• Recent research on schizophrenia has demonstrated that in this disorder the brain is not, strictly speaking, normal. The findings suggest that nonspecific histopathology exists in the limbic system, diencephalon, and prefrontal cortex, that the pathology occurs early in development, and that the causative process is inactive long before the diagnosis is made. If these findings are valid and not epiphenomena, then the pathogenesis of schizophrenia does not appear to fit either traditional metabolic, posttraumatic, or neurodegenerative models of adult mental illness. The data are more consistent with a neurodevelopmental model in which a fixed "lesion" from early in life interacts with normal brain maturational events that occur much later. Based on neuro-ontological principles and insights from animal research about normal brain development, it is proposed that the appearance of diagnostic symptoms is linked to the normal maturation of brain areas affected by the early developmental pathology, particularly the dorsolateral prefrontal cortex. The course of the illness and the importance of stress may be related to normal maturational aspects of dopaminergic neural systems, particularly those innervating prefrontal cortex. Some implications for future research and treatment are considered.

Implications of normal brain development for the pathogenesis of schizophrenia

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

Social Facilitation: A solution is suggested for an old unresolved social psychological problem.

A review of the long-term effects of child sexual abuse

Circadian variation of blood-pressure

The stress of foot shock in rats induces large decreases in the level of brain norepinephrine but does not greatly alter the concentration of serotonin or dopamine in brain. These decrements in norepinephrine are not limited to any region and occur uniformly throughout the brain. However, absolute levels of these amines are not a true indicator of their dynamic state. By various techniques it could be demonstrated that the stress of foot shock accelerates the metabolism of dopamine and serotonin to the same degree as norepinephrine; the only difference being that dopamine and serotonin are rapidly resynthesized, whereas norepinephrine in the brain cannot be regenerated at the same rate. Furthermore, the increased catabolism of brain norepinephrine with stress is blocked by monoamine oxidase inhibitors, whereas catechol-O-methyltransferase inhibitors do not impede accelerated degradation.

Metabolism of norepinephrine, serotonin and dopamine in rat brain with stress.

Adiurnal rhythm in the plasma levels and urinary excretion of corticosteroids by men has been reported previously. Pincus et al. (2) and Romanoff et al. (3) showed that the rate of urinary excretion of phosphomolybdic acid-reducing lipids and formaldehydogenic lipids was greater during the morning than during the remaining 24-hour period. Using a more specific method of hydrolysis of the urinary corticoid conjugates, Sandberg et al. (4) reported the same type of variation; similar results were also reported by Laidlaw et al. (5). In a study of the normal plasma levels of 17-hydroxycorticosteroids (17-OH-CS) in man, Bliss et al. (6) found that in any single subject, the 8 a.m. values were higher than those found later in the day. We have extended this study to include the entire twenty-four hours, with special emphasis on the night period. Observations were also made in individuals whose pattern of activity and sleep was reversed and in blind persons, in an attempt to determine the effect of activity and t...

The diurnal variation of plasma levels and urinary excretion on 17-hydroxycorticosteroids in normal subjects, night workers and blind subjects.

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Eugene L. Bliss

Papers

Metabolism of norepinephrine, serotonin and dopamine in rat brain with stress.

The diurnal variation of plasma levels and urinary excretion on 17-hydroxycorticosteroids in normal subjects, night workers and blind subjects.

The normal levels of 17-hydroxycorticosteroids in the peripheral blood of man.

Chemical, electron microscopic and physiological observations on the role of catecholamines in the carotid body.

Relationship of stress and activity to brain dopamine and homovanillic acid.