Serotonin Release Essay

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We might not have a money tree, but we can have a happiness tree. Dopamine, serotonin, oxytocin and endorphins are the quartet responsible for our happiness. Many events can trigger these neurotransmitters, but rather than being in the passenger seat, there are ways we can intentionally cause them to flow.

Being in a positive state has significant impact on our motivation, productivity, and wellbeing. No sane person would be opposed to having higher levels in those areas.

Here are some simple ways to hack into our positive neurochemicals:

Dopamine

Dopamine motivates us to take action toward goals, desires, and needs, and gives a surge of reinforcing pleasure when achieving them. Procrastination, self-doubt, and lack of enthusiasm are linked with low levels of dopamine. Studies on rats showed those with low levels of dopamine always opted for an easy option and less food; those with higher levels exerted the effort needed to receive twice the amount of food.

Break big goals down into little pieces -- rather than only allowing our brains to celebrate when we've hit the finish line, we can create a series of little finish lines which releases dopamine. And it's crucial to actually celebrate -- buy a bottle of wine, or head to your favorite restaurant whenever you meet a small goal.

Instead of being left with a dopamine hangover, create new goals before achieving your current one. That ensures a continual flow for experiencing dopamine. As an employer and leader, recognizing the accomplishments of your team, e.g. sending them an email, or giving a bonus, will allow them to have a dopamine hit and increase future motivation and productivity.

Serotonin

Serotonin flows when you feel significant or important. Loneliness and depression appears when serotonin is absent. It's perhaps one reason why people fall into gang and criminal activity -- the culture brings experiences that facilitate serotonin release. Unhealthy attention-seeking behavior can also be a cry for what serotonin brings. Princeton neuroscientist Barry Jacobs explains that most antidepressants focus on the production of serotonin.

Reflecting on past significant achievements allows the brain to re-live the experience. Our brain has trouble telling the difference between what's real and imagined, so it produces serotonin in both cases. It's another reason why gratitude practices are popular. They remind us that we are valued and have much to value in life. If you need a serotonin boost during a stressful day, take a few moments to reflect on a past achievements and victories.

Have lunch or coffee outside and expose yourself to the sun for 20 minutes; our skin absorbs UV rays, which promotes vitamin D and serotonin production. Although too much ultraviolet light isn't good, some daily exposure is healthy to boost serotonin levels.

Oxytocin

Oxytocin creates intimacy, trust, and builds healthy relationships. It's released by men and women during orgasm, and by mothers during childbirth and breastfeeding. Animals will reject their offspring when the release of oxytocin is blocked. Oxytocin increases fidelity; men in monogamous relationships who were given a boost of oxytocin interacted with single women at a greater physical distance then men who weren't given any oxytocin. The cultivation of oxytocin is essential for creating strong bonds and improved social interactions.

Often referred to as the cuddle hormone, a simple way to keep oxytocin flowing is to give someone a hug. Dr. Paul Zak explains that inter-personal touch not only only raises oxytocin, but reduces cardiovascular stress and improves the immune system; rather than just a hand shake, go in for the hug. Dr. Zak recommends eight hugs each day.

When someone receives a gift, their oxytocin levels can rise. You can strengthen work and personal relationships through a simple birthday or anniversary gift.

Endorphins

Endorphins are released in response to pain and stress and help to alleviate anxiety and depression. The surging "second wind" and euphoric "runners high" during and after a vigorous run are a result of endorphins. Similar to morphine, it acts as an analgesic and sedative, diminishing our perception of pain.

Along with regular exercise, laughter is one of the easiest ways to induce endorphin release. Even the anticipation and expectation of laugher, e.g., attending a comedy show, increases levels of endorphins. Taking your sense of humor to work, forwarding that funny email, and finding several things to laugh at during the day is a great way to keep the doctor away.

Aromatherapies: The smell of vanilla and lavender has been linked with the production of endorphins. Studies have shown that dark chocolate and spicy foods can lead the brain to release endorphins. Keep some scented oils and some dark chocolate at your desk for a quick endorphin boost.

A version of this article first appeared on The Utopian Life.

Follow Thai Nguyen on Twitter: www.twitter.com/ThaiWins

Question 1. Briefly, what are the anti-PF4 and SRA tests?

The anti-PF4 (ie, heparin-induced platelet antibody) test is an immunologic, enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the platelet factor 4 (PF4)/heparin complex. The assay uses heparin bound to protamine sulfate, and PF4 is supplemented through a platelet lysate.

The SRA test is a functional assay that measures heparin-dependent platelet activation. Patient serum is incubated with donor platelets containing radioactive 14C serotonin and different concentrations of heparin. Antibody present in the patient serum will bind and activate donor platelets, releasing radiolabeled serotonin from the platelet granules. A positive SRA is expected to show >20% release of the 14C serotonin when mixed with patient serum and low-dose heparin. In addition, the high-dose heparin must reduce the % release obtained with low-dose heparin by at least 50% in order to demonstrate that the platelet activation is heparin dependent.

The SRA is considered a better predictor of thrombosis than the anti-PF4 assay.

Question 2. What is the OD result given in the anti-PF4 report and what is its significance?

OD is the optical density; it is an indication of antibody strength. Antibody present in the patient sample binds to the heparin-PF4 coated wells, leading to a color-producing reaction. A higher antibody concentration leads to more color production and a higher OD reading. The positive cutoff is ≥0.300 OD, and high-titer antibodies may yield values up to 3.500 OD.

Question 3. What is the sensitivity of the anti-PF4 and SRA tests?

The anti-PF4 test has a sensitivity of >95% and a specificity ranging from 50% to 89%. However, the higher the OD, the greater the probability is for clinical HIT/HITT. Similarly, the specificity increases when the OD is >1.000.1

The SRA test has a sensitivity of 88% to 100% and a specificity of 89% to 100% for HIT.2

The combined sensitivity of the anti-PF4 and, the SRA is about 99%.3

Question 4. What is meant by the expression “HIT/HITT is a clinical, pathologic diagnosis?”

HIT/HITT is a diagnosis that requires both clinical judgment and laboratory corroboration, ie, a clinical, pathologic diagnosis.

Thrombocytopenia in a hospitalized patient is very common and may be due to a vast number of causes (eg, consumption, dilutional effect from fluids or transfusions, drugs, sepsis, splenic sequestration, etc.). For patients exposed to heparin, HIT/HITT is an important consideration, given the life-threatening potential. Applying a standardized and objective approach to the clinical assessment can help determine the pretest probability of HIT/HITT.4 The most common and widely accepted scoring model is called the 4T’s (ASHeducationbook.hematologylibrary.org/content/2003/1/497/F3.expansion.html). Another diagnostic challenge is that antibodies may be identified in patients with little or no clinical symptomatology.

Question 5. Should one test for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pretest probability of HIT?

No, testing for suspected HIT is not needed in this situation. HIT can be excluded based on a low pretest probability score (4T’s score of 0-3).5

Question 6. What is the significance of a positive anti-PF4 with a negative SRA?

A published algorithm that incorporates the clinical assessment suggests that patients with a moderate pretest probability and the laboratory results above are “indeterminate” for HIT/HITT.4

This scenario may represent a true antibody response, but one that lacks sufficient titer or avidity to activate platelets in vitro. The fact that the antibodies are measurable only with the anti-PF4 ELISA may also be indicative of the assay’s greater sensitivity. While this explanation has a good scientific foundation, some patients may still have clinically significant antibodies, thereby the rationale for the “indeterminate for HIT/HITT diagnosis.” False-positive anti-PF4 ELISA results have also been attributed to cross-reactivity to antiphospholipid antibodies.6

Question 7. Are the tests offered as a reflex or panel?

Quest Diagnostics offers both tests individually, together as a panel, and as a reflex (a positive heparin-induced platelet antibody reflexes to SRA).

A cautionary note when ordering the panel or reflex—if the result interface (connection from Quest Diagnostics to your computer system) does not accept partial results, the anti-PF4 ELISA results will not be received until the SRA is reported. Confirming the status of your interface with an IT specialist is recommended. Alternatively, physicians may view all results irrespective of this issue using the Care 360 product.

Question 8. Is the anti-PF4 ELISA IgG-specific?

Yes. Only IgG antibodies activate platelets, thus IgM and IgA classes are of minor clinical relevance.7,8 Furthermore, the British Society for Haematology recommends that only the IgG isotype be tested.9

Question 9. Does Quest Diagnostics perform the heparin neutralization step in the anti-PF4 ELISA?

Quest Diagnostics does not perform the heparin neutralization procedure, sometimes referred to as a confirmatory step. It is our experience that virtually every positive sample is neutralized, and therefore we concluded that it offered no significant insight beyond that of the OD value. A retrospective study also reported that some patients with high ELISA OD values were misclassified by yielding a confirm negative result despite presence of clinical HIT/HITT.10

Question 10. How long does the patient have to be off heparin before testing?

Given the short half-life (30 minutes to 2 hours) of unfractionated heparin, waiting a minimum of 2 hours is suggested.

Question 11. For the SRA, what is the significance of an indeterminate or low-positive result?

A SRA result is considered indeterminate when there is a >20% release of 14C serotonin in the patient serum/low dose heparin mixture and an absence of inhibition with high-dose unfractionated heparin (UFH). There may be other nonheparin-dependent antibodies present (ie, Class I HLA antibodies or platelet receptor specific antibodies) that may cause platelet activation.

A low-positive SRA is repeated using platelets from a different donor to demonstrate reproducibility. At this point, specific conclusions about a low-positive result cannot be made. It is recommended that the result be considered in the context of all the data at hand, specifically the clinical assessment and anti-PF4 result.

References

  1. Zwicker JI, et al. J Thromb Haemost. 2004;2:2133–2137.
  2. Ortel TL. Hematology Am Soc Hematol Educ Program. 2009;225-232.
  3. Linkins L, et al. Chest. 2012;141(suppl):e495S-e530S.
  4. Arepally GM, Ortel TL. N Engl J Med. 2006;355(8):809-817.
  5. Cuker A, et al. Blood. 2012;120:4160-4167.
  6. Pausner R, et al. J Thromb Haemost. 2009;7(7):1070-1074.
  7. Warkentin TE. Hematology Am Soc Hematol Educ Program. 2011;2011:143-149.
  8. Greinacher A, et al. J Thromb Haemost. 2007;5:1666-1673.
  9. Watson H, et al. Br J Haemotol. 2012;159:528-540.
  10. Whitlatch NL, et al. Thromb Haemost. 2008;100:678–684.

This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.

Document FAQS.06 Version: 2

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Version 1 effective 09/17/2013 to 12/16/2016

Version 0 effective 12/06/2011 to 09/16/2013

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