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.

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 .

http://www.cnn.com/video/#/video/health/2008/10/06/gupta.fit.to.lead.cnn

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.

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

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 8^th 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.