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      Candidate Biomarkers of Suicide Crisis Syndrome: What to Test Next? A Concept Paper

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          Abstract

          Background

          There has been increasing interest in both suicide-specific diagnoses within the psychiatric nomenclature and related biomarkers. Because the Suicide Crisis Syndrome—an emotional crescendo of several interrelated symptoms—seems to be promising for the identification of individuals at risk of suicide, the aim of the present paper is to review the putative biological underpinnings of the Suicide Crisis Syndrome symptoms (entrapment, affective disturbance, loss of cognitive control, hyperarousal, social withdrawal).

          Methods

          A PubMed literature search was performed to identify studies reporting a link between each of the 5 Suicide Crisis Syndrome symptoms and biomarkers previously reported to be associated with suicidal outcomes.

          Results

          Disturbances in the hypothalamic-pituitary-adrenal axis, with dysregulated corticotropin-releasing hormone and cortisol levels, may be linked to a sense of entrapment. Affective disturbance is likely mediated by alterations in dopaminergic circuits involved in reward and antireward systems as well as endogenous opioids. Loss of cognitive control is linked to altered neurocognitive function in the areas of executive function, attention, and decision-making. Hyperarousal is linked to autonomic dysregulation, which may be characterized by a reduction in both heart rate variability and electrodermal activity. Social withdrawal has been associated with oxytocin availability. There is also evidence that inflammatory processes may contribute to individual Suicide Crisis Syndrome symptoms.

          Conclusion

          The Suicide Crisis Syndrome is a complex syndrome that is likely the consequence of distinct changes in interconnected neural, neuroendocrine, and autonomic systems. Available clinical and research data allow for development of empirically testable hypotheses and experimental paradigms to scrutinize the biological substrates of the Suicide Crisis Syndrome.

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          Most cited references137

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          Responses to depression and their effects on the duration of depressive episodes.

          I propose that the ways people respond to their own symptoms of depression influence the duration of these symptoms. People who engage in ruminative responses to depression, focusing on their symptoms and the possible causes and consequences of their symptoms, will show longer depressions than people who take action to distract themselves from their symptoms. Ruminative responses prolong depression because they allow the depressed mood to negatively bias thinking and interfere with instrumental behavior and problem-solving. Laboratory and field studies directly testing this theory have supported its predictions. I discuss how response styles can explain the greater likelihood of depression in women than men. Then I intergrate this response styles theory with studies of coping with discrete events. The response styles theory is compared to other theories of the duration of depression. Finally, I suggest what may help a depressed person to stop engaging in ruminative responses and how response styles for depression may develop.
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            Serotonin transporter genetic variation and the response of the human amygdala.

            A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5- hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
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              Reconsidering anhedonia in depression: lessons from translational neuroscience.

              Anhedonia is a core symptom of major depressive disorder (MDD), the neurobiological mechanisms of which remain poorly understood. Despite decades of speculation regarding the role of dopamine (DA) in anhedonic symptoms, empirical evidence has remained elusive, with frequent reports of contradictory findings. In the present review, we argue that this has resulted from an underspecified definition of anhedonia, which has failed to dissociate between consummatory and motivational aspects of reward behavior. Given substantial preclinical evidence that DA is involved primarily in motivational aspects of reward, we suggest that a refined definition of anhedonia that distinguishes between deficits in pleasure and motivation is essential for the purposes of identifying its neurobiological substrates. Moreover, bridging the gap between preclinical and clinical models of anhedonia may require moving away from the conceptualization of anhedonia as a steady-state, mood-like phenomena. Consequently, we introduce the term "decisional anhedonia" to address the influence of anhedonia on reward decision-making. These proposed modifications to the theoretical definition of anhedonia have implications for research, assessment and treatment of MDD. Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Int J Neuropsychopharmacol
                Int. J. Neuropsychopharmacol
                ijnp
                International Journal of Neuropsychopharmacology
                Oxford University Press (US )
                1461-1457
                1469-5111
                March 2020
                29 November 2019
                29 November 2019
                : 23
                : 3
                : 192-205
                Affiliations
                [1 ] Department of Psychiatry, Mount Sinai Beth Israel , New York, New York
                [2 ] Icahn School of Medicine at Mount Sinai , New York, New York
                [3 ] Department of Psychology, University of Milan-Bicocca , Milan, Italy
                [4 ] Department of Adult Psychiatry, Nîmes University Hospital , Nîmes, France
                [5 ] Department of Psychiatry, University of Texas Dell Medical School , Austin, Texas
                [6 ] INSERM, University of Montpellier, Neuropsychiatry: Epidemiological and Clinical Research , Montpellier, France
                Author notes
                Correspondence: Raffaella Calati, PsyD, PhD, Department of Psychology, University of Milan-Bicocca, Piazza dell’Ateneo Nuovo 1, 20126, Milan, Italy ( raffaella.calati@ 123456gmail.com ).
                Article
                pyz063
                10.1093/ijnp/pyz063
                7171927
                31781761
                43639d81-2c4b-4b69-9b6e-98bdfa867144
                © The Author(s) 2019. Published by Oxford University Press on behalf of CINP.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 19 September 2019
                : 25 November 2019
                : 27 November 2019
                : 29 January 2020
                Page count
                Pages: 14
                Funding
                Funded by: American Foundation for Suicide Prevention, DOI 10.13039/100001455;
                Award ID: RFA-1-015-14
                Categories
                Review
                AcademicSubjects/MED00415
                AcademicSubjects/SCI01870

                Pharmacology & Pharmaceutical medicine
                acuity,biomarkers,review,suicide
                Pharmacology & Pharmaceutical medicine
                acuity, biomarkers, review, suicide

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