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Concepts of Scientific Integrative Medicine Applied to the Physiology and Pathophysiology of Catecholamine Systems

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Abstract

This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine‐related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body's monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback‐regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems—especially Parkinson disease—and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post‐genome era. Published 2013. Compr Physiol 3:1569‐1610, 2013.

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Figure 1. Figure 1. A homeostatic system. The monitored variable is regulated by negative feedback. Afferent information about the monitored variable reaches a comparator homeostat, which drives an effector that influences the monitored variable. (+) sign indicates a positive relationship and (–) a negative relationship.
Figure 2. Figure 2. Monitored variable level in the absence of feedback regulation. In the computer model, the initial level of the “stock,” the monitored variable, is 100 units. The loss rate, indicated by the “pipe and valve,” depends on a rate constant, kLoss (in this case 1 per min), and on the level of the monitored variable (arrows). The level declines as a first order process, meaning the level falls exponentially.
Figure 3. Figure 3. Negative feedback, with proportionate control. The difference between the level of the monitored variable and the homeostat setting, the error signal, determines the rate of increase (Gain Rate) of the monitored variable. Note that with negative feedback, the level of the monitored variable reaches a steady state. As the value for kGain increases, the plateau level of the monitored variable increases; however, with proportionate control the plateau level is below the homeostat setting.
Figure 4. Figure 4. Effect of head‐up tilting on beat‐to‐beat blood pressure in a healthy person. The blood pressure falls transiently but then returns to about the baseline level.
Figure 5. Figure 5. Computer model of a negative feedback loop with both proportionate and integrated control. The rate of increase in the monitored variable (Gain rate) is determined both by the error signal and the integrated error signal.
Figure 6. Figure 6. Predicted values for levels of the monitored variable as a function of time, with negative feedback by both proportionate and integrated control. The level of the monitored variable returns to the baseline level. The rate of attainment of the baseline level depends on the rate constant for the effector (kEffector). The predicted curve fits well the blood pressure response to tilting in Figure 4.
Figure 7. Figure 7. Homeostatic definition of stress. Stress is defined as a condition or state in which there is a sensed discrepancy between afferent information and the homeostatic setting. The sensed discrepancy corresponds to the “error signal” in the computer model of a negative feedback loop.
Figure 8. Figure 8. Introduction of a stressor into the computer model. The stressor augments the loss rate. The computer model predicts return to the set level of the monitored variable, with the time to return depending on the severity of the stressor. The integrated error signal is a measure of the accumulated stress.
Figure 9. Figure 9. Fever as an allostatic state. Changing the set‐point of the homeostat (in this case at 12 h) increases the steady‐state value for the monitored variable, the core temperature.
Figure 10. Figure 10. Stress, allostasis, and allostatic load in the computer model of negative feedback regulation of temperature by a thermostat. Allostasis refers to regulation of the level of the monitored variable at different steady‐state values by adjusting the thermostat setting. Allostatic load refers to accumulated wear and tear on the furnace.
Figure 11. Figure 11. Inherited and acquired determinants of allostatic load. These determinants include genes and gene expression, environmental influences, resilience, and time. Note that decreased effector efficiency from allostatic load can induce a positive feedback loop, with all the relationships within the loop having a “+” sign.
Figure 12. Figure 12. Predicted effects of allostatic load on wellness. Because of wear and tear on the effector, the effector becomes less efficient, and because it is less efficient it has to be “on” more in order to maintain the level of the monitored variable; however, the more it is “on,” the more wear and tear (allostatic load). This positive feedback loop results in accelerated decline in wellness, early onset of symptomatic system failure (arbitrarily placed at 40% of ideal), and premature death.
Figure 13. Figure 13. Relationship between extent of adrenaline and ACTH responses across multiple stressors, from a meta‐analysis of literature ().
Figure 14. Figure 14. Labile blood pressure in patients with baroreflex failure as a late sequela of irradiation of the neck. Blood pressure lability in this setting exemplifies loss of control of the level of the monitored variable, by disruption of the barostatic negative feedback loop.
Figure 15. Figure 15. Some effectors regulating levels of monitored variables. The effectors are grouped arbitrarily into those of the autonomic nervous system (ANS), pituitary/endocrine (Pitu./Endo.) systems, and others. ANS effectors include the sympathetic noradrenergic system (SNS), sympathetic cholinergic system (SCS), sympathetic adrenergic system (SAS), parasympathetic nervous system (PNS), the DOPA‐dopamine system (DDA), and the enteric nervous system (ENS). Pitu./Endo. systems include the hypothalamic‐pituitary‐adrenocortical (HPA) axis, renin‐angiotensin‐aldosterone system (RAS), thyroid hormone (THY), growth hormone (GH), gonadotrophic hormones (GON), prolactin/oxytocin (PRO), arginine vasopressin (AVP), insulin (INS), and glucagon (GLU). Other effectors include cytokines (CYT), endogenous opiate species (EOS), atrial natriuretic peptide (ANP), bradykinins (BRK), and nitric oxide (NO).
Figure 16. Figure 16. Compensatory activation. When a homeostatic system contains more than one effector, disabling of an effector leads to compensatory activation of the other effectors. Compensatory activation is one advantage of having multiple effectors.
Figure 17. Figure 17. Computer model of multiple effectors.
Figure 18. Figure 18. Computer‐generated curves predicting effects of disabling one effector on activity of an alternative effector. As the rate constant for Effector 1 declines (green to red to black curves), the extent of activation of Effector 2 increases (compensatory activation).
Figure 19. Figure 19. Effector sharing. Two homeostatic systems involving negative feedback loops share the same effector.
Figure 20. Figure 20. Computer model of effector sharing. In this model, two homeostats determine the state of activity of the same effector, which in turn affects levels of two monitored variables. Via effector sharing, a stressor affecting levels of one monitored variable results in altered levels of a different monitored variable.
Figure 21. Figure 21. Predicted effects of effector sharing on levels of monitored variables. As the magnitude of stress increases in one homeostatic system (green to red to black curves), the level of the monitored variable for that homeostatic system returns to the baseline value, while the level of the monitored variable for the second homeostatic system reaches a different steady‐state value. Increasing stress therefore results in maintenance of the first monitored variable at the set value, while levels of the second monitored variable increase to a new steady state. The extent of increase in the level of the second monitored variable depends on the extent of activation of the shared effector.
Figure 22. Figure 22. Complex involvement of multiple effectors and homeostats in the integrated response to orthostasis.
Figure 23. Figure 23. Complex involvement of multiple effectors and homeostats in the integrated response to exercise.
Figure 24. Figure 24. Minimum scientific integrative medicine model. The minimum model incorporates at least one monitored variable that is regulated by multiple effectors and at least one effector that is shared by multiple homeostats.
Figure 25. Figure 25. Compensatory activation of alternative effectors upon disabling of the SNS effector.
Figure 26. Figure 26. Catecholaminergic effectors associated with different homeostats. The different effector patterns result in “primitive specificity” of responses to different stressors. Effectors involving the catecholamines norepinephrine (sympathetic nervous system, SNS), epinephrine (sympathetic adrenergic system, SAS), or dopamine (DOPA‐dopamine system, DDS) are in color. Other effectors depicted are the renin‐angiotensin‐aldosterone system (RAS), arginine vasopressin system (AVP), insulin (INS), glucagon (GLU), the parasympathetic nervous system (PNS), the hypothalamic‐pituitary‐thyroid system (HPT), and the sympathetic cholinergic system (SCS).
Figure 27. Figure 27. Primitive specificity in different domains. For each stressor there is a particular pattern of autonomic, somatic changes, and experiential changes.
Figure 28. Figure 28. Cannon's experiment in which he exposed an instrumented cat to a barking dog. Blood taken from the vena cava of the stressed cat relaxed a rhythmically contracting intestinal strip in a bioassay preparation (). “Excited” blood was added at (b) and (f), and “quiet” blood from the same animal was added at (d).
Figure 29. Figure 29. Illustration of Cannon's use of the heart rate of a denervated heart as a measure of adrenal EPI secretion ().
Figure 30. Figure 30. Articles culled from PubMed using the search term, “allostatic load,” as a function of 2‐year periods since 1996. The number of articles on allostatic load increased exponentially.
Figure 31. Figure 31. Diagrams of feedback loops that may be involved in fainting reactions (neurocardiogenic syncope, reflex syncope, vaso‐vagal syncope). According to the collapse firing hypothesis, syncope results from a combination of SNS activation and decreased cardiac filling (such as from orthostasis or acute hemorrhage), which evokes a pattern of SNS withdrawal and PNS stimulation. According to a schema derived from concepts of scientific integrative medicine, syncope results from positive feedback loops and interference with negative feedback loops, at least partly due to sharing of the SNS and SAS effectors. The result is a specific neuroendocrine pattern that includes PNS activation and sympathoadrenal imbalance.
Figure 32. Figure 32. Mean arterial pressure (MAF), forearm vascular resistance (FVR), and arterial plasma levels of catecholamines in a patient with tilt‐induced hypotension and syncope. The arrows emphasize the mirrored trends in FVR and plasma EPI. EPI becomes dissociated from NE (sympathoadrenal imbalance) and FVR falls below baseline several minutes before hypotension and syncope.
Figure 33. Figure 33. Multiple sites of interference with baroreflex regulation in Parkinson disease (PD) with orthostatic hypotension. Carotid wall thickening interferes with transduction of blood pressure information into baroreceptor afferent traffic. Alpha‐synucleinopathy or neuronal loss in brainstem nuclei interferes with central barostatic function. Neuroimaging and neurochemical evidence indicates substantial noradrenergic denervation or dysfunction in the left ventricular myocardium, renal cortex, and other extra‐cranial sites.
Figure 34. Figure 34. The getaway car analogy. A car's engine uses energy for locomotion. The bank robber's getaway car is kept idling, so that the driver can rapidly shift from “park” to “drive.” As the engine idles, toxic combustion products are produced, which are detoxified by a catalytic converter. The oil lubricates the pistons. Eventually, the engine fails, and deposits are found in the engine and oil.
Figure 35. Figure 35. Catecholamine neurons are like the idling getaway car engine. Catecholamines such as dopamine leak from storage vesicles into the cytoplasm, where they undergo enzymatic oxidative deamination catalyzed by MAO‐A to form toxic catecholaldehydes such as DOPAL. DOPAL is detoxified by aldehyde dehydrogenase (ALDH). Eventually the catecholaminergic neurons die, and deposits of alpha‐synuclein are found in Lewy bodies.
Figure 36. Figure 36. The “catecholaldehyde hypothesis.” According to this hypothesis, decreased vesicular sequestration of cytosolic catecholamines and impaired catecholaldehyde detoxification cause the death of catecholamine neurons that characterizes Parkinson disease. Under resting conditions, most of the irreversible loss of dopamine (DA) from the neurons is due to passive leakage from vesicles (DAv) into the cytosol (DAc) and efficient but imperfect vesicular uptake mediated by the type 2 vesicular monoamine transporter (VMAT2). This loss is balanced by ongoing catecholamine biosynthesis from the action of L‐aromatic‐amino‐acid decarboxylase (LAAAD) on 3,4‐dihydroxyphenylalanine (DOPA) produced from tyrosine (TYR) by tyrosine hydroxylase (TH). Release by exocytosis is followed by reuptake mediated by the cell membrane DA transporter (DAT). Intra‐neuronal metabolism of DA is channeled through enzymatic deamination catalyzed by monoamine oxidase (MAO), producing the catecholaldehyde 3,4‐dihydroxyphenylacetaldehyde (DOPAL). DOPAL is detoxified mainly by aldehyde dehydrogenase (ALDH), to form the acid, 3,4‐dihydroxyphenylacetic acid (DOPAC), with 3,4‐dihydroxyphenylethanol (DOPET) a minor metabolite formed via aldose/aldehyde reductase (AR). Both DAc and DOPAL spontaneously auto‐oxidize to quinones, which augment generation of reactive oxygen species (ROS), resulting in lipid peroxidation. 4‐Hydroxynonenal (4HNE), a major lipid peroxidation product, inhibits ALDH. DOPAL cross‐links with proteins, augmenting oligomerization of alpha‐synuclein and inhibiting TH.
Figure 37. Figure 37. Pathogenetic mechanisms resulting in loss of catecholaminergic neurons may reflect induction of a variety of positive feedback loops.
Figure 38. Figure 38. Computer model‐generated curves illustrating that compensatory activation prolongs the time before a disease process manifests clinically. Tracking the rate of compensatory activation may inform decision‐making about appropriate timing for initiation of neuroprotective treatment.


Figure 1. A homeostatic system. The monitored variable is regulated by negative feedback. Afferent information about the monitored variable reaches a comparator homeostat, which drives an effector that influences the monitored variable. (+) sign indicates a positive relationship and (–) a negative relationship.


Figure 2. Monitored variable level in the absence of feedback regulation. In the computer model, the initial level of the “stock,” the monitored variable, is 100 units. The loss rate, indicated by the “pipe and valve,” depends on a rate constant, kLoss (in this case 1 per min), and on the level of the monitored variable (arrows). The level declines as a first order process, meaning the level falls exponentially.


Figure 3. Negative feedback, with proportionate control. The difference between the level of the monitored variable and the homeostat setting, the error signal, determines the rate of increase (Gain Rate) of the monitored variable. Note that with negative feedback, the level of the monitored variable reaches a steady state. As the value for kGain increases, the plateau level of the monitored variable increases; however, with proportionate control the plateau level is below the homeostat setting.


Figure 4. Effect of head‐up tilting on beat‐to‐beat blood pressure in a healthy person. The blood pressure falls transiently but then returns to about the baseline level.


Figure 5. Computer model of a negative feedback loop with both proportionate and integrated control. The rate of increase in the monitored variable (Gain rate) is determined both by the error signal and the integrated error signal.


Figure 6. Predicted values for levels of the monitored variable as a function of time, with negative feedback by both proportionate and integrated control. The level of the monitored variable returns to the baseline level. The rate of attainment of the baseline level depends on the rate constant for the effector (kEffector). The predicted curve fits well the blood pressure response to tilting in Figure 4.


Figure 7. Homeostatic definition of stress. Stress is defined as a condition or state in which there is a sensed discrepancy between afferent information and the homeostatic setting. The sensed discrepancy corresponds to the “error signal” in the computer model of a negative feedback loop.


Figure 8. Introduction of a stressor into the computer model. The stressor augments the loss rate. The computer model predicts return to the set level of the monitored variable, with the time to return depending on the severity of the stressor. The integrated error signal is a measure of the accumulated stress.


Figure 9. Fever as an allostatic state. Changing the set‐point of the homeostat (in this case at 12 h) increases the steady‐state value for the monitored variable, the core temperature.


Figure 10. Stress, allostasis, and allostatic load in the computer model of negative feedback regulation of temperature by a thermostat. Allostasis refers to regulation of the level of the monitored variable at different steady‐state values by adjusting the thermostat setting. Allostatic load refers to accumulated wear and tear on the furnace.


Figure 11. Inherited and acquired determinants of allostatic load. These determinants include genes and gene expression, environmental influences, resilience, and time. Note that decreased effector efficiency from allostatic load can induce a positive feedback loop, with all the relationships within the loop having a “+” sign.


Figure 12. Predicted effects of allostatic load on wellness. Because of wear and tear on the effector, the effector becomes less efficient, and because it is less efficient it has to be “on” more in order to maintain the level of the monitored variable; however, the more it is “on,” the more wear and tear (allostatic load). This positive feedback loop results in accelerated decline in wellness, early onset of symptomatic system failure (arbitrarily placed at 40% of ideal), and premature death.


Figure 13. Relationship between extent of adrenaline and ACTH responses across multiple stressors, from a meta‐analysis of literature ().


Figure 14. Labile blood pressure in patients with baroreflex failure as a late sequela of irradiation of the neck. Blood pressure lability in this setting exemplifies loss of control of the level of the monitored variable, by disruption of the barostatic negative feedback loop.


Figure 15. Some effectors regulating levels of monitored variables. The effectors are grouped arbitrarily into those of the autonomic nervous system (ANS), pituitary/endocrine (Pitu./Endo.) systems, and others. ANS effectors include the sympathetic noradrenergic system (SNS), sympathetic cholinergic system (SCS), sympathetic adrenergic system (SAS), parasympathetic nervous system (PNS), the DOPA‐dopamine system (DDA), and the enteric nervous system (ENS). Pitu./Endo. systems include the hypothalamic‐pituitary‐adrenocortical (HPA) axis, renin‐angiotensin‐aldosterone system (RAS), thyroid hormone (THY), growth hormone (GH), gonadotrophic hormones (GON), prolactin/oxytocin (PRO), arginine vasopressin (AVP), insulin (INS), and glucagon (GLU). Other effectors include cytokines (CYT), endogenous opiate species (EOS), atrial natriuretic peptide (ANP), bradykinins (BRK), and nitric oxide (NO).


Figure 16. Compensatory activation. When a homeostatic system contains more than one effector, disabling of an effector leads to compensatory activation of the other effectors. Compensatory activation is one advantage of having multiple effectors.


Figure 17. Computer model of multiple effectors.


Figure 18. Computer‐generated curves predicting effects of disabling one effector on activity of an alternative effector. As the rate constant for Effector 1 declines (green to red to black curves), the extent of activation of Effector 2 increases (compensatory activation).


Figure 19. Effector sharing. Two homeostatic systems involving negative feedback loops share the same effector.


Figure 20. Computer model of effector sharing. In this model, two homeostats determine the state of activity of the same effector, which in turn affects levels of two monitored variables. Via effector sharing, a stressor affecting levels of one monitored variable results in altered levels of a different monitored variable.


Figure 21. Predicted effects of effector sharing on levels of monitored variables. As the magnitude of stress increases in one homeostatic system (green to red to black curves), the level of the monitored variable for that homeostatic system returns to the baseline value, while the level of the monitored variable for the second homeostatic system reaches a different steady‐state value. Increasing stress therefore results in maintenance of the first monitored variable at the set value, while levels of the second monitored variable increase to a new steady state. The extent of increase in the level of the second monitored variable depends on the extent of activation of the shared effector.


Figure 22. Complex involvement of multiple effectors and homeostats in the integrated response to orthostasis.


Figure 23. Complex involvement of multiple effectors and homeostats in the integrated response to exercise.


Figure 24. Minimum scientific integrative medicine model. The minimum model incorporates at least one monitored variable that is regulated by multiple effectors and at least one effector that is shared by multiple homeostats.


Figure 25. Compensatory activation of alternative effectors upon disabling of the SNS effector.


Figure 26. Catecholaminergic effectors associated with different homeostats. The different effector patterns result in “primitive specificity” of responses to different stressors. Effectors involving the catecholamines norepinephrine (sympathetic nervous system, SNS), epinephrine (sympathetic adrenergic system, SAS), or dopamine (DOPA‐dopamine system, DDS) are in color. Other effectors depicted are the renin‐angiotensin‐aldosterone system (RAS), arginine vasopressin system (AVP), insulin (INS), glucagon (GLU), the parasympathetic nervous system (PNS), the hypothalamic‐pituitary‐thyroid system (HPT), and the sympathetic cholinergic system (SCS).


Figure 27. Primitive specificity in different domains. For each stressor there is a particular pattern of autonomic, somatic changes, and experiential changes.


Figure 28. Cannon's experiment in which he exposed an instrumented cat to a barking dog. Blood taken from the vena cava of the stressed cat relaxed a rhythmically contracting intestinal strip in a bioassay preparation (). “Excited” blood was added at (b) and (f), and “quiet” blood from the same animal was added at (d).


Figure 29. Illustration of Cannon's use of the heart rate of a denervated heart as a measure of adrenal EPI secretion ().


Figure 30. Articles culled from PubMed using the search term, “allostatic load,” as a function of 2‐year periods since 1996. The number of articles on allostatic load increased exponentially.


Figure 31. Diagrams of feedback loops that may be involved in fainting reactions (neurocardiogenic syncope, reflex syncope, vaso‐vagal syncope). According to the collapse firing hypothesis, syncope results from a combination of SNS activation and decreased cardiac filling (such as from orthostasis or acute hemorrhage), which evokes a pattern of SNS withdrawal and PNS stimulation. According to a schema derived from concepts of scientific integrative medicine, syncope results from positive feedback loops and interference with negative feedback loops, at least partly due to sharing of the SNS and SAS effectors. The result is a specific neuroendocrine pattern that includes PNS activation and sympathoadrenal imbalance.


Figure 32. Mean arterial pressure (MAF), forearm vascular resistance (FVR), and arterial plasma levels of catecholamines in a patient with tilt‐induced hypotension and syncope. The arrows emphasize the mirrored trends in FVR and plasma EPI. EPI becomes dissociated from NE (sympathoadrenal imbalance) and FVR falls below baseline several minutes before hypotension and syncope.


Figure 33. Multiple sites of interference with baroreflex regulation in Parkinson disease (PD) with orthostatic hypotension. Carotid wall thickening interferes with transduction of blood pressure information into baroreceptor afferent traffic. Alpha‐synucleinopathy or neuronal loss in brainstem nuclei interferes with central barostatic function. Neuroimaging and neurochemical evidence indicates substantial noradrenergic denervation or dysfunction in the left ventricular myocardium, renal cortex, and other extra‐cranial sites.


Figure 34. The getaway car analogy. A car's engine uses energy for locomotion. The bank robber's getaway car is kept idling, so that the driver can rapidly shift from “park” to “drive.” As the engine idles, toxic combustion products are produced, which are detoxified by a catalytic converter. The oil lubricates the pistons. Eventually, the engine fails, and deposits are found in the engine and oil.


Figure 35. Catecholamine neurons are like the idling getaway car engine. Catecholamines such as dopamine leak from storage vesicles into the cytoplasm, where they undergo enzymatic oxidative deamination catalyzed by MAO‐A to form toxic catecholaldehydes such as DOPAL. DOPAL is detoxified by aldehyde dehydrogenase (ALDH). Eventually the catecholaminergic neurons die, and deposits of alpha‐synuclein are found in Lewy bodies.


Figure 36. The “catecholaldehyde hypothesis.” According to this hypothesis, decreased vesicular sequestration of cytosolic catecholamines and impaired catecholaldehyde detoxification cause the death of catecholamine neurons that characterizes Parkinson disease. Under resting conditions, most of the irreversible loss of dopamine (DA) from the neurons is due to passive leakage from vesicles (DAv) into the cytosol (DAc) and efficient but imperfect vesicular uptake mediated by the type 2 vesicular monoamine transporter (VMAT2). This loss is balanced by ongoing catecholamine biosynthesis from the action of L‐aromatic‐amino‐acid decarboxylase (LAAAD) on 3,4‐dihydroxyphenylalanine (DOPA) produced from tyrosine (TYR) by tyrosine hydroxylase (TH). Release by exocytosis is followed by reuptake mediated by the cell membrane DA transporter (DAT). Intra‐neuronal metabolism of DA is channeled through enzymatic deamination catalyzed by monoamine oxidase (MAO), producing the catecholaldehyde 3,4‐dihydroxyphenylacetaldehyde (DOPAL). DOPAL is detoxified mainly by aldehyde dehydrogenase (ALDH), to form the acid, 3,4‐dihydroxyphenylacetic acid (DOPAC), with 3,4‐dihydroxyphenylethanol (DOPET) a minor metabolite formed via aldose/aldehyde reductase (AR). Both DAc and DOPAL spontaneously auto‐oxidize to quinones, which augment generation of reactive oxygen species (ROS), resulting in lipid peroxidation. 4‐Hydroxynonenal (4HNE), a major lipid peroxidation product, inhibits ALDH. DOPAL cross‐links with proteins, augmenting oligomerization of alpha‐synuclein and inhibiting TH.


Figure 37. Pathogenetic mechanisms resulting in loss of catecholaminergic neurons may reflect induction of a variety of positive feedback loops.


Figure 38. Computer model‐generated curves illustrating that compensatory activation prolongs the time before a disease process manifests clinically. Tracking the rate of compensatory activation may inform decision‐making about appropriate timing for initiation of neuroprotective treatment.
References
 1. Abboud FM . Neurocardiogenic syncope. N Engl J Med 328: 1117‐1120, 1993.
 2. Abboud FM , Eckberg DL , Johannsen UJ , Mark AL . Carotid and cardiopulmonary baroreceptor control of splanchnic and forearm vascular resistance during venous pooling in man. J Physiol 286: 173‐184, 1979.
 3. Ahlskog JE . Does vigorous exercise have a neuroprotective effect in Parkinson disease? Neurology 77: 288‐294, 2011.
 4. Aicher SA , Kurucz OS , Reis DJ , Milner TA . Nucleus tractus solitarius efferent terminals synapse on neurons in the caudal ventrolateral medulla that project to the rostral ventrolateral medulla. Brain Res 693: 51‐63, 1995.
 5. Akashi YJ , Goldstein DS , Barbaro G , Ueyama T . Takotsubo cardiomyopathy: A new form of acute, reversible heart failure. Circulation 118: 2754‐2762, 2008.
 6. Anderson DG , Mariappan SV , Buettner GR , Doorn JA . Oxidation of 3,4‐dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho‐quinone. J Biol Chem 286: 26978‐26986, 2011.
 7. Antonov I , Kandel ER , Hawkins RD . Presynaptic and postsynaptic mechanisms of synaptic plasticity and metaplasticity during intermediate‐term memory formation in Aplysia. J Neurosci 30: 5781‐5791, 2010.
 8. Aston‐Jones G , Rajkowski J , Cohen J . Role of locus coeruleus in attention and behavioral flexibility. Biol Psychiatry 46: 1309‐1320, 1999.
 9. Azdad K , Chavez M , Don Bischop P , Wetzelaer P , Marescau B , De Deyn PP , Gall D , Schiffmann SN . Homeostatic plasticity of striatal neurons intrinsic excitability following dopamine depletion. PloS one 4: e6908, 2009.
 10. Barcroft H , Edholm OG . On the vasodilatation in human skeletal muscle during post‐haemorrhagic fainting. J Physiol 104: 161‐175, 1945.
 11. Bechtold DA , Loudon AS . Hypothalamic clocks and rhythms in feeding behaviour. Trends Neurosci 36: 74‐82, 2013.
 12. Belkin V , Karasik D . Anthropometric characteristics of men in Antarctica. Int J Circumpolar Health 58: 152‐169, 1999.
 13. Berecek KH , Work J , Mitchum TN , Ram S . Effects of chronic peripheral sympathectomy on plasma levels of, and the pressor response to, vasopressin. J, Hypertens 3: 225‐230, 1985.
 14. Bereiter DA , Zaid AM , Gann DS . Effect of rate of hemorrhage on sympathoadrenal catecholamine release in cats. Am J Physiol 250: E69‐E75, 1986.
 15. Best JD , Berghmans S , Hunt JJ , Clarke SC , Fleming A , Goldsmith P , Roach AG . Non‐associative learning in larval zebrafish. Neuropsychopharmacology 33: 1206‐1215, 2008.
 16. Bezard E , Jaber M , Gonon F , Boireau A , Bloch B , Gross CE . Adaptive changes in the nigrostriatal pathway in response to increased 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced neurodegeneration in the mouse. Eur J Neurosci 12: 2892‐2900, 2000.
 17. Biaggioni I , Whetsell WO , Jobe J , Nadeau JH . Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii. Hypertension 23: 491‐495, 1994.
 18. Blanchard EB , Kolb LC , Prins A , Gates S , McCoy GC . Changes in plasma norepinephrine to combat‐related stimuli among Vietnam veterans with posttraumatic stress disorder. J Nerv Ment Dis 179: 371‐373, 1991.
 19. Blumenthal JA , Fredrikson M , Kuhn CM , Ulmer RL , Walsh‐Riddle M , Appelbaum M . Aerobic exercise reduces levels of cardiovascular and sympathoadrenal responses to mental stress in subjects without prior evidence of myocardial ischemia. Am J Cardiol 65: 93‐98, 1990.
 20. Bogen DK . Simulation software for the Macintosh. Science 246: 138‐142, 1989.
 21. Booth FW , Laye MJ , Roberts MD . Lifetime sedentary living accelerates some aspects of secondary aging. J Appl Physiol 111: 1497‐1504, 2011.
 22. Bouhaddi M , Vuillier F , Fortrat JO , Cappelle S , Henriet MT , Rumbach L , Regnard J . Impaired cardiovascular autonomic control in newly and long‐term‐treated patients with Parkinson's disease: Involvement of L‐dopa therapy. Auton Neurosci 116: 30‐38, 2004.
 23. Braak H , Ghebremedhin E , Rub U , Bratzke H , Del Tredici K . Stages in the development of Parkinson's disease‐related pathology. Cell Tissue Res 318: 121‐134, 2004.
 24. Breier A , Davis O , Buchanan R , Listwak S , Holmes C , Pickard D , Goldstein D . Effects of alprazolam on pituitary‐adrenal and catecholaminergic responses to metabolic stress in humans. Biol Psychiatry 32: 880‐890, 1992.
 25. Breier A , Davis O , Buchanan R , Listwak SJ , Holmes C , Pickar D , Goldstein DS . Effects of alprazolam on pituitary‐adrenal and catecholaminergic responses to metabolic stress in humans. Biol Psychiatry 32: 880‐890, 1992.
 26. Bridgers SL , Spencer SS , Spencer DD , Sasaki CT . A cerebral effect of carotid sinus stimulation. Observation during intraoperative electroencephalographic monitoring. Arch Neurol 42: 574‐577, 1985.
 27. Brown CM , Hecht MJ , Neundorfer B , Hilz MJ . Effects of lower body negative pressure on cardiac and vascular responses to carotid baroreflex stimulation. Physiol Res 52: 637‐645, 2003.
 28. Brown DR . Oligomeric alpha‐synuclein and its role in neuronal death. IUBMB Life 62: 334‐339, 2010.
 29. Brown MR , Fisher LA , Webb V , Vale WW , Rivier JE . Corticotropin‐releasing factor: A physiologic regulator of adrenal epinephrine secretion. Brain Res 328: 355‐357, 1985.
 30. Burke WJ , Kumar VB , Pandey N , Panneton WM , Gan Q , Franko MW , O'Dell M , Li SW , Pan Y , Chung HD , Galvin JE . Aggregation of alpha‐synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol 115: 193‐203, 2008.
 31. Burke WJ , Li SW , Chung HD , Ruggiero DA , Kristal BS , Johnson EM , Lampe P , Kumar VB , Franko M , Williams EA , Zahm DS . Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: Role in neurodegenerative diseases. Neurotoxicology 25: 101‐115, 2004.
 32. Burke WJ , Li SW , Williams EA , Nonneman R , Zahm DS . 3,4‐Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: Implications for Parkinson's disease pathogenesis. Brain Res 989: 205‐213, 2003.
 33. Byers B , Cord B , Nguyen HN , Schule B , Fenno L , Lee PC , Deisseroth K , Langston JW , Pera RR , Palmer TD . SNCA triplication Parkinson's patient's iPSC‐derived DA neurons accumulate alpha‐synuclein and are susceptible to oxidative stress. PloS One 6: e26159, 2011.
 34. Calne DB , Zigmond MJ . Compensatory mechanisms in degenerative neurologic diseases. Insights from parkinsonism. Arch Neurol 48: 361‐363, 1991.
 35. Cannon WB. Bodily Changes in Pain, Hunger, Fear and Rage. New York: D. Appleton & Co., 1929a.
 36. Cannon WB . Organization for physiological homeostasis. Physiol Rev 9: 399‐431, 1929b.
 37. Cannon WB . The effects of progressive sympathectomy on blood pressure. Am J Physiol 97: 592‐595, 1931.
 38. Cannon WB. The Wisdom of the Body. New York: W.W. Norton, 1939.
 39. Cannon WB , Britton SW . The influence of motion and emotion on medulliadrenal secretion. Am J Physiol 79: 433‐465, 1927.
 40. Cannon WB , de la Paz D . Emotional stimulation of adrenal gland secretion. Am J Physiol 28: 64‐70, 1911.
 41. Cannon WB , Lissak K . Evidence for adrenaline in adrenergic neurones. Am J Physiol 125: 765‐777, 1939.
 42. Carey LC , Curtin R , Sapira JD . Influence of hemorrhage on adrenal secretion, blood glucose and serum insulin in the awake pig. Ann Surg 183: 185‐192, 1976.
 43. Carlsten A , Folkow B , Grimby G , Hamberger CA , Thulesius O . Cardiovascular effects of direct stimulation of the carotid sinus nerve in man. Acta Physiol Scand 44: 138‐145, 1958.
 44. Caudle WM , Richardson JR , Wang MZ , Taylor TN , Guillot TS , McCormack AL , Colebrooke RE , Di Monte DA , Emson PC , Miller GW . Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci 27: 8138‐8148, 2007.
 45. Chan CC , Kalsner S . Termination of responses to sympathetic nerve stimulation and to noradrenaline in a perfused arterial preparation: The role of neuronal and extraneuronal uptake. J Pharmacol Exp Ther 222: 731‐740, 1982.
 46. Charkoudian N . Skin blood flow in adult human thermoregulation: How it works, when it does not, and why. Mayo Clin Proc 78: 603‐612, 2003.
 47. Charles ST . Strength and vulnerability integration: A model of emotional well‐being across adulthood. Psychol Bull 136: 1068‐1091, 2010.
 48. Chidsey CA , Braunwald E . Sympathetic activity and neurotransmitter depletion in congestive heart failure. Pharmacol Rev 18: 685‐700, 1966.
 49. Chopra M , Das P , Golden H , Dostal DE , Watson LE , Sharma AC . Norepinephrine induces systolic failure and inhibits antiapoptotic genes in a polymicrobial septic rat model. Life sciences 87: 672‐678, 2010.
 50. Chrousos GP , Gold PW . The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. J Am Med Assoc 267: 1244‐1252, 1992.
 51. Claydon VE , Gulli G , Slessarev M , Appenzeller O , Zenebe G , Gebremedhin A , Hainsworth R . Cerebrovascular responses to hypoxia and hypocapnia in Ethiopian high altitude dwellers. Stroke 39: 336‐342, 2008.
 52. Cryer PE . Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N Engl J Med 303: 436‐444, 1980.
 53. Cui J , Durand S , Levine BD , Crandall CG . Effect of skin surface cooling on central venous pressure during orthostatic challenge. Am J Physiol Heart Circ Physiol 289: H2429‐H2433, 2005.
 54. Damasio A. Descartes' Error. Emotion, Reason, and the Human Brain. New York: Avon Books, Inc., 1994.
 55. Damasio A. The Feeling of What Happens. New York: Harcourt Brace & Company, 1999.
 56. Dangovian MI , Jarandilla R , Frumin H . Prolonged asystole during head‐up tilt table testing after beta blockade. Pacing Clin Electrophysiol 15: 14‐16, 1992.
 57. Darlington DN , Shinsako J , Dallman MF . Responses of ACTH, epinephrine, norepinephrine, and cardiovascular system to hemorrhage. Am J Physiol 251: H612‐H618, 1986.
 58. Darwin C. The Expression of the Emotions in Man and Animals. Chicago: Univ. of Chicago Press, 1965.
 59. Davrath LR , Gotshall RW , Tucker A , Sadeh WZ , Luckasen GJ , Downes TR , Coonts CC . The heart is not necessarily empty at syncope. Aviat Space Environ Med 70: 213‐219, 1999.
 60. Dawkins R. The Selfish Gene. New York: Oxford University Press, 1989.
 61.De Boer SF , Slangen JL , Van der Gugten J . Plasma catecholamine and corticosterone levels during active and passive shock‐prod avoidance behavior in rats: Effects of chlordiazepoxide. Physiol Behav 47: 1089‐1098, 1990.
 62. Desir GV . Role of renalase in the regulation of blood pressure and the renal dopamine system. Curr Opin Nephrol Hypertens 20: 31‐36, 2011.
 63. Deuster PA , Chrousos GP , Luger A , DeBolt JE , Bernier LL , Trostmann UH , Kyle SB , Montgomery LC , Loriaux DL . Hormonal and metabolic responses of untrained, moderately trained, and highly trained men to three exercise intensities. Metabolism 38: 141‐148, 1989.
 64. DiBona GF . Neural regulation of renal tubular sodium reabsorption and renin secretion. Fed Proc 44: 2816‐2822, 1985.
 65. DiBona GF . Neural mechanisms in body fluid homeostasis. Fed Proc 45: 2871‐2877, 1986.
 66. DiBona GF . Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens 11: 197‐200, 2002.
 67. DiBona GF . Central angiotensin modulation of baroreflex control of renal sympathetic nerve activity in the rat: Influence of dietary sodium. Acta Physiol Scand 177: 285‐289, 2003.
 68. Dickinson CJ . Fainting precipitated by collapse‐firing of venous baroreceptors. Lancet 342: 970‐972, 1993.
 69. Dietz NM , Halliwill JR , Spielmann JM , Lawler LA , Papouchado BG , Eickhoff TJ , Joyner MJ . Sympathetic withdrawal and forearm vasodilation during vasovagal syncope in humans. J Appl Physiol 82: 1785‐1793, 1997.
 70. Dietz NM , Joyner MJ , Shepherd JT . Vasovagal syncope and skeletal muscle vasodilatation: The continuing conundrum. Pacing Clin Electrophysiol 20: 775‐780, 1997.
 71. Dobrakovova M , Kvetnansky R , Oprsalova Z , Jezova D . Specificity of the effect of repeated handling on sympathetic‐adrenomedullary and pituitary‐adrenocortical activity in rats. Psychoneuroendocrinology 18: 163‐174, 1993.
 72. Douglas PS , O'Toole ML , Katz SE . Prolonged exercise alters cardiac chronotropic responsiveness in endurance athletes. J Sports Med Phys Fitness 38: 158‐163, 1998.
 73. Dronjak S , Jezova D , Kvetnansky R . Different effects of novel stressors on sympathoadrenal system activation in rats exposed to long‐term immobilization. Ann N Y Acad Sci 1018: 113‐123, 2004.
 74. Duan H , Wang J . Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther 335: 743‐753, 2010.
 75. Duan YF , Kopin IJ , Goldstein DS . Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract. Am J Physiol 277: R403‐R411, 1999.
 76. Duan YF , Winters R , McCabe PM , Green EJ , Huang Y , Schneiderman N . Behavioral characteristics of defense and vigilance reactions elicited by electrical stimulation of the hypothalamus in rabbits. Behav Brain Res 81: 33‐41, 1996.
 77. Durand S , Cui J , Williams KD , Crandall CG . Skin surface cooling improves orthostatic tolerance in normothermic individuals. Am J Physiol Regul Integr Comp Physiol 286: R199‐R205, 2004.
 78. Dworkin BR , Filewich RJ , Miller NE , Craigmyle N , Pickering TG . Baroreceptor activation reduces reactivity to noxious stimulation: Implications for hypertension. Science 205: 1299‐1301, 1979.
 79. Dziewierz A , Giszterowicz D , Siudak Z , Rakowski T , Dubiel JS , Dudek D . Admission glucose level and in‐hospital outcomes in diabetic and non‐diabetic patients with acute myocardial infarction. Clin Res Cardiol 99: 715‐721, 2010.
 80. Ebert TJ , Cowley AW Jr . Baroreflex modulation of sympathetic outflow during physiological increases of vasopressin in humans. Am J Physiol 262: H1372‐H1378, 1992.
 81. Edwards TL , Scott WK , Almonte C , Burt A , Powell EH , Beecham GW , Wang L , Zuchner S , Konidari I , Wang G , Singer C , Nahab F , Scott B , Stajich JM , Pericak‐Vance M , Haines J , Vance JM , Martin ER . Genome‐wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann Hum Genet 74: 97‐109, 2010.
 82. Eisenhofer G , Friberg P , Rundqvist B , Quyyumi AA , Lambert G , Kaye DM , Kopin IJ , Goldstein DS , Esler MD . Cardiac sympathetic nerve function in congestive heart failure. Circulation 93: 1667‐1676, 1996.
 83. Eisenhofer G , Goldstein DS , Stull R , Keiser HR , Sunderland T , Murphy DL , Kopin IJ . Simultaneous liquid‐chromatographic determination of 3,4‐dihydroxyphenylglycol, catecholamines, and 3,4‐dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase. Clin Chem 32: 2030‐2033, 1986.
 84. Eisenhofer G , Goldstein DS , Stull RW , Gold PW , Keiser HR , Kopin IJ . Dissociation between corticotrophin and catecholamine responses to isoprenaline in humans. Clin Exp Pharmacol Physiol 14: 337‐341, 1987.
 85. Eisenhofer G , Kopin IJ , Goldstein DS . Leaky catecholamine stores: Undue waste or a stress response coping mechanism? Ann N Y Acad Sci 1018: 224‐230, 2004.
 86. Eisenhofer G , Rundqvist B , Aneman A , Friberg P , Dakak N , Kopin IJ , Jacobs MC , Lenders JW . Regional release and removal of catecholamines and extraneuronal metabolism to metanephrines. J Clin Endocrinol Metab 80: 3009‐3017, 1995.
 87. Eldadah BA , Pacak K , Eisenhofer G , Holmes C , Kopin IJ , Goldstein DS . Cardiac uptake‐1 inhibition by high circulating norepinephrine levels in patients with pheochromocytoma. Hypertension 43: 1227‐1232, 2004.
 88. Eldadah BA , Pechnik SL , Holmes CS , Moak JP , Saleem AM , Goldstein DS . Failure of propranolol to prevent tilt‐evoked systemic vasodilatation, adrenaline release and neurocardiogenic syncope. Clin Sci 111: 209‐216, 2006.
 89. Ellenbogen KA , Morillo CA , Wood MA , Gilligan DM , Eckberg DL , Smith ML . Neural monitoring of vasovagal syncope. Pacing Clin Electrophysiol 20: 788‐794, 1997.
 90. Engel GL . Psychologic distress, vasodepressor (vasovagal) syncope, and sudden death. Ann Int Med 89: 403‐412, 1978.
 91. Engel JE , Wu CF . Neurogenetic approaches to habituation and dishabituation in Drosophila. Neurobiol Learn Mem 92: 166‐175, 2009.
 92. Esler M . The sympathetic system and hypertension. Am J Hypertens 13: 99S‐105S, 2000.
 93. Esler M , Jennings G , Korner P , Blombery P , Sacharias N , Leonard P . Measurement of total and organ‐specific norepinephrine kinetics in humans. Am J Physiol 247: E21‐E28, 1984.
 94. Esler M , Julius S , Randall O , DeQuattro V , Zweifler A . High‐renin essential hypertension: Adrenergic cardiovascular correlates. Clin Sci Mol Med Suppl 3: 181s‐184s, 1976.
 95. Esler MD , Turner AG , Kaye DM , Thompson JM , Kingwell BA , Morris M , Lambert GW , Jennings GL , Cox HS , Seals DR . Aging effects on human sympathetic neuronal function. Am J Physiol 268: R278‐R285, 1995.
 96. Evans JM , Leonelli FM , Ziegler MG , McIntosh CM , Patwardhan AR , Ertl AC , Kim CS , Knapp CF . Epinephrine, vasodilation and hemoconcentration in syncopal, healthy men and women. Auton Neurosci 93: 79‐90, 2001.
 97. Fagius J , Wallin BG , Sundlof G , Nerhed C , Englesson S . Sympathetic outflow in man after anaesthesia of the glossopharyngeal and vagus nerves. Brain 108(Pt 2): 423‐438, 1985.
 98. Ferreira A , Bettencourt P , Pimenta J , Frioes F , Pestana M , Soares‐da‐Silva P , Cerqueira‐Gomes M . The renal dopaminergic system, neurohumoral activation, and sodium handling in heart failure. Am Heart J 143: 391‐397, 2002.
 99. Fitzpatrick AP , Banner N , Cheng A , Yacoub M , Sutton R . Vasovagal reactions may occur after orthotopic heart transplantation. J Am Coll Cardiol 21: 1132‐1137, 1993.
 100. Flaa A , Eide IK , Kjeldsen SE , Rostrup M . Sympathoadrenal stress reactivity is a predictor of future blood pressure: An 18‐year follow‐up study. Hypertension 52: 336‐341, 2008.
 101. Folkow B . Physiological aspects of primary hypertension. Physiol Rev 62: 347‐504, 1982.
 102. Folkow B . Stress, hypothalamic function and neuroendocrine consequences. Acta Med Scand (Suppl 723): 61‐69, 1988.
 103. Frank SM , Higgins MS , Fleisher LA , Sitzmann JV , Raff H , Breslow MJ . Adrenergic, respiratory, and cardiovascular effects of core cooling in humans. Am J Physiol 272: R557‐R562, 1997.
 104. Frank SM , Raja SN , Bulcao CF , Goldstein DS . Relative contribution of core and cutaneous temperatures to thermal comfort and autonomic responses in humans. J Appl Physiol 86: 1588‐1593, 1999.
 105. Fredholm BB , Farnebo LO , Hamberger B . Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6‐OH‐dopamine treatment. Acta Physiol Scand 105: 481‐495, 1979.
 106. Frenzel H , Bohlender J , Pinsker K , Wohlleben B , Tank J , Lechner SG , Schiska D , Jaijo T , Ruschendorf F , Saar K , Jordan J , Millan JM , Gross M , Lewin GR . A genetic basis for mechanosensory traits in humans. PLoS Biol 10: e1001318, 2012.
 107. Friberg P , Meredith I , Jennings G , Lambert G , Fazio V , Esler M . Evidence for increased renal norepinephrine overflow during sodium restriction in humans. Hypertension 16: 121‐130, 1990.
 108. Fukuhara K , Kvetnansky R , Cizza G , Pacak K , Ohara H , Goldstein DS , Kopin IJ . Interrelations between sympathoadrenal system and hypothalamo‐pituitary‐adrenocortical/thyroid systems in rats exposed to cold stress. J Neuroendocrinol 8: 533‐541, 1996.
 109. Funkenstein DH . Nor‐epinephrine‐like and epinephrine‐like substances in relation to human behavior. J Mental Dis 124: 58‐68, 1956.
 110. Gajek J , Zysko D , Krzeminska S , Mazurek W . The influence of a tilt training programme on the renin‐angiotensin‐aldosterone system activity in patients with vasovagal syncope. Acta Cardiol 64: 505‐509, 2009.
 111. Gauthier P , Nadeau R , De Champlain J . Acute and chronic cardiovascular effects of 6‐hydroxydopamine in dogs. Circ Res 31: 207‐217, 1972.
 112. Gebber GL , Snyder DW . Hypothalamic control of baroreceptor reflexes. Am J Physiol 218: 124‐131, 1969.
 113. Geracioti TD Jr. , Baker DG , Ekhator NN , West SA , Hill KK , Bruce AB , Schmidt D , Rounds‐Kugler B , Yehuda R , Keck PE Jr. , Kasckow JW . CSF norepinephrine concentrations in posttraumatic stress disorder. Am J Psychiatry 158: 1227‐1230, 2001.
 114. Geracioti TD Jr. , Baker DG , Kasckow JW , Strawn JR , Jeffrey Mulchahey J , Dashevsky BA , Horn PS , Ekhator NN . Effects of trauma‐related audiovisual stimulation on cerebrospinal fluid norepinephrine and corticotropin‐releasing hormone concentrations in post‐traumatic stress disorder. Psychoneuroendocrinology 33: 416‐424, 2008.
 115. Gerra G , Zaimovic A , Mascetti GG , Gardini S , Zambelli U , Timpano M , Raggi MA , Brambilla F . Neuroendocrine responses to experimentally‐induced psychological stress in healthy humans. Psychoneuroendocrinology 26: 91‐107, 2001.
 116. Gerson MC , McGuire N , Wagoner LE . Sympathetic nervous system function as measured by I‐123 metaiodobenzylguanidine predicts transplant‐free survival in heart failure patients with idiopathic dilated cardiomyopathy. J Card Fail 9: 384‐391, 2003.
 117. Gianaros PJ , Jennings JR , Sheu LK , Greer PJ , Kuller LH , Matthews KA . Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus. Neuroimage 35: 795‐803, 2007.
 118. Giannattasio C , Grassi G , Mancia G . Vasovagal syncope with bradycardia during lower body negative pressure in a heart transplant recipient. Blood Press 2: 309‐311, 1993.
 119. Giordano A , Calcagni ML , Verrillo A , Pellegrinotti M , Frontoni S , Spallone V , Gambardella S . Assessment of sympathetic innervation of the heart in diabetes mellitus using 123I‐MIBG. Diabetes Nutr Metab 13: 350‐355, 2000.
 120. Goddard AW , Ball SG , Martinez J , Robinson MJ , Yang CR , Russell JM , Shekhar A . Current perspectives of the roles of the central norepinephrine system in anxiety and depression. Depress Anxiety 27: 339‐350, 2010.
 121. Golczynska A , Lenders JW , Goldstein DS . Glucocorticoid‐induced sympathoinhibition in humans. Clin Pharmacol Ther 58: 90‐98, 1995.
 122. Gold PW , Goodwin FK , Chrousos GP . Clinical and biochemical manifestations of depression: Relation to the neurobiology of stress (Part 1 of 2 parts). N Engl J Med 319: 348‐353, 1988.
 123. Goldstein D , Fink D , Mettee DR . Cognition of arousal and actual arousal as determinants of emotion. J Pers Soc Psychol 21: 41‐51, 1972.
 124. Goldstein DS. Stress, Catecholamines, and Cardiovascular Disease. New York: Oxford University Press, 1995.
 125. Goldstein DS. The Autonomic Nervous System in Health and Disease. New York, NY: Marcel Dekker, Inc., 2001.
 126. Goldstein DS . Dysautonomia in Parkinson's disease: Neurocardiological abnormalities. Lancet Neurol 2: 669‐676, 2003.
 127. Goldstein DS. Adrenaline and the Inner World: An Introduction to Scientific Integrative Medicine. Baltimore, MD: The Johns Hopkins University Press, 2006.
 128. Goldstein DS . Orthostatic hypotension as an early finding in Parkinson disease. Clin Auton Res 16: 46‐64, 2006.
 129. Goldstein DS . Stress, allostatic load, catecholamines, and other neurotransmitters in neurodegenerative diseases. Cell Mol Neurobiol 32: 661‐666, 2012.
 130. Goldstein DS , Eisenhofer G , Kopin IJ . Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther 305: 800‐811, 2003.
 131. Goldstein DS , Eisenhofer G , Sax FL , Keiser HR , Kopin IJ . Plasma norepinephrine pharmacokinetics during mental challenge. Psychosom Med 49: 591‐605, 1987.
 132. Goldstein DS , Garty M , Bagdy G , Szemeredi K , Sternberg EM , Listwak S , Deka‐Starosta A , Hoffman A , Chang PC , Stull R , Gold PW , Kopin IJ . Role of CRH in glucopenia‐induced adrenomedullary activation in rats. J Neuroendocrinol 5: 475‐486, 1993.
 133. Goldstein DS , Harris AH , Brady JV . Baroreflex sensitivity during operant blood pressure conditioning. Biofeedback Self‐Regul 2: 127‐138, 1977.
 134. Goldstein DS , Holmes C , Frank SM , Naqibuddin M , Dendi R , Snader S , Calkins H . Sympathoadrenal imbalance before neurocardiogenic syncope. Am J Cardiol 91: 53‐58, 2003.
 135. Goldstein DS , Holmes C , Kopin IJ , Sharabi Y . Intra‐neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. J Clin Inv 121: 3320‐3330, 2011.
 136. Goldstein DS , Holmes C , Li ST , Bruce S , Metman LV , Cannon RO III . Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133: 338‐347, 2000.
 137. Goldstein DS , Holmes C , Sharabi Y . Cerebrospinal fluid biomarkers of central catecholamine deficiency in Parkinson's disease and other synucleinopathies. Brain 135: 1900‐1913, 2012.
 138. Goldstein DS , Kopin IJ . Adrenomedullary, adrenocortical, and sympathoneural responses to stressors: A meta‐analysis. Endo Regul 42: 111‐119, 2008.
 139. Goldstein DS , Kopin IJ . Evolution of concepts of stress. Stress 10: 109‐120, 2007.
 140. Goldstein DS , McEwen B . Allostasis, homeostats, and the nature of stress. Stress 5: 55‐58, 2002.
 141. Goldstein DS , Orimo S . Cardiac sympathetic neuroimaging: Summary of the First International Symposium. Clin Auton Res 19: 133‐136, 2009.
 142. Goldstein DS , Ross RS , Brady JV . Biofeedback heart rate training during exercise. Biofeedback Self‐Regul 2: 107‐125, 1977.
 143. Goldstein DS , Sharabi Y , Karp BI , Bentho O , Saleem A , Pacak K , Eisenhofer G . Cardiac sympathetic denervation preceding motor signs in Parkinson disease. Clin Auton Res 17: 118‐121, 2007.
 144. Goldstein DS , Spanarkel M , Pitterman A , Toltzis R , Gratz E , Epstein S , Keiser HR . Circulatory control mechanisms in vasodepressor syncope. Am Heart J 104: 1071‐1075, 1982.
 145. Goldstein DS , Stull R , Eisenhofer G , Gill JR Jr . Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans. Clin Sci 76: 517‐522, 1989.
 146. Goldstein DS , Sullivan P , Cooney A , Jinsmaa Y , Sullivan R , Gross DJ , Holmes C , Kopin IJ , Sharabi Y . Vesicular uptake blockade generates the toxic dopamine metabolite 3,4‐dihydroxyphenylacetaldehyde in PC12 Cells: Relevance to the pathogenesis of Parkinson disease. J Neurochem 123: 932‐943, 2012.
 147. Goldstein DS , Sullivan P , Holmes C , Kopin IJ , Basile MJ , Mash DC . Catechols in post‐mortem brain of patients with Parkinson disease. Eur J Neurol 18: 703‐710, 2011.
 148. Graham DG . Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14: 633‐643, 1978.
 149. Granata AR , Numao Y , Kumada M , Reis DJ . A1 noradrenergic neurons tonically inhibit sympathoexcitatory neurons of C1 area in rat brainstem. Brain Res 377: 127‐146, 1986.
 150. Greenough A , Lagercrantz H , Pool J , Dahlin I . Plasma catecholamine levels in preterm infants. Effect of birth asphyxia and Apgar score. Acta Paediatr Scand 76: 54‐59, 1987.
 151. Habib KE , Weld KP , Rice KC , Pushkas J , Champoux M , Listwak S , Webster EL , Atkinson AJ , Schulkin J , Contoreggi C , Chrousos GP , McCann SM , Suomi SJ , Higley JD , Gold PW . Oral administration of a corticotropin‐releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates. Proc Natl Acad Sci U S A 97: 6079‐6084, 2000.
 152. Haglund ME , Nestadt PS , Cooper NS , Southwick SM , Charney DS . Psychobiological mechanisms of resilience: Relevance to prevention and treatment of stress‐related psychopathology. Dev Psychopathol 19: 889‐920, 2007.
 153. Harris AH , Gilliam WJ , Findley JS , Brady JV . Instrumental conditioning of large‐magnitude, daily, 12‐hour blood pressure elevations in the baboon. Science 182: 175‐177, 1973.
 154. Hasser EM , Bishop VS , Hay M . Interactions between vasopressin and baroreflex control of the sympathetic nervous system. Clin Exp Pharmacol Physiol 24: 102‐108, 1997.
 155. Hein L , Altman JD , Kobilka BK . Two functionally distinct alpha2‐adrenergic receptors regulate sympathetic neurotransmission. Nature 402: 181‐184, 1999.
 156. Heusser K , Tank J , Engeli S , Diedrich A , Menne J , Eckert S , Peters T , Sweep FC , Haller H , Pichlmaier AM , Luft FC , Jordan J . Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension 55: 619‐626, 2010.
 157. Ichinose M , Nishiyasu T . Arterial baroreflex control of muscle sympathetic nerve activity under orthostatic stress in humans. Front Physiol 3: 314, 2012.
 158. Imrich R , Eldadah BA , Bentho O , Pechnik S , Sharabi Y , Holmes C , Goldstein DS . Attenuated pre‐ejection period response to tyramine in patients with cardiac sympathetic denervation. Ann N Y Acad Sci 1148: 486‐489, 2008.
 159. Isnard R , Pousset F , Trochu J , Chafirovskaia O , Carayon A , Golmard J , Lechat P , Thomas D , Bouhour J , Komajda M . Prognostic value of neurohormonal activation and cardiopulmonary exercise testing in patients with chronic heart failure. Am J Cardiol 86: 417‐421, 2000.
 160. Jacobs MC , Goldstein DS , Willemsen JJ , Smits P , Thien T , Dionne RA , Lenders JW . Neurohumoral antecedents of vasodepressor reactions. Eur J Clin Invest 25: 754‐761, 1995.
 161. Jain S , Goldstein DS . Cardiovascular dysautonomia in Parkinson disease: From pathophysiology to pathogenesis. Neurobiol Dis 46: 572‐580, 2012.
 162. Jami L , Laporte Y , Scott JJ . Some effects of sympathetic stimulation and isoprenaline on fatigued tetanic contractions of skeletal muscle in the cat. Brain Res 321: 386‐389, 1984.
 163. Jardine DL , Melton IC , Crozier IG , Bennett SI , Donald RA , Ikram H . Neurohormonal response to head‐up tilt and its role in vasovagal syncope. Am J Cardiol 79: 1302‐1306, 1997.
 164. Jeong KH , Jacobson L , Pacak K , Widmaier EP , Goldstein DS , Majzoub JA . Impaired basal and restraint‐induced epinephrine secretion in corticotropin‐releasing hormone‐deficient mice. Endocrinology 141: 1142‐1150, 2000.
 165. Joyner MJ . Giant sucking sound: Can physiology fill the intellectual void left by the reductionists? J Appl Physiol 111: 335‐342, 2011.
 166. Joyner MJ , Dietz NM . Sympathetic vasodilation in human muscle. Acta Physiol Scand 177: 329‐336, 2003.
 167. Joyner MJ , Pedersen BK . Ten questions about systems biology. J Physiol 589: 1017‐1030, 2011.
 168. Jungermann K , Stumpel F . Role of hepatic, intrahepatic and hepatoenteral nerves in the regulation of carbohydrate metabolism and hemodynamics of the liver and intestine. Hepatogastroenterology 46(Suppl 2): 1414‐1417, 1999.
 169. Kaasinen V , Ruottinen HM , Nagren K , Lehikoinen P , Oikonen V , Rinne JO . Upregulation of putaminal dopamine D2 receptors in early Parkinson's disease: A comparative PET study with [11C] raclopride and [11C]N‐methylspiperone. J Nucl Med 41: 65‐70, 2000.
 170. Kahneman D. Thinking, Fast and Slow. New York: Farrar, Strauss and Giroux, 2011.
 171. Kallio M , Haapaniemi T , Turkka J , Suominen K , Tolonen U , Sotaniemi K , Heikkila VP , Myllyla V . Heart rate variability in patients with untreated Parkinson's disease. Eur J Neurol 7: 667‐672, 2000.
 172. Kalsner S . Role of extraneuronal mechanisms in the termination of contractile responses to amines in vascular tissue. Br J Pharmacol 53: 267‐277, 1975.
 173. Kaludercic N , Carpi A , Menabo R , Di Lisa F , Paolocci N . Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochim Biophys Acta 1813: 1323‐1332, 2011.
 174. Kaludercic N , Takimoto E , Nagayama T , Feng N , Lai EW , Bedja D , Chen K , Gabrielson KL , Blakely RD , Shih JC , Pacak K , Kass DA , Di Lisa F , Paolocci N . Monoamine oxidase A‐mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload. Circ Res 106: 193‐202, 2010.
 175. Kandel ER , Tauc L . Mechanism of heterosynaptic facilitation in the giant cell of the abdominal ganglion of Aplysia depilans. J Physiol 181: 28‐47, 1965.
 176. Karnani M , Burdakov D . Multiple hypothalamic circuits sense and regulate glucose levels. Am J Physiol Regul Integr Comp Physiol 300: R47‐R55, 2011.
 177. Kaufmann H , Goldstein DS . Dysautonomia in Parkinson disease. Handbook Clin Neurol 83: 343‐363, 2007.
 178. Kawada T , Yamazaki T , Akiyama T , Shishido T , Miyano H , Sato T , Sugimachi M , Alexander J Jr. , Sunagawa K . Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility. Am J Physiol 273: H1107‐H1112, 1997.
 179. Kaye DM , Lefkovits J , Jennings GL , Bergin P , Broughton A , Esler MD . Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol 26: 1257‐1263, 1995.
 180. Kenagy DN , Bird CT , Webber CM , Fischer JR . Dextroamphetamine use during B‐2 combat missions. Aviat Space Environ Med 75: 381‐386, 2004.
 181. Kjaer M , Mikines KJ , Christensen NJ , Tronier B , Vinten J , Sonne B , Richter EA , Galbo H . Glucose turnover and hormonal changes during insulin‐induced hypoglycemia in trained humans. J Appl Physiol 57: 21‐27, 1984.
 182. Koob GF . Corticotropin‐releasing factor, norepinephrine, and stress. Biol Psychiatry 46: 1167‐1180, 1999.
 183. Kopin IJ . Definitions of stress and sympathetic neuronal responses. Ann N Y Acad Sci 771: 19‐30, 1995.
 184. Kopin IJ , Rundqvist B , Friberg P , Lenders J , Goldstein DS , Eisenhofer G . Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm. Am J Physiol 275: R165‐R173, 1998.
 185. Kosten TR , Mason JW , Giller EL , Ostroff RB , Harkness L . Sustained urinary norepinephrine and epinephrine elevation in post‐traumatic stress disorder. Psychoneuroendocrinology 12: 13‐20, 1987.
 186. Krum H , Schlaich M , Whitbourn R , Sobotka PA , Sadowski J , Bartus K , Kapelak B , Walton A , Sievert H , Thambar S , Abraham WT , Esler M . Catheter‐based renal sympathetic denervation for resistant hypertension: A multicentre safety and proof‐of‐principle cohort study. Lancet 373: 1275‐1281, 2009.
 187. Kruyt ND , Biessels GJ , Devries JH , Roos YB . Hyperglycemia in acute ischemic stroke: Pathophysiology and clinical management. Nat Rev Neurol 6: 145‐155, 2010.
 188. Kubota T , Yamazaki N , Sudo J , Monma Y , Kaku T , Okuyama T , Tanabe T . Protective effects of adrenoceptor‐blocking agents on myocardial injury induced by epinephrine in mice. J Toxicol Sci 15: 1‐13, 1990.
 189. Kurata C , Uehara A , Ishikawa A . Improvement of cardiac sympathetic innervation by renal transplantation. J Nucl Med 45: 1114‐1120, 2004.
 190. Kurz T , Richardt G , Seyfarth M , Schomig A . Nonexocytotic noradrenaline release induced by pharmacological agents or anoxia in human cardiac tissue. Naunyn Schmiedeberg's Arch Pharmacol 354: 7‐16, 1996.
 191. Kvetnansky R . Stressor specificity and effect of prior experience on catecholamine biosynthetic enzyme phenylethanolamine N‐methyltransferase. Ann N Y Acad Sci 1032: 117‐129, 2004.
 192. Kvetnansky R , Pacak K , Fukuhara K , Viskupic E , Hiremagalur B , Nankova B , Goldstein DS , Sabban EL , Kopin IJ . Sympathoadrenal system in stress. Interaction with the hypothalamic‐pituitary‐adrenocortical system. Ann N Y Acad Sci 771: 131‐158, 1995.
 193. Kvetnansky R , Sun CL , Lake CR , Thoa N , Torda T , Kopin IJ . Effect of handling and forced immobilization on rat plasma levels of epinephrine, norepinephrine, and dopamine‐beta‐hydroxylase. Endocrinology 103: 1868‐1874, 1978.
 194. Lake CR , Ziegler MG , Kopin IJ . Use of plasma norepinephrine for evaluation of sympathetic neuronal function in man. Life sciences 18: 1315‐1325, 1976.
 195. Langston JW , Ballard P , Tetrud JW , Irwin I . Chronic Parkinsonism in humans due to a product of meperidine‐analog synthesis. Science 219: 979‐980, 1983.
 196. Lazarus RS. Emotion and Adaptation. New York: Oxford University Press, 1991.
 197. Leppaluoto J , Westerlund T , Huttunen P , Oksa J , Smolander J , Dugue B , Mikkelsson M . Effects of long‐term whole‐body cold exposures on plasma concentrations of ACTH, beta‐endorphin, cortisol, catecholamines and cytokines in healthy females. Scand J Clin Lab Invest 68: 145‐153, 2008.
 198. Li SW , Lin TS , Minteer S , Burke WJ . 3,4‐Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: Possible role in Parkinson's disease pathogenesis. Brain Res Mol Brain Res 93: 1‐7, 2001.
 199. Lightfoot JT , Rowe SA , Fortney SM . Occurrence of presyncope in subjects without ventricular innervation. Clin Sci 85: 695‐700, 1993.
 200. Linzer M , Pontinen M , Gold DT , Divine GW , Felder A , Brooks WB . Impairment of physical and psychosocial function in recurrent syncope. J Clin Epidemiol 44: 1037‐1043, 1991.
 201. Liu JE , Hahn RT , Stein KM , Markowitz SM , Okin PM , Devereux RB , Lerman BB . Left ventricular geometry and function preceding neurally mediated syncope. Circulation 101: 777‐783, 2000.
 202. Lohmeier TE , Hildebrandt DA , Dwyer TM , Iliescu R , Irwin ED , Cates AW , Rossing MA . Prolonged activation of the baroreflex decreases arterial pressure even during chronic adrenergic blockade. Hypertension 53: 833‐838, 2009.
 203. Lohmeier TE , Iliescu R . Chronic lowering of blood pressure by carotid baroreflex activation: Mechanisms and potential for hypertension therapy. Hypertension 57: 880‐886, 2011.
 204. Lohmeier TE , Iliescu R . Lowering of blood pressure by chronic suppression of central sympathetic outflow: Insight from prolonged baroreflex activation. J Appl Physiol 113: 1652‐1658, 2012.
 205. Lohmeier TE , Iliescu R , Dwyer TM , Irwin ED , Cates AW , Rossing MA . Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am J Physiol 299: H402‐H409, 2010.
 206. Lorenz K. On Aggression. New York: Bantam, 1963.
 207. Low CA , Matthews KA , Kuller LH , Edmundowicz D . Psychosocial predictors of coronary artery calcification progression in postmenopausal women. Psychosom Med 73: 789‐794, 2011.
 208. Lu CC , Diedrich A , Tung CS , Paranjape SY , Harris PA , Byrne DW , Jordan J , Robertson D . Water ingestion as prophylaxis against syncope. Circulation 108: 2660‐2665, 2003.
 209. Lukas A , Ferrier GR . Arrhythmic effects of norepinephrine in a model of cardiac ischemia and reperfusion. Can J Physiol Pharmacol 67: 765‐771, 1989.
 210. Lyon AR , Rees PS , Prasad S , Poole‐Wilson PA , Harding SE . Stress (Takotsubo) cardiomyopathy–a novel pathophysiological hypothesis to explain catecholamine‐induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 5: 22‐29, 2008.
 211. Mahfoud F , Schlaich M , Kindermann I , Ukena C , Cremers B , Brandt MC , Hoppe UC , Vonend O , Rump LC , Sobotka PA , Krum H , Esler M , Bohm M . Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: A pilot study. Circulation 123: 1940‐1946, 2011.
 212. Makinen TM , Mantysaari M , Paakkonen T , Jokelainen J , Palinkas LA , Hassi J , Leppaluoto J , Tahvanainen K , Rintamaki H . Autonomic nervous function during whole‐body cold exposure before and after cold acclimation. Aviat Space Environ Med 79: 875‐882, 2008.
 213. Manhem P , Bramnert M , Hallengren B , Lecerof H , Werner R . Increased arterial and venous plasma noradrenaline levels in patients with primary hypothyroidism during hypothyroid as compared to euthyroid state. J Endocrinol Invest 15: 763‐765, 1992.
 214. Marino F , Sockler JM , Fry JM . Thermoregulatory, metabolic and sympathoadrenal responses to repeated brief exposure to cold. Scand J Clin Lab Invest 58: 537‐545, 1998.
 215. Marshall RD , Garakani A . Psychobiology of the acute stress response and its relationship to the psychobiology of post‐traumatic stress disorder. Psychiatr Clin North Am 25: 385‐395, 2002.
 216. Mastrocola C , Vanacore N , Giovani A , Locuratolo N , Vella C , Alessandri A , Baratta L , Tubani L , Meco G . Twenty‐four‐hour heart rate variability to assess autonomic function in Parkinson's disease. Acta Neurol Scand 99: 245‐247, 1999.
 217. Matsukawa K , Komine H , Nakamoto T , Murata J . Central command blunts sensitivity of arterial baroreceptor‐heart rate reflex at onset of voluntary static exercise. Am J Physiol Heart Circ Physiol 290: H200‐H208, 2006.
 218. Matthews KA , Zhu S , Tucker DC , Whooley MA . Blood pressure reactivity to psychological stress and coronary calcification in the Coronary Artery Risk Development in Young Adults Study. Hypertension 47: 391‐395, 2006.
 219. McEwen B , Stellar E . Stress and the individual. Mechanisms leading to disease. Arch Int Med 153: 2093‐2101, 1993.
 220. McEwen BS . Interacting mediators of allostasis and allostatic load: Towards an understanding of resilience in aging. Metabolism 52: 10‐16, 2003.
 221. McFall ME , Murburg MM , Ko GN , Veith RC . Autonomic responses to stress in Vietnam combat veterans with posttraumatic stress disorder. Biol Psychiatry 27: 1165‐1175, 1990.
 222. Menazza S , Blaauw B , Tiepolo T , Toniolo L , Braghetta P , Spolaore B , Reggiani C , Di Lisa F , Bonaldo P , Canton M . Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy. Hum Mol Genet 19: 4207‐4215, 2010.
 223. Meredith IT , Broughton A , Jennings GL , Esler MD . Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Engl J Med 325: 618‐624, 1991.
 224. Millar RA , Keener EB , Benfey BG . Plasma adrenaline and noradrenaline after phenoxybenzamine administration, and during haemorrhagic hypotension, in normal and adrenalectomized dogs. Br J Pharmacol Chemother 14: 9‐13, 1959.
 225. Molochnikov L , Rabey JM , Dobronevsky E , Bonucelli U , Ceravolo R , Frosini D , Grunblatt E , Riederer P , Jacob C , Aharon‐Peretz J , Bashenko Y , Youdim MB , Mandel SA . A molecular signature in blood identifies early Parkinson's disease. Molec Neurodegen 7: 26, 2012.
 226. Momose M , Inaba S , Emori T , Imamura K , Kawano K , Ueda T , Kobayashi H , Hosoda S . Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine‐123 metaiodobenzylguanidine scintigraphy. Eur J Nucl Med 24: 1132‐1137, 1997.
 227. Montebugnoli L , Montanari G . Vasovagal syncope in heart transplant patients during dental surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87: 666‐669, 1999.
 228. Morgan DA , Balon TW , Ginsberg BH , Mark AL . Nonuniform regional sympathetic nerve responses to hyperinsulinemia in rats. Am J Physiol 264: R423‐R427, 1993.
 229. Morillo CA , Eckberg DL , Ellenbogen KA , Beightol LA , Hoag JB , Tahvanainen KU , Kuusela TA , Diedrich AM . Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation 96: 2509‐2513, 1997.
 230. Morrison SF . Differential regulation of sympathetic outflows to vasoconstrictor and thermoregulatory effectors. Ann N Y Acad Sci 940: 286‐298, 2001.
 231. Mosqueda‐Garcia R , Fernandez‐Violante R , Tank J , Snell M , Cunningham G , Furlan R . Yohimbine in neurally mediated syncope. Pathophysiological implications. J Clin Invest 102: 1824‐1830, 1998.
 232. Mosqueda‐Garcia R , Furlan R , Fernandez‐Violante R , Desai T , Snell M , Jarai Z , Ananthram V , Robertson RM , Robertson D . Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. J Clin Invest 99: 2736‐2744, 1997.
 233. Mosqueda‐Garcia R , Furlan R , Tank J , Fernandez‐Violante R . The elusive pathophysiology of neurally mediated syncope. Circulation 102: 2898‐2906, 2000.
 234. Nagatsu T , Sawada M . Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson's disease: Possible implications of glial cells. J Neural Transm (Suppl) 53‐65, 2006.
 235. Nathan MA , Reis DJ . Chronic labile hypertension produced by lesions of the nucleus tractus solitarii in the cat. Circ Res 40: 72‐81, 1977.
 236. Nesse RM , Williams GC . Why We Get Sick. The New Science of Darwinian Medicine. New York: Times Books, 1994.
 237. Nishida Y , Bishop VS . Vasopressin‐induced suppression of renal sympathetic outflow depends on the number of baroafferent inputs in rabbits. Am J Physiol 263: R1187‐R1194, 1992.
 238. Noble D. The Music of Life: Biology beyond the Genome. Oxford, UK: Oxford University Press, 2006.
 239. Oberg B , Thorten P . Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat. A possible cause of vasovagal reaction. Acta Physiol Scand 85: 164‐173, 1972.
 240. Olanow CW , Hauser RA , Gauger L , Malapira T , Koller W , Hubble J , Bushenbark K , Lilienfeld D , Esterlitz J . The effect of deprenyl and levodopa on the progression of Parkinson's disease. Ann Neurol 38: 771‐777, 1995.
 241. Olanow CW , Rascol O , Hauser R , Feigin PD , Jankovic J , Lang A , Langston W , Melamed E , Poewe W , Stocchi F , Tolosa E . A double‐blind, delayed‐start trial of rasagiline in Parkinson's disease. N Engl J Med 361: 1268‐1278, 2009.
 242. Ostman‐Smith I . Adaptive changes in the sympathetic nervous system and some effector organs of the rat following long term exercise or cold acclimation and the role of cardiac sympathetic nerves in the genesis of compensatory cardiac hypertrophy. Acta Physiol Scand 108: 1‐118, 1980.
 243. Osztovits J , Horvath T , Littvay L , Steinbach R , Jermendy A , Tarnoki A , Tarnoki D , Metneki J , Kollai M , Jermendy G . Effects of genetic vs. environmental factors on cardiovascular autonomic function: A twin study. Diabet Med 28: 1241‐1248, 2011.
 244. Pacak K . Stressor‐specific activation of the hypothalamic‐pituitary‐adrenocortical axis. Physiol Res 49: S11‐S17, 2000.
 245. Pacak K , Palkovits M , Yadid G , Kvetnansky R , Kopin IJ , Goldstein DS . Heterogeneous neurochemical responses to different stressors: A test of Selye's doctrine of nonspecificity. Am J Physiol 275: R1247‐R1255, 1998.
 246. Panneton WM , Kumar VB , Gan Q , Burke WJ , Galvin JE . The neurotoxicity of DOPAL: Behavioral and stereological evidence for its role in Parkinson disease pathogenesis. PLoS One 5: e15251, 2010.
 247. Park ER , Traeger L , Vranceanu AM , Scult M , Lerner JA , Benson H , Denninger J , Fricchione GL . The development of a patient‐centered program based on the relaxation response: The Relaxation Response Resiliency Program (3RP). Psychosomatics 54: 165‐174, 2013.
 248. Patel JN , Coppack SW , Goldstein DS , Miles JM , Eisenhofer G . Norepinephrine spillover from human adipose tissue before and after a 72‐hour fast. J Clin Endocrinol Metab 87: 3373‐3377, 2002.
 249. Patel MB , Loud AV , King BD , Anversa P , Sack D , Hintze TH . Global myocardial hypertrophy in conscious dogs with chronic elevation of plasma norepinephrine levels. J Mol Cell Cardiol 21(Suppl 5): 49‐61, 1989.
 250. Perlmutter JS , Kilbourn MR , Raichle ME , Welch MJ . MPTP‐induced up‐regulation of in vivo dopaminergic radioligand‐receptor binding in humans. Neurology 37: 1575‐1579, 1987.
 251. Pettit SE , Marchand I , Graham T . Gender differences in cardiovascular and catecholamine responses to cold‐air exposure at rest. Can J Appl Physiol 24: 131‐147, 1999.
 252. Polikar R , Kennedy B , Ziegler M , O'Connor DT , Smith J , Nicod P . Plasma norepinephrine kinetics, dopamine‐beta‐hydroxylase, and chromogranin‐A, in hypothyroid patients before and following replacement therapy. J Clin Endocrinol Metab 70: 277‐281, 1990.
 253. Polinsky RJ , Kopin IJ , Ebert MH , Weise V . The adrenal medullary response to hypoglycemia in patients with orthostatic hypotension. J Clin Endocrinol Metab 51: 1401‐1406, 1980.
 254. Polymeropoulos MH , Lavedan C , Leroy E , Ide SE , Dehejia A , Dutra A , Pike B , Root H , Rubenstein J , Boyer R , Stenroos ES , Chandrasekharappa S , Athanassiadou A , Papapetropoulos T , Johnson WG , Lazzarini AM , Duvoisin RC , Di Iorio G , Golbe LI , Nussbaum RL . Mutation in the alpha‐synuclein gene identified in families with Parkinson's disease. Science 276: 2045‐2047, 1997.
 255. Quillen EW Jr. , Cowley AW Jr . Influence of volume changes on osmolality‐vasopressin relationships in conscious dogs. Am J Physiol 244: H73‐H79, 1983.
 256. Randich A , Aicher SA . Medullary substrates mediating antinociception produced by electrical stimulation of the vagus. Brain Res 445: 68‐76, 1988.
 257. Rattanataweeboon P , Vilaichone W , Vannasaeng S . Stress hyperglycemia in patients with sepsis. J Med Assoc Thai 92(Suppl 2): S88‐S94, 2009.
 258. Rea RF , Eckberg DL , Fritsch JM , Goldstein DS . Relation of plasma norepinephrine and sympathetic traffic during hypotension in man. Am J Physiol 258: R982‐R986, 1990.
 259. Rees JN , Florang VR , Anderson DG , Doorn JA . Lipid peroxidation products inhibit dopamine catabolism yielding aberrant levels of a reactive intermediate. Chem Res Toxicol 20: 1536‐1542, 2007.
 260. Rees JN , Florang VR , Eckert LL , Doorn JA . Protein reactivity of 3,4‐dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol. Chem Res Toxicol 22: 1256‐1263, 2009.
 261. Riegger GA , Liebau G , Kochsiek K . Antidiuretic hormone in congestive heart failure. Am J Med 72: 49‐52, 1982.
 262. Riese H , Rijsdijk FV , Ormel J , van Roon AM , Neeleman J , Rosmalen JG . Genetic influences on baroreflex sensitivity during rest and mental stress. J Hypertens 24: 1779‐1786, 2006.
 263. Robertson DA , Johnson GA , Robertson RM , Nies AS , Shand DG , Oates JA . Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man. Circulation 59: 637‐643, 1979.
 264. Robinson BJ , Johnson RH . Why does vasodilatation occur during syncope? Clin Sci 74: 347‐350, 1988.
 265. Rodriguez M , Sabate M , Troncoso E . Time and frequency domain analysis for the assessment of heart autonomic control in Parkinson's disease. J Neural Transm 103: 447‐454, 1996.
 266. Romero‐Bermejo FJ , Ruiz‐Bailen M , Gil‐Cebrian J , Huertos‐Ranchal MJ . Sepsis‐induced cardiomyopathy. Curr Cardiol Rev 7: 163‐183, 2011.
 267. Rona G . Catecholamine cardiotoxicity. J Mol Cell Cardiol 17: 291‐306, 1985.
 268. Satake W , Nakabayashi Y , Mizuta I , Hirota Y , Ito C , Kubo M , Kawaguchi T , Tsunoda T , Watanabe M , Takeda A , Tomiyama H , Nakashima K , Hasegawa K , Obata F , Yoshikawa T , Kawakami H , Sakoda S , Yamamoto M , Hattori N , Murata M , Nakamura Y , Toda T . Genome‐wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41: 1303‐1307, 2009.
 269. Schachter S , Singer J . Cognitive, social, and physiological determinants of emotional state. Psychol Rev 69: 379‐399, 1962.
 270. Scherrer U , Vissing S , Morgan BJ , Hanson P , Victor RG . Vasovagal syncope after infusion of a vasodilator in a heart‐transplant recipient. N Engl J Med 322: 602‐604, 1990.
 271. Schlaich MP , Sobotka PA , Krum H , Lambert E , Esler MD . Renal sympathetic‐nerve ablation for uncontrolled hypertension. N Engl J Med 361: 932‐934, 2009.
 272. Schommer NC , Hellhammer DH , Kirschbaum C . Dissociation between reactivity of the hypothalamus‐pituitary‐adrenal axis and the sympathetic‐adrenal‐medullary system to repeated psychosocial stress. Psychosom Med 65: 450‐460, 2003.
 273. Schultz W . Behavioral dopamine signals. Trends Neurosci 30: 203‐210, 2007.
 274. Scott EM , Greenwood JP , Stoker JB , Mary DA , Gilbey SG . Sympathetic nerve hyperactivity is associated with increased peripheral vascular resistance in hypopituitary patients with growth hormone deficiency. Clin Endocrinol (Oxf) 56: 759‐763, 2002.
 275. Seals DR , Esler MD . Human ageing and the sympathoadrenal system. J Physiol 528: 407‐417, 2000.
 276. Seller H , Illert M . The localization of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of the afferent input. Pflugers Arch 306: 1‐19, 1969.
 277. Selye H. The Physiology and Pathology of Exposure to Stress. A Treatise Based on the Concepts of the General‐Adaptation Syndrome and the Diseses of Adaptation. Montreal, Canada: Acta, Inc., 1950.
 278. Selye H. The Stress of Life. New York: McGraw‐Hill, 1956.
 279. Selye H. Stress without Distress. New York: New American Library, 1974.
 280. Sevoz‐Couche C , Comet MA , Bernard JF , Hamon M , Laguzzi R . Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: Role of the nucleus tractus solitarius 5‐HT2A receptors. Am J Physiol 291: R1007‐R1015, 2006.
 281. Sevoz‐Couche C , Hamon M , Laguzzi R . Antinociceptive effect of cardiopulmonary chemoreceptor and baroreceptor reflex activation in the rat. Pain 99: 71‐81, 2002.
 282. Shah SD , Tse TF , Clutter WE , Cryer PE . The human sympathochromaffin system. Am J Physiol 247: E380‐E384, 1984.
 283. Sharabi Y , Dendi R , Holmes C , Goldstein DS . Baroreflex failure as a late sequela of neck irradiation. Hypertension 42: 110‐116, 2003.
 284. Sharabi Y , Imrich R , Holmes C , Pechnik S , Goldstein DS . Generalized and neurotransmitter‐selective noradrenergic denervation in Parkinson's disease with orthostatic hypotension. Mov Disord 23: 1725‐1732, 2008.
 285. Siegel S . Conditioning of insulin effects. J Comp Physiol Psychol 78: 233‐241, 1972.
 286. Simpson A , Maynard V . A longitudinal study of the effect of Antarctic residence on energy dynamics and aerobic fitness. Int J Circumpolar Health 71: 17227, 2012.
 287. Singal PK , Dhillon KS , Beamish RE , Kapur N , Dhalla NS . Myocardial cell damage and cardiovascular changes due to iv infusion of adrenochrome in rats. Br J Pathol 63: 167‐176, 1982.
 288. Singleton A , Gwinn‐Hardy K , Sharabi Y , Li ST , Holmes C , Dendi R , Hardy J , Crawley A , Goldstein DS . Association between cardiac denervation and parkinsonism caused by alpha‐synuclein gene triplication. Brain 127: 768‐772, 2004.
 289. Singleton AB , Farrer M , Johnson J , Singleton A , Hague S , Kachergus J , Hulihan M , Peuralinna T , Dutra A , Nussbaum R , Lincoln S , Crawley A , Hanson M , Maraganore D , Adler C , Cookson MR , Muenter M , Baptista M , Miller D , Blancato J , Hardy J , Gwinn‐Hardy K . alpha‐Synuclein locus triplication causes Parkinson's disease. Science 302: 841, 2003.
 290. Sofuoglu M , Nelson D , Babb DA , Hatsukami DK . Intravenous cocaine increases plasma epinephrine and norepinephrine in humans. Pharmacol Biochem Behav 68: 455‐459, 2001.
 291. Sossi V , de la Fuente‐Fernandez R , Schulzer M , Troiano AR , Ruth TJ , Stoessl AJ . Dopamine transporter relation to dopamine turnover in Parkinson's disease: A positron emission tomography study. Ann Neurol 62: 468‐474, 2007.
 292. Southwick SM , Bremner JD , Rasmusson A , Morgan CA, III, Arnsten A , Charney DS . Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biological Psychiatry 46: 1192‐1204, 1999.
 293. Spillantini MG , Schmidt ML , Lee VM , Trojanowski JQ , Jakes R , Goedert M . Alpha‐synuclein in Lewy bodies. Nature 388: 839‐840, 1997.
 294. Sterling P , Eyer J . Allostasis: A new paradigm to explain arousal pathology. In: Fisher J , Reason J , editors. Handbook of Life Stress, Cognition, and Health. New York: Johns Wiley & Sons Inc., 1988, pp. 629‐649.
 295. Sverrisdottir YB , Elam M , Herlitz H , Bengtsson BA , Johannsson G . Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. J Clin Endocrinol Metab 83: 1881‐1885, 1998.
 296. Szatalowicz VL , Arnold PE , Chaimovitz C , Bichet D , Berl T , Schrier RW . Radioimmunoassay of plasma arginine vasopressin in hyponatremic patients with congestive heart failure. N Engl J Med 305: 263‐266, 1981.
 297. Tatar P , Bulas J , Kvetnansky R , Strec V . Venous plasma adrenaline response to orthostatic syncope during tilting in healthy men. Clin Physiol 6: 303‐309, 1986.
 298. Taylor TN , Caudle WM , Shepherd KR , Noorian A , Jackson CR , Iuvone PM , Weinshenker D , Greene JG , Miller GW . Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity. J Neurosci 29: 8103‐8113, 2009.
 299. Theopistou A , Gatzoulis K , Economou E , Sideris S , Hantzos K , Stefanadis C , Toutouzas P . Biochemical changes involved in the mechanism of vasovagal syncope. Am J Cardiol 88: 376‐381, 2001.
 300. Thomas CB . Experimental hypertension from section of moderator nerves. BullJohnsHopkinsHosp 74: 335‐377, 1944.
 301. Thomas JA , Marks BH . Plasma norepinephrine in congestive heart failure. Am J Cardiol 41: 233‐243, 1978.
 302. Thoren P , Skarphendinsson JO , Carlsson S . Sympathetic inhibition from vagal afferents during severe hemorrhage in rats. Acta Physiol Scand Suppl 571: 97‐105, 1988.
 303. Tsutamoto T , Nishiyama K , Sakai H , Tanaka T , Fujii M , Yamamoto T , Yamaji M , Horie M . Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure. Eur J Heart Fail 10: 1208‐1214, 2008.
 304. Turkka JT , Tolonen U , Myllyla VV . Cardiovascular reflexes in Parkinson's disease. Eur Neurol 26: 104‐112, 1987.
 305. Uchiyama M , Otsuka T , Sakai K . Response of plasma renin activity to postural change in vasovagal syncope in children, with observations on syncope. Horm Res 23: 147‐150, 1986.
 306. Udelsman R , Goldstein DS , Loriaux DL , Chrousos GP . Catecholamine‐glucocorticoid interactions during surgical stress. J Surg Res 43: 539‐545, 1987.
 307. Uschold‐Schmidt N , Nyuyki KD , Fuchsl AM , Neumann ID , Reber SO . Chronic psychosocial stress results in sensitization of the HPA axis to acute heterotypic stressors despite a reduction of adrenal in vitro ACTH responsiveness. Psychoneuroendocrinology 37: 1676‐1687, 2012.
 308. Vaddadi G , Esler MD , Dawood T , Lambert E . Persistence of muscle sympathetic nerve activity during vasovagal syncope. Eur Heart J 31: 2027‐2033, 2010.
 309. Vaddadi G , Esler MD , Dawood T , Lambert E . Persistence of muscle sympathetic nerve activity during vasovagal syncope. European Heart J 31: 2027‐2033, 2010.
 310. Valappil RA , Black JE , Broderick MJ , Carrillo O , Frenette E , Sullivan SS , Goldman SM , Tanner CM , Langston JW . Exploring the electrocardiogram as a potential tool to screen for premotor Parkinson's disease. Movement Disorders 25: 2296‐2303, 2010.
 311. Virtanen R , Jula A , Salminen JK , Voipio‐Pulkki LM , Helenius H , Kuusela T , Airaksinen J . Anxiety and hostility are associated with reduced baroreflex sensitivity and increased beat‐to‐beat blood pressure variability. Psychosom Med 65: 751‐756, 2003.
 312. Vissing SF . Differential activation of sympathetic discharge to skin and skeletal muscle in humans. Acta Physiol Scand Suppl 639: 1‐32, 1997.
 313. von Euler US . A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relations to adrenaline and nor‐adrenaline. Acta Physiol Scand 12: 73‐96, 1946.
 314. Wallin BG , Sundlof G . Sympathetic outflow to muscles during vasovagal syncope. J Autonom Nerv Sys 6: 287‐291, 1982.
 315. Watabe T , Tanaka K , Kumagae M , Itoh S , Takeda F , Morio K , Hasegawa M , Horiuchi T , Miyabe S , Shimizu N . Hormonal responses to insulin‐induced hypoglycemia in man. J Clin Endocrinol Metab 65: 1187‐1191, 1987.
 316. Weil‐Malherbe H , Axelrod J , Tomchick R . Blood‐brain barrier for adrenaline. Science 129: 1226‐1227, 1959.
 317. Wey M , Fernandez E , Martinez PA , Sullivan P , Goldstein DS , Strong R . Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: Implications for Parkinson's disease. PLoS ONE 7: e31522, 2012.
 318. Williams GC . Pleiotropy, natural selection, and the evolution of senescence. Evolution 11: 398‐411, 1957.
 319. Winner B , Jappelli R , Maji SK , Desplats PA , Boyer L , Aigner S , Hetzer C , Loher T , Vilar M , Campioni S , Tzitzilonis C , Soragni A , Jessberger S , Mira H , Consiglio A , Pham E , Masliah E , Gage FH , Riek R . In vivo demonstration that {alpha}‐synuclein oligomers are toxic. Proc Natl Acad Sci U S A 108: 4194‐4199, 2011.
 320. Wittstein IS , Thiemann DR , Lima JA , Baughman KL , Schulman SP , Gerstenblith G , Wu KC , Rade JJ , Bivalacqua TJ , Champion HC . Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 352: 539‐548, 2005.
 321. Wolfovitz E , Grossman E , Folio CJ , Keiser HR , Kopin IJ , Goldstein DS . Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans. Clin Sci 84: 549‐557, 1993.
 322. Wong ML , Kling MA , Munson PJ , Listwak S , Licinio J , Prolo P , Karp B , McCutcheon IE , Geracioti TD Jr. , DeBellis MD , Rice KC , Goldstein DS , Veldhuis JD , Chrousos GP , Oldfield EH , McCann SM , Gold PW . Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin‐releasing hormone. Proc Natl Acad Sci U S A 97: 325‐330, 2000.
 323. Xu Q , Park Y , Huang X , Hollenbeck A , Blair A , Schatzkin A , Chen H . Physical activities and future risk of Parkinson disease. Neurology 75: 341‐348, 2010.
 324. Zakowski SG , Hall MH , Klein LC , Baum A . Appraised control, coping, and stress in a community sample: A test of the goodness‐of‐fit hypothesis. Ann Behav Med 23: 158‐165, 2001.
 325. Zeng C , Zhu Z , Liu G , Hu W , Wang X , Yang C , Wang H , He D , Tan J . Randomized, double‐blind, placebo‐controlled trial of oral enalapril in patients with neurally mediated syncope. Am Heart J 136: 852‐858, 1998.
 326. Ziegler D , Weise F , Langen KJ , Piolot R , Boy C , Hubinger A , Muller‐Gartner HW , Gries FA . Effect of glycaemic control on myocardial sympathetic innervation assessed by [123I]metaiodobenzylguanidine scintigraphy: A 4‐year prospective study in IDDM patients. Diabetologia 41: 443‐451, 1998.
 327. Zigmond MJ , Abercrombie ED , Berger TW , Grace AA , Stricker EM . Compensations after lesions of central dopaminergic neurons: Some clinical and basic implications. Trends Neurosci 13: 290‐296, 1990.
 328. Zimlichman R , Goldstein DS , Zimlichman S , Keiser HR . Angiotensin II increases cytosolic calcium and stimulates catecholamine release in cultured bovine adrenomedullary cells. Cell Calcium 8: 315‐325, 1987.
 329. Zimlichman R , Levinson PD , Kelly G , Stull R , Keiser HR , Goldstein DS . Derivation of urinary dopamine from plasma dopa. Clin Sci 75: 515‐520, 1988.
 330. Zohar J , Yahalom H , Kozlovsky N , Cwikel‐Hamzany S , Matar MA , Kaplan Z , Yehuda R , Cohen H . High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: Interplay between clinical and animal studies. Eur Neuropsychopharmacol 21: 796‐809, 2011.
 331. Zuckerman‐Levin N , Tiosano D , Eisenhofer G , Bornstein S , Hochberg Z . The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: A study in isolated glucocorticoid deficiency. J Clin Endocrinol Metab 86: 5920‐5924, 2001.

CORRIGENDUM

David S. Goldstein. Concepts of Scientific Integrative Medicine Applied to the Physiology and Pathophysiology of Catecholamine Systems. Compr Physiol 2013, 3:1569-1610. doi: 10.1002/cphy.c130006

The text on p. 1597 has been changed from: "A reasonable societal goal of medical research is to enable each individual to live as long and productive a life as his or her genes endow, and then all body systems at the same time" to "A reasonable societal goal of medical research is to enable each individual to live as long and productive a life as his or her genes endow, and then all body systems fail at the same time."

The word “fail” was missing from the originally published article.


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David S. Goldstein. Concepts of Scientific Integrative Medicine Applied to the Physiology and Pathophysiology of Catecholamine Systems. Compr Physiol 2013, 3: 1569-1610. doi: 10.1002/cphy.c130006