On a Mechanism for the Mood and Personality Changes of Adult and Later Life: A Psychobiological Hypothesis

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This paper is an attempt at synthesizing the languages of neurobiology and subjective phenomenology by drawing on recent research findings in biogenic amine regulation, temporal lobe limbic neurophysiology, psychomotor epilepsy, bilateral hemispheric specialization, and the mechanisms of action of some psychotropic drugs.

Descending and reciprocal inhibition of endogenous excitation in the brain and the reduction with aging of levels and/or rates of synthesis of biogenic amines suggest that aging may bring decreased thresholds for the emergence of neural expression. In this context the concomitants of three phenomena may be particularly instructive; namely, electrophysiological kindling in animals and humans, i.e., progressive decrease in thresholds for limbic hypersynchrony, which leads to two distinct behavioral states reflecting both classical seizure phenomena and, in contrast, a diffuse internal event experienced as euphoric. Psychomotor epilepsy, a syndrome of limbic disinhibition, is associated likewise with classic seizure phenomena and related dysphoric and/or amnesic features and, as well, contrasting interictal episodes of intense ecstasy. Across species, electrical stimulation involving the amygdala is associated with the former, and disinhibition of the hippocampal/ septal circuits with the latter type of phenomena. Gradual personality changes in temporal lobe epileptic patients are also of two kinds and there is apparent association between the location of their foci or spikes and the clusters of personality traits that emerge. Several lines of evidence suggest that progressive disinhibition of the dominant hemisphere leads to the expression of dysphoric, obsessional, and depressive personality features, but the personality becomes more hypomanic, hysterical, and impulsive when the non-dominant lobe is affected.

Heretofore, study of the serotonergic system (s) in various mood-related behaviors has tended to suggest functional models representing specific information-processing circuitry or a simple hydrodynamic pump model, neither of which has proved definitive in understanding the role of serotonin in the human brain. An intermediate level, dualistic model presented here considers the functional regulatory potential of the degree of hemispheric asymmetry in the mesolimbic and mesostriatal serotonergic systems, asymmetry that has now been observed in biogenic amine concentrations (dopamine as well as serotonin) and in the activity and kinetic conformations of the rate-limiting biosynthesizing enzyme (s), which are alterable by various psychotropic drugs. Tricyclic drugs, for example, affect the conformation of tryptophan hydroxylase so as to enhance serotonin synthesis more on one side than on the other; lithium decreases the asymmetry of these measures, invoking similar enzyme conformations in both hemispheres. Alternation and reciprocity in biogenic amine inhibitory regulation could result in differential inhibition, allowing dominance of one or the other hemisphere at different times and/or in response to different agents. A model is proposed that suggests the potential usefulness of the notion of integration or reintegration of the hemispheric modalities at the neurobiological level for successful treatment at the level of subjective phenomenology.

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