetes drug to boot.

GSK was found guilty of illegally marketing antidepressants Paxil and Wellbutrin and downplaying safety risks of diabetes drug Avandia.

This put GSK in hot water–times three.

Under the criminal indictment alone, the company was accused of the following:

a. Paxil: Antidepressant Paxil was never approved for treating depression in children. Yet from from April 1998 to August 2003, according to the criminal complaint filed in Massachusetts, GSK promoted Paxil for treating depression in patients under age 18.

Apparently GSK went so far as to sponsor dinner, lunch, and even and spa programs for doctors to promote the use of Paxil in children and adolescents.

Caught with their hand in the cookie jar, GSK agreed to plead guilty.

b. Wellbutrin: In the early 200s, the FDA had approved Wellbutrin only for use in Major Depressive Disorder.

That didn’t stop GSK from promoting Wellbutrin for weight loss, the treatment of sexual dysfunction, substance addictions and Attention Deficit Hyperactivity Disorder.

In a truly elegant touch, the Wellbutrin sales reps referred to the drug as ’the happy, horny, skinny pill’ to remind doctors of its possible (unapproved) uses.

GSK pleaded guilty to misbranding Wellbutrin, agreeing that its labeling did not bear adequate directions for these off-label uses.

  • For the Paxil and Wellbutrin misbranding offenses, GSK will pay a criminal fine of $757,387,200.

c. Avandia: From 2001 to 2007 GSK –how shall I put this?–failed to be fully forthcoming in its reports to the FDA about Avandia. They neglected to include data about two studies concerning the cardiovascular safety of the drug. This was a serious omission.

The data, when found out, was dangerous enough to warrant two black box warnings on the Avandia label–one about the risk of congestive heart failure and the other, heart attack. It’s so easy to forget these small little points.

The upshot? GSK agreed to plead guilty to failing to report data to the FDA and to pay a criminal fine in the amount of $242,612,800 for its unlawful conduct.

The rest of their $3 billion fine is made up of the civil settlement agreement, covering:

1. Off-label promotion and kickbacks. This one’s wide and deep, including promoting its asthma drug Advair for mild asthma patients even though it wasn’t medically approved for that, promoting mood-stabilizing drug Lamictal for pain management, and promoting Zofran, approved for post-operative nausea, for treatment of morning sickness in pregnant women. Further, GSK paid kickbacks to healthcare providers to ‘encourage’ them to prescribe these drugs–and drugs Latronex, Flovent and Valtrex.

These little tricks cost GSK $1.043 billion in fines.

2. Promoting Avandia to health care providers with false and misleading representations about Avandia’s safety profile, causing false claims to be submitted to federal health care programs. The fine for that one is $657 million, of which the federal share is $508 million and the state share is $149 million.

3. False drug price reporting, which led to GSK’s underpaying rebates owed under the Medicaid Drug Rebate Program. GSK will pay $300 million to resolve these allegations, including $160,972,069 to the federal government, $118,792,931 to the states, and $20,235,000 to certain Public Health Service entities who paid inflated prices for the drugs at issue.

That’s just about how you get to the largest healthcare settlement–ever.

So far, that is.