Soldiers' Stress: What Doctors Get Wrong about PTSD

A growing number of experts insist that the concept of post-traumatic stress disorder is itself disordered and that soldiers are suffering as a result

By David Dobbs

In 2006, soon after returning from military service in Ramadi, Iraq, during the bloodiest period of the war, Captain Matt Stevens of the Vermont National Guard began to have a problem with PTSD, or post-traumatic stress disorder. Stevens's problem was not that he had PTSD. It was that he began to have doubts about PTSD: the condition was real enough, but as a diagnosis he saw it being wildly, even dangerously, overextended.

Stevens led the medics tending an armored brigade of 800 soldiers, and his team patched together GIs and Iraqi citizens almost every day. He saw horrific things. Once home, he said he had his share of "nights where I'd wake up and it would be clear I wasn't going to sleep again."

He was not surprised: "I would expect people to have nightmares for a while when they came back." But as he kept track of his unit in the U.S., he saw troops greeted by both a larger culture and a medical culture especially in the Veterans Administration (VA) that seemed reflexively to view bad memories, nightmares and any other sign of distress as an indicator of PTSD.

"Clinicians aren't separating the few who really have PTSD from those who are experiencing things like depression or anxiety or social and reintegration problems or who are just taking some time getting over it," Stevens says. He worries that many of these men and women are being pulled into a treatment and disability regime that will mire them in a self-fulfilling vision of a brain rewired, a psyche permanently haunted.

Stevens, now a major and still on reserve duty while he works as a physician's assistant, is far from alone in worrying about the reach of PTSD. Over the past five years or so, a long-simmering academic debate over PTSD's conceptual basis and incidence has begun to boil over. It is now splitting the practice of trauma psychology and roiling military culture. Critiques originally raised by military historians and a few psychologists are now advanced by a broad array of experts indeed, giants of psychology, psychiatry and epidemiology. They include Columbia University's Robert L. Spitzer and Michael B. First, who oversaw the last two editions of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, the DSM-III and DSM-IV; Paul McHugh, former chair of Johns Hopkins University's psychiatry department; Michigan State University epidemiologist Naomi Breslau; and Harvard University psychologist Richard J. McNally, a leading authority in the dynamics of memory and trauma and perhaps the most forceful of the critics. The diagnostic criteria for PTSD, they assert, represent a faulty, outdated construct that has been badly overstretched so that it routinely mistakes depression, anxiety or even normal adjustment for a unique and especially stubborn ailment.

This quest to scale back the definition of PTSD and its application stands to affect the expenditure of billions of dollars, the diagnostic framework of psychiatry, the effectiveness of a huge treatment and disability infrastructure, and, most important, the mental health and future lives of hundreds of thousands of U.S. combat veterans and other PTSD patients. Standing in the way of reform is conventional wisdom, deep cultural resistance and foundational concepts of trauma psychology. Nevertheless, it is time, as Spitzer recently argued, to "save PTSD from itself."

Casting a Wide Net
The overdiagnosis of PTSD, critics say, shows in the numbers, starting with the seminal study of PTSD prevalence, the 1990 National Vietnam Veterans Readjustment Survey (NVVRS). The NVVRS covered more than 1,000 male Vietnam vets in 1988 and reported that 15.4 percent of them had PTSD at the time and that 31 percent had suffered it at some point since the war. That 31 percent has been the standard estimate of PTSD incidence among veterans ever since.

In 2006, however, Columbia epidemiologist Bruce P. Dohrenwend, hoping to resolve nagging questions about the study, reworked the numbers. When he had culled the poorly documented diagnoses, he found that the 1988 rate was 9 percent and the lifetime rate 18 percent.

McNally shares the general admiration for Dohrenwend's careful work. Soon after it was published, however, McNally asserted that Dohrenwend's numbers were still too high because he counted as PTSD cases those veterans with only mild, subdiagnostic symptoms, people rated as "generally functioning pretty well." If you included only those suffering "clinically significant impairment" the level generally required for diagnosis and insurance compensation in most mental illness the rates fell yet further, to 5.4 percent at the time of the survey and 11 percent lifetime. It was not one in three veterans who eventually developed PTSD, but one in nine and only one in 18 had it at any given time. The NVVRS, in other words, appears to have overstated PTSD rates in Vietnam vets by almost 300 percent.

"PTSD is a real thing, without a doubt," McNally says. "But as a diagnosis, PTSD has become so flabby and overstretched, so much a part of the culture, that we are almost certainly mistaking other problems for PTSD and thus mistreating them."

The idea that PTSD is overdiagnosed seems to contradict reports of resistance in the military and the VA to recognizing PTSD denials of PTSD diagnoses and disability benefits, military clinicians discharging soldiers instead of treating them, and a disturbing increase in suicides among veterans of the Middle East wars. Yet the two trends are consistent. The VA's PTSD caseload has more than doubled since 2000, mostly because of newly diagnosed Vietnam veterans. The poor and erratic response to current soldiers and recent vets, with some being pulled quickly into PTSD treatments and others discouraged or denied, may be the panicked stumbling of an overloaded system.

Overhauling both the diagnosis and the VA's care system, critics say, will ensure better care for genuine PTSD patients as well as those being misdiagnosed. But the would-be reformers face fierce opposition. "This argument," McNally notes, "tends to really piss some people off." Veterans send him threatening e-mails. Colleagues accuse him of dishonoring veterans, dismissing suffering, discounting the costs of war. Dean G. Kilpatrick, a University of South Carolina traumatologist and former president of the Inter national Society for Traumatic Stress Studies (ISTSS), once essentially called McNally a liar.

A Problematic Diagnosis
The DSM-IV, the most recent edition (published in 1994), defines PTSD as the presence of three symptom clusters reexperiencing via nightmares or flashbacks; avoidance by numbing or withdrawal; and hyperarousal, evident in irritability, insomnia, aggression or poor concentration that arise in response to a life-threatening event [To see related sidebar please purchase the digital edition].

The construction of this definition is suspect. To start with, the link to a traumatic event, which makes PTSD almost unique among complex psychiatric diagnoses in being defined by an external cause, also makes it uniquely problematic, for the tie is really to the memory of an event. When PTSD was first added to the DSM-III in 1980, traumatic memories were considered reasonably faithful recordings of actual events. But as research since then has repeatedly shown, memory is spectacularly unreliable and malleable. We routinely add or subtract people, details, settings and actions to and from our memories. We conflate, invent and edit.

In one study by Washington University memory researcher Elizabeth F. Loftus, one out of four adults who were told they were lost in a shopping mall as children came to believe it. Some insisted the event happened even after the ruse was exposed. Subsequently, bounteous research has confirmed that such false memories are common [see "Creating False Memories," by Elizabeth F. Loftus; Scientific American, September 1997].

Soldiers enjoy no immunity from this tendency. A 1990s study at the New Haven, Conn., VA hospital asked 59 Gulf War veterans about their experiences a month after their return and again two years later. The researchers asked about 19 specific types of potentially traumatic events, such as witnessing deaths, losing friends and seeing people disfigured. Two years out, 70 percent of the veterans reported at least one traumatic event they had not mentioned a month after returning, and 24 percent reported at least three such events for the first time. And the veterans recounting the most "new memories" also reported the most PTSD symptoms.

To McNally, such results suggest that some veterans experiencing "late-onset" PTSD may be attributing symptoms of depression, anxiety or other subtle disorders to a memory that has been elaborated and given new significance or even unconsciously fabricated.

"This has nothing to do with gaming or working the system or consciously looking for sympathy," McNally says. "We all do this: we cast our lives in terms of narratives that help us understand them. A vet who's having a difficult life may remember a trauma, which may or may not have actually traumatized him, and everything makes sense."

To make the diagnosis of PTSD more rigorous, some have suggested that blood chemistry, brain imaging or other tests might be able to detect physiological signatures of the disorder. Some studies of stress hormones in groups of PTSD patients show differences from normal subjects, but the overlap between the normal and the PTSD groups is huge, making individual profiles useless for diagnostics. Brain imaging has similar limitations, with the abnormal dynamics in PTSD heavily overlapping those of depression and anxiety.

With memory unreliable and biological markers elusive, diagnosis depends on clinical symptoms. But as a study in 2007 starkly showed, the symptom profile for PTSD is as slippery as the would-be biomarkers. J. Alexander Bodkin, a psychiatrist at Harvard's McLean Hospital, screened 90 clinically depressed patients separately for PTSD symptoms and for trauma, then compared the results. First he and a colleague used a standardized screening interview to assess symptoms. Then two other PTSD diagnosticians, ignorant of the symptom reports, used another standard interview to see which patients had ever experienced trauma fitting DSM-IV criteria.

If PTSD arose from trauma, the patients with PTSD symptoms should have histories of trauma, and those with trauma should show more PTSD. It was not so. Although the symptom screens rated 70 of the 90 patients positive for PTSD, the trauma screens found only 54 who had suffered trauma: the diagnosed PTSD "cases" outnumbered those who had experienced traumatic events. Things got worse when Bodkin compared the diagnoses one on one. If PTSD required trauma, then the 54 trauma-exposed patients should account for most of the 70 PTSD-positive patients. But the PTSD-symptomatic patients were equally distributed among the trauma-positive and the trauma-negative groups. The PTSD rate had zero relation to the trauma rate. It was, Bodkin observed, "a scientifically unacceptable situation."

More practically, as McNally points out, "To give the best treatment, you have to have the right diagnosis."

The most effective treatment for patients whose symptoms arise from trauma is exposure-based cognitive-behavioral therapy (CBT), which concentrates on altering the response to a specific traumatic memory by repeated, controlled exposure to it. "And it works," McNally says. "If someone with genuine PTSD goes to the people who do this really well, they have a good chance of getting better." CBT for depression, in contrast, teaches the patient to recognize dysfunctional loops of thought and emotion and develop new responses to normal, present-day events. "If a depressed person takes on a PTSD interpretation of their troubles and gets exposure-based CBT, you're going to miss the boat," McNally says. "You're going to spend your time chasing this memory down instead of dealing with the way the patient misinterprets present events."

To complicate matters, recent studies showing that traumatic brain injuries from bomb blasts, common among soldiers in Iraq, produce symptoms almost indistinguishable from PTSD. One more overlapping symptom set.

"The overlap issue worries me tremendously," says Gerald M. Rosen, a University of Washington psychiatrist who has worked extensively with PTSD patients. "We have to ask how we got here. We have to ask ourselves, 'What do we gain by having this diagnosis?'"

Disabling Conditions
Rosen is thinking of clinicians when he asks about gain. But what does a veteran gain with a PTSD diagnosis? One would hope, of course, that it grants access to effective treatment and support. This is not happening. In civilian populations, two thirds of PTSD patients respond to treatment. But as psychologist Christopher Frueh, who researched and treated PTSD for the VA from the early 1990s until 2006, notes, "In the two largest VA studies of combat veterans, neither showed a treatment effect. Vets getting PTSD treatment from the VA are no more likely to get better than they would on their own."

The reason, Frueh says, is the collision of the PTSD construct's vagaries with the VA's disability system, in which every benefit seems structured to discourage recovery.

The first benefit is health care. PTSD is by far the easiest mental health diagnosis to have declared "service-connected," a designation that often means the difference between little or no care and broad, lasting health coverage. Service connection also makes a vet eligible for monthly disability payments of up to $3,000. That link may explain why most veterans getting PTSD treatment from the VA report worsening symptoms until they are designated 100 percent disabled at which point their use of VA mental health services drops by 82 percent. It may also help explain why, although the risk of PTSD from a traumatic event drops as time passes, the number of Vietnam veterans applying for PTSD disability almost doubled between 1999 and 2004, driving total PTSD disability payments to more than $4 billion annually.

Perhaps most disastrously, these payments continue only if you are sick. For unlike a vet who has lost a leg, a vet with PTSD loses disability benefits as soon as he recovers or starts working. The entire system seems designed to encourage chronic disability. "In the several years I spent in VA PTSD clinics," Frueh says, "I can't think of a single PTSD patient who left treatment because he got better. But the problem is not the veterans. The problem is that the VA's disability system, which is 60 years old now, ignores all the intervening research we have on resilience, on the power of expectancy, and on the effects of incentives and disincentives. Sometimes I think they should just blow it up and start over." But with what?

Richard A. Bryant, an Australian PTSD researcher and clinician, suggests a disability system more like that in place Down Under. An Australian soldier injured in combat receives a lifelong "noneconomic" disability payment of $300 to $1,200 monthly. If the injury keeps him from working, he also gets an "incapacity" payment, as well as job training and help finding work. Finally a crucial feature he retains all these benefits for two years once he goes back to work. After that, incapacity payments taper to zero over five years. But noneconomic payments a kind of financial Purple Heart continue forever. And like all Australians, the soldier gets free lifetime health care. Australian vets come home to an utterly different support system from ours: theirs is a scaffold they can climb. Ours is a low-hanging "safety net" liable to trap anyone who falls in.

Two Ways to Carry a Rifle
When a soldier comes home, he must try to reconcile his war experience with the person he was beforehand and the society and family he returns to. He must engage in what psychologist Rachel Yehuda, who researches PTSD at the Bronx VA Hospital, calls "recontextualization" the process of integrating trauma into normal experience. It is what we all do, on various scales, when we suffer breakups, job losses or the deaths of loved ones. Initially the event seems an impossible aberration. Then slowly we accept the trauma as part of the complex context that is life.

Major Matt Stevens recognizes that this adjustment can take time. Even after two years at home, the war still occupies his dreams. Sometimes, for instance, he dreams that he is doing something completely normal while carrying his combat rifle: "One night I dreamt I was bird-watching with my wife. When we saw a bird, she would lift her binoculars, and I would lift my rifle and watch the bird through the scope. No thought of shooting it. Just how I looked at the birds."

It would be easy to read Stevens's dream as a symptom of PTSD, expressing fear, hypervigilance and avoidance. Yet it can also be seen as demonstrating his success in recontextualizing his experience: reconciling the man who once used a gun with the man who no longer does.

Saving PTSD from itself, Spitzer, McNally, Frueh and other critics say, will require a similar shift seeing most postcombat distress not as a disorder but as part of normal, if painful, healing. This turnaround will involve, for starters, revising the rubric for diagnosing PTSD currently under review for the new DSM-V due to be published in 2012 so it accounts for the unreliability of memory and better distinguishes depression, anxiety and phobia from true PTSD. Mental health evaluations need similar revisions so they can detect genuine cases without leading patients to impose trauma narratives on other mental health problems. Finally, Congress should replace the VA's disability system with an evidence-based approach that removes disincentives to recovery and even go the extra mile and give all combat veterans, injured or not, lifetime health care.

These changes will be hard to sell in a culture that resists any suggestion that PTSD is not a common, even inevitable, consequence of combat. Mistaking its horror for its prevalence, most people assume PTSD is epidemic, ignoring all evidence to the contrary.

The biggest longitudinal study of soldiers returning from Iraq, led by VA researcher Charles Milliken and published in 2007, seemed to confirm that we should expect a high incidence of PTSD. It surveyed combat troops immediately on return from deployment and again about six months later and found around 20 percent symptomatically "at risk" of PTSD. But of those reporting symptoms in the first survey, half had improved by the second survey, and many who first claimed few or no symptoms later reported serious symptoms. How many of the early "symptoms" were just normal adjustment? How many of the later symptoms were the imposition of a trauma narrative onto other problems?

Stevens, for one, is certain these screens are mistaking many going through normal adjustment as dangerously at risk of PTSD. Even he, though functioning fine at work and home and in society, scored positive in both surveys; he is, in other words, one of the 20 percent at risk. Finally, and weirdly, both screens missed about 75 percent of those who actually sought counseling a finding that raises further doubts about the evaluations' accuracy. Yet this study received prominent media coverage emphasizing that PTSD rates were probably being badly undercounted.

A few months later another study the first to track large numbers of soldiers through the wars in Iraq and Afghanistan provided a clearer and more consistent picture. Led by U.S. Navy researcher Tyler Smith and published in the British Medical Journal, the study monitored mental health and combat exposure in 50,000 U.S. soldiers from 2001 to 2006. The researchers took particular care to tie symptoms to types of combat exposure. Among some 12,000 troops who went to Iraq or Afghanistan, 4.3 percent developed diagnosis-level symptoms of PTSD. The rate ran about 8 percent in those with combat exposure and 2 percent in those not exposed.

These numbers are about a quarter of the rates Milliken found. But they are a close match to PTSD rates seen in British Iraq War vets and to rates McNally calculated for Vietnam veterans. The contrast to the Milliken study, along with the consistency with British rates and with McNally's NVVRS calculation, should have made the Smith study big news. Yet the media, the VA and the trauma psychology community almost completely ignored the study. "The silence," McNally wryly noted, "was deafening."

This silence may be merely a matter of good news going unremarked. Yet it supports McNally's contention that we have a cultural obsession with trauma. The selective attention also supports the assertion by military historian and PTSD critic Ben Shephard that American society itself gained something from the creation of the PTSD diagnosis in the late 1970s: a vision of war's costs that, by transforming warriors into victims, lets us declare our recognition of war's horror and absolves us for sending them for we were victimized, too, fooled into supporting a war we later regretted. We should recognize war's horror. We should feel the soldier's pain. But to impose on a distressed soldier the notion that his memories are inescapable, that he lacks the strength to incorporate his past into his future, is to highlight our moral sensitivity at the soldier's expense.

PTSD exists. Where it exists we must treat it. But our cultural obsession with PTSD has magnified and finally perhaps become the thing itself a prolonged failure to contextualize and accept our own collective aggression. It may be our own postwar neurosis.

Atypical antipsychotics: too hard a sell?

Use of drugs such as Abilify, Seroquel and Zyprexa for treatment-resistant depression is gaining ground. Some see an 'unmet need' for medication. Others worry about side effects.

By Melissa Healy

April 13, 2009

About a year ago, patients began trooping into the office of UCLA psychiatrist Andrew Leuchter, asking whether an antipsychotic drug called Abilify "might be right for them." Few appeared to be delusional, plagued by hallucinations or suffering fearsome mood swings. Mostly, they were depressed or anxious, and frustrated by the pace of their recovery.

Leuchter wondered what was up: Depressed patients didn't usually seek out drugs used to quell psychiatry's most disturbing symptoms.

What was up, he soon discovered, was spending on a new advertising campaign touting Abilify as an "add-on" treatment for depression. For the first time since the arrival of a new generation of antipsychotic medications -- six drugs called the "atypicals" because they work differently from the earlier generation of antipsychotic drugs -- the makers of one, Abilify, had been granted the legal right to market to a vast new population of patients beyond those with schizophrenia or bipolar disorder.

This week, a Food and Drug Administration advisory panel recommended that the agency should grant the makers of a second atypical antipsychotic drug -- Seroquel XR -- similar latitude. The drug giant AstraZeneca wants permission to market the drug as a treatment for depression or anxiety that has not yielded to antidepressants alone.

But this time, it wasn't quite so easy a sell. The panel did say the drug was safe and effective for such purposes when used with other drugs, recommending approval for its use as an "add-on" treatment. But the panel recommended against the drug as a stand-alone treatment. And this time, the panel -- echoing an issue expressed by the FDA in convening the meeting -- cited safety concerns about the drugs' use in a greatly expanded population of patients.

Mounting research has made clear that the atypical antipsychotics are not only less safe than originally thought; they are not, on balance, any safer or more effective than older drugs for schizophrenia. And for the population of depressed or anxious patients that some are now proposed to treat, studies suggest the benefits are extremely modest.

The accumulated findings on the larger group of drugs had prompted the FDA to ask its advisory panel whether expanding the population of patients taking Seroquel XR would be wise. Like other members of this class of drugs, Seroquel has been linked to weight gain extreme enough to cause diabetes and to an often irreversible disorder characterized by involuntary tics and jerking movements.

As for Abilify, Sonia Choi, a Bristol-Myers Squibb spokeswoman, said the company "is continually monitoring the safety of Abilify, including the metabolic data, as part of our regular practice and is committed to disclosing clinical trials results" on the medication as they become available.

The concerns expressed by the FDA and its advisory panel, many public health experts say, come too late. In less than a decade, physicians have embraced the broad use of the atypical antipsychotics to treat mental disorders far less severe than schizophrenia and bipolar disorder -- afflictions such as anxiety, sleep difficulties, depression, attention deficit disorder and autism. First prescribed almost exclusively to adults, the drugs are now often used in the treatment of adolescents and kids as young as 2.

The sales of atypical antipsychotics have skyrocketed in recent years, propelling overall sales of antipsychotic drugs past all other classes, to $14.6 billion in 2008, according to IMS Health, a private firm that tracks drug trends. In 2008, 50 million prescriptions for antipsychotics, mostly the new ones, were filled in the U.S. -- a 5% hike in one year alone.

In the process, the spreading use of these costly drugs is raising -- for the nation as well as individual patients -- the rates and the risks of weight gain, diabetes, strokes, fatal heart attacks, an array of movement disorders and potentially, suicide, according to a wide range of critics.

"This is very worrisome; frankly I have serious concerns about these drugs," says Dr. Steven Nissen, who is chairman of the Cleveland Clinic's cardiovascular medicine department and serves as an ad hoc advisor for FDA panels. Studies point to a "very questionable balance between efficacy and safety" for the class, he said. But that message, he said, has been lost in an apparent "marketing bonanza" for the companies that make the medications. A recent report by the consulting firm Decision Resources found the makers of the atypicals spent $993 million in 2006 to promote the drugs to doctors and patients.

That's not to say the drugs haven't helped people.

Leuchter, who has prescribed Abilify for some with treatment-resistant depression, says that for certain patients and in certain circumstances, it works. "These are very effective medications, and like all medications, they have side effects," he says. But he adds: "I wouldn't want people to think this is the first thing they should reach for when a patient doesn't respond well to first-line antidepressants."

Newer drugs 'safer'

Introduced through the 1990s and early 2000s, the atypical antipsychotics -- drugs marketed as Abilify, Seroquel, Zyprexa, Geodon, Clozaril and Risperdal -- were widely hailed as superior to older schizophrenia drugs such as Thorazine and Haldol, which began to be used in the 1950s and 1960s, respectively. The first-generation antipsychotics could be highly effective at taming hallucinations and delusions. But some studies indicated that as many as 1 in 5 who took them developed involuntary tics and muscle movements called tardive dyskinesia, a condition that frequently cannot be reversed.

The newer drugs were supposed to be safer and more effective. That claim has now been roundly challenged.

A landmark 2005 study concluded that the drugs have brought marginal improvements at much greater expense than traditional antipsychotics in their primary use of treating schizophrenia. The CATIE study (for Clinical Antipsychotic Trials of Intervention Effectiveness) compared four of the atypicals -- Zyprexa, Geodon, Seroquel and Risperdal -- with the first-generation antipsychotic perphenazine (Trilafon), a drug costing on average a tenth the price of the newer drugs. It found the risk of tremors and tardive dyskinesia to be the same for all. And while all the antipsychotics are associated with weight gain, it was more frequent and more likely to be extreme among patients taking atypicals -- leading many to develop diabetes.

Last December, the British journal Lancet published a comprehensive analysis that further punctured the new drugs' claims to superiority. A separate study found Seroquel by many measures to be no more effective in treatment of schizophrenia symptoms than Haldol. And a 2008 study on Abilify found it was little better at banishing depressive symptoms than a placebo.

"The results are extremely unimpressive," said Dr. Daniel Carlat, a Massachusetts psychiatrist who publishes a respected monthly report on psychiatric research. "They just squeak by."

Many forces -- chief among them medical need and commercial imperatives -- have converged to make the atypical antipsychotics the prescription drug of the moment.

Psychiatrists and patients, disappointed in the effectiveness of antidepressants, have been hungry for treatments capable of curing depression, not just easing its hold on patients. Atypical antipsychotics influence different brain chemicals than do most current-generation antidepressants; their mode of action is thought to complement the ways in which standard antidepressant drugs affect the brain, and boost their effects on mood.

"There certainly is an unmet need out there," says UCLA's Leuchter, who has conducted extensive research on antidepressants' effectiveness. "Only about half the patients [on antidepressant drugs] will improve, and fewer than a third will get well with the first antidepressant they try."

That "unmet need" represents a potentially huge business opportunity for drug firms. Each year, as many as 10 million to 12 million depressed Americans could still be seeking relief after trying an antidepressant -- many more than the number who suffer from schizophrenia (2.4 million adults) and bipolar disorder (5.6 million adults). About 6.8 million adults suffer from generalized anxiety disorder.

"The story's pretty clear, and pretty embarrassing for the profession of psychiatry, which has allowed itself to be led by marketing," says Robert Rosenheck, a psychiatrist at Yale University who has studied the effectiveness and expanded use of the atypical antipsychotics. "We know now what these companies' strategies are: The number of people with schizophrenia is limited, so the road to profitability goes through soccer moms. They need to market these drugs to ordinary people who have dissatisfactions in life."

Side effects

In the run-up of use across the nation, weight gain and metabolic changes quickly emerged as a worrisome side effect. And in August 2008, the FDA, responding to a flurry of new research, required all antipsychotics to carry the agency's most urgent warning: The drugs' use in geriatric patients with dementia (by then very common) would raise their risk of dying from any cause.

Recent research has darkened the drugs' safety profile even further.

* Early this year, a Lancet Neurology study concluded that Alzheimer's disease patients given the drug to control aggression were nearly twice as likely to die of any cause than those not given the drug.

* Another study published in August 2008 -- this one in the British Medical Journal -- concluded that taking any antipsychotic medication raises a patient's likelihood of suffering a stroke, and added that "the risk of stroke might be higher in patients receiving atypical antipsychotics."

* Then, in January, the New England Journal of Medicine delivered a further blow to the new class of drugs. A federally funded study compared the rate of fatal heart attacks in patients taking the newer class of antipsychotic drugs, those on the older class, and patients taking neither. Patients on any antipsychotic drug -- new or old -- were twice as likely to die of a heart attack as those not on such medications.

Although drug makers are forbidden to promote, market or advertise drugs for any indication other than those approved by the FDA, that hasn't stopped physicians from legally writing "off-label" prescriptions. Rosenheck estimates roughly 60% of prescriptions for atypical antipsychotics have been written off-label.

In January, Eli Lilly & Co., which makes the atypical antipsychotic Zyprexa, was ordered by the Justice Department to pay more than $1.4 billion in penalties in connection with alleged illegal off-label marketing efforts. The company admitted no wrongdoing. The attorneys general of several states have sued the makers of Seroquel and Risperdal, alleging they've unlawfully marketed their medications to state Medicare and Medicaid agencies. The suits, still pending, allege that widespread prescribing of the drugs, encouraged by pharmaceutical companies that downplayed risks, caused harm to patients and unjustified cost to taxpayers.

One spokesperson for AstraZeneca, which makes Seroquel, says the company "fully supports the work of the FDA" in assessing the drug's benefits and risks in the treatment of depression and anxiety.

Responding to allegations made in several states' suits, another spokesman, Tony Jewell, said Seroquel's detailed package insert "has always provided adequate and appropriate information and warnings based on available data."

Currently, of all the atypical antipsychotics, only Abilify -- the drug that Leuchter's patients began asking about -- may legally be promoted as a treatment for psychiatric conditions other than schizophrenia and bipolar disorder. In November 2007, the FDA granted permission to its maker, Bristol-Myers Squibb, to promote the drug as a treatment for depression that has failed to respond to one or more antidepressants.

The FDA's decision on Abilify came without calling a hearing of its advisory panel on psychopharmacological drugs. In considering AstraZeneca's petition for Seroquel's new use, however, the FDA proceeded with greater caution, asking the committee to sift through the evidence and offer its recommendation.

Brain scan may reveal risk for Alzheimer's disease

• Key structural changes seen in brain scans of some patients with memory loss
• One year later, many patients with brain changes had developed Alzheimer's
• Memory-loss patients without these changes were mostly stable one year later
• Brain scans could identify who gets Alzheimer's, help with drug testing
  

The bottom line: The average person can't run out and get an MRI that shows if they're on the road to Alzheimer's just yet. But these findings could help drugmakers as well as patients in the future.

Overview

Brain scans may identify which patients suffering from mild cognitive impairment, or MCI, are likely to progress to Alzheimer's disease, and who will probably not develop the disease, according to a new study. The findings, published in April 2009 issue of the journal Radiology, could help in developing new drugs for Alzheimer's. More than 5 million Americans have Alzheimer's disease, about 3.5 million have mild cognitive impairment.
Questions and answers

What did the brain scans show?

Dr. Sanjay Gupta, CNN chief medical correspondent: This was a small but significant study in the fact that it may lead researchers to determine who will develop Alzheimer's disease and who may not. I had a chance to view the brain scans used in this study and they were truly fascinating. The images of patients with Alzheimer's showed many areas throughout the brain where the cells and tissue have begun to deteriorate or have already died. We know Alzheimer's is a neurodegenerative disease and when the cells die, patients begin to experience loss of cognitive function. Although all the patients with MCI experienced mild memory problems, not affecting their daily life, inside their brains looked very different. One group looked very similar to the brain of the Alzheimer's patients. The other MCI group showed very little cell damage.

What does this mean for patients with MCI?

Gupta: What this tells us is no two patients with MCI are the same. And some may progress to an Alzheimer's diagnosis in less that a year. These researchers looked at follow-up imaging a year later and found 30 percent of the group whose brains showed signs of cell loss were now Alzheimer's patients. This is a potential clue in trying to figure out who is most likely to develop Alzheimer's later on in life. Not ready for prime time yet, in terms of patients having access to these scan results, but it could be available a few years from now.

Is there anything people can do as they age to keep their brain strong?

Gupta: Yes, various cognitive exercises and memory activities can help keep your brain healthy and maintain cell production. But there isn't a lot of evidence showing that it can somehow reverse the effects of cell loss after getting an Alzheimer's diagnosis. What I found even more interesting, is something I started to incorporate into my own life: simple physical exercise. I am not talking about necessarily strenuous exercise, but simple, regular daily activity. Studies show it has a way of fueling your brain and even ward off Alzheimer's. I would say cognitive and physical activity is your best bet for now.

Background

CNN interviewed Bill Thies, the chief medical and scientific officer at the Alzheimer's Association, about this study. Here are some of his observations:

"This is an interesting study. Right now, we make an MCI diagnosis from talking to people; it requires symptoms to be there to make a diagnosis. And now people are looking at all sort of high-tech tools and imaging to track the signs inside their brain. MCI is often a very sporadic condition, a person might have symptoms of MCI one day and the next day might be normal. Part of the reason is different things can cause MCI -- depression, anxiety, its not always Alzheimer's disease."

"At the ultimate extent, based on this research, you'd be able to take any individual and take a picture of their brain structure and get a decision one way or another if they will develop Alzheimer's disease. It would be extremely valuable, especially for a MCI patient."

"Everybody wants better medication for Alzheimer's disease, even the people who already make the drugs want to develop something better. We all recognize, as we look to the next 40 or 50 years, that the number of cases are going to increase. And it is a very expensive disease for society. If we don't have a better way to treat it, it will have disastrous effects on society."

Suicidal behavior may run in families

By Elizabeth Landau
CNN

The poet Sylvia Plath, who made a name for herself through prose and poetry that conveyed a sense of depression and suicidal tendencies, famously died by asphyxiating herself in an oven in 1963.

The recent reported suicide of her son, marine biologist Nicholas Hughes, brings to light a known psychiatric phenomenon: the heredity of suicidal behavior.

A first-degree relative -- a parent, sibling or child -- of a person who has committed suicide is four to six times more likely to attempt or complete a suicide, said Dr. David Brent, psychiatrist at the University of Pittsburgh Medical Center.

Studies on twins have shown that suicidal behavior is between 30 and 50 percent due to heritable factors, he said. Suicide victims' biological relatives who were adopted away also show an increased risk of suicide, he said.

The rate of suicide in America is 10.9 suicide deaths per 100,000 people, according to the latest information from the National Institute of Mental Health. That means, although the likelihood of suicidal behavior increases in families, a completed suicide is still a rare event, Brent said.

"Genetics is not destiny," he said. "The odds are still very much against you having this happening to another relative."

Family history of suicide and family history of mental disorder are two risk factors that the National Institute of Mental Health lists.

More than 90 percent of people who die by suicide have depression or another mental disorder, or a substance abuse disorder in combination with another mental problem, according to the National Institute of Mental Health. Learn about the link between depression and creativity

Research shows that depression runs in families. A new study in the Proceedings of the National Academy of Sciences shows biological markers for the inherited condition. The researchers found, in a sample of 131 people, that the biological offspring of depressed people had structural differences in their brain. Some of these people had been followed for more than 25 years. Learn more about mood disorders »

People at high risk of developing depression had a 28 percent thinning of the right cortex, the brain's outermost surface, the study found. Those with an extra thinning abnormality in the left cortex were most likely to develop depression or anxiety.

The data set shows that this brain surface thinning was present before these people developed mental problems, and was found in both children and grandchildren of depressed people, said Dr. Bradley Peterson, psychiatrist at Columbia University Medical Center and co-author of the study.

The new study may point toward more individualized medicine -- one day people may be screened for these brain abnormalities that indicate high depression risk, and receive treatment based on that, he said.

Researchers believe the cortical thinning causes depression by interfering with the processing of emotional stimuli, he said. A person with these brain abnormalities may benefit from therapy targeted at responding to social stimuli more appropriately, he said.

With both depression and suicide, research suggests that causal factors are a combination of genetics and environment, Peterson said.

The best way to prevent suicide is to treat the underlying psychiatric disorder, Brent said.

Besides Hughes and Plath, famous examples of two or more close relatives committing suicide include Ernest Hemingway's family -- Hemingway's father, brother, sister and granddaughter, in addition to the famous novelist himself, killed themselves.

The poet John Berryman jumped off a Minneapolis bridge in 1972; his father had committed suicide when the poet was a child. More recently, the playwright Spalding Gray apparently killed himself in 2004; his mother had taken her own life many years earlier.

Do relatives of people who killed themselves imitate suicide? This is possible, but hard to prove or disprove, Brent said. In fact, there is more evidence of copycat suicides among people who did not know the victim well, but merely learned about him or her through the news.

If you've actually lost a relative to suicide and go through the bereavement process, you may be more likely to understand the aftermath of suicide, Brent said.

Suicide "can also represent the learned or transmitted way of coping with unbearable stress," Peterson said.

What exactly gets transmitted in families with suicide? One theory is that it's a difficulty in emotional regulation.

"Not necessarily depression per se, but it's the ability to restrain yourself from acting on suicidal thoughts," Brent said.

The American Association of Suicidology is one place for online information if you or someone you know is contemplating suicide.

For immediate assistance, contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255).

All AboutDepression • Suicide

Head injury: Do you need to go to the ER?

By Elizabeth Cohen
CNN Senior Medical Correspondent

(CNN) -- Connie and Donald McCracken were watching CNN one evening last week when they learned of the tragic death of actress Natasha Richardson from a head injury. Immediately, their minds turned to their 7-year-old daughter, Morgan, who was upstairs getting ready for bed.

Two days earlier, Morgan, her father, and brother had been playing baseball in the yard of their Mentor, Ohio, home when her father hit a line drive that landed just above Morgan's left temple. A lump formed, but the McCrackens iced it down and the swelling subsided within an hour.

"For the next two days, she was perfectly fine," Donald McCracken says. "She had no symptoms. She went to school both days and got an A on her spelling test as usual. There were no issues whatsoever."

But after hearing about Richardson's death, the McCrackens wondered if Morgan was really as OK as she seemed. After all, Richardson had been talking and lucid immediately after her fatal injury.

When they went upstairs to kiss Morgan good night, she complained of a headache. "Because of Natasha, we called the pediatrician immediately. And by the time I got off the phone with him, Morgan was sobbing, her head hurt so much," McCracken says.

The McCrackens took Morgan to the emergency room at LakeWest Hospital in neighboring Willoughby, where doctors ordered a CT scan and immediately put Morgan on a helicopter to Rainbow Babies and Children's Hospital in Cleveland, with her father by her side.

"I knew it was bad when she had to get there by helicopter in six minutes, instead of the 30 minutes it would have taken to get to Cleveland in an ambulance," McCracken said.

When the helicopter arrived at Rainbow, the McCrackens were greeted by Dr. Alan Cohen, the hospital's chief of pediatric neurosurgery. He whisked Morgan into the operating room, pausing for a moment to tell McCracken that his daughter had the same injury as Richardson: an epidural hematoma.

McCracken remembers standing in the emergency room, feeling like the life had just been sucked out of him. "My heart sank," he says. "It just sank."

Unlike Richardson's, Morgan's story has a happy ending. After surgery and five days in the hospital, she's at home and doing fine. "Dr. Cohen told us that if we hadn't brought her in Thursday night, she never would have woken up," McCracken says.

Now the McCrackens sometimes wonder if they waited too long to get Morgan to a doctor. After hearing about Richardson's death, many people are asking themselves the same question: Do all head injuries need attention, even ones that seem minor?

"Sometimes there's a gray zone, and there's no right answer," Cohen says.

In most cases, it's pretty clear when someone needs medical attention after a head injury, says Greg Ayotte, a spokesperson for the Brain Injury Association of America and a cognitive rehabilitation therapist. "They're confused, they're agitated, or they might be dizzy or unresponsive," he says.

But then there's what doctors call the "talk and die" scenario, where someone seems fine, only to die hours, or sometimes even days later.

"Talk and die" can happen with several different kinds of brain injuries. In the case of epidural hematomas, the injury Richardson and Morgan had, blood pools in the area between the lining of the brain and the skull. "Fluid is building up in a contained space, creating pressure. Something's got to give, and that something is the brain," Ayotte says. If you don't get to the hospital to have surgery to drain the fluid, "the deterioration can happen very quickly."

Here, from Ayotte and other experts, is a list of what to do after someone has suffered a head injury.

1. Be vigilant

Keep an eye on someone who has hit his head, even if the person never lost consciousness. "A lot of folks are still under the assumption that as long as you're not knocked out, you're OK, and that's not true," Ayotte says.

2. Look for dizziness, vomiting, headache and confusion

If the injured person has these signs, take him or her to an emergency room, says Dr. Jam Ghajar, clinical professor of neurological surgery at Weill Cornell Medical College in New York, and president of the Brain Trauma Foundation.

3. Look for changes in symptoms and behavior

Any sudden change, such as Morgan's headache going from mild to severe in minutes, means the person needs medical attention. For example, Ghajar says, if a person gets suddenly sleepy in the first 12 hours after a hit, it may mean the parts of the brain responsible for staying awake are experiencing pressure from a bleed.

4. Be especially wary if someone has been drinking alcohol or is on blood thinners

It's tough to distinguish brain-injured behavior from drunken behavior, so when in doubt, take the person to the hospital, Ghajar says. Also, blood thinners can turn a mild bleed into a major bleed, so be especially vigilant if the injured person is taking blood thinners such as warfarin.

He also warns people to be extra vigilant when an elderly person hits his or her head. The Centers for Disease Control and Prevention has information on traumatic brain injury and senior citizens.

5. Go to a certified trauma center if you can

The American College of Surgeons has a list of certified trauma facilities; a hospital that's not a trauma center may not have a neurosurgeon on call.

The McCrackens say they look back and still can't believe Morgan suffered such a severe injury and didn't show any signs for 48 hours. "She didn't black out, her speech wasn't slurred, she wasn't dizzy, she wasn't any of the things you'd expect," McCracken says. "And you don't want to be one of those panicky parents who takes their child to the emergency room all the time."

Cohen's advice after a head injury: When in doubt, go. "It's always better to err on the side of being conservative," he says.

Brain Images Reveal the Secret to Higher IQ

The integrity of neural wiring is a big factor in determining intelligence. It's also inheritable.

By Emily Singer

New research suggests that the layer of insulation coating neural wiring in the brain plays a critical role in determining intelligence. In addition, the quality of this insulation appears to be largely genetically determined, providing further support for the idea that IQ is partly inherited.

The findings, which result from a detailed study of twins' brains, hint at how ever-improving brain-imaging technology could shed light on some of our most basic characteristics.

"The study answers some very fundamental questions about how the brain expresses intelligence," says Phillip Shaw, a child psychiatrist at the National Institute of Mental Health, in Bethesda, MD, who was not involved in the research.

The neural wires that transmit electrical messages from cell to cell in the brain are coated with a fatty layer called myelin. Much like the insulation on an electrical wire, myelin stops current from leaking out of the wire and boosts the speed with which messages travel through the brain--the higher quality the myelin, the faster the messages travel. These myelin-coated tracts make up the brain's white matter, while the bodies of neural cells are called grey matter.

White matter is invisible on most brain scans, but a recently developed variation of magnetic resonance imaging, called diffusion-tensor imaging (DTI), allows scientists to map the complex neural wiring in our brains by measuring the diffusion of water molecules through tissue. Thanks to the fatty myelin coating, water diffuses along the length of neural wires, while in other types of brain tissue it moves in all different directions. Researchers can calculate the direction of fastest diffusion at each point in the brain and then construct a picture of the brain's fiber tracts. A well-organized brain has well-functioning myelin, in which water can be seen clearly moving along specific paths. "Diffusion imaging gives a picture of how intact your brain connections are," says Paul Thompson, a neuroscientist at the University of California, Los Angeles, who lead the study.

Thompson and his colleagues took DTI scans of 92 pairs of fraternal and identical twins. They found a strong correlation between the integrity of the white matter and performance on a standard IQ test. "Going forward, we are certainly going to think of white matter structure as an important contributor of intelligence," says Van Wedeen, a neuroscientist at Massachusetts General Hospital in Boston, who was also not involved in the research. "It also changes how you think about what IQ is measuring," says Wedeen. The research was published last month in the Journal of Neuroscience.

If white matter is linked to both processing speed and IQ, this raises the question: is intelligence merely a function of how fast your brain works? Previous research has linked processing speed to IQ, but the tests used in the study are measures of general intelligence, including verbal skills, math, and logic. "Processing speed plays a big part in how intelligent you are, but it's not the only factor," says Shaw.

The new study is among the first to link a specific neural architecture to IQ in healthy individuals. "Most people have focused on grey matter," says Shaw. "This is good evidence we should be looking at white matter as well." Previous studies using DTI have linked white matter damage to Alzheimer's disease, chronic alcoholism, and traumatic brain injury.

The UCLA researchers took the study a step further by comparing the white matter architecture of identical twins, who share almost all their DNA, and fraternal twins, who share only half. Results showed that the quality of the white matter is highly genetically determined, although the influence of genetics varies by brain area. According to the findings, about 85 percent of the variation in white matter in the parietal lobe, which is involved in mathematics, logic, and visual-spatial skills, can be attributed to genetics. But only about 45 percent of the variation in the temporal lobe, which plays a central role in learning and memory, appears to be inherited.

Thompson and his collaborators also analyzed the twins' DNA, and they are now looking for specific genetic variations that are linked to the quality of the brain's white matter. The researchers have already found a candidate--the gene for a protein called BDNF, which promotes cell growth. "People with one variation have more intact fibers," says Thompson.

The search for the genetic and neuroanatomical basis of intelligence has been controversial, largely because opponents fear it will spawn a deterministic view of abilities and education. "People worry that if something is genetic, they have no power to influence it," says Thompson. "But that's not true at all." For example, both an average runner and a genetically gifted one can benefit from training.

But the debate may be moot since, as Wedeen points out, it is unlikely that an individual brain scan could predict a person's IQ. "The report described aggregate data over number of individuals," he says. "That's not the same as saying we can do a scan and determine a person's intelligence. That may be in the offing, but we don't know that yet."

Consciousness signature' discovered spanning the brain

Brain scans have long been used to try to find the "seat of consciousness" in the brain.

17 March 2009 by Anil Ananthaswamy

Electrodes implanted in the brains of people with epilepsy might have resolved an ancient question about consciousness.

Signals from the electrodes seem to show that consciousness arises from the coordinated activity of the entire brain. The signals also take us closer to finding an objective "consciousness signature" that could be used to probe the process in animals and people with brain damage without inserting electrodes.

Previously it wasn't clear whether a dedicated brain area, or "seat of consciousness", was responsible for guiding our subjective view of the world, or whether consciousness was the result of concerted activity across the whole brain.

Probing the process has been a challenge, as non-invasive techniques such as magnetic resonance imaging and EEG give either spatial or temporal information but not both. The best way to get both simultaneously is to implant electrodes deep inside the skull, but it is difficult to justify this in healthy people for ethical reasons.
Brainy opportunity

Now neuroscientist Raphaël Gaillard of INSERM in Gif sur Yvette, France, and colleagues have taken advantage of a unique opportunity. They have probed consciousness in 10 people who had intercranial electrodes implanted for treating drug-resistant epilepsy.

While monitoring signals from these electrodes, Gaillard's team flashed words in front of the volunteers for just 29 milliseconds. The words were either threatening (kill, anger) or emotionally neutral (cousin, see).

The words were preceded and followed by visual "masks", which block the words from being consciously processed, or the masks following the words weren't used, meaning the words could be consciously processed. The volunteers had to press a button to indicate the nature of the word, allowing the researchers to confirm whether the volunteer was conscious of it or not.

Between the 10 volunteers, the researchers received information from a total of 176 electrodes, which covered almost the whole brain. During the first 300 milliseconds of the experiment, brain activity during both the non-conscious and conscious tasks was very similar, indicating that the process of consciousness had not kicked in. But after that, there were several types of brain activity that only occurred in the individuals who were aware of the words.
Lost seat

First, there was an increase in the voltage levels of the signals in their brains. Second, the frequency and phase of neurons firing in different parts of the brain seemed to synchronise. Then some of these synchronised signals appeared to be triggering others. For example, activity in the occipital lobe seemed to cause activity in the frontal lobe.

Because this activity only occurred in volunteers when they were aware of the words, Gaillard's team argue that it constitutes a consciousness signature. As much of this activity was spread across the brain, they say that consciousness has no single "seat". "Consciousness is more a question of dynamics, than of a local activity," says Gaillard.

Bernard Baars of the Neuroscience Institute in San Diego, California, who proposed a "global access" theory of consciousness in 1983 agrees: "I'm thrilled by these results."

He says they provide the "first really solid, direct evidence" for his own theory. He also says that having such a signature will make it easier to look for signs of consciousness in people with brain damage, infants and animals with the help of non-invasive techniques such as EEG.