Sympathetic Nervous System Activity in Major Depression

Veith, Richard C.; Lewis, Nancy; Linares, Oscar A.; Barnes, R. F.; Raskind, Murray A.; Villacres, Enrique C.; Murburg, M. Michele; Ashleigh, E. Alexandra; Castillo, Sonia Velasco del; Peskind, Elaine R.; Pascualy, Marcella; Halter, Jeffrey B.

doi:10.1001/archpsyc.1994.03950050071008

Cited by 391 publications

(101 citation statements)

References 75 publications

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“…The increases at Weeks 4 and 6 in urinary NMN replicate earlier studies from our laboratory in which Schildkraut et al (1966) observed gradual increases in levels of 24-hour urinary NMN (the metabolite of extraneuronal NE) during the period of definitive clinical improvement in depressed patients treated with imipramine. Taken together, our findings suggest the presence of an increase in the extraneuronal accumulation of NE during chronic desipramine treatment at a time when there is also a reduction in plasma NE clearance (Veith et al, 1994).…”

Section: Discussionsupporting

confidence: 64%

“…This decrease in firing of locus coeruleus cells persisted during subchronic (48 hours) treatment with desipramine (Linnér et al, 1999). In depressed patients following 48-hours of desipramine treatment, Veith et al (1994) observed a short-term reduction in plasma NE accompanied by suppression of both the rates of extravascular and vascular NE appearance, which are compatible with a reduction in sympathetic nervous system activity.…”

Section: Discussionmentioning

confidence: 67%

“…These findings during chronic treatment have been attributed to α 2 -adrenergic desensitization (Svensson & Usdin, 1978;Linnér et al, 1999;McMillen et al, 1980); and significant desensitization of cortical α 2 -adrenergic receptors has been observed in animals following long-term treatment with desipramine and other antidepressants (Mateo et al, 2001). Veith et al (1994) observed a rise in plasma NE after 4 weeks of desipramine treatment in depressed patients. Using an isotope-dilution, plasma NE kinetic technique, they attributed the increase in plasma NE concentrations to a progressive reduction in plasma NE clearance.…”

Section: Discussionmentioning

confidence: 85%

“…Secondly, while we made every effort to collect information on the completeness of urine collections at the time of each visit, our results are limited by the actual compliance with the instructions given to each outpatient subject during their participation in this study. Thirdly, we did not employ repeated infusions of 3 H-NE in this research and so we could not directly study such parameters as the plasma clearance rate of NE (Veith et al, 1994) or the rate of NE entry into the extravascular compartment (Kopin et al, 1998) during our study. However, changes in plasma and 24 hr urinary catecholamines have mirrored changes in muscle sympathetic nerve activity in a variety of circumstances (Tataranni et al, 1999;Miyajima & Yamada, 1999;Miyajima et al, 2000), and changes in urinary NE and urinary NMN reflected increased plasma NE levels during infusions of NE into human subjects (Moleman et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Enhanced norepinephrine output during long-term desipramine treatment: A possible role for the extraneuronal monoamine transporter (SLC22A3)

Mooney

Samson

Hennen

et al. 2008

Journal of Psychiatric Research

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To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-hour urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be an important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. The ClinicalTrials.gov Identifier for this study is NCT00320632.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Enhanced norepinephrine output during long-term desipramine treatment: A possible role for the extraneuronal monoamine transporter (SLC22A3)

Mooney

Samson

Hennen

et al. 2008

Journal of Psychiatric Research

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“…34 Given the left-lateralization of our neuroimaging findings in the subgenual PFC, 1 these lesion analyses suggest the hypothesis that dysfunction of the left subgenual PFC in mood disorders specifically results in the heightened affective, neuroendocrine and sympathetic autonomic arousal seen in depression. 26,29,30,35 Lesions of the ventromedial PFC also alter parasympathetic autonomic function in rats in a manner that shows an intriguing parallel with autonomic abnormalities reported in humans with MDD. Frysztak and Neafsey 32 found that rats with lesions of the prelimbic and infralimbic cortex show reduced beat-to-beat variability of the heart rate both at rest and during exposure to fear-conditioned stimuli.…”

Section: Potential Implications Of Subgenual Pfc Dysfunctionmentioning

confidence: 78%

Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders

1998

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The prefrontal cortex (PFC) ventral to the genu of the corpus callosum has been implicated in the modulation of visceral responses to stressful and emotionally provocative stimuli, based upon analysis of lesion effects involving this area in humans and experimental animals. In a recent magnetic resonance imaging (MRI) study of familial mood disorders, we demonstrated that the mean grey matter volume of this cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of their treatment status or current mood state. Moreover, in preliminary histopathological assessments of subgenual PFC tissue taken post mortem from subjects with MDD and bipolar disorder we obtained results suggesting that this decrement in grey matter volume is associated with a reduction in glia without an equivalent loss of neurons. The potential functional significance of these neuroimaging and microscopic abnormalities is discussed with respect to evidence that subgenual PFC dysfunction may disturb stress-related autonomic and neuroendocrine responses and reward-related mesolimbic dopamine function. These data may thus hold important implications for the development of neural models of mood disorders that can account for the abnormal hedonic, motivational, neuroendocrine, and autonomic manifestations evident in these idiopathic conditions. Keywords: anterior cingulate; glia; MRI; PET; major depression; bipolar disorder; emotionIn a recent neuroimaging study of mood disorders we reported that the grey matter volume of the prefrontal cortex (PFC) ventral to the genu of the corpus callosum is reduced in familial bipolar disorder and familial major depressive disorder (MDD). 1 The magnetic resonance imaging (MRI)-based neuromorphometric measures acquired to demonstrate this abnormality in the 'subgenual' PFC were guided by positron emission tomographic (PET) images that showed an abnormal reduction of cerebral blood flow (BF) and glucose metabolism in this area in depression. [2][3][4] Because antidepressant treatment did not reverse these physiological abnormalities, the MRI measures of grey matter volume were obtained to determine whether the decrements in regional BF and metabolism were at least partly explained by a corresponding reduction in cortex. 5 This hypothesis was confirmed, as the mean grey matter volume of the left subgenual PFC was reduced by 39% and 48% in the bipolar disordered and unipolar depressed samples, respectively, relative to the controls (F = 9.8; P Ͻ 0.0002, after covarying for age, gender and whole brain volume). 1 This volumetric Correspondence: WC Drevets, MD, B 938,

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Inflammation, Sanitation, and Consternation

Raison¹,

Lowry²,

Rook³

2010

Arch Gen Psychiatry

154

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Context Inflammation is increasingly recognized as contributing to the pathogenesis of major depressive disorder (MDD), even in individuals who are otherwise medically healthy. Most studies in search of sources for this increased inflammation have focused on factors such as psychosocial stress and obesity that are known to activate inflammatory processes and increase the risk for depression. However, MDD may be so prevalent in the modern world not just because proinflammatory factors are widespread, but also because we have lost contact with previously available sources of anti-inflammatory, immunoregulatory signaling. Objective To examine evidence that disruptions in co-evolved relationships with a variety of tolerogenic microorganisms that were previously ubiquitous in soil, food, and the gut, but that are largely missing from industrialized societies, may contribute to increasing rates of MDD in the modern world. Data Sources Relevant studies were identified using PubMed and Ovid MEDLINE. Study Selection Included were laboratory animal and human studies relevant to immune functioning, the hygiene hypothesis, and major depressive disorder identified via PubMed and Ovid MEDLINE searches. Data Extraction Studies were reviewed by all authors, and data considered to be potentially relevant to the contribution of hygiene-related immune variables to major depressive disorder were extracted. Data Synthesis Significant data suggest that a variety of microorganisms (frequently referred to as the “old friends”) were tasked by coevolutionary processes with training the human immune system to tolerate a wide array of nonthreatening but potentially proinflammatory stimuli. Lacking such immune training, vulnerable individuals in the modern world are at significantly increased risk of mounting inappropriate inflammatory attacks on harmless environmental antigens (leading to asthma), benign food contents and commensals in the gut (leading to inflammatory bowel disease), or self-antigens (leading to any of a host of autoimmune diseases). Loss of exposure to the old friends may promote MDD by increasing background levels of depressogenic cytokines and may predispose vulnerable individuals in industrialized societies to mount inappropriately aggressive inflammatory responses to psychosocial stressors, again leading to increased rates of depression. Conclusion Measured exposure to the old friends or their antigens may offer promise for the prevention and treatment of MDD in modern industrialized societies.

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Sympathetic Nervous System Activity in Major Depression

Cited by 391 publications

References 75 publications

Enhanced norepinephrine output during long-term desipramine treatment: A possible role for the extraneuronal monoamine transporter (SLC22A3)

Enhanced norepinephrine output during long-term desipramine treatment: A possible role for the extraneuronal monoamine transporter (SLC22A3)

Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders

Inflammation, Sanitation, and Consternation

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