What are the main causes of norepinephrine deficiency. How does low norepinephrine affect mood and cognitive function. Can norepinephrine imbalances contribute to depression and anxiety. What are the treatment options for low norepinephrine levels.

Understanding Norepinephrine: Function and Importance

Norepinephrine, also known as noradrenaline, is a crucial neurotransmitter and hormone that plays a vital role in the human body. It is one of the “Big 5” neurotransmitters, alongside dopamine, serotonin, acetylcholine, and GABA, which collectively regulate mood, memory, sleep, and energy levels. Produced in the central nervous system and adrenal glands, norepinephrine has far-reaching effects on various physiological processes.

What are the primary functions of norepinephrine in the body? Norepinephrine acts as an excitatory neurotransmitter, influencing:

• Heart rate regulation
• Blood pressure control
• Stress response (fight-or-flight)
• Attention and focus
• Mood regulation
• Chronic inflammation reduction

As a key component of the body’s stress response system, norepinephrine prepares the body for action in the face of perceived threats or challenges.

Norepinephrine Deficiency: Causes and Mechanisms

Recent research has shed light on the mechanisms behind norepinephrine deficiency. A study titled “Norepinephrine Deficiency Is Caused by Combined Abnormal mRNA Processing and Defective Protein Trafficking of Dopamine β-Hydroxylase” reveals that the deficiency results from a combination of two key factors:

1. Abnormal mRNA processing
2. Defective protein trafficking of dopamine β-hydroxylase (DBH)

How do these factors contribute to norepinephrine deficiency? The abnormal mRNA processing affects the production of DBH, the enzyme responsible for converting dopamine to norepinephrine. Additionally, defective protein trafficking impairs the proper distribution and function of DBH within cells. Together, these issues lead to insufficient norepinephrine production and availability in the body.

Symptoms and Effects of Low Norepinephrine

When norepinephrine levels are low, individuals may experience a range of symptoms that can significantly impact their quality of life. What are the common signs of norepinephrine deficiency?

• Lethargy and fatigue
• Difficulty concentrating and poor attention span
• Lack of motivation
• Depression, particularly atypical and inflammatory types
• Anxiety
• Sleep disturbances
• Low blood pressure
• Decreased heart rate

It’s important to note that while sudden bursts of norepinephrine can lead to anxiety and hyperactivity, chronically low levels can result in the opposite effect, causing a general sense of lethargy and inattention.

The Interplay Between Neurotransmitters and Hormones

Understanding norepinephrine deficiency requires a holistic approach that considers the complex interrelationships between neurotransmitters, hormones, and the immune system. How do these systems interact?

• Hormonal changes can influence neurotransmitter balance
• Neurotransmitter imbalances can affect hormone production and function
• Some neurotransmitters, like norepinephrine, also act as hormones

This intricate web of interactions highlights the importance of comprehensive testing and personalized treatment approaches. By examining the levels of various neurotransmitters, adrenal hormones, thyroid hormones, and reproductive hormones, healthcare professionals can gain a more complete picture of an individual’s physiological state.

Diagnostic Challenges in Neurotransmitter Imbalances

Identifying and diagnosing neurotransmitter imbalances, including norepinephrine deficiency, presents several challenges in modern medicine. Why is diagnosing these conditions often difficult?

• Symptoms can be non-specific and overlap with other conditions
• The dynamic nature of neurotransmitter levels can lead to fluctuating symptoms
• Similar symptoms may arise from different underlying imbalances
• Conversely, different symptoms may stem from the same biological imbalance

To address these challenges, healthcare professionals are increasingly turning to biomarker testing, including neurotransmitter level assessments. These tests provide objective data that can help guide diagnosis and treatment decisions.

The Role of Neurotransmitter Testing in Personalized Medicine

Neurotransmitter testing has emerged as a valuable tool in the field of integrative psychiatry and personalized medicine. How does neurotransmitter testing contribute to patient care?

• Provides a comprehensive view of an individual’s unique neurochemical status
• Allows for the identification of specific imbalances, including norepinephrine deficiency
• Enables healthcare providers to tailor treatment plans to address individual needs
• Facilitates monitoring of treatment effectiveness over time

By incorporating neurotransmitter testing into clinical practice, healthcare professionals can move beyond symptom-based approaches and develop more targeted, effective treatment strategies.

Treatment Approaches for Norepinephrine Deficiency

Addressing norepinephrine deficiency often requires a multifaceted approach that may include various therapeutic interventions. What are some potential treatment options for low norepinephrine levels?

• Medications: Certain antidepressants, such as selective norepinephrine reuptake inhibitors (SNRIs), can help increase norepinephrine levels in the brain
• Nutraceuticals: Specific supplements may support norepinephrine production and function
• Herbal adaptogens: Certain herbs may help modulate the stress response and support adrenal function
• Dietary changes: A balanced diet rich in protein and essential nutrients can support neurotransmitter production
• Lifestyle modifications: Regular exercise, stress management techniques, and adequate sleep can help regulate neurotransmitter levels
• Hormone therapy: In some cases, addressing hormonal imbalances may indirectly improve norepinephrine function

The optimal treatment plan will vary depending on the individual’s specific needs, underlying causes of deficiency, and overall health status. A personalized approach, guided by comprehensive testing and ongoing monitoring, is often the most effective strategy for addressing norepinephrine deficiency and related conditions.

The Importance of a Holistic Approach to Mental Health

Understanding norepinephrine deficiency and its implications for mental health underscores the need for a holistic, integrative approach to psychiatric care. Why is this approach beneficial?

• Addresses the complex interplay between neurotransmitters, hormones, and the immune system
• Considers both biological and lifestyle factors that may contribute to imbalances
• Allows for personalized treatment plans that target specific underlying causes
• Emphasizes the importance of ongoing monitoring and adjustment of treatments
• Incorporates a range of therapeutic options, from conventional medications to complementary therapies

By adopting this comprehensive approach, healthcare providers can offer more effective, tailored solutions for individuals struggling with norepinephrine deficiency and related mental health concerns.

Ongoing Research and Future Directions

As our understanding of neurotransmitter function and regulation continues to evolve, ongoing research is likely to yield new insights into the diagnosis and treatment of norepinephrine deficiency. What are some potential areas of future research?

• Improved diagnostic tools for neurotransmitter imbalances
• Novel therapeutic approaches targeting specific aspects of norepinephrine production and function
• Further exploration of the genetic factors influencing neurotransmitter metabolism
• Investigation of the long-term effects of various treatment modalities on neurotransmitter balance
• Development of more targeted, personalized interventions based on individual neurochemical profiles

As research progresses, it is likely that our ability to effectively diagnose and treat norepinephrine deficiency and related conditions will continue to improve, offering hope for individuals struggling with these complex health issues.

The Role of Patient Education and Empowerment

In addressing norepinephrine deficiency and other neurotransmitter imbalances, patient education and empowerment play crucial roles. How can healthcare providers support patients in this regard?

• Providing clear, accessible information about neurotransmitter function and imbalances
• Explaining the rationale behind various diagnostic tests and treatment options
• Encouraging patients to actively participate in their treatment planning and decision-making
• Offering guidance on lifestyle modifications that can support overall neurotransmitter health
• Promoting a collaborative approach to care that respects patient preferences and values

By empowering patients with knowledge and involving them in their care, healthcare providers can foster better treatment adherence and outcomes in the management of norepinephrine deficiency and related conditions.

Integrating Conventional and Complementary Approaches

The field of integrative psychiatry seeks to combine the best of conventional medicine with evidence-based complementary therapies. How does this approach benefit patients with norepinephrine deficiency?

• Offers a wider range of treatment options to address individual needs
• Allows for the incorporation of both pharmacological and non-pharmacological interventions
• Addresses the multifaceted nature of neurotransmitter imbalances
• Promotes a focus on overall health and well-being, not just symptom management
• Supports the body’s natural healing processes while providing targeted interventions when needed

By integrating conventional and complementary approaches, healthcare providers can offer more comprehensive, personalized care for individuals struggling with norepinephrine deficiency and related mental health concerns.

The Impact of Stress on Norepinephrine Levels

Chronic stress can have a significant impact on norepinephrine levels and overall neurotransmitter balance. How does stress affect norepinephrine function?

• Initially increases norepinephrine production as part of the stress response
• Over time, can lead to depletion of norepinephrine reserves
• May alter the sensitivity of norepinephrine receptors
• Can disrupt the balance between norepinephrine and other neurotransmitters
• May contribute to inflammation, further impacting neurotransmitter function

Addressing chronic stress through stress management techniques, lifestyle modifications, and targeted interventions is often a crucial component of treating norepinephrine deficiency and promoting overall mental health.

The Connection Between Norepinephrine and Inflammation

Emerging research has highlighted the intricate relationship between norepinephrine and inflammation in the body. How do these two factors interact?

• Norepinephrine can modulate inflammatory responses
• Chronic inflammation may alter norepinephrine production and function
• Inflammatory processes can affect the blood-brain barrier, influencing neurotransmitter levels
• Addressing inflammation may help improve norepinephrine balance and overall mental health
• Anti-inflammatory interventions may complement traditional treatments for norepinephrine deficiency

Understanding the norepinephrine-inflammation connection provides new avenues for research and potential therapeutic interventions in the treatment of mental health disorders associated with norepinephrine imbalances.

The Role of Genetics in Norepinephrine Function

Genetic factors can play a significant role in an individual’s susceptibility to norepinephrine deficiency and related conditions. How do genetics influence norepinephrine function?

• Genetic variations can affect the production of enzymes involved in norepinephrine synthesis
• Certain genetic polymorphisms may influence norepinephrine receptor sensitivity
• Genetic factors can impact the metabolism and clearance of norepinephrine
• Understanding an individual’s genetic profile can help guide personalized treatment approaches
• Genetic testing may provide insights into potential risk factors for norepinephrine-related disorders

As our understanding of the genetic basis of neurotransmitter function continues to grow, it may become increasingly possible to tailor treatments based on an individual’s genetic profile, leading to more effective and personalized interventions for norepinephrine deficiency and related conditions.

Low Norepinephrine – Depressed, Inflamed & in Pain

• Last Modified: June 13, 2023

by Dr.Dave on Jan 18, 2015     

Norepinephrine, also known as noradrenaline, is an excitatory neurotransmitter produced in the central nervous system as well as by the adrenal glands. It is one of the Big 5 neurotransmitters that regulate mood, memory, sleep, and energy, the others being dopamine, serotonin, acetylcholine, and GABA. Norepinephrine also has widespread influence regulating heart rate and blood pressure and helping lower chronic inflammation.

As one of your “first responders” in response to stress, norepinephrine prepares you for action by initiating your fight-or-flight response to imminent danger. That is why sudden bursts of norepinephrine are often linked to anxiety, elevated blood pressure, and hyperactivity. Low levels, on the other hand, can cause lethargy, inattention, and lack of focus and concentration. Low levels have been found in patients with depression, particularly the atypical and inflammatory types of depression.

One of the reasons we at Integrative Psychiatry emphasize neurotransmitter testing has to do with the intricate interrelationships among your neurotransmitters, hormones (thyroid, adrenal, and reproductive), and immunity.  For example, alterations in sex and adrenal hormones can cause neurotransmitter imbalances. At the same time, neurotransmitter imbalances will influence the production and function of various hormonal systems. And some neurotransmitters, like norepinephrine, function as hormones as well as neurotransmitters. It gets complicated pretty quickly.

For more detailed information on norepinephrine and other neurotransmitters, visit our webpage:  https://www.integrativepsychiatry.net/neurotransmitters/.

Among the challenges of modern medicine is figuring out where on the stress roller-coaster you and your neurotransmitters are. Symptoms can offer clues. But chronic complex health conditions are often masked by symptoms so common that those symptoms can lose their diagnostic value. In fact, patients with significantly different underlying conditions may experience a similar set of symptoms. Likewise, people with vastly different symptoms may be suffering from the same underlying biological imbalances. And how you feel today may not be the way you felt last week. The good news is that even complex health conditions are associated with measurable biomarkers like neurotransmitter levels.

Measuring and monitoring your neurotransmitters and, for that matter, your adrenal and reproductive hormones as well, provides us with a comprehensive view of your unique status. This, in turn, allows us to personalize your treatment whether that be with medications, nutraceuticals, herbal adaptogens, hormones, diet, lifestyle changes or some combination of these.

Related Products:

Share this article:

Meet Dr.

Dave

Dr. David Scheiderer MD, MBA, DFAPA, is the Chief Medical Officer and Director of Education for Integrative Psychiatry, Inc. 

An accomplished clinician, educator, and lecturer, Dr. Dave has established himself as a key opinion leader in the fields of both mainstream psychiatry and functional medicine. Dissatisfied with the patient outcomes using only conventional treatments, he began treating his patients by addressing biological imbalances with lifestyle improvements, nutrition and nutraceuticals to get better outcomes. His integrative approach provided much improved results. Dr. Dave is passionate about helping the community he serves by personalizing treatments and educating the public about mental health and healthy aging. He has formulated several of our supplements and sat on the advisory board for many others, ensuring the products we carry are based on science and experience and have the best efficacy rates and highest ingredient quality available.

Epinephrine vs. norepinephrine: What to know

Epinephrine and norepinephrine are neurotransmitters. They deliver signals between nerve cells, and hormones. They feature in medications for cardiovascular problems. Low levels can contribute to depression, anxiety, and other health issues.

Epinephrine and norepinephrine have similar chemical structures. However, they produce different effects on the body. Both play a role in the regulation of the sympathetic nervous system, which is responsible for the body’s “fight or flight” response.

Another name for epinephrine is adrenaline, and some refer to norepinephrine as noradrenaline.

In this article, we discuss the similarities and differences between epinephrine and norepinephrine, along with their functions and medical uses. We also outline the health effects of having too much or too little of either compound in the body.

Both epinephrine and norepinephrine are chemical messengers. They function as hormones, as well as neurotransmitters.

As hormones, epinephrine and norepinephrine travel through the bloodstream, along with other hormones that the endocrine and reproductive organs make. They tell organs and tissues to work in different ways.

Neurotransmitters have a similar function. However, they only occur in nerve cells and travel across synapses, which are junctions where two nerve fibers meet. Nerves cells produce neurotransmitters in response to electrical impulses.

The adrenal medulla is the inner portion of the adrenal gland. It regulates and secretes both epinephrine and norepinephrine in response to stress and other imbalances in the body, such as low blood pressure.

What does epinephrine do?

When the brain perceives danger, the amygdala triggers the hypothalamus to activate the autonomic nervous system (ANS).

Signals from the ANS stimulate the adrenal gland to start pumping epinephrine into the bloodstream. People often refer to this surge of epinephrine as an adrenaline rush or the fight or flight response.

Epinephrine activates alpha- and beta-adrenoreceptors in the cells of various body organs and tissues, including:

• the heart
• the lungs
• the muscles
• the blood vessels

The release of epinephrine into the bloodstream brings about several physiological changes, such as:

• increased heart rate and blood flow
• faster breathing
• raised blood sugar levels
• increased strength and physical performance

What does norepinephrine do?

The adrenal medulla produces norepinephrine in response to low blood pressure. Norepinephrine promotes vasoconstriction, which is a narrowing of the blood vessels. This, in turn, increases blood pressure.

Like epinephrine, norepinephrine also stimulates alpha-adrenoreceptors in the cells of the blood vessels. It increases heart rate and blood sugar levels.

Synthetic forms of epinephrine and norepinephrine have several medical uses.

Epinephrine

Doctors prescribe epinephrine to treat severe medical conditions that affect the heart and airways, such as anaphylaxis.

Anaphylaxis is a severe and life threatening allergic reaction that can interfere with a person’s ability to breathe. Epinephrine counters anaphylactic shock by:

• narrowing the blood vessels to increase blood pressure
• increasing heart rate to improve blood flow
• relaxing the muscles and airways, allowing a person to breathe

People at risk of anaphylaxis can carry an epinephrine autoinjector with them at all times.

Doctors may also use epinephrine to treat the following:

• severe asthma attacks
• cardiac arrest
• septic shock

During asthma attacks, doctors use epinephrine in a nebulized or inhaled form, rather than injecting it.

In cases of septic shock, doctors may use epinephrine and norepinephrine at the same time, delivering it via an IV line.

Norepinephrine

Norepinephrine can help raise systolic blood pressure (SBP) in people who have had a heart attack. Systolic blood pressure refers to the pressure that occurs when the heart is contracting and ejecting blood. A heart attack can damage and weaken the heart muscle, resulting in low SBP.

Doctors may also use norepinephrine to treat the following:

• Critical hypotension: This is the medical term for dangerously low blood pressure.
• Septic shock: This is a life threatening condition in which blood pressure drops dangerously low following an infection. Doctors may combine norepinephrine with IV fluids and antibiotics to treat septic shock.
• Pericardial tamponade: This is another life threatening condition in which the heart is unable to fully expand and fill with blood due to fluid in the pericardium, which is the membrane surrounding the heart. Doctors treat it via pericardiocentesis, which removes the excess fluid, as well as norepinephrine.
• Neurogenic shock: This occurs when damage to the nervous system causes difficulty maintaining a stable heart rate, blood pressure, and temperature.

Certain factors can affect the body’s ability to produce or respond to epinephrine and norepinephrine, including:

• chronic stress
• poor nutrition
• certain medications
• certain health conditions

Additionally, a rare condition known as genetic dopamine beta-hydroxylase deficiency (GDBhD) prevents the body from converting dopamine into norepinephrine.

According to a 2018 review article, GDBhD results from a mutation in the norepinephrine transporter gene g237c. The authors concluded that this condition might decrease sympathetic nerve activity and increase the risk of damage to the heart and blood vessels.

Low levels of epinephrine and norepinephrine can result in physical and mental symptoms, such as:

• anxiety
• depression
• changes in blood pressure
• changes in heart rate
• low blood sugar, or hypoglycemia
• migraine headaches
• problems sleeping

In addition, norepinephrine plays a role in focus and promotes periods of sustained attention. Low levels of norepinephrine may contribute to the development of attention deficit hyperactivity disorder (ADHD).

The following medications can increase levels of norepinephrine:

• amphetamines, such as methylphenidate (Ritalin) and dextroamphetamine (Adderall)
• serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor) and duloxetine (Cymbalta)

Certain medical conditions can affect the adrenal glands, causing excess production of epinephrine and norepinephrine. Examples include:

• chronic stress
• obesity
• tumors

Symptoms of high levels of epinephrine or norepinephrine can include:

• excessive sweating
• rapid or irregular heartbeat
• high blood pressure
• jitteriness or shakiness
• intense headaches
• pale or cold skin

A 2018 review article states that having high levels of norepinephrine can increase a person’s risk of cardiovascular and kidney damage.

An epinephrine overdose can occur in people who use epinephrine injections to treat certain medical conditions. An overdose of injected epinephrine can lead to dangerously high blood pressure, stroke, or even death.

Epinephrine and norepinephrine are similar chemicals that act as both neurotransmitters and hormones in the body. Both substances play an important role in the body’s fight or flight response, and their release into the bloodstream causes increases in blood pressure, heart rate, and blood sugar levels.

Epinephrine acts on the alpha- and beta-adrenoreceptors in the muscles, lungs, heart, and blood vessels. Norepinephrine is a metabolite of dopamine that primarily acts on the alpha-adrenoreceptors in the blood vessels.

Doctors may prescribe epinephrine to treat potentially life threatening conditions, such as anaphylaxis, severe asthma attacks, and cardiac arrest. A doctor may prescribe norepinephrine to raise dangerously low blood pressure following a heart attack, critical hypotension, or septic shock.

In the bowels of the brain: what neurotransmitters control our emotions and reactions

How Neurologists Understand Emotions

Before we start talking about how and what substances control our emotions, let’s designate the optics through which we will consider them. The cognitive-behavioral approach seems to be the most complete. It is he who is called the gold standard of modern psychotherapy [1].

The cognitive-behavioral approach, working with unconscious attitudes and behavioral reactions, distinguishes 3 levels:

1. Jet . This is the level of basic, or vital, emotions that exist in one form or another in all vertebrates. In a child, they appear already in the first days of life. They direct us to helpful stimuli like food and help us avoid those that are harmful. The reactive level is provided by the deep structures of the brain, which in children are not yet controlled by the cortex. The child cries desperately when the mother leaves the room, and does not calm down until he is picked up.

2. Casual . This level is needed for social interactions. For example, we are more pleased to deal with a person who shows empathy and interest. This means that even business communication based on understanding the emotional state of another and sincere interest will be much more effective. Such emotions do not require reflection: we experience them, we understand what they mean, but we do it instinctively.

3. Reflective . Associated with thinking. Only humans have this, and we owe this to the prefrontal cortex and the frontal lobes of the brain – the centers through which we can evaluate and control our behavior. The reflexive level is associated with safety, but, unlike reactive emotions, it is a conscious feeling of the presence or absence of danger. In children, reflective emotions appear only at about 3–4 years of age. Therefore, you cannot explain to a small child that a person in a white coat will only look to see if his throat is red. The child remembers that once someone in a white coat gave him an injection, which means that it will hurt again. On the other hand, even those adults who feel uncomfortable in the dark still understand that their fear is irrational and there is absolutely nothing to be afraid of in their bedroom.

What brain structures are responsible for emotions and reactions

Let’s talk about where and how our emotions and reactions are born . To do this, let’s look into the depths of the human brain [2].

• Thalamus . It is a coordinating structure. Its function is to translate what is perceived from the outside – a rumble, a touch, a flash of light – into a nerve impulse.
• Amygdala or amygdala . If you like, this is our panic button. In children under 3–4 years of age, the amygdala functions independently of the cortex. The genetic predisposition to anxiety is precisely due to the work of the amygdala. It is also responsible for the expression of emotions, memory and learning.
• Hippocampus . This is our book of memory, written on the basis of experience. This structure stores information, retrieves it, and helps you figure out how to behave in similar circumstances next time. Everyone knows that confusion is the primary reaction to everything new. This is precisely due to the fact that the hippocampus simply cannot find this or that situation in previous records.
• Prefrontal cortex of the frontal lobes . Necessary for a conscious assessment of what is happening. As we have already noted, the prefrontal cortex does not work fully in children under 3-4 years old.
• Hypothalamus . Responsible for such vegetative manifestations as palpitations, sweating and others. Did you blush when you heard an uncomfortable question? It’s simple: the hypothalamus worked.

Let us now consider how these structures work when a pleasant or, on the contrary, undesirable stimulus appears. The scheme depends on the strength of the stimulus. If it is sharp and strong, the impulse is transmitted immediately along the path of the thalamus – amygdala – hypothalamus. If the stimulus is not strong enough and is not perceived as dangerous right now, we observe a different routing: thalamus – prefrontal cortex – hippocampus – hypothalamus. Here, due to the inclusion of such components as a conscious assessment and comparison of the situation with previous experience, the response is delayed. That is, we do not act immediately, but analyze different models of behavior, choosing the most appropriate one.

What are neurotransmitters

Brain neurotransmitters are precisely those substances that ensure the operation of the described mechanisms. Without them, nerve impulses could not be transmitted clearly, and nerve pathways would not form.

Consider the mechanism of neurotransmitters. In the nervous tissue there are many synapses – the smallest formations that connect neurons. Inside the cell, neurotransmitters are compactly packed into special synaptic vesicles. When excited, the bubbles burst and, being released outside the cell, these substances enter the synaptic cleft – the contact intercellular space. From there, their molecules get to the receptors of the next neuron in the chain. So the impulse propagates along the fiber, forming a nerve path.

This method of generating nerve impulses is called chemical. Once upon a time there was a theory that they are transmitted and distributed only with the help of electrical synapses, that is, without the participation of special substances. As neuroscience developed, it became apparent that electrical transmission was not the most efficient. First, it is extremely inaccurate, since the excitation is distributed indiscriminately, to all the neurons around. On the other hand, the discharge, passing through the nerve fiber, decays. The action of neurotransmitters, on the contrary, is precise and goes without loss [3].

Classification of neurotransmitters

Traditionally, there are three groups of neurotransmitters :

• brake
• stimulants
• modulating

As you might guess, the first includes substances that inhibit the activity of neighboring neurons. The role of excitatory neurotransmitters, on the contrary, is to activate nerve cells. As for the third group, they change the susceptibility of neurons to inhibitory or excitatory influences.

In terms of chemical structure, we can talk about a variety of types of neurotransmitters, for example:

• Amino acids (glutamate and GABA)
• Peptides (oxytocin and endorphins)
• Monoamines (serotonin, epinephrine, norepinephrine, dopamine, histamine, etc. )

Functions of neurotransmitters

It seems logical to divide these substances into 2 large groups: facilitating and hindering the storage and retrieval of information.

Neurotransmitters for information storage and retrieval

Thanks to them, we respond to a stimulus – we get scared, angry, rejoice. These reactions arise from experience, and memory plays a key role here.

Glutamate

Most of all in the brain it is his: he is necessary for each new process. So, thanks to the release of glutamate, the brain remembers that the sound of a crunching chair is associated with a fall. The next time we hear that sound, we will reflexively try to stand up. The brighter the event, the more it stands out.

In this light, it does not seem so surprising that some people step on the same rake, choose the same behaviors, similar partners, and so on. In such cases, behavior modification requires a lot of work and often the help of a psychotherapist is needed. The goal of psychotherapy here is to break the old glutamate chains and form new ones.

Norepinephrine

Blocks the cortex at the time of stress. His task is to tell us: “Do not think – save yourself!”. Suppose a dog is chasing you. It is unlikely that you will think about who runs faster – you or the dog. Rather, you simply run forward.

This monoamine also ensures the accuracy of finding information and suppresses fear. You have probably heard stories of people jumping out of windows without breaking anything under extreme stress, such as a sudden fire or escaping from persecution. Of course, the body’s neurotransmitters have nothing to do with it: these people were lucky and the height, most likely, was low. However, norepinephrine may have helped them navigate and correctly assess which window is best to jump out of and where and how to land.

Cortisol

Enhances the action of norepinephrine and increases the excitability of the amygdala, adapting the body to the regime of hyper-anxiety. If you’ve ever heard the expression “knee-deep sea”, know that it’s about cortisol. In this state, we are ready to fight an opponent much stronger than us. The biblical hero Samson, according to legend, tore the mouth of a lion. Probably, the legendary Samson owed the success of this fight to this monoamine.

Cortisol is interesting in that it can distort the work of the hippocampus, our book of memory, including downplaying the significance of an event in the past. Its reverse effect is based on this property: when its level is high, the extraction of information is difficult.

Dopamine

This is our basis of mindfulness and receptivity to the environment. They say that fear has big eyes – this is just the result of the work of the dopamine system. Imagine that you are walking through a dark forest or cemetery at night and you hear footsteps behind you. The typical norepinephrine response in this situation is to run, while the dopamine response is to freeze and listen.

It also provides motivation and control of activities towards the goal. Let’s say you dream of a beautiful muscular relief, because the beach season is ahead. It’s evening now, and you’re happy that you’ve done so many reps in the gym. At the same time, tomorrow you are ready to set a new record – and all for the sake of one goal. If so, you should be congratulated: you do not suffer from a lack of dopamine, and you can envy your motivation.

Neurotransmitters that interfere with the storage and retrieval of information

These substances give what can be defined as happiness in the moment. Happy hours, as you know, are not observed, and it’s all thanks to them.

Serotonin

Monoamine, which reduces the need for information. Here you can remember that slight fatigue after some pleasant activity, such as sex. Do you want to scroll the news feed in this state?

The same action is very evident as a side effect in the treatment of anxiety disorders and depression with SSRIs (selective serotonin reuptake inhibitors). As we have already said, if serotonin rises, the patient feels good here and now. True, sometimes in this state, not only anxiety goes away, but also motivation: there is no need to go beyond what is called the comfort zone. I recall a case when SSRIs brought relief to an anxious patient who was then strenuously preparing for exams. But another problem arose: the patient abandoned the preparation and could not force himself to study. Of course, the drug had to be changed. This sometimes occurs, but this should not be afraid: it is quite possible to pick up another SSRI.

Serotonin also mediates what is called an objective view from the outside. Suppose the boss was harsh with us. Of course, we will be upset, but we can also look at what happened differently. “Oh, yes,” we recall, “he recently divorced his wife.” As if nothing had happened, we continue to work on and are almost not angry with the boss.

Endorphins

Like serotonin, they reduce alertness. They also block the transmission of pain impulses and cause euphoria. Here we can mention a curious state, familiar, for example, to participants in sports marathons. The effect is that at a certain point the athlete stops feeling tired and in pain and experiences something akin to a slight intoxication. This state, also known as runner’s euphoria, develops due to the release of endorphins.

Gamma-aminobutyric acid

This substance is the main inhibitory neurotransmitter in the central nervous system. Its main function is to prevent overexcitation. Drugs like Phenazepam, sometimes used in the treatment of anxiety, act specifically on the GABA system, causing a feeling of calm and security.

How neurotransmitters are associated with disease

Low serotonin levels are associated with depressed mood. Such patients often experience difficulty falling asleep, and when they wake up, they do not feel cheerful. It is difficult for them to enjoy the usual things, they are focused on problems and try to find ways to solve them. From them, others often hear something like “I never succeed” or “Only everything is bad with me.”

A lack of serotonin underlies anxiety disorders. With its deficiency and an imbalance of other neuroamines, patients develop depression, a mechanism known in science as the monoamine theory of depression [4].

A decrease in norepinephrine leads to the emergence of a chronic pain syndrome, when the pain torments for months. This is due to the fact that with such a long-term preservation of pain, norepinephrine is depleted, and then even a minor stimulus causes a full-fledged pain syndrome.

Low norepinephrine leads to a decrease in serotonin and, possibly, depression associated with this.

An excess of dopamine provokes arousal. It is known that schizophrenia, delusional disorders, and bipolar disorder in the stage of mania are associated with this, when a depressive episode is replaced by a period of motor and mental excitement. In this state, the patient sees or hears something that is not there. It suddenly begins to seem to him that he is under the influence of a person who, perhaps, does not even know about his existence.

It also influences the quality of movement, providing coordination and fluidity, and mediates motor automatisms such as those that allow us to move our feet when we walk or tie our shoelaces without thinking. Decrease in dopamine gives Parkinson’s disease. In such patients, trembling of the limbs, high muscle tone and slow movements are noticeable. Excess, on the contrary, manifests itself in obsessive uncontrolled movements.

The dopamine system is also responsible for the formation of addictions. Psychoactive substances alter the physiology of motivation by providing positive reinforcement in the form of euphoria that occurs after use. It is curious that the dopamine basis is also found in other addictions, such as digital addiction. It has been proven that the latter is associated with the growth of dopamine receptors against the background of high norepinephrine and low serotonin.

Speaking of addictions, one cannot fail to mention gamma-aminobutyric acid. Alcohol affects the GABA system, which gives a feeling of some calmness. This is exactly the effect that those who say that alcohol helps them relieve stress have in mind. The problem is that GABA receptors get “tired” when overstimulated. So there is a need to increase the dose and alcoholism develops.

Terminals

1. Cognitive behavioral therapy distinguishes 3 levels of emotions: reactive (biological), everyday (social) and reflective (conscious). They involve different parts of the brain: from the simpler ones from an evolutionary point of view to the more complex ones.

2. Key structures that mediate emotion and response include the thalamus, amygdala, hippocampus, prefrontal cortex, and hypothalamus. Important is the fact that emotions are mediated by memory and past experience, but can also be formed without the participation of the cortex.

3. The functioning of the above structures and levels as a whole is possible due to the systems of neurotransmitters – biologically active substances that accurately and efficiently transmit nerve impulses.

4. Neurotransmitters are classified on various grounds. For example, by action (inhibitory, excitatory and modulating) and by chemical composition (amino acids, peptides, monoamines, etc.).

5. Speaking about the participation of the main neurotransmitters in the control of emotions and reactions, it is convenient to divide them into 2 groups: those that contribute to the storage and retrieval of information, and those that hinder this.

6. Low serotonin provokes anxiety disorders and depression. Lack of norepinephrine can also lead to depression. It is also involved in the formation of chronic pain syndrome. Diseases associated with dopamine occur both against the background of its decrease (Parkinson’s disease) and during its increase (delusional disorders, schizophrenia, bipolar disorder in the phase of mania). In addition, the dopamine system is involved in the formation of addictions, and alcohol addiction is also associated with the GABA system.

Clinic Nashe Vremya is a place where you will be helped. Make an appointment to get a consultation with a neurologist and choose a treatment.

Sources

David D., Cristea I., Hofmann S. G. Why cognitive behavioral therapy is the current gold standard of psychotherapy // Front Psychiatry. — 2018; 9:4.
Duus P. Topical diagnosis in neurology. Anatomy. Physiology. Clinic // IPC “Vazar Ferro”. — Moscow, 1996; 199–248.
Purves D., Augustine G.J., Fitzpatrick D., et al., editors. What defines a neurotransmitter? // Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates. — 2001.
Deakin J. The role of serotonin in depression and anxiety // European Psychiatry. — 1998; 13(2):57–63.

dopamine, norepinephrine, serotonin / Sudo Null IT News

Neurotransmitters are a holiday that is always with you. We constantly hear that they give feelings of joy and pleasure, but we know little about how they work. In the first part of a small educational course, Atlas talks about the three most famous neurotransmitters, without which our life would be simply disgusting.

How neurotransmitters work

Nerve cells communicate with each other with the help of processes – axons and dendrites. The gap between them is the so-called synaptic cleft. This is where neurons interact.

Mediators are synthesized in the cell and delivered to the end of the axon – to the presynaptic membrane. There, under the action of electrical impulses, they enter the synaptic cleft and activate the receptors of the next neuron. After activation of the receptors, the neurotransmitter returns back to the cell (the so-called reuptake occurs) or is destroyed.

Neurotransmitters themselves are not proteins, so there is no “dopamine gene” or “adrenaline gene”. Proteins perform all the auxiliary work: enzyme proteins synthesize the substance of the neurotransmitter, transporter proteins are responsible for delivery, receptor proteins activate the nerve cell. Several proteins can be responsible for the correct functioning of one neurotransmitter, which means several different genes.

Dopamine

By activating neurons in different areas of the brain, dopamine plays several roles. Firstly, it is responsible for motor activity and gives the joy of movement. Secondly, it gives a feeling of almost childish delight from learning new things – and the desire to search for novelty. Third, dopamine performs an important function of reward and reinforcement of motivation: as soon as we do something useful for the life of the human species, neurons give us a reward – a feeling of satisfaction (sometimes called pleasure). At a basic level, we receive a reward for simple human joys – food and sex, but in general, the options for achieving satisfaction depend on the tastes of everyone – someone will get a “carrot” for the added code, someone for this article.

The reward system is related to learning: a person gets pleasure, and new causal associations are formed in his brain. And then, when the pleasure passes and the question arises of how to get it again, a simple solution will arise – to write another article.

Dopamine looks like a great stimulant for work and study, as well as an ideal drug – most drugs (amphetamine, cocaine) are associated with the action of dopamine, only there are serious side effects. An “overdose” of dopamine leads to schizophrenia (the brain works so actively that it begins to manifest itself in auditory and visual hallucinations), and a lack of it leads to a depressive disorder or the development of Parkinson’s disease.

Dopamine has five receptors, numbered from D1 to D5. The fourth receptor is responsible for the search for novelty. It is encoded by the DRD4 gene, the length of which determines the intensity of dopamine uptake. The lower the number of repetitions, the easier it is for a person to reach the peak of pleasure. Such people will most likely have enough of a delicious dinner and a good movie.

The more repetitions – and there can be up to ten – the more difficult it is to enjoy. Such people have to work hard to get a reward: go on a trip around the world, conquer the top of a mountain, do somersaults on a motorcycle, or put all their fortune on red in Las Vegas. Such a genotype is associated with the range of migration of ancient people from Africa across Eurasia. There is also sad statistics: the “unsatisfactory” variant of DRD4 is more common among those convicted in prisons for serious crimes.

Norepinephrine

Norepinephrine is a neurotransmitter for wakefulness and quick decision making. It is activated during stress and in extreme situations, it is involved in the “fight or flight” reaction. Norepinephrine causes a surge of energy, reduces the feeling of fear, increases the level of aggression. At the somatic level, under the influence of norepinephrine, the heartbeat quickens and blood pressure rises.

Norepinephrine is the favorite mediator of surfers, snowboarders, motorcyclists and other extreme sports enthusiasts, as well as their counterparts in casinos and gaming clubs – the brain does not make a difference between real events and imaginary ones, so the life-safe risk of losing your fortune in cards is enough for norepinephrine activation.

A high level of norepinephrine leads to a decrease in vision and analytical abilities, and a lack of it leads to boredom and apathy.

The SLC6A2 gene encodes the norepinephrine transporter protein. It provides reuptake of norepinephrine into the presynaptic membrane. How long norepinephrine will act in the human body depends on its work after it has successfully coped with a dangerous situation. Mutations in this gene can cause attention deficit disorder (ADHD).

Serotonin

We are accustomed to hearing about it as a “hormone of happiness”, while serotonin is not a hormone at all, and with “happiness” everything is not so simple. Serotonin is a neurotransmitter that not only brings positive emotions, but reduces susceptibility to negative ones. It provides support to the “neighboring” neurotransmitters – norepinephrine and dopamine; serotonin is involved in motor activity, reduces general pain, and helps the body in the fight against inflammation. Also, serotonin increases the accuracy of the transmission of active signals in the brain and helps to concentrate.

An excess of serotonin (for example, when using LSD) increases the “loudness” of secondary signals in the brain, and hallucinations occur. A lack of serotonin and an imbalance between positive and negative emotions are the main cause of depression.

The 5-HTTLPR gene encodes a serotonin transporter protein. The gene sequence contains a region of repeats, the number of which may vary. The longer the chain, the easier it is for a person to maintain a positive attitude and switch from negative emotions. The shorter, the more likely the negative experience will be traumatic. The number of repetitions is also associated with sudden infant death syndrome, aggressive behavior in the development of Alzheimer’s disease, and a tendency to depression.

Destruction of neurotransmitters

The action of neurotransmitters is like a holiday, as if everyone went out into the street in a joyful crowd to watch the fireworks. But the holiday cannot (and should not) last forever, and neon roses in the night sky must give way to familiar constellations and dawn.
For this, the body has a transmitter reuptake function – when the substance returns from the synaptic cleft back to the axon presynaptic membrane and the action of the neurotransmitter stops. But sometimes reuptake is not enough, and more effective measures are needed – the destruction of the neurotransmitter molecule. These functions are also performed by proteins.

The COMT gene encodes the enzyme catechol-O-methyltransferase, which destroys norepinephrine and dopamine. The work of the protein depends on how well you will cope with stressful situations. Owners of the active form of the COMT gene – warriors by nature – receive a reduced level of dopamine in the frontal lobe of the brain, which is responsible for information processing and pleasant sensations. Such people adapt better to stressful situations, they are open to communication, they have a better memory. But due to low levels of dopamine, they get less pleasure from life, are more prone to depression, and their motor functions are less developed. An inactive variant of the COMT gene reverses the situation. Those with an inactive mutation have good fine motor skills, are more creative, but have a poor tolerance for pain, and as soon as they get into a stressful situation, they sink into irritability, impulsiveness, and anxiety. Mutations in the COMT gene are also associated with parskinsonism and hypertension.

The monoamine oxidase A enzyme gene MAOA is responsible for the deactivation of monoamines – neurotransmitters with one amino group, which include adrenaline, norepinephrine, serotonin, melatonin, histamine, dopamine. The better the MAOA gene works, the faster the “mind fog” caused by a stressful situation is neutralized and the faster a person is able to make informed decisions.

Sometimes even the MAOA gene is called the “criminal gene”: certain gene mutations contribute to the emergence of pathological aggression.