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New Brain Discoveries
Salerian Brain Laws #1 and #2 (SBL1 and SBL2):
Frontal Cortex Function and Dopamine Govern Mood and Executive Function
By Alen J. Salerian, MD
I am excited to share two of my discoveries of brain function and dysfunction, two novel theories I advance about the essence of all neuropsychiatric disorders. Region specific dysfunction and abnormal neurotransmission regulated by thermoregulation laws govern all neuropsychiatric disorders.
The precise scientific details of my theories are going to be published in peer-reviewed journals by the end of 2009, yet my wish to help people with serious neuropsychiatric disorders prompted me to immediately reveal my findings.
Salerian Brain Law #1 suggests two factors govern all neuropsychiatric disorders: region-specific brain dysfunction and abnormal neurotransmission mediated by thermodynamic laws. In essence, Salerian Brain Law #1 proposes that the laws which govern neurological disorders also govern neuropsychiatric illnesses as diverse as schizophrenia, bipolar disorder, depression, post-traumatic stress disorder, addictions. Thus, Salerian Brain Law suggests the majority of neuropsychiatric disorders are biological in origin, the presenting symptoms, the severity and the course of the disorder defined by a specific region of the brain influenced by the specific neurotransmitters responsible in regulating the neuropsychiatric function of that particular brain region.
The second Salerian Law of the Brain suggests that the prefrontal cortex dictates human mood and executive function, consistent with its evolutionary neurobiological supremacy over the rest of the brain. Thus, only when the prefrontal cortex function is less than perfect or only when the prefrontal cortex function is dysfunctional that a Homo sapien brain exhibits any mood or executive dysfunction.
In essence, the prefrontal cortex is the king with full authority over a chemical cocktail of complex neurobiological homeostasis, and hence, no mood or executive dysfunction can develop in the presence of a robust and functional prefrontal cortex.
The above-mentioned interactions frequent occur in lower species, yet they are not as profound for the extraordinary superiority of the prefrontal cortex to perceive, process, mediate and master the sensory input from other parts of the brain as they are in Homo sapien brain function. This is precisely why, for any clinical entity with diminished executive function, compromised initiative and lowered energy, motivation, mood and self-confidence to develop, there must always be some disturbance or dysfunction of prefrontal cortex function.
As to the notion of complexity of brain function, mental state and the countless factors that may influence neurobiology, hence the prefrontal cortex, one can merely state that the final outcome remains the same; to use a common if not so scientific language that the bottom line does not change the evolutionary superiority of the prefrontal cortex over the rest of the brain.
The use of the Salerian Laws or any section of this paper without the written consent of Alen J. Salerian, MD and Washington Center for Psychiatry is prohibited.
The Schedule of Controlled Substances was established in 1970 and classified various substances for their addictive potential on a schedule of I to V with Schedule I representing the most addictive and V the least addictive. This formula used by the Food and Drug Administration and other governmental agencies is not based upon any scientific premise, although it has been widely utilized since 1970 and had a profound impact on policy as well as research of various substances with addictive potential.
Today it is with great joy that I share my discovery of an algebraic formula that expresses the addictive potential of any substance: A = E/Tmax x T1/2, where A represents the addictive potency, E is the euphoric potency on a scale of 0 to 10 with 10 representing the strongest and 0 the weakest, TMAX is the time necessary to reach the maximum plasma concentration and T1/2 is the plasma elimination half life.
The scientific logic and clinical evidence that led to my discovery will be published soon in a peer-reviewed journal, yet the importance of my discovery made me decide not to wait to share the formula with the public immediately. Animal studies and clinical evidence suggest that three factors i.e. the euphoric potency, the onset of action and the severity of withdrawal symptoms contribute to addictive properties of any substance (Weinberger DR (1995): Neurodevelopmental perspectives on Schizophrenia. In Psychopharmacology: The Fourth Generation of Progress (F.E. Bloom and D.J. Kupfer, Eds.), pp.1171-1183. Raven Press, New York).
All rights of the above formula are reserved. No one is permitted to use the Salerian Euphoric Equation without the written consent of Alen J. Salerian, MD, PC and Washington Center for Psychiatry.
By Alen J. Salerian, MD
Richmond Times
February 24, 2009
Sometime in the near future, modern psychiatry’s unborn holy book, the DSM-V, the Diagnostic and Statistical Manual of Mental Disorders, will arrive. In fact, an early draft of the fifth edition of this guidebook of diagnostic criteria for mental disorders, which mental health professionals, researchers, health insurance companies, and pharmaceutical companies use as the basis for their work, is expected to be released later this year for comment.
The bad news is that DSM-V, as its heritage, is cursed with the same bad genes that handicapped modern psychiatry during the past century: a paucity of science.
All scientific arguments must be transparent and open to scholarly scrutiny. If that is true, why have the gurus who are revising the guidebook — the American Psychiatric Association — mandated that the revision process be carried out in secret? Psychiatrists working on the new fifth edition have been required to sign a confidentiality agreement. The total secrecy surrounding the birth of DSM-V is blatantly unscholarly.
The bigger concern, however, is the great likelihood that DSM-V will be an improved version of a system that has already proven to be broken. Regardless of how much improvement can be generated, it is not possible to upgrade DSM-V into a workable guidebook as long as it is based upon a descriptive approach to the definition of very complex neuropsychiatric disorders.
IT IS AS IF a bunch of high school students were to write a diagnostic manual on “how to fix cars”: The book says if the smoke is too black or too thick and comes from the left side, this may suggest a flat left front tire. But there is no discussion about the visual, manual, or mechanical evaluations of different body parts and not even a suggestion that someone must at least lift the hood to check the engine.
Thanks to advances in neuroscience, there are plenty of tests that are crucial in psychiatric diagnosis, including neuroimaging studies (PET or MRI scans of the brain) or laboratory studies.
DSM-IV never included any diagnostic tests. This itself presents a huge problem for modern psychiatry. That is, according to the guidelines of DSM-IV, a psychiatric diagnosis is made without any logical discussion about neuroanatomy, neurophysiology, or highly complex and relevant neurotransmitters such as serotonin, dopamine, glutamate, histamine, acetylcholine, or testosterone that influence human mood and behavior and hence all neuropsychiatric conditions.
The result seems devilish and intellectually impossible. How can a scientific discipline declare a mother and father guilty of inflicting consciously or unconsciously a horrific misery, “depression,” or “schizophrenia” as modern psychiatry did throughout the 20th century?
The very people who came up with the absurd ideas of blaming bad mothers and fathers for psychiatric disorders were also the same people who came up with DSM-I, II, III, and IV — and are now getting ready for V. How long and how many centuries will it take for American psychiatry to take corrective action to catch up with science? Is this a measure of progress for psychiatry or medicine? And if it is, what is progress? How could it be justified or still defended that modern psychiatric terminology does not have any connection to neuroanatomy, neurophysiology, and neurotransmission? How can American psychiatry get away with such nonsense and at the same time promote the idea that until the new holy book is born, secrecy is the best thing? And how can American psychiatry name various psychiatric disorders with pejorative terms such as “borderline personality?”
THE BEST REASON to declare the current DSM system dead is that it is a barrier to progress in the treatment of serious neuropsychiatric disorders. The difference or conflict between modern psychiatry and scientific knowledge partly explains why progress in neuroscience, for example in the treatment of schizophrenia, has been excruciatingly slow when compared with other equally destructive and progressive disorders, such as AIDS, tuberculosis, syphilis, diabetes, or hypertension.
Many schizophrenic symptoms can be logically explained consistent with our current knowledge of brain physiology and neuroanatomy — e.g., symptoms such as hallucinations, paranoia, delusions, agitation, or intellectual decline. Science says such symptoms are rooted in neurotransmitter dysfunction of specific brain regions such as amygdala, hippocampus, hypothalamus, or the brain cortex. But none of these relevant data can be found anywhere in the DSM system.
What modern psychiatry faces today is not much different from Galileo Galilei’s conflicts with the church during the dark ages. How can we address problems with a complex illness like schizophrenia without offending the established powers of APA, NIMH, and even the judicial system, which heavily relies on DSM-based diagnoses incompatible with science?
The good news is there is no reason to delay progress. It is possible to develop a simple and biologically sound system that will be the premise for defining psychiatric disorders. Basically, the mental health professions should adopt a medical approach.
The truth is, we have all the knowledge to be able to do it, yet our current bureaucratic and institutional systems must be ready for a paradigm shift. The truth is also that until the world of psychiatry changes its approach to diagnosis of mental disorders, we will still be locked in the dark ages of science and medicine.
Alen J. Salerian, a psychiatrist, is the medical director of the Washington Center for Psychiatry. Contact him at (202) 244-3815 or rcolbert@salerianbrain.com .
Higher Education Weblog
Posted February 19, 2009
From kings to criminals, politicians to prostitutes, Dr. Alen J. Salerian explored the darker edges of the human mind as a high-profile psychiatrist. But he had no idea just how dark it could get-until he was sent to interview a mass murderer 15 years ago.
Salerian found himself in a prison interview room near Washington, DC. Two guards brought in the patient: A man who converted his van into a militaristic killing machine, crashed through the gates of a corporate office park, and opened fire. Several people died; dozens more were injured. The patient answered Salerian’s questions with a decidedly matter-of-fact manner, which made the experience all the more haunting.
Salerian, who served as special consultant to the FBI throughout most of the last decade, found the whole episode unnerving. “I spent a lot of time with him,” he recalls. “To see someone so insane, chillingly and dispassionately describing what he did, and how he’d do again, was an eerie experience.”
Common Ground
Salerian’s career sounds like a cross between Silence of the Lambs and Traffic-with a healthy dose of High Society mixed in. He has been called upon to fly overseas and treat the royal families of both England and Bahrain. Here at home, he might treat a criminal or a congressman on any given day.
Though he came to America as a stranger, unfamiliar with the customs of our country, Salerian’s story is about more than overcoming cultural barriers to achieve success. It’s about the universality of professional skills and how they are applicable to a myriad of societies. Salerian knows how to build sound minds, and he eventually landed in the thick of world events. Several years ago, for example, he conducted psychological debriefings for FBI personnel involved in the Waco incident. He helped several agents deal with the emotional impact of that tragedy.
Whether treating someone at society’s highest or lowest level, Salerian finds common ground. This underlying belief inspired Salerian to pursue psychiatry after graduating from the University of Istanbul School of Medicine in 1971. “Psychiatry is fascinating because it gives you an opportunity to enter people’s lives and have a sense of what they really go through,” he says. “People are, in an incredible way, so very trusting. It’s a privilege to be in a position where I see the poorest of people-five percent of my patients pay me nothing-and family members of kings and senators and congressmen.”
More Than a Job
That kind of clientele comes with respected standing. Salerian’s research has appeared in the American Journal of Psychiatry and he’s made over 200 presentations on psychiatric topics. Since December 1997, he has served as medical director of the outpatient clinic for the Psychiatric Institute of Washington. In addition to the FBI work, he also teaches at the George Washington University (GWU) School of Medicine.
He came to the nation’s capital for a medical internship at Providence Hospital in 1971-and decided to stay in the states permanently. He was named chief resident at the GWU Medical Center in 1976. “What always amazed me throughout my career is that human nature isn’t any different,” he says, “whether you’re at the top of your game or at the bottom of society. Human suffering is human suffering. But the answer, always, is within you. You must fix the problem, no matter if you’re a prince or a pimp.”
When he counsels others seeking to join his profession, Salerian encourages people to be open to anything. “Psychiatry is a wide-open practice,” he affirms. “It’s a matter of risk taking and opening up your mind. That’s why I ended up in the FBI and going overseas. When the call comes in, I want to take the job. I want to cross the line. It’s not recklessness, it’s just pursuing an unfamiliar avenue.”
Dr. Salerian in the News
On Saturday October 11, 2008 at 8pm Dr. Salerian will appear on CNN’s special investigation “Fit To Lead”, hosted by Dr. Sanjay Gupta. The program uncovers health secrets of presidents past and future as we are in the throws of a hotly contested presidential race where judgment and decision making are deciding factors for many voters.
http://www.cnn.com/video/#/video/health/2008/10/06/gupta.fit.to.lead.cnn
By Alen J. Salerian, MD
The high point of my graduation from medical school was a dinner celebration on Princess Island off the coast of Istanbul as cheers and toasts were finally fading. I was surrounded by happy faces and watery eyes in all directions when my cousin Joe, a skinny, tall man known to us as “Nervous Joe,” spoke loudly on a Friday evening some 25-plus years ago. “Come on Alen, now that you are a real doctor, tell me, what can you do for my hands?” with both of his hands and arms extended, over half-filled wine glasses, we all stared at his red, chapped hands.
Hmm! What help could I offer? There were too many possibilities. “Hey, Joe, you need a dermatologist!” I offered.
A phone call, a visit, and a few weeks later, cousin Joe shared with me his diagnosis: Compulsive hand washing secondary to obsessive-compulsive disorder (OCD).
There was a time not many centuries ago when OCD was viewed as a satanic possession treatable with exorcism. Not until the mid 1980s did we discover that OCD was not a rare disease. The Epidemiologic Catchment Area Study that the National Institute of Mental Health sponsored identified a lifetime prevalence rate of OCD in about 2.5% of the general population, greater than the rate of panic disorder or schizophrenia.
Increasingly, the profession is recognizing that for most patients OCD is a lifelong illness. Approximately 65% of patients develop OCD before age 25 and less than 15% of patients will develop the disorder after age 36.
Postulated Causes
The past century has witnessed a gradual transformation of the theories explaining the underlying causes of OCD. No longer can Freudian psychodynamic explanations of OCD survive scientific scrutiny. Still, the exact causes of OCD are not known. Yet, there seems to be increasing evidence that biological factors play an important role and that genetic and environmental factors may contribute to particular symptoms.
Serotonergic dysregulation has been proposed as the basis of OCD. And not surprisingly, the most efficacious agents for OCD have been SSRIs or medications that have potent effects on selective serotonin reuptake inhibition such as clomipramine. A number of studies suggest a genetic link to OCD. Some report that about 25% of OCD patients have a first-degree relative with OCD.
Comorbidity
Statistics strongly suggest that patients with OCD may present with other psychiatric disorders. At the time of OCD diagnosis, 31% of patients suffer from major depression, and the prevalence of depression in OCD patients ranges from 67% to 78%. Similarly, the lifetime prevalence of a core existing anxiety disorder is also high, ranging from 22% to 28% for simple phobias and 12% to 15% for panic disorder.
Treatment Strategies
During the past several decades, various treatment strategies including pharmacotherapy, behavior therapy, and psychosurgery emerged as somewhat effective in treating OCD.
Pharmacotherapy
Approximately 65% to 75% of patients with OCD report moderate improvements with serotonergic agents. In spite of the relatively dirty effect profile (i.e., dizziness, weight gain, constipation, somnolence and dry mouth), many clinicians still view clomipramine (Anafranil) as the gold standard of OCD treatment. Understandably, because of their more favorable side effect profiles, SSRIs (fluoxetine, fluvoxamine, sertraline, paroxetine) should be considered first.
Two factors, inadequate dosage and inadequate duration of treatment, have often been linked to treatment failures. A 12-week trial with dosages up to 300 mg of clomipramine, 200 mg with sertraline, 80 mg with fluoxetine, 300 mg with fluvoxamine, and 60 mg with paroxetine are necessary prior to a realistic evaluation of medication efficacy. In spite of early disappointing results with various psychological treatments such as psychoanalytic psychotherapy, relaxation therapy, hypnosis, and biofeedback, the past decade also witnessed the positive outcome of behavior therapy for patients with OCD.
Electroconvulsive Treatment
How about electroconvulsive treatment (ECT) or augmentation strategies? To date, there has not been any convincing evidence to support using ECT for OCD patients. And unlike treatment-resistant depressed patients who may respond favorably to adjunct lithium, liothyronine, methylphenidate or buspirone, the current psychiatric literature remains, at best, controversial about the efficacy of augmenting agents for OCD when monotherapy fails.
Psychosurgery
What about psychosurgery? Ever since its introduction, psychosurgery has offered hope and triggered apprehension for patients with OCD. And rarely has a medical approach been vilified as much as psychosurgery has. Yet, few people know much about the recent reports indicative of moderate success for treatment-resistant patients with OCD.
Even though using very conservative outcome criteria, different studies suggest a 41% to 56% moderate improvement; the current psychiatric consensus remains unchanged. Consider psychosurgery only for severely incapacitated patients for whom all other treatments failed.
More on OCD from DSM-IV
According to the DSM-IV, OCD is classified as one of the anxiety disorders. OCD may be diagnosed if the patient demonstrates obsessions or compulsions that cause marked distress, are time consuming (generally an hour or more per day), or significantly interfere with social or role functioning.
Obsessions are defined by:
-Recurrent and persistent thoughts, impulses or images that are experienced, at some point during the disturbance, as intrusive and inappropriate, and cause marked anxiety or distress.
-The thoughts, impulses, or images are not simply excessive worries about real-life problems.
-The person attempts to ignore or suppress such thoughts or impulses or neutralizes them with some other thought or action.
-The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind (not imposed from without as in thought insertion).
Compulsions are defined by:
-Repetitive behaviors (e.g., handwashing, ordering, or checking) or mental acts (e.g., praying, counting or repeating words silently) that are performed in response to an obsession, or according to rules that might be applied rigidly.
-The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent or are clearly excessive.
By Alen J. Salerian, MD
Tim Russert, the popular NBC television reporter and the host of “Meet the Press,” an award-winning program, died of a heart attack on June 13, 2008. What we don’t know at present is whether his death was preventable.
Of course, it is easy to speculate. Yet, there is something unnerving about a 58-year-old man who has been receiving good medical care to die of an acute heart attack, what modern medicine would define as a sudden cardiac event from a thrombotic occlusion of the coronary arteries. By now, we know that cardiac disease including high blood pressure, high cholesterol and coronary insufficiency are diagnosable and treatable.
 We may never know what truly happened to Tim Russert and his particular problems. As somebody who has not only treated but participated in the care of VIPs – for however it is defined, whether this is synonymous with wealth, power or success – one impression has been predominant. VIPs, not only in the United States but at any other place on our planet, get imperfect care. This may sound surprising for the most privileged not to get perfect care. Yet, it is also true. It was almost too late, for instance, for President Clinton to get cardiac surgery for his long recognized problems of coronary artery disease and hypercholesterolemia. Other presidents have had the misfortune of getting second-class care, perhaps the most notable being President Roosevelt’s mediocre care before his hypertensive‑induced cardiac problems. Problems which had been grossly neglected by his personal White House physician, Dr. James McIntyre. Of other not so fortunate U.S. presidents, Ronald Reagan stands out for his delayed diagnosis of Alzheimer’s.
Whether you are the head of a multibillion dollar entity or a President of a country or a Hollywood star or just simply privileged, watch out. Medical care is compromised because VIPs are often successful people who insist on dictating their own care and their physicians may overly accommodate their personal wishes at the risk of reasonable medical treatment or diagnosis.
For the physician to be effective, he must not only be good but he should feel he is in charge of the diagnosis and treatment, and in the doctor‑patient relationship, the patient’s VIP status often has an adverse impact.
This is, of course, all speculation when it comes to sudden death and cardiac disease. Anyone with alarming symptoms suggestive of heart trouble must consult an expert in cardiology. Various medical tests are considered standard and they include electrocardiogram, stress test, blood homocysteine and C-reactive protein levels. Evidence is compelling that even in highly ambiguous situations, angiograms with visualization of coronary arteries and heart scans can be particularly effective in correctly diagnosing an otherwise dormant cardiac abnormality. So for any heart attach victum VIP or not, some questions and answers of course would help; such as did the victim have a heart scan or a angiogram or any other study visually establishing his or her precise health.
By Alen J. Salerian, MD
“No way I’ll take that pill,” muttered the young man in his 30s, who had admitted himself voluntarily to the Psychiatric Institute’s adult treatment center because of cocaine abuse. “Why not,” I inquired, watching his protruding cheekbones and wondering whether his frail frame and skinny features were complications of his cocaine abuse. “I’m not depressed,” he answered. “I am not prescribing this medication for depression,” I said. “This one may help you with your drug addiction.” And that was not the only time that day I had offered a similar remark. “Yes, I am prescribing an antidepressant. Yes, I agree, you are not depressed and this medication may still help you.” The fact that antidepressants help people with depressive disorders is no longer disputable; however, what has also emerged during the last several decades has been the impressive evidence of how antidepressants benefit millions who are not  depressed. In numerous controlled studies, antidepressants have proven their usefulness in such myriad psychiatric/medical conditions as tobacco dependence, phobias, obsessive-compulsive disorders, alcoholism, generalized anxiety disorders and premenstrual dysphoric disorder (1). From a biological perspective, all available antidepressants alter the brain’s neurotransmission of serotonin, dopamine and norepinephrine. Therefore, it is not surprising that antidepressants may also mediate a variety of such human functions as fear, anxiety and emotional memory regulated by the same system. Understandably, during the last decade the use of antidepressants has moved from the narrow indication for depression to a much larger spectrum of medical and psychiatric disorders. Historically and far too often, the clinical use of antidepressants has not been fully consistent with the current FDA-approved indications for these agents. For instance, selective serotonin reuptake inhibitors have only recently been approved for post-traumatic stress disorders, phobias and panic disorders; where as many experienced physicians have used SSRIs to treat the same conditions for years. Among the reasons many doctors cited for non-FDA use of antidepressants are the published scientific data supporting their use, their well-established safety record and the lack of FDA-approved efficacious agents for these same conditions. Recent psychiatric literature is rich with reports supporting using antidepressants for a variety of medical conditions ranging from chronic fatigue syndrome to tobacco dependence. However, many of these reports do not meet strict scientific criteria and often we, the treating physicians, are faced with a common dilemma – using a non-FDA approved yet potentially promising medication or maintaining status quo with a treatment-refractory patient.
Chronic Fatigue Syndrome
Perhaps chronic fatigue syndrome, a somewhat common disorder – a medical condition with criteria of a six-month history of worsening fatigue and the presence of four of eight symptoms that include memory and sleep impairment as well as joint and muscular pain – illustrates the dilemma. Several studies support using nefazodone for people with chronic fatigue syndrome (2, 3).
Sleep Disorders
The use of antidepressants as sleep aids is a good example of how, even without FDA approval, we can successfully treat troubling symptoms. No antidepressant is currently approved for insomnia. Yet, for years, many physicians prescribed antidepressants such as Elavil, Desyrel and Sinequan to treat insomnia by pharmacologically exploiting the sedative properties of these medications.
Substance Abuse
Also increasing in the last decade is evidence supporting the relationship between subgroups of individuals with alcohol or drug dependencies and their biological propensity to a variety of psychiatric disorders (e.g., bipolar, mood, anxiety, attention deficit). Antidepressants may prove helpful for many of these conditions (7, 8).
The Downside of Off-Label Use
With every new approach there also is the potential of unforeseen complications. Recent medical history about the rise and fall of fen-phen to treat obesity illustrates the dangers associated with untested medical approaches. Several years ago, due to the increased risk of pulmonary hypertension, the FDA banned fen-phen only after many fatalities occurred. Mixing prescription drugs with non-prescription medications may even present a greater risk to our patients. Sadly, a common myth that medications considered natural only because they happen to the products of the earth are safe remains popular. Tobacco, cocaine and poison ivy are natural but are they harmless? The experience with St. John’s Wort, a highly popular antidepressants introduced as a natural supplement to help depression, may highlight some of the dangers associated with substances that are mistakenly identified as natural and safe. Since its introduction to the U.S. market, St. John’s Wort has been reported to cause serious complications due to interactions with other drugs. Of significance have been St. John’s Wort’s effects on calcium channel blockers and cyclosporine, an immunosuppressant commonly used to prevent organ rejection for transplant patients (1). Also not to be overlooked are the reported cases of St. John’s-induced hypomania (4, 5) or the potential risk of “serotonin syndrome” when St. John’s is combined with a standard SSRI. Recent psychiatric literature also reports mania induced by ginseng, a highly popular herbal remedy marketed as an energy booster (6).
Conclusion
While we must be careful about assuming that antidepressants may help all our patients, we may not be far from reconsidering the term antidepressant and perhaps entertain newer labels such as anti-anger agents, anti-worry meds, sleep aids, anti-smoking meds and so on.
References
- Susman E. Off-Label Use of Psychiatric Drugs. Primary Psychiatry. October 2000, Volume 7, No. 10.
- Goodnick P.J., Jorge C.M. Treatment of Chronic Fatigue Syndrome with Nefazodone. American Journal of Psychiatry. 1999; 156: 797-798.
- Hickie I. Nefazodone for Patients with Chronic Fatigue Syndrome. Aust NZ Journal of Psychiatry. 1999; 33: 278-280.
- Schneck C. St. John’s Wort and Hypomania [letter]. Journal of Clinical Psychiatry. 1998; 59: 258.
- O’Breasnail A.M., Argourch S. Hypomania and St. John’s Wort [letter]. Canadian Journal of Psychiatry. 1998; 43: 747.
- Gonzalez-Seijo J.C., Ramos Y.M., Lastra I. Manic Episode and Ginseng: Report of a Possible Case. Journal of Clinical Psychopharmacology. 1995; 15: 447-448.
- Cornelius J.R., Salloum I.M., Ehler G, et al. Fluoxetine in Depressed Alcoholics: A Double Blind, Placebo-Controlled Trial. Archives of General Psychiatry. 1997; 54: 700-705.
- Roy A. Placebo-Controlled Study of Sertraline in Depressed Recently Abstinent Alcoholics. Biological Psychiatry. 1998; 44: 633-637.
By Alen J. Salerian, MD
Okay, I admit it. Lies are bad and lying to your mother is simply wrong.
And, just as importantly, I still feel good for having convinced my identical twin, Garo, a 60 year old almost saint of a scientist, who, at the time lived in Saudi Arabia, to join me at a dinner in Istanbul with Mama to celebrate our Nobel award in medicine – although the celebration was based on fantasy, not evidence, for our discovery that cooler people live longer.
The journey from Washington, DC, my home, to Istanbul, my birthplace and where Mama lived, felt longer than 15 hours despite the modern comforts of airline hospitality. I was worried about Garo. What if he changed his mind, and what if his ethics made it impossible for him to fake it? What if he could not smile the right way to convince Mama that indeed her twin boys were the first twins to become Nobel laureates?
The truth was Garo and I published in Medical Hypotheses, a peer-reviewed British journal, our hypothesis, “Salerian-Saleri Thesis of Temperature (SSTT)”. We explained that longevity was governed by body temperature and lowering core body temperature slowed down neurodegeneration, hence prolonging life.
I continued to worry. “What if Garo refused to go along with my white lie?”
“My intentions are honorable,” I had argued with him over the phone during our hour-long during our hour long Dharan – Washington DC debate a few months before Mama’s death. “Let’s say, thank you Mom, great job. We owe you our success and with to express our gratitude in front of family and friends in your presence at home rather than in Stockholm after you are gone.”
Garo’s thick transatlantic silence in response felt eerie. Yet I pressed on.
“Garo, don’t you see our lives imitating hers?”
“Isn’t this poetic justice?” I argued. Mom, the child prodigy with a brilliant brush of vision, color and imagination, painting herself to places of extraordinary privilege – Pompidou of Paris, Gulbenkian of Lisbon, and the Fine Arts Museum in Istanbul – despite her psychosocial handicaps, her gender and ethnicity.
“Isn’t this a triumph of some sort for us, her twin boys, to follow her footsteps from Paris to Stockholm? So what if the Nobel people are uninformed of our discovery to help our fellow man live 20—30 years longer or the fact that our discovery would slow down the ravages of Alzheimer’s, Parkinson’s and Lou Gherig’s disease? Mama and Papa always taught us that 2+2=4 regardless of how many people chant otherwise. So, if the world can not notice us yet, we can still celebrate with Mama!??”
Garo’s stern voice in response said, “Just remember Arrhenius. The truth is lots of smart men with great ideas have not been fully appreciated by science or history. Even you did not know who Arrhenius was until our paper. Equal to the greatness of Newton or Einstein, not many PhDs or MDs know his name.
“You’re right,” I yielded.
Svante Arrhenius had won the Nobel award in the late 18th century for his discovery: The speed of all chemical reactions in the universe is exponentially dependent on temperature. The higher the temperature, the faster the chemical reaction. So it was understandable that in higher ambient temperatures all things in the universe oxidized, hence aged exponentially faster.
It was simply our good luck to realize that the word “exponential” was overlooked by so many brilliant minds of medicine in the past century. Therefore, Garo and I had the opportunity to hypothesize that lowering body temperature from 37°C to 36°C or perhaps 35.5°C, which is easily compatible with life, would significantly prolong life perhaps 20-30 years.
What made our hypothesis more exciting was the availability of safe and practical strategies to induce and maintain hypothermia such as medications (melatonin or sodium oxybate) and physical fitness.
To our surprise, with a few exceptions, the medical world did not notice our hypothesis.
Then came the big news: The publication of Science on November 3, 2006, by Bruno Conti and his colleagues of the “Cool Mice Live Longer” article and a scientific commentary elaborating on the clinical significance of their findings by Dr. Clifford Saper of Harvard. In essence, Conti and his colleagues through their work with mice or “cool mice” with lower than normal body temperature, demonstrated that cool mice, regardless of their weight of food consumption, live longer than mice with normal body temperature.
As if it were yesterday, I still recall the exhilaration I felt when I called Garo at 2 o’clock in the morning, his local time in Saudi Arabia, to give him the news that our hypothesis was proven correct. Not surprisingly, Marina, my dear sister-in-law, first refused to wake her husband.
“No,” I insisted. “This is not a dream. It’s true. It’s great news.” I was yelling.
Finally, Garo picked up the phone. “It’s wonderful, wonderful,” he agreed and then asked, “Are we referenced?”
For a few moments I felt brainless. A few moments later, I realized the ugly truth. Our published work was overlooked and not mentioned.
Garo calmly said, “Mistakes occur all the time. I will email Dr. Saper. He will correct the omission.”
History proved Garo wrong. Not only Dr. Saper but also the editors of the Science acted as if we had not published our hypothesis on year prior to the Science publication.
Mama, frail and half deaf, did manage to smile and sip her raki and smoke her favorite Marlboro cigarette to celebrate the victory of her twin boys. She hesitated for a second with her voice cracking before she rose to talk. Her limp arm erect, eyes visiting all the eyes around the table, eyes with soul, fire, color and vibrancy, she locked her eyes into Garo’s and then asked, “Tell me, Garo, is your twin dreaming?”
Garo stared at me. So did my sister Rehan, brother-in-law Bernard and dozens of others. Hot, Fahrenheit or Celsius, I did not care.
“Miracles do happen,” Garo spoke calmly. “My twin has a wild imagination, but this time he is telling the truth,” he said.
Mama quietly sobbed. All our relatives made various noises of joy, surprise, celebration and ecstasy. Strangely, my chest felt tighter than it had ever felt.
Just then I spoke. “Here is the truth, Mama,” I said. “Does it really matter whether we won or not? The truth is we are enjoying you. This is our little Nobel. No, we didn’t with the Nobel yet, but we did not want to wait until we win and you are gone, and from Stockholm we would be pointing our fingers to the sky and expressing our love. We thought this way would be better. We thank you.”
Mama smiled and said, “Thank you for lying to me. I love this,” and we all laughed before she continued, “In Stockholm, do not forget to remember Papa too.”
By Alen J. Salerian, MD
Soon after The Lancet – the British symbol of scholarly medical research – declared Zoloft and several other antidepressants ineffective, unsafe and potentially deadly for children and adolescents with depression in April 2004, my patient, Ann, quit her Zoloft.
Before Zoloft, Ann had been withdrawn, depressed and had problems with her 8th grade school work. She said, Zoloft was her little miracle. Here is what she wrote in her suicide note after stopping Zoloft: “If being alive means uncertainty of when my torture would end I would rather not live.”
Not taking Zoloft hurt Ann. For a lot of kids and teenagers, medications like Zoloft, which improve their brain chemistry, have extraordinary gifts of modern science. Zoloft and similar medications have allowed many kids to smell and taste success for the first time in their lives.
The sad truth is that The Lancet article should never have been published because it was fundamentally flawed and unfit for any scholarly medical journal. Most importantly, it had slender contact with scientific objectivity. Any scientific study must respect The Golden Rule: A comprehensive review of all the potential limitations to the study.
Dr, Whittington and his colleagues were naively dismissive of the possibility that a good many factors could have rendered their conclusions that, “all antidepressants are ineffective, unsafe, and potentially deadly for children with depression” incorrect.
Dr. Whittington and his colleagues failed to realize that the majority of the studies they analyzed had a fundamental and often serious error of design: Not to exclude from the study, the depressed kids and adolescents with an increased risk for future bipolar disorder. Neuroscience has already discovered that anyone with a bipolar illness is at high risk for adverse response to the administration of an antidepressant. Dr. Whittington’s oversight was understandable because of our collective knowledge of the complex biological and psychological factors contributing to various mood disorders were limited in the 1980’s and 1990’s when some of these studies began.
Dr. Whittington’s error was akin to research solely devoted to the personality traits of bus passengers based upon ten buses serving a college hockey tournament. An inexperienced researcher might conclude that most bus passengers enjoy hockey and frequently visit orthopedic surgeons.
The Lancet editorial, accompanying Dr. Whittington’s study was not kind to the pharmaceutical industry. “People around the world understand the desire to achieve success and to work in a profitable environment. They will not, however, tolerate the notion that in biomedical research, this could be at the expense of the children’s lives.”
Of course, the pharmaceutical companies are not angels and at times try to increase their profits, but it is a lie that they are all unethical, blinded by profit, and offer little for real health. But, an industry that tackles massive and complex brain disorders cannot be simple or error free.
Sometimes, the deep-rooted paranoia and prejudice against that pharmaceutical industry is capable of greed and destruction, so is mental illness. A depressed or unreasonably angry and volatile teenager could destroy or trigger havoc. If that sounds too alarming, remember the facts: the Columbine massacre and the sad truth that teen suicide is the third leading cause of death for teenagers.
The quickest way to score with public opinion is to expose a mean child killer. The British government immediately banned all antidepressants (with the exception of Prozac) for children. With hostile winds blowing, the FDA sent numerous warnings to parents and physicians about the dangers of antidepressants.
My patient Ann, many other patients and their parents heard the indignant shrills of The Lancet, The British government and the FDA as is they were sounds from hell.
“I felt The Lancet and the FDA put a knife through me,” said Ann’s father. While there is a presumed risk with Zoloft, without Zoloft my daughter almost died. A week after she restarted her Zoloft, she was feeling remarkably better.”
There comes a point in any public debate when common sense dictates and logic must prevail. That time is now for psychiatry, to face the truth that the number of kids and adolescents with depression is on the rise. The reasons for increased suicide and depression are complex. Yet, it is clear that genetic, biological, psychosocial and environmental factors have all been responsible for the dramatic worsening of our children’s mental health.
The lessons to be learned from the recent controversy is that the seemingly benevolent forces, such as the FDA and The Lancet may be as potentially harmful to our children as the presumed mean giants of the pharmaceutical industry.
Indeed, our children and teenagers have greatly benefited from both sides. The monumental challenges awaiting us and future generations of dealing with complex mental disorders will continue to require the muscle and brain of the pharmaceutical industry and the watchful and protective minds of countless government and independent scientists. For sure the new frontiers of brain research should spare a few behaviors: loss of objectivity and unnecessary pontification.
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