Chemical Bases Of Behavior

TABLE 1. Incidence of Schizophrenia in Consanguineous Groups
FULL

		GRANDCHILDREN	CHILDREN
0.85	3.9	4.3	16.4	7.0
SIBLINGS	TWINS	TWINS (total)	MONOZYGOTIC SEPARATED PAIRS	NONSEPARATED PAIRS
14.3	14.7	85.8	77.6	91.5

Efforts to relate behavior to chemical substances and events in the brain date from ancient Greek physiology and medicine. Hippocrates speculated that the human body consists chemically of four humors: bile, black bile, phlegm, and blood. Temperamental differences between persons were supposed to reflect differences in the proportions of these humors. The adjectives in our own language which correspond to Hippocrates' four basic temperaments still reveal the influence of these humoral notions. They are choleric, melancholic, phlegmatic, and sanguine.

Significant progress in understanding the chemical bases of behavior has been a very recent development. Progress had to await the development of adequate technics for measuring behavioral changes which accompany chemical changes in the brain. Also, there are special problems involved in experimentally manipulating the chemical composition of the brain. The brain as a whole has a remarkable tendency to maintain its chemical constancy (homeostasis). This is due in part to a functional barrier between the blood and the brain tissue which prevents all but a few chemicals from entering the brain proper. The anatomic location of this blood-brain barrier is a matter of dispute but most authorities place it at the capillary wall or glial mantle. The barrier appears to function to protect the brain against the myriad chemical fluctuations reflected in the blood.

This chemical isolation is probably necessary in order for the brain to carry on its intricate functions as a receiver, processor, and transmitter of signals (information) with itself and the rest of the nervous system. Thus, substances important in brain function may produce no behavioral effects when administered outside the central nervous system due to blockage at the blood-brain barrier. To get around this, chemical precursors of behaviorally active substances which do cross the blood-brain barrier in significant concentrations have been used in some experiments. Experiments to be described later with the neurohormone, serotonin, and its precursor, 5-hydroxytryptophan, illustrate this technic. Another technic has been to deliver small quantities of chemicals by micropipettes directly into the brain substance or ventricular system (42). These technics, however, introduce new methodologic problems and possible sources of error.

The earliest sources of information about chemical factors in behavior were the natural experiments provided by nature in her vicissitudes. These clinical observations have provided us with much information. Other methods include observing the behavioral effects of administering chemicals directly into the brain or in the periphery, determining the metabolic fate of test loads of naturally occurring bodily substances important in behavior, and the metabolic changes which accompany experimentally induced changes in behavior. Instances of each of these technics are described in this chapter.

Like other tissues of the body, the brain depends upon a continuous supply of oxygen for its normal functioning. However, the tolerance of mature central nervous system tissue to oxygen deprivation is particularly low, irreversible changes occurring within a few minutes of oxygen lack. The giddiness and loss of critical ability, self-criticism, and judgment seen in the test pilot with an inadequate accessory supply of oxygen at high altitudes are changes resulting from a small degree of hypoxia.

In complete and sudden oxygen deprivation, as in strangulation or drowning, profound changes occur in mental functioning which soon lead to irreversible changes and death within a very brief period.

Normal brain function is also dependent upon an adequate and continuous supply of glucose, which is the only major energy source for brain metabolism. Thus, the diabetic who develops a slight hypoglycemia from an overdosage of insulin becomes irritable, shows poor judgment, and changes in mood. More profound hypoglycemia results within minutes in loss of consciousness, deep coma, and death. Disturbance in the acid-base balance of the blood has immediate behavioral effects also. Increased alkalinity is associated with a general irritability and restlessness, whereas acidity more commonly produces lethargy and narcosis. The dependence of normal brain function upon the equilibrium of bodily substances is further illustrated by disturbances in water and electrolyte balance. Weakness, lethargy, and eventually delirium accompany excessive salt loss from the body (low-salt syndrome). Serious disturbances in mental function follow other changes in brain chemistry as well.

Vitamins

Vitamins play an important role in body chemistry generally, several being necessary for the activation of important enzymes (co-enzymes). Deficiencies in thiamine and niacin in particular are associated with mental disturbances. Deficiency of thiamine causes disturbances in sleep, loss of appetite, lethargy, and fatiguability. Severe niacin deficiency is associated with similar symptoms and, in addition, impairment in memory, orientation, and intellectual functioning generally (chronic brain syndrome). This is part of the picture of the disease, pellagra, once common in some parts of the United States.

Endocrines

The classical endocrine system has an important regulatory action on body metabolism generally and, like the nervous system, is concerned with the integrated functioning of the organism. It differs from the nervous system in this role in that its chemically coded messages are less specific than those of the nervous system, influencing many body tissues simultaneously. Also, the body's response to the hormonal message is slower to occur and longer in duration. The two systems interact with each other, however, at many levels (see Chapter 3). The dependence of behavior on hormonal factors will be briefly illustrated with thyroid hormones, sex steroids, and adrenocorticoids.

Thyroid. The hormones of the thyroid gland have a general stimulating effect on metabolic rate. Underfunctioning of the thyroid (hypothyroidism) is associated with a general sluggishness, lethargy, and lack of spontaneity. Severe hypothyroidism produces cretinism when it is present early in life and myxedema when it occurs in adulthood. In both of these conditions severe mental malfunctioning occurs (chronic brain syndrome). Hyperthyroidism is associated with restlessness, irritability, and often an abnormally elevated mood (euphoria). Severe anxiety and sometimes psychotic behavior may be precipitated by hyperthyroidism. Paradoxically, clinical hyperthyroidism is often precipitated by anxiety and stress.

Sex Hormones. Profound changes occur in complex patterns of behavior when gonadal hormones are manipulated. It is well known, for example, that castrated bulls become weak and docile. On the other hand, the pecking order in fowl, an index of their aggressiveness or assertiveness, can be manipulated by administering male sex hormones (androgens) to the more submissive birds. Perhaps more dramatic is the artificial induction of complex periodic behavior by sex hormones. Nesting and maternal behavior toward foster newborn rats can be induced in nulliparous rats by the injection of prolactin, a pituitary gonadotropin. This complex behavior is normally seen only in recently pregnant female rats.

Although complex human behavior seems less immediately dependent upon gonadal hormones than in the case of lower animals, alterations in endocrine function in humans is accompanied by changes in behavior. Castration of human males has been practiced since antiquity as a means of altering behavior and personality. Systematic psychologic assessment of human male castrates reveals changes in attitude and other aspects of personality functioning. The medical and psychologic importance of disturbances in endocrine function, as well as the role of endocrine maturation in the development of personality generally, is discussed in Chapter 11.

Adrenocorticoids and ACTH. For many years various steroids of the adrenal cortex, and their synthetically produced analogues, have been used in the treatment of a variety of medical disorders. The prolonged administration of these drugs, or of ACTH, the pituitary hormone which stimulates the release of corticoids from the adrenal glands, is sometimes accompanied by restlessness, euphoria, or anxiety. Withdrawal of the steroids is sometimes followed by lethargy and depression. These clinical observations suggest a relationship between adrenocorticoids and anxiety. Experimental investigation of this relationship is discussed under Anxiety.

The remainder of this chapter will deal with some recent developments, based largely on experimental studies, in our understanding of the chemical bases of behavior. These topics are anxiety, neurohormones, psychotomimetics, brain metabolism in abnormal mental states, and behavioral-assay technics.