Posted by jrbecker on March 11, 2004, at 9:42:03
I just wanted to advertise McMan's Depression and Bipolar Weekly website and newsletter. It's by far one of the most informative and no-nonsense ways to stay informed on issues related to mental disability. Below is a copy of their most recent [free] newsletter. You can sign up for the newsletter at www.mcmanweb.com
"Knowledge is necessity," as John McManamy likes to say...
McMan's Depression and Bipolar Weekly
March 10, 2004 Vol 6 No 5
Welcome
Lead story: A breakthrough study identifies a cellular bipolar breakdown lane.Also in this issue: That time of year again, Cymbalta withdrawal, Paxil for PMDD, Atkins diet thumbs down, Tardive dyskinesia, Speeding up your AD, Teen brains, Capitol Hill tragedy, Laura’s Law, Homeless in Minnesota, Benzo withdrawal, Omega-3, rTMS, Natural light for pain, Reducing suicidality, Spalding Gray, Princess Di, Treating BP II McMan's Web, Donations.
Mitochondraic
Is bipolar disorder the result of a mitochondrial malfunction? Wait! What on earth are mitochondria? Funny you should ask. Mitochondria are specialized organelles in the cell vital to the production of cellular energy. Sugar is broken down in the cytoplasm by a process known as glycolosis to produce ATP, then pyruvate. The pyruvate then enters the mitochondrion, where it is further sliced and diced to kickstart a complex chemical reaction you may vaguely recall from high school biology called the Krebs cycle. The stripped-away electrons from the Krebs cycle are coupled with oxygen in the inner mitochondrial membrane that result in the release of chemical energy in the form of ATP.
"If any part of a human cell truly contains what the ancients called the fire of life," says biologist Kenneth Miller PhD of Brown University, "it's the mitochondrion. Interrupt, even for a moment, the flow of electrons to oxygen, and that fire will go out." The poison cyanide acts by blocking mitochondrial electron transport, which explains why it is so deadly. Can bipolar have a similar, albeit more subtle, effect?
In 2000, Tadafumi Kato MD and Nobumasa Kato MD, PhD of the University of Tokyo proposed the mitochondrial dysfunction hypothesis based, among other things, on abnormal brain energy metabolism in bipolar patients measured by MRS scans and mitochondrial depletion in autopsied bipolar brains. Their search for mutant mitochondrial DNA turned up two suspect genes.
In an article in this month’s Archives of General Psychiatry, Christine Konradi PhD and her colleagues at Harvard and McLean Hospital report on a breakthrough study that may place the humble mitochondrion front stage center in bipolar research. Postmortem tissue samples were extracted from the hippocampi of the brains of nine individuals with bipolar, eight with schizophrenia, and 10 healthy controls. The hippocampus attracted the investigators’ interest, as it is an area in the brain where neurogenesis (new brain cell growth) takes place, as well as being involved in short term memory and emotion. Moreover, there is evidence from brain imaging that the hippocampus functions differently in bipolar patients and in schizophrenia.
The researchers used gene array technology to determine how 12,558 nuclear genes switched on or off proteins in the hippocampus, finding that the expression of 43 were decreased in the bipolar sample but not a single gene in the schizophrenia group. Of these 43 genes, 18 coded for mitochondrial proteins involving several chemical processes. The authors theorize that gene mutations are at best only a partial explanation for their findings, that bipolar disorder may result in reduced numbers of mitochondria in the neuron or that selective neurons are lost. Alternatively, various mechanisms that control DNA transcription may affect gene expression.
Significantly, even though it was a small study and there was some variation in the brains, all the bipolar brains "seemed to have the same pattern," Dr Konradi told this writer. This indicates that mitochondrial malfunction may affect all of us rather than just a small subset of patients, further suggesting obvious places to look for new treatments.. There are no meds for mitochondrial disorders, but Dr Konradi reported that "if our findings are reproduced, it should be quite an incentive for the pharmaceutical industry to come up with something."
Like real soon?
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Cymbalta Repercussions
Eli Lilly has announced it will lengthen the withdrawal period to wean study participants off its new antidepressant, Cymbalta (duloxetine). On Feb 7, a college student, Traci Johnson, committed suicide while in a Cymbalta trial. The company has doubled the tapering period from four to eight days. The drug has been FDA-approved to treat depression, contingent upon Lilly resolving manufacturing quality control issues.
Paxil for PMDD
The FDA has approved Paxil for the intermittent treatment of premenstrual dysphoric disorder (PMDD). Women can take the drug during the two weeks prior to the onset of their menstrual cycle rather than throughout the month. The drug is already approved for the continuous treatment of PMDD.
Atkins Diet May Make People Depressed
The Guardian reports that diet specialist Judith Wurtman PhD of MIT warns that the Atkins diet - which essentially says eat as many quarter pounders with cheese as you like but throw away the buns - may make many people depressed. When we stop eating carbohydrates, says Dr Wurtman, our brains stop producing serotonin. If a person eats protein instead of the carbohydrates that the brain is craving, he or she will get grumpy or irritable, according to Dr Wurtman, while eating fat will make you an emotional zombie. As well as being crucial to mood, serotonin also curbs appetite. Dr Wurtman is the promoter of her own diet program, called Adara, and pushes a patented drink called Serotrim.
Tardive Dyskinesia
A multi-center meta-analysis of 11 long-term studies involving 2,769 patients receiving atypical antipsychotics such as Zyprexa and Risperdal or the first generation antipsychotic Haldol has found that those on the atypicals had a reduced risk of tardive dyskinesia (involuntary spasms) compared to those on Haldol (0.0 to 1.5 percent vs 5.4 percent), though the doses of Haldol in the studies were relatively high.
Pindolol to Speed Up Antidepressant Response
A University Hospital Lewisham (London) study of 78 patients with moderate to severe depression found that those given pindolol - used to treat high blood pressure - added to their antidepressant (an SNRI milnacipran, available in Europe) found improved depression scores at week one and that the drug was well-tolerated over six weeks, leading the authors of the study to conclude that augmenting an antidepressant with pindolol "represents a rational strategy for the possible acceleration or potentiation of antidepressant action."
Adults Are From Earth, Teenagers Are From Outer Space
In an interview with PBS, Deborah Yurgelum-Todd PhD of McLean Hospital related how adults tend to react more with the prefrontal part of the brain, responsible for thinking functions, while teens, particularly males, will have more of an emotional response, from the "gut region of the brain." In a small pilot study, as opposed to all of the adults, none of the teenagers were able to recognize fear in images of faces. Says Dr Yurgelum-Todd: "The teenager is not going to take the information that is in the outside world, and organize it and understand it the same way we do."
Senator Speaks Out on Family Tragedy
Oregon Senator Gordon Smith recently disclosed that when son Garrett killed himself last fall at his college apartment, "for me, time stopped." Garrett had struggled with bipolar. Senator Smith is supporting a Senate bill on suicide prevention.
Laura’s Law
Last year, California passed Laura’s Law, intended to force severely mentally ill people into outpatient treatment. But lack of money to treat people, whether they ask for help or not, is resulting in virtually no takers. Only Los Angeles county has acted, according to the LA Times, with a pilot program treating 15 patients. New York, which passed a forced treatment law in 1999, along with funding to go with it, has since treated more than 3,000 people.
Homeless in Minnesota
According to the Wilder Center survey, cited in the Minneapolis Star Tribune, 47 percent of the Minnesota’s homeless are mentally ill, up from 36 percent in 2000, 32 percent in 1997, and 20 percent in 1994. An estimated 8,800 to 8,900 people in Minnesota are homeless.
Benzo Withdrawal
A Laval University study of 76 older sleep disorder patients who had been on benzodiazepines (such as Ativan or Xanax) found 85 percent of those who received cognitive therapy plus a medication taper had a successful withdrawal from the drug vs 48 percent receiving medication taper alone and 54 percent receiving cognitive therapy alone. Those on cognitive therapy perceived greater sleep improvement.
Omega-3 Lays an Egg
A Finnish/National Cancer Institute survey of 29,133 Finnish men, aged 50 to 69, has found that "there were no associations between the dietary intake of omega-3 fatty acids or fish consumption and depressed mood, major depressive episodes, or suicide."
rTMS
An Austrian study of 41 depressed patients has found that repetitive transcranial magnetic stimulation (rTMS) was no more effective when performed bilaterally than when applied over either the right or left dorsolateral prefrontal contex. There was no statistical difference between the groups receiving rTMS and the control group receiving sham treatment.
rTMS is an experimental technique involving passing a magnetic coil over the skull to induce a secondary current in the brain.
Let There Be Light
There may be something to fresh air and sunshine, after all. A University of Pittsburgh study of 89 spinal fusion surgery patients has found that those in rooms with lots of natural light had lower stress levels and felt less pain than those in darker rooms.
Intervention Helps
A multi-center study of 598 elderly patients with suicidal depression has found that 70 percent of those who received interpersonal psychotherapy from a care manager were free of suicidal thoughts vs 44 percent of usual care patients after eight months.
Requiem for a Humorist
Monologist Spalding Gray, last seen on the Staten Island Ferry two months ago, was found in the East River, the victim of an apparent suicide. Author of "Swimming to Cambodia," "Gray’s Anatomy," and other absurdly humorous works that turned his daily escapades into a career, Spalding suffered a debilitating car accident in 2001 that left him with an even more debilitating depression that resulted in at least two suicide attempts. Spalding, who had bipolar and whose mother also committed suicide, leaves behind a wife and two young children.
No Fairy Tale
The late Princess Diana, in tapes broadcast on NBC, disclosed how she cut her wrists with razors, used a penknife to scratch her chest and thighs, and hurled herself down a flight of stairs when she was pregnant with William. "I hated myself so much. I didn't think I was good enough, "she confided. "The public side - they wanted a fairy princess, someone who touched them and everything would turn to gold. Little did they realize that the individual was crucifying herself inside because she didn't think she was good enough."
Treating Bipolar II
Little study has been done on bipolar II and its treatment. A review article In the Feb Bipolar Disorders by Yatham et al of the University of British Columbia reports on the few studies that apply to bipolar II:
Lithium: A major long-term Sardinian study has found those in the sample with bipolar II fared better on lithium that those with bipolar I.
Anticonvulsants: No significant difference in one study between lithium and Tegretol for bipolar II maintenance, though there was a clear difference in the same study in favor of lithium for bipolar I maintenance. A study of rapid-cyclers on Lamictal found no significant difference between those on the drug and on a placebo, but when the bipolar II patients in the study were analyzed separately, 46 percent of patients remained stable for six months without relapse vs 18 percent on a placebo. An open study involving eight treatment-resistant depressed bipolar II patients on Lamictal found five very much improved. A 12-week trial of Depakote monotherapy on 19 bipolar II patients found significant benefit for 63 percent of the patients. Very weak evidence of adjunctive use of Neurontin.
Antipsychotics: A six-month study of bipolar II patients on Risperdal found 73 percent were responders in terms of mania and 78 percent improved or much improved in terms of depression.
Antidepressants: Conflicting studies, some finding increased likelihood of antidepressant-induced switches into hypomania or cycle acceleration, others not. One study found depressed bipolar II patients responded faster to Effexor than unipolar depressed subjects.
Dopamine agonists (pramipexole and ropirinole): Eight of 18 patients in a treatment-refractory depressive episode responded.
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"Knowledge is necessity."Copyright 2004 John McManamy
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