Chapter 16. Psychopathology: Biological Basis of Behavior Disorders

  

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Mothering Malnutrition: Moms' depression weighs on infants in Pakistan

Bruce Bower In southern Asia, where an estimated 75 million children qualify as malnourished, lack of food may only be part of the problem. A prospective study in rural Pakistan finds that mothers who became depressed shortly before or after giving birth had babies far more likely to experience stunted growth and bouts of diarrhea than were babies with psychologically healthy mothers. Maternal depression critically contributes to high rates of malnutrition and failure to thrive among infants in this part of the world, conclude psychologist Atif Rahman of the University of Manchester in England and his colleagues. Most people living in southern Asia now have access to adequate food supplies, the researchers note. In the new study, maternal depression exhibited a stronger link to poor infant health during the first year after birth than did other factors associated with slowed physical growth, including low birth weight and having poor, uneducated parents. This finding raises particular concern, according to the scientists, because several other reports indicate that the depression rate of 10 to 15 percent among expectant and new mothers in Western nations nearly doubles in southern Asia. Copyright ©2004 Science Service. Keyword: Depression; Development of the BrainPosted: 09.18.2004

Panic Disorder

With cars blurring past to her left and right, Judy Niosi pried her fingers around the steering wheel as she drove along a major highway, struggling to come to grips with what she thought was a heart attack. "I was feeling was that my heart started pounding—forcefully—to the point where I thought my chest was going to explode," recalls the 37-year-old graphic artist. "My hands became sweaty and I had the constant thoughts that I was going to die." Niosi gulped down air, talked to herself in a soothing tone and somehow rumbled up her driveway a short while later. By then, her symptoms had disappeared. "I immediately got on the Internet looking for things, you know, heart attack symptoms to make sure that I wasn't having a heart attack," she says. "And I came across panic attacks and then I realized it must've been a panic attack." Her physician confirmed her suspicions. Doctors have long suspected that panic attacks like Niosi's—characterized by repeated bouts of intense fear that seem to come out of nowhere—could be hereditary and may result from the way our brains are wired. Piling up is new evidence that this may be the case. Psychiatrist Alexander Neumeister, an assistant professor at Yale University, reported in the Journal of Neuroscience that key brain receptors that receive chemical signals from other cells are deficient in those who suffer from panic attacks. The receptors help move the brain chemical serotonin—it regulates emotion—around the brain. © ScienCentral, 2000- 2004. Keyword: EmotionsPosted: 09.17.2004

Panel Urges Child Antidepressants Warning

By LAURAN NEERGAARD WASHINGTON -- All drugs used to treat

 

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depressed children should carry a "black box" warning of the antidepressants' link to increased suicidal thoughts and actions, says a panel of federal advisers. The warning, among the strongest in the Food and Drug Administration's arsenal, should reach doctors no matter how they get drug information and would extend to drug advertising directed at patients. That's the majority opinion of federal advisers, who heard testimony Monday about antidepressants' powers and perils from doctors, researchers and relatives of patients who killed themselves after taking such medication. The panel spent the bulk of Tuesday deliberating before issuing its recommendation. The black box option is more strident than the bold-letter warnings the same federal advisers suggested be added to antidepressant labels this March. Antidepressant prescription rates to children were unchanged by the earlier warning. Unlike the earlier red flag, advisers said this new warning should make clear that antidepressants have been linked to two to three more children per 100 having heightened suicidal thoughts and behaviors. Copyright © 2004, The Associated Press Keyword: Depression; Development of the BrainPosted: 09.16.2004

FDA considers antidepressant risks for kids

Erika Check Advisers to the US Food and Drug Administration (FDA) have told the agency to issue a sweeping new warning about the risks of all antidepressants in children. The warning would state that such medicines cause some children to try to commit suicide. This is a step up from warning labels adopted by the FDA in March, which say that antidepressant drugs are associated with a risk of suicide in children, but do not necessarily cause it. The warning would appear on all antidepressants on the market, as well as those approved in the future. The committee said antidepressants should also be sold with a guide that tells parents to monitor children on the drugs for suicidal tendencies. The advisers came to their conclusions last night after a two-day hearing, in which they examined data from 24 clinical trials, as well as hearing passionate testimony from patients, parents and doctors who work with depressed children. The FDA convened the hearing on 13 September to ask its advisory committee how to interpret the clinical trials, which examined the effect in children and teenagers of nine antidepressant medications on five types of mental illness. The FDA usually adopts its advisory committee's recommendations, but will discuss them internally before announcing a decision, says Robert Temple director of the Office of Drug Safety in the agency's drug evaluation centre. ©2004 Nature Publishing Group Keyword: Depression; Development of the BrainPosted: 09.16.2004

Prozac raises child suicide risk

Children who take the anti-depressant Prozac are at greater risk of attempting suicide, say US experts. The drug is currently the only anti-depressant which doctors can prescribe to under-18s in the UK. Other similar drugs are considered too dangerous because previous studies have linked them to an increase in suicidal tendencies. However, an analysis by the US Food and Drug Administration has found that Prozac too may pose a risk. The analysis was overseen by Dr Robert Temple, director of the FDA office of drug evaluation, who gave evidence on Tuesday at a hearing to determine whether tougher warning labels were needed for anti-depressants. He said: "I think we now all believe there is an increase in suicidal thinking and action that is consistent across all

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the drugs." The FDA decided that all antidepressant drugs should carry the strongest possible warnings that they could cause children to harm themselves. In future, the drugs will have to black boxes spelling out the potential risks. On average, the analysis, carried out by experts at Columbia University, New York, found anti-depressants taken by children will cause an extra 2% to 3% to have increased suicidal thoughts. (C)BBCKeyword: Depression; Development of the BrainPosted: 09.15.2004

New Warnings Sought on Antidepressants

By GARDINER HARRIS When the Food and Drug Administration opens an advisory committee hearing tomorrow into the safety of antidepressants, several committee members will push for tougher warnings saying that a child or teenager given the drugs can become suicidal in the first weeks of therapy, they said in interviews. "I want the warning strengthened," said Dr. Richard Gorman, a member of the committee and a pediatrician from Ellicott City, Md. "I would also like the pharmaceutical companies to send out letters to doctors saying that, in kids, this stuff doesn't work." Dr. James McGough, another committee member and a professor of clinical psychiatry at the University of California, Los Angeles, also said he wanted stronger warnings. For more than a year, agency officials have struggled to find the appropriate balance between warning patients about the possible suicide risk of antidepressants and reassuring those patients that drug therapy can be an effective and safe remedy. Copyright 2004 The New York Times Company Keyword: Depression; Development of the BrainPosted: 09.13.2004

Gene May Link Alcoholism and Depression

By CHERYL WITTENAUER, Associated Press Writer ST. LOUIS -- Scientists say they've identified a gene that appears to be linked to both alcoholism and depression, a finding that may one day help identify those at higher risk for the diseases and guide new treatments. Previous studies of twins and adopted siblings have suggested there likely are genes in common underlying alcoholism and depression, and that the two disorders seem to run in families. But the lead researcher of the new study says this is the first report of a specific gene that seems to increase risk for both disorders. "Clinicians have observed a connection between these two disorders for years, so we are excited to have found what could be a molecular underpinning for that association," said Alison Goate, the Washington University School of Medicine researcher who led the study. Follow-up research might help reveal the underlying biology that makes some people susceptible to alcoholism, others to depression, some to both diseases, and others to neither. Goate says a variation or alteration of the CHRM2 gene influences those four separate conditions. The study is published in the September issue of the journal Human Molecular Genetics. Copyright © 2004, The Associated Press Keyword: Drug Abuse; DepressionPosted: 09.09.2004

Prescribing Antidepressants for Depression in Bipolar Disorder--Point/Counterpoint

Psychiatric Times August 2004 Vol. XXI Issue 9 It Is Reasonable To Try and Treat Depression in BD Primarily With Antidepressants by Lori Altshuler, M.D. Bipolar disorder (BD) affects approximately 1% of the population and is associated with a high morbidity and mortality

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(Goodwin and Jamison, 1990). Bipolar disorder is recurrent in almost all cases, and most patients will spend more time in the depressed than the manic phase of their illness over their lifetime. This is true for patients with bipolar I disorder (BD-I) as well as bipolar II disorder (BD-II) (Goodwin and Jamison, 1990; Judd et al., 2002). Suicide attempts and completed suicides are high in this population (Goodwin and Jamison, 1990). Most Patients With BD Do Not Need, or Would Not Benefit From, Antidepressants by S. Nassir Ghaemi, M.D. Voltaire is reputed to have held his contemporary medical colleagues in low regard, saying: "Doctors pour drugs of which they know little, to cure diseases of which they know less, into human beings of whom they know nothing." There is, no doubt, a herd mentality, codified in the "standard-of-care" legal criterion, that physicians share with all of mankind. Progress in medicine depends, however, on the ability to critically examine one's assumptions and a willingness to apply standards of evidence that share at least some aspects of scientific method. © 2004 Psychiatric TimesKeyword: Schizophrenia; DepressionPosted: 09.09.2004

Applications of Transcranial Magnetic Stimulation to Therapy in Psychiatry

by Antonio Mantovani, M.D., Ph.D., and Sarah H. Lisanby, M.D. Psychiatric Times August 2004 Vol. XXI Issue 9 Transcranial magnetic stimulation (TMS) is a non-invasive means of stimulating focal regions of the brain using magnetic fields. Since its introduction in 1985, TMS has been used to study localization of brain functions, connectivity of brain regions and pathophysiology of neuropsychiatric disorders. The potential uses of TMS to treat psychiatric disorders are under active study. This article reviews the state of knowledge about the therapeutic potential of TMS in psychiatry. Transcranial magnetic stimulation is an investigational medical procedure performed by placing an electromagnetic coil on the scalp (Figure). High-intensity current is rapidly turned on and off in the coil through the discharge of a capacitor. This produces a time-varying magnetic field that lasts for about 100 to 200 microseconds. The magnetic field strength is about 1.5 to 2 tesla (about the same intensity as the static magnetic field used in clinical magnetic resonance imaging) at the surface of the coil, but the strength of the magnetic field drops off exponentially with distance from the coil. The proximity of the brain to the time-varying magnetic field results in current flow in neural tissue and in membrane depolarization. Transcranial magnetic stimulation is experimental; it is not approved by the U.S. Food and Drug Administration for the treatment of any disorder. A striking effect of TMS occurs when one places the coil on the scalp over the primary motor cortex. A single TMS pulse of sufficient intensity causes involuntary movement in the muscle represented by that region of cortex. © 2004 Psychiatric Times.Keyword: DepressionPosted: 09.09.2004

Indicting the Drug Industry's Practices

By JANET MASLIN Dr. Marcia Angell is a former editor in chief of The New England Journal of Medicine and spent two decades on the staff of that publication. If much of that time was devoted to reviewing papers on pharmacological research, it must have been spent in a state of near-apoplexy. Her new book, 'THE TRUTH ABOUT THE DRUG COMPANIES', is a scorching indictment of drug companies and their research and business practices. "Despite all its excesses, this is an important

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industry that should be saved - mainly from itself," she writes. This turns out to be one of her book's more forgiving pronouncements, since the rest of it is devoted to assertions of shady, misleading corporate behavior. If she is accurate in her assumptions about big drug companies' feistiness and tenacity, Dr. Angell is likely to be on the receiving end of angry rebuttals. She is sometimes vague enough to leave room for such attacks. ("I have heard that morale in some parts of the F.D.A. is extremely low, and I can certainly understand why it might be.") But over all, Dr. Angell's case is tough, persuasive and troubling. Arguing that in 1980 drug manufacturing changed from a good business into "a stupendous one," thanks to changes in government regulations. She adds, "Of the many events that contributed to their sudden great and good fortune, none had to do with the quality of the drugs the companies were selling." Copyright 2004 The New York Times Company Keyword: Miscellaneous; DepressionPosted: 09.07.2004

911 PTSD Therapy

We know them as heroes, but many of the first-responders who survived 9-11 felt far from heroic. Instead they were shattered by post-traumatic stress. As this ScienCentral News video reports, some software engineers scrambled to help. Stephen King, a retired New York City fire fighter, got out of the World Trade Center alive on September 11th, 2001. But the trauma didn't end that day. "It overtook every aspect of my life," says King. "I couldn't enjoy anything, I couldn't get basic necessities like sleep…I was like a walking zombie, literally. All the things that always kept me occupied and busy just nothing seemed to matter anymore." King reached out for help and found out he was suffering from post-traumatic stress disorder or PTSD. Psychiatrist JoAnn Difede, director of the Program for Anxiety and Traumatic Stress Studies and a psychiatry professor at Weill Medical College of Cornell University, began working with King using the first-line, or first choice treatment for PTSD, called imaginal exposure therapy. "We ask the patient to imagine the event as if it were occurring again in their own imagination," she explains. "You want the person to relive the experience and process the memories. If they can't access their memories then they really can't process it and get better." That's what happened to King. He felt he made some initial progress, then "hit a plateau." © ScienCentral, 2000- 2004. Keyword: StressPosted: 09.07.2004

Mouse study shows NPAS3 and NPAS1 genes may be linked to psychosis

DALLAS – Mice with specific genetic mutations exhibit behavior similar to human psychosis, report UT Southwestern Medical Center at Dallas researchers, providing further support to the notion of a genetic link to schizophrenia. The researchers genetically engineered mice with a mutation in the gene NPAS3, a mutation in the gene NPAS1 or a mutation in both genes. Both genes encode proteins that switch other genes on and off in brain cells. "These mice display certain deficits that are potentially consistent with schizophrenia," said Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and senior author of the study that will appear in an upcoming issue of the Proceedings of the National Academy of Sciences and is to be posted online this week. "It's too early to tell whether the abnormal behavior we observed in these mutated mice can be directly connected with human disease. On the other hand, we find it intriguing that members of a Canadian family

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carrying a mutation in the human NPAS3 gene have been reported to suffer from schizophrenia." Normal mice in a pen will climb over each other and interact, but the mice with the genetic mutations fail to socialize in this way. Instead, the mutants dart about wildly, avoiding interaction with their normal siblings. Keyword: Schizophrenia; Genes & BehaviorPosted: 08.31.2004

Brain may produce its own antipsychotic drug

A cannabis-like substance produced by the brain may dampen delusional or psychotic experiences, rather than trigger them. Heavy cannabis use has been linked to psychosis in the past, leading researchers to look for a connection between the brain's natural cannabinoid system and schizophrenia. Sure enough, when Markus Leweke of the University of Cologne, Germany, and Andrea Giuffrida and Danielle Piomelli of the University of California, Irvine, looked at levels of the natural cannabis-like substance anandamide, they were higher in people with schizophrenia than in healthy controls. The team measured levels of anandamide in the cerebrospinal fluid (CSF) of 47 people suffering their first bout of schizophrenia, but who had not yet taken any drugs for it, and 26 people who had symptoms of psychosis and have a high risk of schizophrenia. Compared with 84 healthy volunteers, levels were six times as high in people with symptoms of psychosis and eight times as high in those with schizophrenia. "This is a massive increase in anandamide levels," Leweke told the National Cannabis and Mental Illness Conference in Melbourne, Australia, last week. And that is just in the CSF. Levels could be a hundred times higher in the synapses, where nerve signalling is taking place, he says. © Copyright Reed Business Information Ltd. Keyword: Schizophrenia; Drug AbusePosted: 08.30.2004

Bitter Medicine

Two books on the (big) business of the pharmaceutical industry. Reviewed By Shannon Brownlee Every author should be so lucky. While Jerome Kassirer and Marcia Angell were holed up in their offices, typing away, Congress launched an investigation into financial entanglements between industry and the National Institutes of Health. Then Pfizer was hit with nearly half a billion dollars in fines for paying doctors to hype its anti-seizure drug Neurontin for unapproved—and largely unproven—uses. Now, New York state attorney general Eliot Spitzer has accused another drug giant, GlaxoSmithKline, of burying evidence that the antidepressant Paxil can trigger suicide. It's great news for Angell's and Kassirer's book sales, bad news for the rest of us. These stories about the unholy alliance between the pharmaceutical industry, researchers, and doctors may have seemed, to the casual observer, like nothing more than isolated blips. Sad to say—as these surprisingly bare-knuckled books by the last two editors-in-chief at the New England Journal of Medicine make clear—such accounts provide a mere glimpse of the corruption of medical science. In the last two decades, the drug and biotech industries have gained unprecedented leverage over what doctors and patients know—and don't know—about the $200 billion worth of prescription pharmaceuticals consumed by Americans each year. Industry has gained that leverage by funding and, increasingly, controlling medical research. It has also used its deep pockets to effectively buy the loyalty of physicians in private practice and to sway the opinion of thought-leaders in academia. Grasp the full scope of

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industry influence over medical science and practice, and it's enough to make anybody think twice before filling a prescription. © 2004 The Foundation for National Progress Keyword: DepressionPosted: 08.27.2004

Glaxo Agrees to Post Results of Drug Trials on Web Site

By GARDINER HARRIS In a settlement that the New York attorney general said would transform the drug industry, GlaxoSmithKline agreed yesterday to post on its Web site the results of all clinical trials involving its drugs. "This settlement is transformational in that it will provide doctors and patients access to the clinical testing data necessary to make informed judgments," the attorney general, Eliot Spitzer, said. While the case involves only GlaxoSmithKline, the British drug maker, Mr. Spitzer predicted that other companies would follow its lead by posting the results of their studies online. Eli Lilly, for example, has said it would create a Web site on which it would list the results of clinical tests of approved drugs. Other companies, including Johnson & Johnson and Merck, have said they support the concept of a public database that would list trial results. Mr. Spitzer filed suit in June against GlaxoSmithKline, contending that it committed fraud by publicizing the results of only one of five trials studying the effect of its antidepressant, Paxil, in children. That single study showed mixed results. The others not only failed to show any benefit for the drug in children but demonstrated that children taking Paxil were more likely to become suicidal than those taking a placebo. Copyright 2004 The New York Times Company Keyword: Depression; Development of the BrainPosted: 08.27.2004

Patient with mad-cow-like brain ailment dies

By Sandi Doughton, Seattle Times staff reporter The woman treated at Harborview Medical Center this summer for a mysterious brain ailment related to mad-cow disease has died. An autopsy was performed, and should help national experts in their quest to identify the disease, said epidemiologist Dr. Jo Hofmann, of the Washington Department of Health. "There will be brain tissue obtained from multiple parts of the brain, that will definitely provide more information," Hofmann said. The tissue will be sent to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland. The woman, who Hofmann said was under the age of 60, was not a resident of Washington and did not die here. The woman has not been identified to protect her family's privacy. She was treated at Harborview, where doctors performed a brain biopsy, collecting a tiny sample of brain tissue they hoped would help them diagnose the baffling illness, characterized by dementia. Keyword: PrionsPosted: 08.26.2004

Pain common side effect of depression

Physical symptoms are nearly as common as emotional ones in patients suffering from depression, according to Indiana University School of Medicine research published in the August issue of the Journal of General Internal Medicine. Patients with depression frequently talk to their physicians about symptoms such as headache, back or muscle pain, stomach ache and dizziness instead of symptoms more commonly associated with depression such as fatigue, lack of motivation and

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moodiness, says Kurt Kroenke, M.D., professor of medicine in the Division of General Internal Medicine and Geriatrics at IU and a research scientist at the Regenstrief Institute, Inc. "Depression is a risk factor for symptoms of pain," he said. "The most reports of pain – such as muscle pain, headaches, leg pain – are two or three times more common in people with depression." Physical symptoms also may serve as a barometer for physicians to gauge the effectiveness of common antidepressant treatments, he said. "Physical symptoms may not respond to common antidepressant treatment as much as the emotional symptoms," says Dr. Kroenke. "Even though the physical symptoms may be related to or aggravated by the depression, they can linger longer than the emotional symptoms." Keyword: DepressionPosted: 08.26.2004

New Therapy on Depression Finds Phone Is Effective

By BENEDICT CAREY Debates about the safety and effectiveness of treatments for depression miss a basic reality about the disease: most people affected by it do not seek help at all, and those who do commonly neglect to complete counseling or drug regimens recommended by doctors. For at least a third of the people who try them, treatments of any kind fall short, surveys show. But improving success rates may be a matter of picking up the phone, according to a report today in the Journal of the American Medical Association. In a large-scale, 18-month study, doctors in Seattle found that they could significantly increase recovery rates for patients taking antidepressants by providing several 30- to 40-minute counseling sessions over the phone. In previous studies, researchers showed that phone calls from nurses or other clinic staff members providing emotional support could help people trying to quit smoking, stay on medication or shake low moods. The Seattle study is the first to test the effect of a standardized form of counseling, cognitive behavior therapy, delivered entirely over the phone. Copyright 2004 The New York Times Company Keyword: DepressionPosted: 08.25.2004

Combination Treatment Most Effective in Adolescents with Depression

A clinical trial of 439 adolescents with major depression has found a combination of medication and psychotherapy to be the most effective treatment. Funded by the NIH’s National Institute of Mental Health (NIMH), the study compared cognitive-behavioral therapy (CBT) with fluoxetine, currently the only antidepressant approved by the U.S. Food and Drug Administration for use in children and adolescents. John March, M.D., Duke University, and colleagues, report on findings of the multi-site trial in the August 18, 2004, Journal of the American Medical Association (JAMA). The results of the first 12 weeks of the Treatment for Adolescents with Depression Study (TADS), conducted at 13 sites nationwide, show that 71 percent responded to the combination of fluoxetine and CBT. The other three treatment groups, of participants between the ages of 12 and 17, also showed improvement, with a 60.6 percent response to fluoxetine-only treatment, and 43.2 percent response from those receiving only CBT. The response rate was 34.8 percent for a group that received a placebo. The difference in response rates for the latter two treatment groups was not statistically significant. The $17 million study is the first large, federally funded study using an antidepressant medication to treat adolescents suffering with moderate to severe depression. TADS was conducted between the spring of the

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year 2000 and the summer of 2003. Keyword: Depression; Development of the BrainPosted: 08.21.2004

Teens with depression show most improvement when medication and therapy combined

DALLAS – – Teenagers suffering from depression improved more with a combination of an antidepressant and cognitive-behavior therapy than they did when treated with either separately, a multicenter study published today in the Journal of the American Medical Association shows. Results of a national, yearlong government-funded study in which UT Southwestern Medical Center at Dallas researchers participated also showed that depressed teens treated only with cognitive-behavior therapy did little better than teens given placebos. Cognitive-behavior therapy is a form of psychotherapy that emphasizes the role of thinking in creating subsequent feelings and behaviors. The study, designated the Treatment for Adolescents with Depression Study (TADS), is the first to directly compare psychotherapy and medication treatment for teenagers, said Dr. Graham Emslie, professor of psychiatry and director of UT Southwestern's child and adolescent psychiatry division.

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