Mechanism of action

As we lack understanding of the causes of the common mental disorders, so we lack knowledge of the mechanisms by which seizures alter mental functions. When convulsive therapy was first considered effective, its most prominent side-effect was amnesia, and much debate centred on whether amnesia was, in fact, the mechanism for improving thought and mood. Psychodynamic theories that saw the cause of mental disorders in disturbed early life experiences encouraged that view, because when memories of these experiences surfaced in later life and became intolerable, the amnesia induced by ECT successfully erased them.

Others focused on the physiological effects of seizures, especially the changes in the interseizure EEG. Such changes were found to be necessary, but not sufficient, for recovery.(68) Recent studies have revived an interest in this hypothesis.(69)

Brain neurohumours and neurohumour receptors, so important in our present views of the action of drug therapies, are emphasized by many to explain the benefits of ECT. But here, too, the experimental data fail to find reasonable correlations.

My own view is that the neuroendocrine system is the most likely agent of change brought about by ECT. Neuroendocrine dysregulation is prominent in patients with the mental disorders for which ECT is effective. Thyroid, adrenal, sex gland, and hypothalamic dysfunction are common in patients with disorders in mood, thought, motor activity, feeding, sleep, sex, growth, and maturation. Indeed, every aspect of body physiology and mental activity is affected by these glands, as seen in the action of the adrenal glands in depressive mood disorders.

In the severely depressed patient, the adrenal glands produce too much cortisol. In turn, the high levels in the blood disrupt the normal diurnal rhythms of other glandular discharges, and the glands do not respond to the usual feedback mechanisms. The most prominent features of depression—failure to eat, loss of weight, inability to sleep, loss of interest in sex, inability to concentrate thoughts, and difficulties in memory—are distortions in functions regulated by the adrenal glands acting interdependently with the pituitary and hypothalamic cells, in a self-adjusting feedback. (70)

Each seizure stimulates the hypothalamus to discharge its hormones, which cause the pituitary gland to discharge its products, which then affect the level of cortisol. The first effects of this cascade of events are transitory, but repeated seizures restore the normal interactions of the hypothalamic-pituitary-adrenal axis hormones. Feeding and sleep become normal; motor activity, mood, memory, and thought follow suit.

How does a seizure cause such profound changes in physiology? In electroshock, the currents from the stimulating electrodes on each temple pass through the central parts of the brain, stimulating both the hypothalamus to discharge its hormones and the centrencephalic structures to produce a bilateral grand mal seizure. (One of the flaws in unilateral electrode placement is that the currents have to take indirect routes to affect the pertinent areas of the brain.)

The massive amounts of hypothalamic and pituitary hormones that enter the bloodstream during ECT are measurable within a few minutes. They circulate throughout the body, affecting all the body's cells—a compelling and welcome sign of recovery.

After some courses of ECT, the return to normal endocrine function persists. At other times, the glands revert to their abnormal activities, and the mental disorder becomes evident again. In these cases, repeated stimulation of the hypothalamus and the pituitary by continuation ECT can restore and sustain the normal glandular functions and normal mental state.

These experiences indicate that the brain secretes substances that regulate mood and thought. Although we have not yet identified these substances, their action seems analogous to those of insulin on sugar metabolism, thyroxin on cellular metabolism, and parathormone on calcium metabolism. The secretion that seems most likely is thyrotrophin-releasing hormone, a tripeptide produced by the hypothalamus. When it is injected into a patient, it has euphoriant and antidepressant effects. Because it is rapidly metabolized, however, its action is short. (71) Finding a congener of thyrotrophin-releasing hormone that has a robust resistance to metabolic degradation seems a reasonable target of chemical research, especially since it is apparent that ECT is an effective treatment for severe mental disorders, with actions that differ from those of psychoactive drugs.

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