Annals of the New York Academy of Sciences
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The somatic marker hypothesis proposes that both the amygdala and the orbitofrontal cortex are parts of a neural circuit critical for judgment and decision-making. Although both structures couple exteroceptive sensory information with interoceptive information concerning somatic/emotional states, they do so at different levels, thus making different contributions to the process. We define "primary inducers" as stimuli that unconditionally, or through learning (e.g., conditioning and semantic knowledge), can (perceptually or subliminally) produce states that are pleasurable or aversive. ⋯ However, once this orbitofrontal system is developed, the induction of somatic states by secondary inducers via the orbitofrontal system is less dependent on the amygdala system. Perhaps the amygdala is equivalent to the hippocampus with regard to emotions, that is, necessary for acquiring new emotional attributes (anterograde emotions), but not for retrieving old emotional attributes (retrograde emotions). Given the numerous lesion and functional neuroimaging studies illustrating the involvement of the amygdala in complex cognitive and behavioral functions, including "social cognition," we suggest that this involvement is a manifestation of a more fundamental function mediated by the amygdala, which is to couple stimuli/entities with their emotional attributes, that is, the processing of somatic states from primary inducers.
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Ann. N. Y. Acad. Sci. · Apr 2003
ReviewConsideration of a unified model of amygdalar associative functions.
This paper considers issues arising from presentations by Barry Everitt and Gorica Petrovich concerning amygdalar involvement in appetitive conditioning. Studies reported by these researchers are beginning to unravel the distribution of associative functions among amygdalar nuclei and their efferent targets. ⋯ Most students of this issue will agree that no prima facie integration is readily apparent in current scholarship. Although we do not here provide the definitive integration, we do attempt to take some preliminary, broad-brush steps towards that goal.
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Ann. N. Y. Acad. Sci. · Sep 2002
ReviewAssociation of hypertension and hypokalemia with Cushing's syndrome caused by ectopic ACTH secretion: a series of 58 cases.
Cushing's syndrome is associated with hypertension in approximately 80% of cases. Hypertension contributes to the marked increased mortality risk of past or current Cushing's syndrome, largely because of increased cardiovascular risk. Observation of the pathophysiological effect of chronically elevated ACTH and cortisol values in patients with ectopic ACTH secretion complements the available data from acute studies of the effects of ACTH and glucocorticoid infusions in normal volunteers. ⋯ In addition, we did not find blood pressure severity to be related to UC excretion or ACTH levels. Urine and plasma cortisol and cortisol metabolite measurements suggest that cortisol may act as a mineralocorticoid when in excess, perhaps by saturating the 11beta-hydroxysteroid-dehydrogenase (11beta-HSD2 enzyme) that inactivates cortisol at the renal tubule. The current data suggest that high cortisol levels may be the principal cause of hypokalemic alkalosis in Cushing's syndrome, rather than inhibition of the 11betaHSD2 enzyme by ACTH or the effects of adrenal steroid biosynthetic intermediaries with mineralococorticoid activity.
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Ann. N. Y. Acad. Sci. · Sep 2002
ReviewNew insights into the genetics of familial chromaffin cell tumors.
We review genetic aspects and recent advances in our understanding of the molecular pathogenesis of familial chromaffin cell tumors (pheochromocytoma, paraganglioma). About 10 percent of pheochromocytomas are familial and occur as part of multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau (VHL) disease, and neurofibromatosis type 1 (NF 1). A subset of paragangliomas, tumors that can also produce and secrete catecholamines, are also familial and occur in patients with germline mutations in genes that encode subunits of the mitochondrial complex II. ⋯ Tumorigenesis of NF1-associated pheochromocytomas remains unknown, as does tumor formation (i.e., carotid body tumor) in patients with germline mutations in SDHB, SDHC, and SDHD, genes that encode subunits of the mitochondrial complex II, the smallest complex in the respiratory chain. Many genetic alterations have been found in sporadic chromaffin cell tumors. However, at present such genetic changes are difficult to place into context with regard to tumor formation and progression.
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Ann. N. Y. Acad. Sci. · Jun 2002
Review Comparative StudyCell-mediated immune response in MDMA users after repeated dose administration: studies in controlled versus noncontrolled settings.
Acute administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") produces time-dependent immune dysfunction in humans. Recreational use of MDMA generally includes repeated drug consumption, often in association with other drugs, such as alcohol and cannabis. In the laboratory setting, repeated MDMA administration to healthy MDMA consumers produced a time-dependent immune dysfunction similar to that observed with the ingestion of a single dose, and the first of the two administrations paralleled the time-course of MDMA-induced cortisol stimulation kinetics and MDMA plasma concentrations. ⋯ By contrast, NK cells in MDMA consumers were reduced to one-third of those from healthy persons. A statistically significant decrease in affected immune parameters was recorded during a 2-year observation period in a subgroup of recreational MDMA users. These permanent alterations in immunologic homeostasis may result in impairment of general health and subsequent increased susceptibility to infection and immune-related disorders.