Theory for Anxiety Disorders

Abstract

“Anxiety” is part of our lives and is frequently generated by unhandled stress, but people with “anxiety disorders” have repetitive episodes of excessive “anguish” and “anxiety” that interfere with their daily activities. At the present time, the causes of “anxiety disorders” are not fully understood as diseases, where doctors can diagnose or evaluate the level of diseases using mainly medical lab tests or biomedical imaging, identifying the cause as infection, inflammation, or other physical factors that can be treated with medication or surgery or even prevented by vaccines. Based on the logical assertion that “in order for something to be improved, it must be understood and measured”. The objective of the “theory of anxiety disorder” is to understand it and identify body parameters that can be measured in a “subjective mode”, and I recommend some new experimental “objective mode”, to detect the degree of physical altered symptoms and mental abnormal reactions classified as “anxiety disorder”, which is characterized by a consistent sense of feeling pressured and overwhelmed. The steps to understanding the process by which “anxiety” is generated and how it could be analyzed and measured as evolving into “anxiety disorder”.

1. Introduction

The “anxiety” process usually begins with “anguish”, which is an “emotional distress” or emotional suffering or emotional pain that causes physiological emotions such as “fear”, sorrow, and others. These emotions generate a mental state identified as “stress” that shows strain in adverse situations. “Anxiety” includes a wide range of symptoms that are usually temporary, showing a mental condition with excessive nervousness about imminent threats that could be real or just perceived, leading to avoidance behaviors, and showing evidence of physical symptoms such as muscle tension, increased heart rate, and others. “Anxiety” is a normal reaction for natural survival, but when this process is repetitive, it opens up for “stress accumulation” symptoms, that could evolve over time into “anxiety disorder”. Which is an extremely debilitating mind state with excessive fear, negative behavioral and emotional consequences that frequently detect false threats that make the body spend unreasonable energy levels on something that is not really a threat [1].

When we feel afraid of a present situation, “emotional distress” is generated as “anguish”, the body reacts, showing “physical emotion” as fear, and “emotional strain by the adverse situation” is observed as “stress” symptoms. Occasional “stress” is known as “acute stress,” presenting dramatic physiological and psychological reactions for a short-term period of time. To handle the situation, our brain releases a group of “hormones” identified as “stress hormones.” They regulate the process and handle the affection index and severity degrees of the process that our brain relates with memory mechanisms to modulate consolidation and retrieval processes associated with past emotional episodic events that were stored in memory, such as fear and extinction situations that were already learned. When these fearful situations are repeated constantly, the process is altered, showing longer durations, creating “stress accumulation”, identified as “chronic stress”. That constantly alters our “nervous neuron system” with processes that are evaluated constantly as “excitatory and/or inhibitory state changes,” presenting physical altered symptoms and mind abnormal reactions classified as “anxiety disorder,” characterized by a consistent sense of feeling pressured and overwhelmed.

2. “Anxiety disorder”

“Disorder” is a collection of symptoms that come together to alter the mental health condition and disrupt how the human mind works. At the present time, the causes of “anxiety disorders” are not fully understood as diseases, where doctors can diagnose or evaluate the level of disease using mainly medical lab-tests or biomedical imaging, identifying the cause as infection, inflammation, or other physical factors that can be treated with medication or surgery or even prevented by vaccines. Diagnosing or evaluating “anxiety disorders” is not an easy task, even for doctors. Frequently, the primary care provider, the one that checks for “anxiety disorder” signs and, if he suspects some of them, generates a patient reference to a mental health specialist such as a “psychiatrist or psychologist” to confirm or not the disorder. They must evaluate and identify the kind of “stress”, that is divided into three main categories: “anxiety related disorders”, “obsessive-compulsive, and related disorders,” and “trauma- and stressor-related disorders” [2]. That is characterized as follows:

• “Anxiety related disorders” with sense of excessive fear, with emotional responses to actual perceived threats and/or future ones. Presenting negative behaviors with emotional consequences.

• “Obsessive-compulsive, and related disorders” with persistent intrusive thoughts known as obsessions triggering compulsive behaviors of “anxiety”.

• “Trauma- and stressor-related disorders” are closely related to traumatic experiences in his or her life.

And if possible, find the reason as “specific phobia”, “social anxiety disorder (SAD)”, “panic anxiety disorder”, “post-traumatic stress disorder (PTSD)”, “generalized anxiety disorder (GAD)”, and many others. The medical diagnoses by specialists are based on five main types of analysis: “assessment evaluations”, “anxiety physical symptoms”, “medical history review”, “current prescriptions”, and “lab-tests and/or biomedical imaging”. Where each one can be described as:

1. “Assessment evaluation,” which are psychological questionnaires to evaluate the mental health of the patients, many doctors use the standard criteria: “Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association” [3].

   “Assessment evaluations” are in “subjective mode,” where the responses depend on each patient’s point of view, as opposed to “objective mode,” as lab-tests are measured values.

2. “Anxiety physical symptoms,” evaluating each of them and paying special attention to recurrent events that last for a longer time than normal, such as restlessness, nausea or digestive troubles, muscle contractions, palpitations, cold or sweaty hands, compression of nerves in hands or feet, shortness of breath, increased heart rate, high blood pressure, dry mouth, hot flashes or chills, essential tremors, stomach pain, sleep problems, weakness, or fatigue, and special focuses on avoidance of situations that may cause “anguish” emotions such as “fear” and many others.

   “Anxiety physical symptoms” where only some of them are under “objective mode”, and others are under “subjective mode”. The main problem is that many “anxiety symptoms” are very similar to those of other illnesses and/or diseases.

3. “Medical history review” to detect body changes through time such as weight, heart rate, blood pressure, illness, diseases, injuries, etc.

   “Medical history” is recommended to review to find physical or mental changes in the past.

4. “Current prescriptions” that are taken to analysis their interactions and possibility to develop “anxiety” symptoms.

   “Doctors have access to many electronic databases online that are continuously updated, including new medication uses and dosing, regimens for drug interactions, drug allergies, and duplicate therapies, helping them to ensure accurate medication doses.

5. “Lab-tests and/or biomedical imaging” to detect other illnesses or body lesions as possible causes for “anxiety” to eliminate the possibility of them having similar symptoms as:

   1. “Postural Orthostatic Tachycardia Syndrome” (POTS) is an autonomic system disorder that increases heart rate (tachycardia) and often drops blood pressure upon standing [4].

   2. “Endometriosis” is a women’s disease with chronic pain in the lower back and pelvis, bowel movements, urinating after sex activity or in menstrual periods, and other activities presenting frequently other symptoms as fatigue, anxious mood, depression, and others [5].

   3. “Crohn’s Disease,” also known as inflammatory bowel disease (IBD), is observed as digestive tract inflammation, mainly in the small and large intestine, with symptoms of diarrhea, fatigue, stool blood, and others [6].

   4. “Fibromyalgia disorder” presents generalized muscle pain, joints, and nerves with symptoms of fatigue, cognitive problems, sleep disturbances, anxiety, depression, and others [7].

   5. “Hyperthyroidism” happens when the thyroid gland fails to produce thyroid hormone, presenting symptoms of poor concentration, tiredness, muscle weakness, and others such as fatigue, weight gain, cold intolerance, and others [8].

   6. “Addison’s disease,” also known as “adrenal insufficiency” of the hormone cortisol, happens when the adrenal glands do not produce normal cortisol levels. Low cortisol levels can actually cause anxiety and depression [9].

   7. “Ankylosing spondylitis” is a type of arthritis that affects the spine and large joints with inflammation, causing pain in the ribs and shoulders, damaging the joint between the spine and the hipbone, and also causing bone bridges between vertebrae in the spine, fusing those bones. “Ankylosing spondylitis” mimics pain from a panic attack [10].

   8. “Pseudo bulbar affect disorder (PBA)” that is characterized by episodes of sudden emotions of crying/laughing without control. This disorder if frequently a symptom of neurologic diseases [11]

And many others neurologic diseases as “Parkinsonism*,” “Alzheimer’s”, and many others that may include “anxiety” as one of their collection of symptoms.

Note*: “Parkinsonism” is a nervous system disorder that affects areas of the brain that process body movements. It worsens with time with symptoms such as slowed movements, tremors, rigidity, stiffness, shaking in upper and lower limbs, and others with symptoms such as unbalanced walking gait, freezing, stooped posture, and many more.

3. Theory for anxiety disorder- general overview

“Theory for Anxiety Disorder,” seen in a general way, can be explained in two chain reactions: “anxiety” and “anxiety disorder,” as shown in Figure 1.

• “Anxiety” is a normal chain reaction of internal processes for natural convenience when there is a threat event, as indicated in Figure 1a. It begins with emotional distress as “anguish”, reacts with physical emotion as “fear”, and reacts with emotional strain from adverse situations as “acute stress”. That process involves the “retrieval of episodic memories” of danger that reacts with “anxiety”, which is expressed with mind and body symptoms alterations.

• “Anxiety disorder” is another chain reaction based on repetitive thoughts of being under threat, showing a sense of feeling pressured and overwhelmed for frequent mind evaluation of the “anxiety” chain reaction as indicated in Figure 1b. It usually begins with a sequence of events and reactions that are frequently analyzed. They evolved as a kind of “stress accumulation” identified as “chronic stress” characterized by longer episodes, due to the frequent alterations of neuronal network stability, that continuously evaluate how to handle the nervous neuron network alterations, by excitatory and inhibitory neurotransmitter signals that could request excessive secretion of “stress hormones” to stabilize the body and mind alterations that are reflecting in the human body with a wide range of symptoms of a physical reaction with a mental condition that indicates excessive nervousness about imminent threats, that could be real or just mentally perceived as “Anxiety Disorder”.

Figure 1.

The “Theory for Anxiety Disorders-General Overview” can be explained in two chain reactions: (a) “anxiety” normal process for natural supervenience as shown in the top secction, and (b) “Theory for Anxiety Disorder” explain the sense of feeling pressured and overwhelmed as a result of frequent “anxiety” chain reaction as shown in the bottom section.

The physical and mental chain reactions of frequently “anxiety” are generally explained by the “Theory for Anxiety Disorder-General Overview”, resulting in the expression of the sense of feeling pressured and overwhelmed by frequently “anxiety” chain reactions events that are shown externally with physical body alterations and mind abnormal responses triggered by fast changes on the neuronal network’s stability neurotransmitters expressing the excessive “stress hormones” involved in the process for stabilizing the series of frequently threats.

4. Theory for anxiety disorder: details overview

To understand the “Theory for Anxiety Disorder: Details Overview” it is necessary to document all the elements and actions involved in the “anxiety chain reaction” and how it evolves into an “anxiety disorder chain reaction”. These elements are organized on: “chemical messenger types”, “endocrine system glands that release stress hormone”, “neurotransmitters involve handling stress and anxiety”, “the endocrine system and stress hormone system”, “HPA axis loops,” and “the theory for anxiety disorder: details overview.”

4.1 Chemical messenger types

The human organism is composed of “living cells,” and extracellular body cells are the physical substance of organic materials organized into tissues, organs, and systems. The body’s “living cells” detect the activity around them and respond in real time, sending and receiving millions of messages using “chemical signals” generally known as “chemical messengers.” These are proteins or other types of molecules that are often secreted from the cell and released into the “extracellular space,” which can be close or not. Each “chemical signal molecule” is received only by the right “receptor cells” for that specific signal. When the specific “chemical signal” reaches the right receptor, it binds into the “receptor cell”. This process is known as “ligand”, and it triggers a change inside the “receptor cell”.

In other words, “intercellular signals between-cells” are converted into “intracellular signals within cells” that trigger a response.

Generally, there are four categories of “chemical signal messenger” according to the distance that the signal travels through the organism to reach the “receptor cell”, These are: “autocrine”, “paracrine”, “endocrine”, and “neurotransmitter”. Each category can be described as follows:

• “Autocrine chemical messenger” stimulates the cell that originally secreted it. i.e., “white blood cells (WBC)” secreted during an infection.

  Many types of WBCs can stimulate their own replication to rapidly increase the total number of them.

• “Paracrine chemical messenger” acts locally on nearby cells into the extracellular fluid that affects surrounding “receptor cells” i.e., “Histamine” released by certain WBC types.

  The histamine released by WBC during allergic reactions stimulates vasodilation in nearby blood cells.

• “Endocrine chemical messengers” are secreted into the bloodstream by certain glands and cells as a part of the “endocrine system”.

  “Endocrine chemical messengers” travel through the “circulatory system” to reach their “target cells”.

• “Neurotransmitter chemical messengers” are secreted by “nerve cells or neurons” that activate other adjacent “neurons,” “muscle cells,” or “glandular cells.”

  “Neurotransmitter chemical messengers” are secreted into a “synaptic cleft” in a synapse chemical environment at the end of the neuron cell that connects to other neurons.

In this research book chapter, we focus especially on “endocrine chemical messengers” and “neurotransmitter chemical messengers”. Where:

• “Endocrine chemical messengers” are special “hormones” that are secreted by glands as a part of the “endocrine system” into the bloodstream, i.e., “adrenal glands” and released into the bloodstream to act on their specific “target cells”,

• “Neurotransmitter chemical messengers” that are produced by the brain’s glands as a part of the “autonomic nervous system (ANS)”. They are molecules used by the ANS to transmit messages between neurons (nervous cells) or neurons to muscles. The place for communication between two connected neurons is the “synaptic cleft”, which is a small gap between neurons that is commonly known as a “synapse,” as shown in Figure 2b.

  “ANS” regulates the body’s internal environment with specific functions without conscious control, such as respiration, circulation, digestion, body temperature, metabolism, sweating, and many other internal functions.

Figure 2.

(a) Two neurons connected, (b) “synaptic clef” amplified showing the chemical synapse process, and (c) the four human brain lobes, cerebellum and spinal cord.

4.2 The endocrine and stress hormone systems

The “endocrine system” is in charge of continuously monitoring and regulating all processes in the human body through hormones that are secreted into the blood stream by glands. The main glands are the “pineal gland, adrenal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, hypothalamus, and adrenal glands” [12]. The “endocrine system” provides a more generalized regulation by secreting hormones into the systemic circulation in the path of circulation between the heart and the rest of the body. The “ANS” and “endocrine system” have a high level of integration in the brain, with the ability to influence processes in distant regions of the body and maintain the tendency toward a relatively stable equilibrium between interdependent elements in physiological processes identified as “homeostasis”. Using both systems as “chemical messengers” for the transmission of information from cells Several glands that signal each other in sequence are usually referred to as an axis. The most important for “stress” and “anxiety” is definitely the “hypothalamic-pituitary-adrenal axis.” The “stress hormone system” is identified in the “hypothalamic-pituitary-adrenal axis (HPA axis)” that stimulates the “pituitary gland” to secrete ‘adrenocorticotropic hormone (ACTH)” and stimulates the “adrenal cortex” to release “glucocorticoids” to function to maintain “physiological homeostasis”.

The “HPA axis*” is a major component in the “stress” response that allows physiological adaptation to the stressor to maintain “homeostasis”.; Note*: To be explained in sections 4.5, “HPA axis loops,” and 4.6, “the theory for anxiety disorder: details overview.”

4.3 Endocrine systems glands that release stress hormones

The “endocrine system” is responsible for regulating a range of bodily functions through the release of hormones. In this research, we focus on how it is activated when a stressful situation happens and produces hormones secreted by “glands” to handle “stress” and, by consequence, anxiety (as shown in Figure 3) to respond to the altered situation. These are identified as “stress hormones” and mainly they are “cortisol”, “adrenaline”, “norepinephrine”, and “glucocorticoids”.

• “Cortisol,” a “glucocorticoid steroid hormone” from the “adrenal glands” located on top of each kidney as shown in Figure 3, produces hormones that regulate metabolism, immune system, blood pressure, response to stress, and development of sexual characteristics, among others. It is an “endocrine chemical messenger” that suppresses inflammation in all bodily tissues and controls metabolism in muscles, fat, the liver, and bones, besides affecting the “sleep-wake cycles” [13].

  “The body produces “cortisol” every day, according to a daily rhythm where our levels begin to rise in the last hours of sleep. They reach their peak levels about 30 to 40 minutes after we wake up. Then, they decrease until they are almost nothing unless a stressful situation is present.

• “Adrenaline” and “norepinephrine” are hormones from the “adrenal medulla,” as shown in Figure 3. Where: Norepinephrine,“ also identified as noradrenaline,” is a “hormone” released by the “adrenal glands,” and it is also a “neurotransmitter chemical messenger” that helps transmit nerve signals across nerve cells, muscle cells, or gland cells. “Norepinephrine” travels directly and indirectly to the brain, influencing learning and memory processes, and is involved in the initiation and maintenance of “fear” and “anxiety”, modulating “episodic memory”, fear conditioning, and fear reconsolidation [14]. “Adrenaline”, also known as “epinephrine,” is a hormone produced by the “adrenal medulla” inside the “adrenal glands”. Its main function is to aid in the regulation of the sympathetic branch of the “autonomic nervous system”.

  “Adrenaline” and “norepinephrine” are hormones that rapidly increase in the nervous system and metabolic system activity during “stress.”

• “Glucocorticoids (glucose + cortex + steroid)” are “steroid hormones” that are secreted by the “adrenal glands” as anti-inflammatory and immunosuppressive actions that regulate “glucose metabolism” as a part of the “immune system” feedback to reduce inflammation [15].

Figure 3.

Steps in the theory of anxiety disorder: Details and overview.

4.4 Neurotransmitters involve handling stress and anxiety

Each of the two “brain hemispheres” has four sections identified as lobes, as shown in Figure 2c; these are: frontal, parietal, temporal, and occipital.

• The “frontal lobe” in the front of the head is involved in personality characteristics, decision making, movement, small recognition, and speech ability.

• The “parietal lobe” is in the middle of the brain and is involved in identifying objects and understanding spatial relationships, besides interpreting pain, touch, and helping the brain to understand spoken languages.

• The “occipital lobe” is on the back of the brain, and it is the place where vision is processed.

• The “temporal lobe” is on both sides of the brain, and many processes are executed for important functions, including short-term memory, speech, musical rhythm, and the smell recognition subprocess.

Deep in the brain, there are structures and glands that regulate “hormones” including the “pituitary gland”, “hypothalamus”, “hippocampus”, “amygdala”, and “pineal gland”, as shown in Figure 3. Each brain organ function can be described as follows:

• The “pituitary gland” acts as a “master gland” controlling the function of other glands in the body and regulating the flow of hormones that are secreted on the “thyroid”, “adrenals”, and others. The “pituitary gland” is located just below the “hypothalamus” and connected to it through blood vessels and nerves identified as the “pituitary stalk”, which is used for communication between the hypothalamus and the “anterior pituitary lobe” as bloodstream hormones and the “posterior lobe” through nerve as a neuronal connection [16], as shown in Figure 3.

  The pituitary gland secretes “(ACTH)” to stimulate the “adrenal cortex” part of the “endocrine system” to secrete glucocorticoids.

• “Hypothalamus” controls the “pituitary gland” sending “chemical messages” that control its function. Bedsides, plays a role in some aspects of memory and attention and regulates body temperature, synchronize sleep patterns, it also controls hunger and thirst.

  “Corticotropin-releasing hormone (CRH)” is secreted by the “paraventricular nucleus” in the hypothalamus as a response to stress, and it is identified as a central driver of the “stress hormone system,” as shown in Figure 3.

• The “hippocampus,” is an elongated ridge on the floor of each lateral ventricle of the brain hemispheres, is part of the “limbic system,” as shown in Figure 3. It plays important roles in the consolidation of information in memory, including “short-term”, “long-term”, and “spatial” [17].

  The “hippocampus” is considered the center of emotion, memory, learning, navigation, perception of space, and the autonomic nervous system.

Note*: “Limbic systems” are structures and interacting areas involved in motivation, emotion, and memory. Besides, it is an important element in the body’s response to “stress.”

• “Amygdala” is part of the “limbic system” that regulates emotion and memory and is associated with the “reward system”, “stress,” and the responses when someone perceives a threat.

• “Pineal gland” is indicated in Figure 3. It helps in the regulation of female hormone levels, contributing to cardiovascular health and mood stability. It responds to light and darkness to secrete melatonin, which regulates “circadian rhythms” and the sleep-wake system [13]. “Circadian rhythms” are physical, mental, and behavioral changes that follow a 24-hour cycle. The “pineal gland” releases melatonin during the darkness of the night and decreases its production during daylight.

• “Cerebral Cortex” or “gray matter” is the brain’s outermost layer of nerve cell tissue, consisting of nerve cell bodies, including the end portion of nerves called “dendrites,” as shown in Figure 2a. They are the part of a nerve cell that receives the chemical message from another nerve cell. It plays a key role in memory, thinking, learning, reasoning, consciousness, emotions, and functions related to the senses.

The relationship of the “amygdala” to the “hippocampus” and “prefrontal cortex” is rich in “glucocorticoid” receptors and highly sensitive to stress, making them a very important circuit for fear conditioning [18].

“Anxiety” is frequently associated in many previous research papers with “sleep and circadian rhythms alterations” [19].

There is evidence that the “prefrontal cortex” has a critical function in executive functions that monitor and manage “episodic memory,” as shown in Figure 3. These are “subjective experiences” captured to be remembered with details of past events that are triggered by present anxiety situations [20].

4.5 HPA axis loops

The “hypothalamic-pituitary-adrenal axis (HPA axis)” is a major component in the “stress” response that allows physiological adaptation to the stressor to maintain “homeostasis.” This axis has three organs that interact to control reactions to handle “stress” and regulate many body processes such as digestion, immune responses, mood, emotions, sexual activity, and energy storage and expenditure with direct influences and feedbacks to maintain relatively stable equilibrium between them. These are the “hypothalamus”, “pituitary gland” and “adrenal glands”. The “HPA axis “is a neuroendocrine pathway and feedback loop for many purposes; but it is mainly a “stress hormone system central driver” that stimulates the “pituitary gland“ in the deep brain to secrete “adrenocorticotropic hormone (ACTH)” and stimulates the “adrenal cortex” to release “glucocorticoids” [21].

Understanding how the “HPA axis” works is essential to understanding how “stress” is handled by orders and feedback, which are explained in the next section.

4.6 The theory for anxiety disorder-details overview

The general overview of the “theory for anxiety disorders” is shown in Figure 1. In this section with details, we will overview the integration of the “HPA axis loops”, visualize their integration with the “theory for anxiety disorders,” as shown in Figure 3, and explain it in the following steps:

1. “The sensory nervous system senses external possible threat events.” The “sensory nervous system,” as a part of the nervous system, is responsible for processing external sensory information by sensory receptor neurons in vision, hearing, touch, taste, smell, and even internal visceral sensations as movements, inflammation, and pain from internal body organs alter, including heart palpitations, stomach inflammation, intestine cramps, kidney pain, and other unpleasant sensations [22].

2. “Episodic memory retrieval” is the concept of a memory system from our own experiences, including temporally dated information and spatiotemporal relations, that allows the re-experience of specific previous experiences with the possibility of being repeated for actual sensed events. “Episodic memory retrieval” is the interaction of many brain regions, including the temporal, parietal, and frontal cortices, mainly handled by the “prefrontal cortex”, diencephalon as part of the forebrain, and cerebellum [23].

3. “Corticotropin-releasing hormone (CRH)”. When the treat event detected is related to past experiences retrieved, the “CRH” is secreted by the “hypothalamus”. It is the body’s direct response to many forms of “stress”, including physical and emotional stresses and internal and external stresses. Specifically, it is released by the “paraventricular nucleus” of the “hypothalamus” with the purpose of stimulating the “pituitary gland” as a part of the “HPA axis”.

   Note*: An exaggerated increase in “CRH” production has been observed to be associated with Alzheimer’s disease and depression [24].

4. “Adrenocorticotropic hormone (ACTH)” is secreted by the “pituitary gland” stimulated by “CRH” from the “hypothalamus”, and travels via the “bloodstream” to both “adrenal glands” that are at the top of each kidney.

5. “Adrenal glands secrete a special kind of hormone identified as stress hormones”. When the “adrenal glands” in the top of each kidney are stimulated by “ACHT” they secrete hormones such as “cortisol”, “glucocorticoids”, “epinephrine,” and “norepinephrine”. “Cortisol” known as the “stress hormone”, has many functions, including regulating stress response and metabolism, maintaining blood pressure, increasing, and regulating blood sugar levels, limiting inflammation*, and helping control the “sleep-wake cycle.” “Cortisol is sent via the bloodstream” as a response to “stress”.

The “sensory system” is in charge of detecting and processing information that is sensed in different places from the exterior senses and the interior as visceral sensation. It consists of sensory neurons, neural pathways, and brain parts involved in their processing.

Episodic memory retrieval is an internal process that finds, identifies, and mentally reconstructs past experiences related to learned lessons and compares them with the actual situation to determine the degree of the actual danger.

The “hypothalamus” makes many more hormones to communicate with and stimulate your pituitary gland: corticotrophin-releasing hormone (CRH), dopamine, gonadotrophin-releasing hormone (GnRH), and others.

ACTH is a hormone secreted as the body responds to “stress”. It stimulates the “adrenal glands” to produce different hormones with the purpose of balancing the situation that generated the actual event of “stress”.

Notes*: High levels of “cortisol” in the blood can lead to inflammation in a weakened immune system [25].

“The adrenal medulla secretes catecholamines; they are “hormones” that also function as “neurotransmitters”. They are produced in the brain, nerve tissues, and “adrenal glands”. The “adrenal medulla” secretes “catecholamines” to help the body respond to “stress”. The main types of catecholamines include “norepinephrine” and “epinephrine”. The main differences between them are summarized in Figure 4.

• “Norepinephrine,” also known as “noradrenaline,” is a part of the “HPA axis loop back” and plays an important role in the body’s “acute stress” and when stress situations are repetitive, as in “chronic stress,” with responses increasing alertness, arousal, attention, and focus, besides “constricting blood vessels to help maintain blood pressure when stress is present” and other functions such as increasing blood sugar levels.

• “Epinephrine” also known as “adrenaline” is secreted by the “adrenal medulla” in response to low blood sugar levels or exercise, helping the body to deliver extra oxygen to muscles, increase blood pressure and heart output, and “widen small arteries”. It has two roles as a “hormone” that is released by the “adrenal glands” in response to “stress” but is also a “neurotransmitter” that participates in the “synapses” cells as shown in Figure 2 as a part of the “sympathetic nervous system”, Its reaction causes many changes in the body during stressful events commonly known as the “fight-or-flight response”; this is a response to stay and fight the dangerous event or run to safety. These reactions occur when the brain perceives danger, nerves in the “hypothalamus” send a signal down to the “spinal cord and then to all body organs and tissues”: pupils are dilated in the eyes, skin turns pale because blood vessels divert blood that needs more oxygen as muscles fight or run away, the heart pumps harder to deliver more oxygenated blood to muscles for more strength, glycogen is stored in the liver to be ready to be converted to glucose, breathing is deeper and faster for more oxygen in the muscles, etc. These reactions continue until the brain senses that it is out of danger.

• The “adrenal cortex” secretes “glucocorticoids” as a part of the “HPA axis loop back”, these are “natural steroids” with many functions as interrupt inflammation by moving into cells and suppressing the proteins that promote inflammation.

Figure 4.

Differences between “norepinephrine” and “epinephrine”. Besides, two special comments about “cortisol” and “dopamine”.

“Dopamine” is another main type of catecholamine; it is a neurotransmitter that sends fast signals throughout the nervous system. It helps regulate the following: movement, emotions, and memory, and it is the brain’s reward mechanism.

“Glucocorticoids (GCs = glucose + cortex + steroid)” are “steroid hormones,” and they are essential for the termination of the stress response.

4.7 Summarizing main differences between hormones and neurotransmitters

The human body to function properly needs “hormones” and “neurotransmitters”, both are chemical messenger as explained on Section 4.3 and 4.4, the main differences between them are summarized on Table 1.

Characteristic	Hormones	Neurotransmitters
Molecules	Are mainly peptides, amines, terpenes* or steroids.; * Terpenes are bioactive compounds that are easily absorbed and accepted by the body and aid in balancing the production of crucial neurotransmitters like serotonin and dopamine. They have a positive impact on our mood	Less varied: usually peptide molecules, amino acids, or gases
Transmission mode	via the bloodstream to affect other tissues	Strict “synaptic” method of communication between cells.
Function Range	“Long-range”: organs or tissues that target hormones are sent a distance by the bloodstream	“Limited range” only affects cells that are connected through synaptic junction
Tissues range	Usually multi-targeted, various organs/tissues	Only in adjacent cells, mostly in the same tissue, with the exception of neuromuscular synapse
Response time	Tend to last, with effects that can take from minutes to days after reaching the target tissue.	Fractions of a second.
Effects modulation	The purpose of stabilizing blood levels, fluctuation, inhibiting or promoting the release of hormones to other tissues, and receptor availability	Neurotransmitters that are transmitted in the synapse, produce effect that depends on the affected cell type and are “all or nothing”, depending on whether or not the next cell is activated.

Table 1.

Main differences between hormones and neurotransmitters.

The steps for the “Theory for Anxiety Disorder: Details Overview” can be visualized in the estimated time each “neurotransmitter chemical messenger” and “endocrine chemical messenger” takes to reach their receptor, as shown in the chain reaction sequence response in Figure 5.

Figure 5.

Estimated autonomic nervous system and endocrinology system hormone response times for the “Theory for Anxiety Disorder: Details Overview”.

5. Conclusions

Integrating the information shown in Figures 1 and 2, it is noticeable that the interaction of the ‘HPA axis“ with neuroendocrine pathways and the feedbacks has different travel times; some are through the “autonomic nervous system“ and others through the “bloodstream“ as the blood circulates through the body. Both are necessary, but the event response time between them seems to overlap when “anguish“ and “anxiety” events are constantly triggered, as shown in Figure 3 and when visualizing the event time response in Figure 5.

The most important issue result of this research for “anxiety disorder” is: “Neurotransmitters” allow communications between neurons and other cells to “happen in fractions of a second,” represented in milliseconds in Figure 5, while “hormones” are secreted by the “endocrine system” travel via bloodstream to allow the regulation of many functions of the body to tend to last with effects that can take from minutes to days after reaching the target tissue, represented in minutes in Figure 5.

Summarizing the “theory for anxiety disorder” exposed in this research, there are at least three concepts that deserve immediate attention: Frequency of stress situations. Failure to react to avoid repeated exposure to stress situations, and Finding ways to handle and turn off unnecessary responses to false threats. All three affect the increased risk for the development of an “anxiety disorder”, and as far as is known, they can be treated with “cognitive behavioral therapy (CBT)”. CBT focuses on teaching the anxiety patient to develop specific skills to improve the symptoms and return to normal activities step by step. But it is also possible to develop cognitive computing applications to help with this kind of treatments, as explained in my book “Applied Biomedical Engineering Using Artificial Intelligence and Cognitive Models” [26].

Some commons reasons that trigger “anxiety” continuously are:

• “Hard times for humanity” are confronting a huge number of continuous disasters.

• “Climate change” is affecting our environment.

• “Bacteria and viruses” of different kinds that have been evolving as a treat for pandemic times,

• “Economic daily impacts” in our expenses compared with the cost of living incremented continuously to cover the cost of the basic needs such as healthy food, clean water, clean air quality, and the inevitable need to sleep well.

• “Smart devices with artificial intelligence” technological advances that are programed to take continuous attention, making frequent changes in our way of living, widen the amount of information that we receive and process on a daily basis [27].

• Genetics reasons, and many others.

6. Recommendation

“In order for something to be improved,; It must be understood and measured.”; There is an urgent need to develop methods to evaluate “anxiety” and “anxiety disorder” with objective mode methods that measure real values, beside the actual “subjective mode”. I will allow me to mention some of the many research papers doing this that I hope to have the opportunity to document and analyze in a future book chapter.

Some research has found “measuring hair cortisol concentration ranges by automated methods”, “associations between chronic stress and hair cortisol concentration” and “evaluation of chronic stress on the hypothalamic-pituitary-adrenal (HPA) axis”:

• “Measuring hair cortisol concentration ranges by automated methods [28]”, they found that hair cortisol concentration median measurements by an automated method are:

  1. For a healthy individual with low levels of stress, 55 picograms per milligram of hair (pg/mg) with a 2.5–97.5 percentile (40–128),

  2. For stressed individuals is 250 pg./mg of hair (range 182–520).

• “Associations between chronic stress and hair cortisol concentration (HCC)” when stressful life events within the past 6 months show a congruent time of stress with HCC stronger pooled correlation in thirteen studies from five countries with 1455 participants [29].

• “Evaluation of chronic stress on the hypothalamic-pituitary-adrenal (HPA) axis [30].” “Cortisol” is a recommended hormone for evaluation of “chronic hyperactivity” of the “hypothalamic-pituitary-adrenal (HPA) axis” in situations of “chronic stress”.

These cortisol ranges values can be used as a reference for other cortisol research papers and labs tests.

This research confirms the relation between chronic stress and cortisol, deducted in the theory for anxiety disorders in this chapter.

They found that cortisol variability during the circadian rhythm can be measured in the growing hair follicle that is incorporated into hair sections as it grows; they also claim that 3 cm of hair would reflect the cortisol levels of a patient in the last 3 months.

Thanks to all previous research that apportioned invaluable information and results with their research work on “anxiety” and “anxiety disorders”.

Notices: Knowledge and best practice in this field are constantly changing as new research and experience broaden our understanding, and changes in research methods, professional practices, or medical treatment may become necessary. To the fullest extent of the law, neither the publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence, or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein [31].