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.

GABA (GABA-GAMMA-AMNIOBUTYRIC ACID)
GABA is an elegant force of your calm and inner peace.  For example, a brain with sickly GABA has recurrent seizures and is almost always irritable, edgy, and combative.  In less traumatic cases, sickly GABA may make you fearful, easily reactive, and may cause insomnia.

DOPAMINE
Dopamine gives you energy, concentration, alertness, initiative, and perhaps most importantly the ability to enjoy life.  When your dopamine is out of sorts, so is your joy.

NOREPINEPHRINE
Norepinephrine is a good friend of dopamine and offers you energy, alertness, and concentration.

ACETYLCHOLINE
Acetylcholine is the champion defender of your memory.  For example, a brain with Alzheimer’s disease has lost its acetylcholine.  However, there are lesser degrees.  Perhaps acetylcholine is just getting tired with age.  Maybe you lose your keys more often, can’t always remember what you just said, forget phone numbers you always knew by heart or annoy your daughter by calling her husband George when his name is Bill.

SEROTONIN
So what do you say to a woman who is irritable, easily frustrated, and highly moody for a week before her menstrual cycle?  Your serotonin is low!  Serotonin is a brain fuel which helps you cope with anger, irritability and fear.  If you are phobic about flying or public speaking, feel plagued with unnecessary worry, get mad at red lights, fight road rage, or become overly agitated at every little thing your partner does, any pill that normalizes your serotonin will help relieve your symptoms.

The influence of these brain fuels does not negate the impact of life events or behavior.  These angels, however, often play a defining role in all areas of your behavior.  In a genetically predetermined manner, your angels often function in concert with one another and silently relay messages back and forth in response to input from the outside world.  In other words, like our height, skin, or eye color, the general traits of your particular angels are programmed at birth. In essence, the brain fuels are the genetic color of your brain and have a profound impact on you and your environment.

No one would challenge the fact that an individual’s sensitivity to sunlight depends upon skin color.  People with fair skin are more susceptible to sunburn and skin cancer than people of darker complexion.  In a similar manner, the brain’s chemistry determines sensitivity to rejection, mood, fear, irritability, and concentration.  It is critical to understand the specific functions of each chemical fuel.

Rats Have Angels (Every Living Creature Does!)
Your brain fuels are highly sensitive to external and internal events:  they expand or shrink, grow stronger or weaker, depending on your overall health, diet, exercise, sunlight exposure, and conflicts or tension in your life.

What are your brain fuel’s greatest friends and worst foes?  Exercise, sunlight, and good health are the angels’ best friends.  Their enemies include chronic unresolved anger, frustration, and any circumstances that trigger real or imagined feelings of being entrapped.  No other human dynamic is as universally toxic and potentially deadly to the human spirit and your angels as the perception of entrapment.  This dynamic, with its multiple faces – such as people in miserable marriages or financial desperation, or hostile job environments, people living in poverty, or children of abusive homes – directly and mercilessly assault your angels.

The collapse of hope is a serious injury to your angels and depletes their power and functionality.

Let me share a study about rats.  Rats are great teachers if we learn from them.

Put some rats in a cage and separate them from their food source.  Create a path to the food source but make sure there is an obstacle such as a glass gate which keeps them from their food. Watch the rats: observe how many times and for how long they will try to get to the food before giving up.

The rats have two challenges:  physical stamina and mental determination (potentially including willpower, drive, confidence, and mood).  Age is a factor as well:  if you give them a temporary break and let them dine even once, they will renew their efforts.

The main lesson: the majority of rats stop trying after a predictable number of times, well before they are physically incapable.

Simple enough. So, where are their angels?

Evidence suggests that after repeated failures, the angels shut down.  They collapse. Their magical powers suddenly disappear.  The angels stop flying, communicating or showing any signs of life.

The Similarities Between Rats and Humans

Entrapment equals hopelessness.  Hopelessness equals death.

People who haven’t experienced clinical depression may not easily appreciate the fact that severely depressed people, unable to see their way out of psychological torture, will seriously consider suicide.  It’s not hard to find thousands of examples of suicide where the act was an expression of entrapment and hopelessness rather than depresion.

Rats, humans, and your angels are all controlled by life, emotions, chemicals, and our perceptions.  When you feel trapped, your angels are injured; when they are sick you end up feeling trapped even if you aren’t.  Your brain is you; your angels are you; and your life affects your angels.

Pills, Angels, and Rats
What if you gave a rat a pill to replenish his brain fuels?  He would try harder and longer and not give up as his unmedicated counterparts do.  It’s as if the medicated rats have thicker skin against frustration, disappointment, and early resignation because the now healthier angels can provide them with extra protection.

We know that what occurs in the human brain is similar to actions and reactions in rat brains. It should not surprise you that the majority of newly introduced medications for sleep, mood, anxiety, and energy disorders were first studied and discovered in pre-clinical rat studies.

Special to The Washington Post

Tuesday , June 20, 2000

By Alen J. Salerian, MD

During my first session with Sarah, a married, 40-year-old lawyer, she
complained about frustrating failures she had experienced in
treatment of her depression.

“After all this therapy and all these medications, I still don’t feel
like getting out of bed in the morning,” she said. She leaned forward
and gently placed a piece of paper on my desk. It was a printout of all
the medications she had taken during the past two years: Zoloft at
200 mg for six months. Prozac at 60 mg for three months. Sixty mg of
Paxil for six months, then 400 mg of Wellbutrin for three months.
Serzone at 600 mg for two months. Finally, 1,500 mg of lithium for
two months.

There were two- or three-week breaks between medications. She had seen
several doctors. Her frustration was understandable.

But her worry changed to surprise when I suggested that, instead of
continuing to try different drugs in sequence, she pursue a
“combination strategy” – taking more than one of these drugs at a time.

A combination strategy was something I’d been sharing with medical
students and patients for years. It arises from understanding the
role of what I call “the three tenors,” the three key neurotransmitters
in the brain that regulate mood – serotonin, dopamine and
norepinephrine. As an opera lover, I like to see them as voices singing
in the mind. When they sing in harmony and balance, they can
make a person feel comfortable in life. But when one of the tenors is
out of sync, the music can be disturbing, even frightening.

It may be ordinary knowledge for a psychiatrist to appreciate how each
neurotransmitter works – that serotonin regulates worry and
anger, that dopamine is critical for initiative and pleasure and that
norepinephrine controls alertness and energy. But this information is
rarely shared with those being treated. It should be, because it is
often the foundation for a successful treatment, one that manages to
work even after many others have failed.

A little history is helpful. From the days when the first
antidepressant, iproniazid, was serendipitously discovered in the
1950s, many advances have occurred in the treatment of depression.
Yet the central biological challenge has remained the same: how to
make one, two or all three tenors sing in harmony.

The first group of antidepressants, called tricyclics and monoamine
oxidase inhibitors, were an effective but unfriendly bunch. They
indeed helped all three tenors sing vibrantly, but they produced very
unpleasant noises along the way. To reach their effective levels,
one had to suffer horrible side effects. For example, the trycyclic
antidepressant Elavil caused such intense drowsiness that many
patients reported feeling like zombies. Other medications caused dry
mouth, constipation, sedation and other less severe problems.

The introduction in 1988 of Prozac, the first drug of a class called
selective serotonin reuptake inhibitors, or SSRIs, marked a
significant breakthrough in treatment. It was based on the discovery
that elevating serotonin levels was crucial in alleviating
depression. Prozac was the first “designer” antidepressant, which
selectively targeted serotonin alone. Consequently it produced
significantly fewer and less severe side effects than its predecessors.

Thanks to the subsequent development of the many similarly targeted
SSRIs, by the late 1990s American psychiatrists had at least 20
antidepressants to choose from to treat depression. Most psychiatrists
quickly learned that Prozac and Paxil would increase serotonin but
would not alter norepinephrine or dopamine, whereas Wellbutrin would
elevate brain dopamine concentrations without much effect on
serotonin. And Effexor would increase both norepinephrine and
serotonin. Regardless of the mechanism or action, all were considered
similarly efficacious–which is to say sometimes they worked and
sometimes they didn’t.

Gradually among American psychiatrists, a simple protocol was adopted to
treat cases of depression: Choose an antidepressant that treated one
lead tenor. If that didn’t work, try another. And keep trying different
ones until the desired effect was achieved. Yet most researchers agreed
that even with the best combination of psychotherapy and the most
effective single medication, still roughly 30 percent of individuals
with depression would not improve.

Luckily for patients like Sarah, in the last several years many quiet
discoveries have been made in the clinical practice of psychiatry.
First, it was discovered that not all antidepressants are effective for
severe depressions. Also, that antidepressants with dual action – those
that influenced two tenors, like serotonin and norepinephrine – often
performed better than the antidepressants that target a solo tenor.
And further, that combining antidepressants often worked better than
using a single one.

Sarah’s case illustrates the point.

I asked Sarah to tell me more about her depression. “What troubles you
most?”

“Worry,” she responded. “I keep thinking I’m going to miss something
important. That I’m going to hurt somebody. In reality I know I do a
good job as a criminal attorney, yet I’m afraid I’m going to screw up.
I know there’s no basis for it, but the fear of hurting one of my
clients paralyzes me. There are days when I can’t even leave home
because of it.”

Sarah stared into her lap, then looked up at me. “So what can you do for
me?”

“What I can do for you is put you on Paxil and Wellbutrin.”

“I’ve tried both and neither worked,” she said. “Not to mention that
Paxil made me sleepy and edgy.”

“Your medication history indicates that you never took these medications
in combination. And there is good evidence that what we call
‘augmentation therapy’ works better.”

She was skeptical. She said this sounded very “aggressive,” and wondered
whether she was my “guinea pig” in an experiment.

Six weeks later, after trying the regimen, Sarah had fully recovered.

“I cannot tell you how good and worry-free I feel,” she said. “It’s like
a burden has been lifted.” But recovery had not been an easy ride – or
without a change in course.

Extreme fatigue and nausea troubled her, yet once she had decided to try
the combination therapy, she wasn’t going to stop her medical trial. By
the end of the fourth week – a reasonable point to evaluate the overall
response to treatment – Sarah had reported being “60 percent better” but
said she still lacked energy and zip.

I recommended she add Adderall – an amphetamine-like medication often used
to treat attention deficit disorder – to further boost her dopamine.

And finally, Sarah’s tenors began to sing, thanks to a combination of
Wellbutrin, Paxil and Adderall.

Sarah is not an exception. I’ve treated hundreds of patients who have
responded well to combination strategies.

Recent research is also promising for the use of various hormones – such
as testosterone, estrogen, DHEA and thyroid hormones – to augment the
efficacy of various antidepressants. Again, augmentation therapy appears
to be a novel way to stimulate a pleasant mood.

A few things about treating depression are clear. Poor response to
treatment should always be a reason to search for a new strategy.
And it is critical to educate patients about the chemistry of mood and
how serotonin, norepinephrine and dopamine affect the way the
brain responds to life. Just as the three tenors sing best when they
work together, the three neurotransmitters make the best mood
music for the brain when they’re balanced harmoniously.

Which is largely why I believe that most depressions are curable – and
that most patients are able, eventually, to hear the music.

Alen J. Salerian, MD, is medical director of the Washington Psychiatric
Center outpatient facility for the Psychiatric Institute of
Washington. He has just completed a novel, “Red Zone,” about abuses in
psychiatric managed care.

2000 The Washington Post Company ]]> http://salerianbrain.com/2000/06/making-the-three-tenors-sing/feed/ 0