Simple EKG Can Determine Whether Patient Has Depression or Bipolar Disorder

Simple EKG Can Determine Whether Patient Has Depression or Bipolar Disorder

Summary: Heart rate variability can indicate whether a person has bipolar disorder or major depression, a new study reports.

Source: Loyola University Health System.

A groundbreaking Loyola Medicine study suggests that a simple 15-minute electrocardiogram could help a physician determine whether a patient has major depression or bipolar disorder.

Bipolar disorder often is misdiagnosed as major depression. But while the symptoms of the depressive phase of bipolar disorder are similar to that of major depression, the treatments are different and often challenging for the physician.

In bipolar disorder, formerly called manic depression, a patient swings between an emotional high (manic episode) and severe depression. Treatment for the depressed phase includes an antidepressant along with a safeguard such as a mood stabilizer or antipsychotic drug to prevent a switch to a manic episode. A physician who misdiagnoses bipolar disorder as major depression could inadvertently trigger a manic episode by prescribing an antidepressant without a safeguard mood stabilizing drug.

The study found that heart rate variability, as measured by an electrocardiogram, indicated whether subjects had major depression or bipolar disorder. (Heart rate variability is a variation in the time interval between heartbeats.) The study, by senior author Angelos Halaris, MD, PhD and colleagues, was published in the World Journal of Biological Psychiatry.

“Having a noninvasive, easy-to-use and affordable test to differentiate between major depression and bipolar disorder would be a major breakthrough in both psychiatric and primary care practices,” Dr. Halaris said. Dr. Halaris said further research is needed to confirm the study’s findings and determine their clinical significance.

Dr. Halaris is a professor in Loyola’s department of psychiatry and behavioral neurosciences and medical director of adult psychiatry.

Major depression is among the most common and severe health problems in the world. In the United States, at least 8 to 10 percent of the population suffers from major depression at any given time. While less common than major depression, bipolar disorder is a significant mental health problem, affecting an estimated 50 million people worldwide.

The Loyola study enrolled 64 adults with major depression and 37 adults with bipolar disorder. All subjects underwent electrocardiograms at the start of the study. Each participant rested comfortably on an exam table while a three-lead electrocardiogram was attached to the chest. After the patient rested for 15 minutes, the electrocardiographic data were collected for 15 minutes.

Using a special software package, researchers converted the electrocardiographic data into the components of heart rate variability. These data were further corrected with specialized software programs developed by study co-author Stephen W. Porges, PhD, of Indiana University’s Kinsey Institute.

In measuring heart rate variability, researchers computed what is known to cardiologists as respiratory sinus arrhythmia (RSA). At the baseline (beginning of the study), the subjects with major depression had significantly higher RSA than those with bipolar disorder.

In a secondary finding, researchers found that patients with bipolar disorder had higher blood levels of inflammation biomarkers than patients with major depression. Inflammation occurs when the immune system revs up in response to a stressful condition such as bipolar disorder.


The study is titled “Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression.” In addition to Drs. Halaris and Porges, other co-authors are Brandon Hage, MD, a graduate of Loyola University Chicago Stritch School of Medicine now at the University of Pittsburgh (first author); Stritch student Briana Britton; Loyola psychiatric resident David Daniels, MD; and Keri Heilman, PhD of the University of North Carolina.

Source: Jim Ritter – Loyola University Health System
Publisher: Organized by
Image Source: image is in the public domain.
Original Research: Abstract for “Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability” by Hsin-An Chang Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Chuan-Chia Chang, Terry B. J. Kuo & San-Yuan Huang in World Journal of Biological Psychiatry. Published online November 14 2017 doi:10.3109/15622975.2015.1017606

Loyola University Health System “Simple EKG Can Determine Whether Patient Has Depression or Bipolar Disorder.” NeuroscienceNews. NeuroscienceNews, 20 November 2017.


Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability

Objectives. Bipolar II (BPII) depression is commonly misdiagnosed as unipolar depression (UD); however, an objective and reliable tool to differentiate between these disorders is lacking. Whether cardiac autonomic function can be used as a biomarker to distinguish BPII from UD is unknown.

Methods. We recruited 116 and 591 physically healthy patients with BPII depression and UD, respectively, and 421 healthy volunteers aged 20–65 years. Interviewer and self-reported measures of depression/anxiety severity were obtained. Cardiac autonomic function was evaluated by heart rate variability (HRV) and frequency-domain indices of HRV.

Results. Patients with BPII depression exhibited significantly lower mean R–R intervals, variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV but higher LF/HF ratio compared to those with UD. The significant differences remained after adjusting for age. Compared to the controls, the patients with BPII depression showed cardiac sympathetic excitation with reciprocal vagal impairment, whereas the UD patients showed only vagal impairment. Depression severity independently contributed to decreased HRV and vagal tone in both the patients with BPII depression and UD, but increased sympathetic tone only in those with BPII depression.

Conclusions. HRV may aid in the differential diagnosis of BPII depression and UD as an adjunct to diagnostic interviews.

“Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability” by Hsin-An Chang Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Chuan-Chia Chang, Terry B. J. Kuo & San-Yuan Huang in World Journal of Biological Psychiatry. Published online November 14 2017 doi:10.3109/15622975.2015.1017606

Dopamine and Serotonin in Depression

Based on the symptoms experienced as a result of lower levels of dopamine, it is thought that dopamine plays just as big of a role as serotonin in treating depression. Why then are medications used to treat depression primarily dealing with targeting serotonin only? Because people have been brainwashed by pharmaceutical companies? Maybe. It could be though that many people simply have not tried increasing their dopamine to determine whether they notice an antidepressant effect.

Depression itself is pretty subjective and can have a number of causes. It could be caused by trauma, a difficult childhood, abuse, drug usage, and other external events. It can also be caused by genetics and biological factors. Someone may have experienced developmental problems in the womb or have been exposed to certain toxins. This may lead to the development of depression. There is absolutely no clear cut evidence that low neurotransmitter levels even cause depression.

However, many people believe that “serotonin” may have something to do with depression because SSRI’s are the primary class of drugs used to treat it. Although serotonin may be the neurotransmitter most talked about when it comes to depression, my guess is that dopamine plays just as big of a role – if not a bigger role in depression.

Low dopamine vs. low serotonin… Which causes depression?

The reason I tend to think dopamine plays a huge role in treating depression is because if you look at individuals with low dopamine, they have difficulties with memory, thinking, organization, and experience an inability to feel pleasure. Many people with schizophrenia have abnormally low dopamine and as a result aren’t able to get motivated or stay productive.


Low dopamine: Tends to result in symptoms similar to Parkinson’s disease. People with abnormally low levels of dopamine may have difficulties with thinking, memory, and have slow reaction times. They may also experience anhedonia or lack of ability to feel pleasure. They may also feel similar to individuals with negative symptoms of schizophrenia in regards to having no motivation (avolition).

Low serotonin: Results in OCD-like symptoms including obsessive thoughts and compulsive behaviors. It also may result in impulsivity, feeling suicidal, aggressive behavior, etc. Lower levels of serotonin are linked to mood swings, sugar cravings, worrying, insomnia, and sadness.

There is some overlap between serotonin and dopamine that cannot be ignored. Some people do respond very well to SSRI’s and the increase in serotonin may be helping. With that said, many drugs like Paxil may indirectly affect dopamine receptors in the brain and actually improve them. So there can be certain links between SSRI’s and dopamine.

Dopamine vs. Serotonin for Depression Treatment

I tend to think that in most cases, people who respond well to SSRI antidepressants should just stay on them – they have been proven to work. With that said, there are many people for whom these drugs do not work very well. They also come with unwanted side effects and many people have gone through the entire wringer of medications only to find no relief. What ends up happening is that people end up staying on these medications and come off them with abnormally low levels of serotonin.

So the withdrawal is overwhelmingly difficult and the people have a difficult time coping with low serotonin. In many cases, the original problem wasn’t necessarily low serotonin, it may have been abnormally low dopamine. In this case, now the individual has abnormally low serotonin as well as low dopamine. If the individual would have targeted their dopamine first, they may have had success than experimenting with drugs that primarily affect serotonin.

I have had success in using Adderall for depression as well as anxiety. My personal experience is that some individuals with depression and/or anxiety may respond very well to medications that deal with dopamine more than they do serotonin.

Triple Reuptake Inhibitors: New Antidepressants

It seems as though researchers are catching on though and are trying to develop medications that target serotonin, norepinephrine, as well as dopamine. I tend to think that although this development could be useful, it sounds a bit overcomplicated. Many people do not need to tinker with all three neurotransmitters at the same time.

It would be much more favorable to simply target either dopamine or serotonin in my opinion and determine which class of drugs works better. The triple reuptake of neurotransmitters serotonin, norepinephrine, and dopamine sounds more and more like taking an illicit drug. I can only imagine how horrendous the withdrawal would be from something that tinkers with that many neurotransmitters.

The major difference between these medications and older ones is that they include the reuptake inhibition of dopamine. Although Wellbutrin can inhibit reuptake dopamine, it does it to a very little degree. Most dopamine reuptake inhibitors are weak in their reuptake of actual dopamine. With that said, this could be a reason why using Wellbutrin for ADHD works in some cases.

Early first 12 years of brain growth via learning

In a study about human memory, brain growth and learning, the first 12 yrs of human growth and learning is very critical to the future brain health.

In contrast, the rats exposed to the shock compartment at 24 days of life learned and retained the memory for a long time and avoided this place—revealing a memory similar to that of .

Rats develop rapidly during infancy and become sexually mature at about 6 weeks of age. Humans, on the other hand, develop slowly and don’t hit puberty until about age 12-13 years (range: 8 to 16 years).

To address this, the scientists focused on the brain’s hippocampus, which previous scholarship has shown is necessary for encoding new . Here, in a series of experiments similar to the box tests, they found that if the hippocampus was inactive, the ability of younger rats to form latent memories and recall them later by reminders as they got older was diminished. They then found that mechanisms of “critical periods” are fundamental for establishing these infantile memories.

A critical period is a developmental stage during which the nervous system is especially sensitive to environmental stimuli. If, during this period, the organism does not receive the appropriate stimuli required to develop a given function, it may be difficult or even impossible to develop that function later in life. Well-known examples of critical period-based functions are sensory functions, like vision, and language acquisition.

The study shows that there is a critical period for episodic learning and that during this period the hippocampus learns to become able to efficiently process and store memories long-term.

“Early in life, while the brain cannot efficiently form long-term memories, it is ‘learning’ how to do so, making it possible to establish the abilities to memorize long-term,” explains Alberini. “However, the brain needs stimulation through learning so that it can get in the practice of formation—without these experiences, the ability of the neurological system to learn will be impaired.”

These studies, the researchers observe, suggest that using learning and environmental interventions during a critical period may significantly help to address learning disabilities.

A balance of dopamine and serotonin for your brain function

5htp rich food

Having a proper balance of Serotonin and Dopamine can have a positive influence on many things in both body and mind.

Some mental factors are: energy, attention, mood, excessive appetite (brain can crave aminos in food), memory, thinking ability, etc…  Boosting serotonin and dopamine is used to treat nerve damage and head-trauma, Parkinson’s, Alzheimer’s, Anxiety, ADHD/ADD, of course Depression, obesity, and excessive appetite, Chromes Disease, etc…

Serotonin and Dopamine

Serotonin is synthesized from HTP.  Dopamine is synthesized from Tyrosine.  The two act as competitors; when you raise one the other gets pushed down (and vise versa). Therefore, to avoid a depletion of one, these two are always taken together.  Dr Martin Hinz (the inventor of an amino acid program) has access to 75,000 lab tests on 7,500 patients and spent 7 years to develop a process of supplementing patients with amino acids.  Dr Hinz tells providers that they should not attempt to adjust this initial ratio, it will be counter-productive.  This doses of HTP and Tyrosine are always given in a 1:10 ratio.

I’m praising Dr Hinz because his methods are working for me. His information is freely available and uses standard easy to obtain amino-acids.  Dr Hinz’s research may be used independent of his products.   Finally, the volume of free material published by Hinz and his associates is impressive.  It is enough to keep me very busy for quite some time.


Both Dr Hinz and Dr Kalish publish recommended Max doses that do not require a lab test. Dr Kalish does some public speaking to non-medical persons.  He is also trained and in contact with Dr Hinz about the amino acid program.

Dr Kalish’s, in a radio blog interview (2), gives what he calls a conservative maximum of 300 mg HTP and 3000 mg Tyrosine per day.

Cofactors for 5-HTP and or L-Tyrosine (per day per 300 mg of HTP and 3000 mg Tyrosine):
Vitamin C 1000 mg

B6 75 mg

Calcium Citrate 220 mg

  • I’m not concerned about dividing these down as much as I am about making sure they are included in the minimum amounts. The cofactors are just as important as the precursors (htp/tyrosine). They team-up with the pre-cursors rather than compete.Dr Kalish’s Interview
    Here are my a few take-away-points from the Dr Kalish interview (2):Dr Kalish has been studying the brain for 8 yearsLow Serotonin & Low Dopamine
  • Excessive Appetite (Food Cravings)
  • crave sweets but protein is needed
  • Weight Gain
  • Depression
  • Feeling better after overeating
  • Low Dopamine
  • Focus Concentration
  • Low Serotonin
  • Unduly Sad
  • Overly Sensitive
  • Anxious

Dopamine acts like a dimmer switch (over time) while serotonin acts like a light switch (sudden changes)

Neurotoxicity caused by chemicals (and pesticides) dumped into the environment eventually making their way to the brain.

  • L-cysteine HCL (cysteine)
    Dr Hinz starts all patients with L-cysteine and cofactors (3). In Dr Hinz’s research, L-cysteine is added to compensate for L-tyrosine-induced depletion of sulfur amino acids. Dr Hinz’s doses for L-cysteine are also used for lab-testing purposes. If I divide down the doses for L-cysteine to match the recommended 500 mg per day on the bottle sold in the USA, I get the following really small doses for the co-factors:
    Selenium 45 μg
  • Folic Acid (folate) 45 μg

Dr Hinz’s packages L-cysteine in a trademarked product called CysReplete. These exact ratios above are present in each pill. Each pill contains:
1500 mg, Selenium – 134 mcg, Folate – 133 mcg
I take between 2 and 3 pills of l-cysteine a day.  I will adjust this up or down based on how I feel and may increase to satisfy any substance craving I might have.  I may decrease or increase either the htp/tyrosine together (keeping the 1:10 ratio) or decrease/increase the l-cysteine based on how I feel.  Due to the 1/wk adjustment period, I’m more likely to leave the primary treatment does for htp/tyrosine alone and change the dose of the l-cysteine.  These issues lessen as I get use to the dose and are replaced by enhanced mood and energy.

Drink L-cysteine with a big glass of water.

Dr Hinz uses the HCL form of L-Cysteine.  Whole-foods carries a different form called N-Acetyl Cysteine (NAC).  Although this may have higher bioavailability, I choose to stick with the HCL form used in the research. The HCL form is about half the price of the NAC.

Here is an example the HCL form:
So, that is great news, this is the HCL form used in Dr Hinz’s CysReplete brand.
There are other benefits with L-cysteine including its ability to remove heavy metals from the body and it being an anti-oxidant.

Info about cysteine (4):

Supplemental cysteine may also be prescribed to reduce nausea and vomiting caused by chemotherapy.

  • detoxifying heavy metals and chemical
  • protecting cells from free-radical damage
  • breaking down excess lung mucous
  • Deficiencies may decrease your body’s production of cysteine, such as

  • methionine,
  • vitamin B6,
  • vitamin B12,
  • s-adenosylmethionine known as SAMe, and
  • folic acid

Chronic obstructive pulmonary disease (COPD) — Maryland Health Center 600 milligrams taken twice daily may prove beneficial

HIV or AIDS, you may as high as 4,000 milligrams cysteine per day
WARNING: if your body can’t metabolize cysteine you could suffer neurodegeneration

If you are concerned about loose hair follicles (see the Reference 1) you should investigate L-lysine. Notice, the doses of L-cystine in reference 1 are much greater, so L-lysine may not be needed.

Interactions with:

  • Nitroglycerin ( headaches and even cause you to faint)
  • Activated charcoal
  • Side Effects:  nausea, vomiting, diarrhea, allergic reactions, low blood pressure, heart beat irregularities, breathing problems, and even death
  • asthma sufferers experiencing L-Cysteine side effects due to accidental inhalation of the supplement powder

Other Ingredients: Cellulose, gelatin, magnesium stearate, medium chain triglycerides, silica.
This is the TwinLabs version brand in the dark uv-protectant glass bottle.  Also says “Well tolerated by the most highly allergic individuals.”
Dr Kalish says that lab test are required for anyone under 18-16 years of age. He says Children respond wonderfully to the treatment and that they are extremely sensitive to the dose.

Relative nutritional deficiencies associated with centrally acting monoamines


“At the initial visit it is recommended that the following adult amino acid dosing values be initiated: L-cysteine 4500 mg, L-tyrosine 3000 mg, vitamin C 1000 mg, L-lysine 500 mg, 5-HTP 300 mg, calcium citrate 220 mg, vitamin B6 75 mg, folate 400 μg, and selenium 400 μg. The pediatric dosing values (<17 years) are half the adult dosing values. A full discussion of the scientific basis for each of these amino acid and cofactor nutrients is covered in previous writings by the authors. A brief overview is as follows:

L-tyrosine and 5-HTP are dopamine and serotonin precursors, respectively. Vitamin C, vitamin B6, and calcium citrate are cofactors required in the synthesis of serotonin and/or dopamine. Folate is required for optimal synthesis of sulfur amino acids. Selenium is given in response to the ability of cysteine to concentrate methylmercury in the central nervous system. L-lysine prevents loose hair follicles in a bariatric medical practice. L-cysteine is administered to compensate for L-tyrosine-induced depletion of sulfur amino acids.3,4,6,12

Dr Kalish’s interview

A collection of all documents related to this topic:

More notes…

You need a sulfur amino that works as a methyl donor (like Cysteine HCL or SAMe). NAC is safer but does not work for this purpose. Cysteine is more cost-effective. This is why Cysteine and L-5-MTHF must be taken together  to achieve this safely without raising Homo-cysteine (easily tested) levels too much. Dr Chad Oler can explain this much better than I can.

Also google Dr Mercola on Dopamine Depression Parkinson

Eat these foods for your brain:

  1. Seaweed
  2. Egg Whites
  3. Cottage Cheese
  4. Salmon
  5. Turkey
  6. Pumpkin Flesh
  7. Pork
  8. Mustard Greens
  9. Chicken
  10. Buffalo
  11. Cod
  12. Tuna
  13. Sesame Seeds
  14. Kidney Beans
  15. Spinach
  16. Avocado
  17. Banana


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