Adrenal glands' influence on brain behavior

• TYPE OF PSYCHOLOGY: Biological bases of behavior
• SUMMARY: The paired adrenal glands, situated above the kidneys, are each divided into two portions, a cortex and a medulla. The cortex produces steroid hormones, involved in the control of metabolism, inflammation, and other important processes; the medulla produces amino acid–derived catecholamines, which are thought to be important in brain behavior.

Introduction

The adrenal glands are a pair of triangular , one lying on top of each of the kidneys. These glands secrete several that are essential to life in that they regulate the body’s metabolism of fats, carbohydrates, and proteins; help maintain appropriate amounts of body fluids, thus participating in blood-pressure regulation; fight the effects of stress and injury on the body; participate in the ; and function in nerve-impulse transmission and brain function.

Endocrine glands produce one or more hormones and secrete them into the blood so that they can serve as intercellular messengers. In contrast, exocrine glands secrete their chemical products through ducts (such as the kidney, pancreas, or stomach). Hormones themselves are trace chemicals—present in tiny amounts—that act as extracellular messengers, controlling body processes in target organs far from the endocrine gland that produced them. A target organ is one that responds to a hormone by changing its biological capabilities.

Adrenal Corticosteroids

The adrenal gland is divided into an outer and an inner medulla. The cortex produces about three dozen hormones, all fat-like steroids. These adrenal corticosteroids are divided into two main groups, glucocorticoids and ; the adrenal cortex also produces steroid sex hormones. Glucocorticoids, whose production is controlled mostly by the pituitary gland through the adrenocorticotropic hormone (ACTH), mediate how the body breaks down and uses fats, carbohydrates, and proteins. The most abundant and potent of these hormones is cortisol (hydrocortisone). In times of stress (such as injury, extreme temperature change, illness, surgery, or ingestion of toxic chemicals), ACTH stimulates the production of glucocorticoids. The glucocorticoids also have tremendous ability as anti-inflammatory agents, fighting inflammation caused by arthritis and allergic reactions. For this reason, they are used medically to combat allergies, asthma, and arthritis. In some instances, overdosage of glucocorticoids can cause abnormal mental behavior.

The second major group of adrenal corticosteroids is the mineralocorticoids. These hormones control the body’s salt levels (sodium and chloride ions), which are important to the maintenance of body water balance and to the cellular import and export of both nutrients and wastes. If too much sodium chloride is retained in blood and tissues, the total fluid volume in the blood vessels increases and produces high blood pressure. Mineralocorticoids also control potassium levels, which is important because this ion is essential to nerve-impulse transport. The main mineralocorticoid, aldosterone, interacts with a kidney protein called renin to maintain appropriate blood volume by controlling the rate of salt and water excretion. Diseases of underproduction or overproduction of adrenal steroids, including sex hormones, can have serious consequences.

The adrenal steroids all act by forming complexes with special proteins in target organs, transporting hormone-receptor complexes to cell nuclei, and stimulating the production of key cell proteins by interaction with the hereditary material (gene derepression) in cell nuclei. Proteins are amino acid polymers that have many biological functions, including acting as enzymes (biological catalysts) and hormone receptors. Receptors are proteins that interact with a specific hormone to enable it to carry out messenger functions in target organs.

The adrenal medulla—which arises from fetal nervous tissue—produces amino-acid-derived hormones called catecholamines, stores them, and releases them on receiving an appropriate signal. The primary catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. These chemicals are linked with the nervous system in several ways. First, epinephrine and norepinephrine are hormones that control the fight-or-flight responses that enable the body to respond to emergencies by anger or fear reactions. Such responses are partly attributable to the linkage between the adrenal medulla and the sympathetic nervous system, which can produce the signals that cause the release of catecholamines in times of stress.

Such release has many useful effects, including the dilation of eye pupils to allow better sight; elevation of the blood pressure and increase of the heartbeat to allow better transport of energy-producing food; release of energy reserves of sugar from the liver and muscles; and contraction of blood vessels near the skin, to minimize bleeding if wounds should occur. Epinephrine, norepinephrine, and dopamine also heighten the reactions of the central nervous system, acting as neurotransmitters in different parts of the brain and evoking responses needed for fight, flight, and normal brain function. Research indicates that the chemicals produced by the adrenal gland, such as cortisol, help consolidate memories during times of heightened emotion. However, persistent, excessive stress may cause too much cortisol to reach the brain's hippocampus, causing trouble with working memory, decision-making skills, and attention.

These actions of catecholamines can be harmful, as is evidenced in a disease called hereditary paraganglioma-pheochromocytoma, in which adrenal medulla hormones are overproduced because of tumors of the medulla or the sympathetic nervous system. Persons with this condition will exhibit symptoms that include high blood pressure, heart palpitations, nervousness, , and neurotic symptoms. Abnormalities of catecholamine levels are implicated in a primary fashion in many psychological disorders. Catecholamine actions, like those of steroid hormones (a hormone that is a fat-like chemical derived from cholesterol), involve specific receptors. However, catecholamine-related processes do not involve hormone-receptor interactions with the hereditary material. Rather, they use a “second messenger” mechanism in which already-existing proteins are activated. Several other health conditions interfere with the adrenal gland’s ability to regulate bodily functions. For example, in individuals with Addison's Disease, the adrenal glands do not make enough cortisol, while Cushing's Syndrome is caused by the presence of too much cortisol in the body. Tumors caused by adrenal gland cancer or aldosterone-producing adenoma also interfere with adrenal function, causing excessive aldosterone production, among other symptoms.

Relationship to Mental Disorders

Mental illness is frequently divided into two basic types: organic and functional. Organic mental illness is a consequence of a known disease, such as diabetes or a tumor of the adrenal gland, that alters the structure of the brain or its ability to function correctly or that produces a malfunction of some other part of the nervous system. Cure of organic mental illness may involve surgery or other methods that eradicate the causative disease. In contrast, the exact basis for functional mental illness has often evaded understanding and has long been viewed as deriving from operational flaws of mental function. Among the most widely publicized mental disorders are and .

Relatively clear understanding began developing for bipolar disorder in the twenty-first century. People with bipolar disorder alternate rapidly between an excessively happy (manic) state and a severely depressed (depressive) state. The alternation is so severe that it renders patients unable to cope with the world around them. Understanding this disorder begins with consideration of the function and malfunction of the human nervous system, composed of a central computer—the brain—and a network of wires—nerves—that communicate with the rest of the body via . When nerve impulses pass through the nervous system correctly, they allow recognition of and appropriate response to the world. Malfunction of nerve-impulse generation and passage through the nerves or brain is believed to produce some functional mental health conditions.

Nerve cells (neurons) are separated from one another by minute synaptic gaps, and the passage of nerve impulses through a nerve requires the impulses to cross thousands of such gaps. Nerve-impulse transport across synaptic gaps is mediated by biochemicals called neurotransmitters. The best known of these is acetylcholine, which acts in cholinergic nerves. The dysfunction of cholinergic nerves, via disruption of acetylcholine action, is thought to be a major component of functional mental disease. This theory derives partly from observation of impaired mental function in people exposed to nerve gases and insecticides that act by disrupting acetylcholine production and use.

Other neurotransmitters associated with mental disorders include catecholamines and chemicals called indoleamines. The main catecholamine neurotransmitters are the adrenal medulla hormones epinephrine, norepinephrine, and dopamine. The catecholamines control nerve-impulse transmission by adrenergic portions of the nervous system. The indoleamines (especially serotonin) act in neurons related to sleep and sensory .

Role in Depression

Some theories of depression and have arisen from the catecholamine (actually, norepinephrine) of Harvard psychiatrist and researcher Joseph Schildkraut and others. This hypothesis proposes that depression is attributable to suboptimum production or utilization of norepinephrine (decreased noradrenergic activity) and that mania arises from increased noradrenergic activity. Acceptance of this theory has led to the examination of norepinephrine levels in normal and mental disease states; use of observed levels of the neurotransmitter to explain how existing drugs, electric shock therapy, and other psychiatric treatments affect functional mental illness; choice of therapeutic drugs on the basis of their effects on norepinephrine levels; and study of the effects of other catecholamines and related biogenic amines.

These efforts have demonstrated that dopamine, a catecholamine cousin of norepinephrine, is implicated in central nervous system dysfunction. Researchers observed that several important tranquilizers, among them reserpine, decreased both norepinephrine and dopamine levels. Consequently, the catecholamine hypothesis has expanded to include dopamine. In fact, low levels of dopamine have been shown to be more intimately involved in depression than are low epinephrine levels.

The biogenic indoleamine serotonin was next implicated in depression because it is also depleted by tranquilizers such as reserpine. It was then shown that the action of therapeutic drugs called tricyclic antidepressants is also related mostly to the alteration of serotonin levels. Because of this, an indoleamine (serotonin) corollary was added to the catecholamine hypothesis of affective disease.

In 1972, David Janowsky and coworkers at Vanderbilt University’s psychiatry department proposed a new hypothesis of affective disease. Their hypothesis focused on the cholinergic neurotransmitter acetylcholine but expanded the conceptual basis for functional mental illness. Unlike preceding concepts, it recognized the importance of interaction between the various systems participating in nerve-impulse transmission and suggested that the affective state of any individual represents a balance between adrenergic and cholinergic activity. Furthermore, the hypothesis proposed depression as a disease of relative cholinergic predominance, while mania was said to be attributable to relative adrenergic predominance.

Therapeutic Drugs

Until the advent of the catecholamine (and later indoleamine) hypothesis of affective mental disorder and the connection between the adrenal medulla horomone and psychiatric disorders, the primary treatments attempted for functional mental disease included procedures such as lobotomy, electroconvulsive (shock) therapy, and insulin coma. These procedures are viewed in the twenty-first century as imprecise at best, though some use of each has persisted, most often as part of mixed psychotherapy (which incorporates them alongside psychoanalysis and treatment with psychotherapeutic drugs) or therapy involving patients who are extremely difficult to treat.

Much of the basis for the use of such drugs evolved from examinations of therapeutic drugs to determine their ability to alter catecholamine and indoleamine levels. Among the first psychotherapeutic drugs were the tricyclic antidepressants, organic chemicals that affected catecholamine and serotonin levels. Another useful family of these drugs is a group of chemicals called monoamine oxidase inhibitors (MAOIs). MAOIs prevent biological modification of catecholamines by the enzyme monoamine oxidase, prolonging their presence in the body. In addition, the importance of lithium-containing chemicals in fighting functional mental illness is also believed to be attributable to a mechanism that includes alterations of catecholamine and indoleamine concentrations in the nervous system.

Contributions

The developing understanding of the role of the adrenal medulla in both normal and pathological processes in the nervous system has led to a more complete understanding of the basis for the utility of major tranquilizers in the treatment of individuals with severe mental illness. It has also enabled better differentiation of schizophrenia from —functional mental disorders associated with emotions or feelings—and led to explanations of the causes of the psychogenic manifestations of many illegal addictive drugs. Understanding of the adrenal gland has also led to the discovery of additional neurotransmitter chemicals that promise better understanding of the nervous system. Furthermore, examination of the steroid hormones of the adrenal cortex has shown that those hormones can produce some psychopathology.

Bibliography

"Adrenal Gland Disorders." National Institute of Child Health and Human Development, National Institutes of Health, www.nichd.nih.gov/health/topics/adrenalgland. Accessed 10 Dec. 2024.

"Adrenal Insufficiency." Endocrine Society, 24 Jan. 2022, www.endocrine.org/patient-engagement/endocrine-library/adrenal-insufficiency. Accessed 10 Dec. 2024.

Alviña, Karina, et al. “Long Term Effects of Stress on Hippocampal Function: Emphasis on Early Life Stress Paradigms and Potential Involvement of Neuropeptide Y.” Journal of Neuroscience Research, vol. 99, no. 1, 2021, pp. 57–66, doi:10.1002/jnr.24614. Accessed 10 Dec. 2024.

Janowsky, David S., et al. “Neurochemistry of Depression and Mania.” Depression and Mania. Ed. Anastasios Georgotas and Robert Cancro. Elsevier, 1988.

Janowsky, David S., et al. “A Cholinergic-Adrenergic Hypothesis of Mania and Depression.” Lancet, vol. 300, no. 7778, 1972, pp. 632–35, doi:10.1016/S0140-6736(72)93021-8. Accessed 10 Dec. 2024.

Linos, Dimitrios, and Jon A. van Heerden, editors. Adrenal Glands: Diagnostic Aspects and Surgical Therapy. Springer, 2005.

Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 8th ed., W. H. Freeman, 2021.

Valenstein, Elliot S. Great and Desperate Cures: The Rise and Decline of Psychosurgery and Other Radical Treatments for Mental Illness. Basic, 1986.