Edward J. Sachar

Twenty-four-Hour Cortisol Secretory Patterns in Depressed and Manic Patients

Publisher Summary This chapter focuses on the patterns of cortisol secretion in depressed and manic patients. The 24-hr secretory pattern of cortisol is significantly disturbed in both severely depressed and severely manic patients. With regard to the depressed patients, it appears that the hypersecretion cannot be accounted for entirely by generalized stress or arousal factors alone, and may well reflect a central neuroendocrine abnormality associated with the illness. There are several reasons for suspecting that 24-hr hormonal secretory patterns might be affected in the depressive and manic depressive illnesses. Many clinical features of depressive illness suggest hypothalamic involvement—particularly, disturbances in mood, appetite, sexual and aggressive drives, and autonomic function. Hypothalamic neuroendocrine regulation might well be involved as well. In addition, depressive illness is usually associated with significant sleep disturbance, and often with a diurnal variation in the intensity of symptomatology, clinical features that might well find their correlates in altered 24-hr secretory patterns of those hormones closely associated with circadian and sleep-wake cycles.

Dopamine receptor alteration in schizophrenia: Neuroendocrine evidence

Growth hormone (hGH) responses to centrally acting dopamine agonists were used as indices of CNS dopaminergic function in order to test hypotheses implicating dopaminergic alteration in the etiopathology of schizophrenia. Apomorphine, a direct acting dopamine receptor agonist, and L-Dopa, an indirect agonist dependent upon presynaptic conversion to dopamine for its action, both elicited elevations in plasma hGH in most young male schizophrenic-and control-subjects. A highly significant difference was seen between the distribution of hGH responses to apomorphine for schizophrenics and that for controls. Unsually high hGH response to apomorphine was seen in schizophrenics who subsequently failed to respond to neuroleptic therapy; intermediate hGH response was seen in controls; and low hGH response was seen in subsequent neuroleptic responders; differences in hGH response were statistically significant for all intergroup comparisons. No such differences were seen in response to L-Dopa. An inverse relationship was seen between responses of individuals to L-Dopa and apomorphine.The findings suggest that the variability of hGH response to apomorphine is a reflection of dopamine receptor sensitivity, and that this variability may be an index of non-endocrine related dopaminergic sensitivity. They are consistent with hypotheses relating schizophrenia to alteration in dopamine receptors, although the type of receptor and the direction of alteration may be complex.

Biological Aspects of Affective Psychoses

The past two decades have witnessed an extraordinary thrust of research into the biology of the depressive illnesses and manic-depressive psychoses. The assumption implicit in most of this work is that these illnesses are associated with disturbances in hypothalamic and limbic system functions and that an important role in these disturbances may be played by alterations in brain neu-rochemistry, particularly in the metabolism of the monaminergic neurotransmitters.

Psychological Factors Relating to Activation and Inhibition of the Adrenocortical Stress Response in Man: A Review

Publisher Summary This chapter reviews the behavior of the adrenal cortex in normals under stress, and during the course of schizophrenic and depressive illnesses. It not only describes some psychological factors associated with increases in adrenocortical activity in these conditions but also discusses the psychological functions that usually serve to maintain emotional and endocrine homeostasis. In the animal paradigm, a group of rats or monkeys are exposed to a noxious psychological stimulus, and a substantial adrenocortical response generally occurs. In humans exposed to stress, however, it appears that the situation is more complex. The animal model fails to take into account the elaborate system of psychological coping mechanisms, highly developed in humans, that process and evaluate threatening stimuli, serving to minimize their emotional impact and inhibiting the associated adrenocortical response. This is an especially useful way of studying the intrinsic circadian rhythm of plasma cortisol, because it captures the segment of the day when plasma cortisol moves from its nadir to its zenith. Because the observations are made during sleep, it offers the opportunity to study intrinsic adrenocortical activity in the patient relatively removed from environmental influences.

An Unusual Adverse Reaction to Self-Medication with Prednisone: An Irrational Crime during a Fugue-State

During five years of self-medication with Prednisone, a forty-one-year old asthmatic businessman experienced periods of euphoria, psychomotor hyperactivity, and poor judgment; a period of depression and anxiety during temporary steroid withdrawal; and finally, with resumption of Prednisone, episodes of grandiosity and bizarre fugue-like behavior, with adoption of a second identity and culminating in an irrational crime. Steroids were then withdrawn, and the patient resumed his premorbid personality, but had amnesia for much of his previous behavior. The literature on hysterical fugues and corticosteroid-induced mental disturbance is reviewed. The patients reactions are analyzed in terms of his premorbid neurotic conflicts, the psychological stresses acting upon him, and the effects of Prednisone on his central nervous system.

PSYCHOTROPIC DRUGS AND NEUROENDOCRINE FUNCTION IN PSYCHOPATHOLOGICAL CONDITIONS

Abstract 1 Plasma prolactin (Prl) can serve as an indicator of hypothalamic tuberoinfundibular dopamine (TIDA) activity in humans. 2 All major classes of neuroleptic (NL) or antipsychotic (AP) drugs were studied in humans. Clinically efficaceous drugs consistently stimulate Prl while other psychotropic drugs do not. 3 The Prl response is graded according to dose (within a limited range) and correlates highly with clinical potency. 4 The Prl test should be useful in evaluating potentially efficaceous AD drugs in man. 5 Normal and schizophrenic subjects do not differ in their Prl responses suggesting that the TIDA system is not involved in schizophrenia.