Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.

Posted on March 3, 2012 by Maurice Preter MD

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):730-43. Epub 2010 Aug 5.
Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.
Gardner A, Boles RG.
Source

Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden. agtorndal@odenhall.se
Abstract

For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression. High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the “affective spectrum disorders”, and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders. We propose that interactions among monoamines, mitochondrial dysfunction and inflammation can inspire explanatory, rather than mere descriptive, models of these disorders.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID:
20691744
[PubMed – indexed for MEDLINE]

Posted in Psychiatry/Neurology | Tagged |

The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes.

Posted on March 3, 2012 by Maurice Preter MD

Neuropsychiatr Dis Treat. 2010 May 6;6:123-36.
The relationship between depression, anxiety, and cardiovascular outcomes in patients with acute coronary syndromes.
Huffman JC, Celano CM, Januzzi JL.
Source

Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street/Blake 11, Boston, MA, USA. jhuffman@partners.org
Abstract

Depression and anxiety occur at high rates among patients suffering an acute coronary syndrome (ACS). Both depressive symptoms and anxiety appear to adversely affect in-hospital and long term cardiac outcomes of post-ACS patients, independent of traditional risk factors. Despite their high prevalence and serious impact, mood and anxiety symptoms go unrecognized and untreated in most ACS patients and such symptoms (rather than being transient reactions to ACS) persist for months and beyond. The mechanisms by which depression and anxiety are linked to these negative medical outcomes are likely a combination of the effects of these conditions on inflammation, catecholamines, heart rate variability, and endothelial function, along with effects on health-promoting behavior. Fortunately, standard treatments for these disorders appear to be safe, well-tolerated and efficacious in this population; indeed, selective serotonin reuptake inhibitors may actually improve cardiac outcomes. Future research goals include gaining a better understanding of the combined effects of depression and anxiety, as well as definitive prospective studies of the impact of treatment on cardiac outcomes. Clinically, protocols that allow for efficient and systematic screening, evaluation, and treatment for depression and anxiety in cardiac patients are critical to help patients avoid the devastating effects of these illnesses on quality of life and cardiac health.

PMID:
20505844
[PubMed]
PMCID:
PMC2874336

Free PMC Article

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Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.

Posted on March 3, 2012 by Maurice Preter MD

Psychosom Med. 2010 May;72(4):365-9. Epub 2010 Apr 21.
Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
Kiecolt-Glaser JK.
Source

Department of Psychiatry, The Ohio State Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, Ohio 43210-1228, USA. Janice.Kiecolt-Glaser@osumc.edu
Abstract

Inflammation is the common link among the leading causes of death. Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation, including sympathetic activity, oxidative stress, transcription factor nuclear factor-kappaB activation, and proinflammatory cytokine production. Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes. If the joint contributions of diet and behavior to inflammation were simply additive, they would be important. However, several far more intriguing interactive possibilities are discussed: stress influences food choices; stress can enhance maladaptive metabolic responses to unhealthy meals; and diet can affect mood as well as proinflammatory responses to stressors. Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation; in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut. As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors. A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.

PMID:
20410248
[PubMed – indexed for MEDLINE]
PMCID:
PMC2868080

Free PMC Article

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Polyunsaturated fatty acids, neuroinflammation and well being.

Posted on March 3, 2012 by Maurice Preter MD

Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):295-303. Epub 2010 Mar 15.
Polyunsaturated fatty acids, neuroinflammation and well being.
Layé S.
Source

Psychoneuroimmunology, Nutrition and Genetic (PsyNuGen), UMR INRA 1286, CNRS 5226, University Bordeaux 2, Bordeaux, France. sophie.laye@bordeaux.inra.fr
Abstract

The innate immune system of the brain is principally composed of microglial cells and astrocytes, which, once activated, protect neurons against insults (infectious agents, lesions, etc.). Activated glial cells produce inflammatory cytokines that act specifically through receptors expressed by the brain. The functional consequences of brain cytokine action (also called neuroinflammation) are alterations in cognition, mood and behaviour, a hallmark of altered well-being. In addition, proinflammatory cytokines play a key role in depression and neurodegenerative diseases linked to aging. Polyunsaturated fatty acids (PUFA) are essential nutrients and essential components of neuronal and glial cell membranes. PUFA from the diet regulate both prostaglandin and proinflammatory cytokine production. n-3 fatty acids are anti-inflammatory while n-6 fatty acids are precursors of prostaglandins. Inappropriate amounts of dietary n-6 and n-3 fatty acids could lead to neuroinflammation because of their abundance in the brain and reduced well-being. Depending on which PUFA are present in the diet, neuroinflammation will, therefore, be kept at a minimum or exacerbated. This could explain the protective role of n-3 fatty acids in neurodegenerative diseases linked to aging.

Copyright 2010 Elsevier Ltd. All rights reserved.

PMID:
20227866
[PubMed – indexed for MEDLINE]

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Black sheep get the blues: a psychobiological model of social rejection and depression.

Posted on March 3, 2012 by Maurice Preter MD

Black sheep presumably also get less Vitamin D.

Neurosci Biobehav Rev. 2010 Sep;35(1):39-45. Epub 2010 Jan 18.
Black sheep get the blues: a psychobiological model of social rejection and depression.
Slavich GM, O’Donovan A, Epel ES, Kemeny ME.
Source

Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0848, USA. george.slavich@ucsf.edu
Abstract

Major life events involving social rejection are strongly associated with onset of depression. To account for this relation, we propose a psychobiological model in which rejection-related stressors elicit a distinct and integrated set of cognitive, emotional, and biological changes that may evoke depression. In this model, social rejection events activate brain regions involved in processing negative affect and rejection-related distress (e.g., anterior insula, dorsal anterior cingulate cortex). They also elicit negative self-referential cognitions (e.g., “I’m undesirable,” “Other people don’t like me”) and related self-conscious emotions (e.g., shame, humiliation). Downstream biological consequences include upregulation of the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, and inflammatory response. Pro-inflammatory cytokines play an important role in this process because they induce a constellation of depressotypic behaviors called sickness behaviors. Although these changes can be short-lived, sustained inflammation may occur via glucocorticoid resistance, catecholamines, sympathetic innervation of immune organs, and immune cell aging. This response also may be moderated by several factors, including prior life stress, prior depression, and genes implicated in stress reactivity.

PMID:
20083138
[PubMed – indexed for MEDLINE]
PMCID:
PMC2926175

Free PMC Article

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