| 1. |
- Serafini, Gianluca, et al.
(författare)
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Abnormalities in kynurenine pathway metabolism in treatment-resistant depression and suicidality : a systematic review
- 2017
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Ingår i: CNS and Neurological Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 16:4, s. 440-453
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Forskningsöversikt (refereegranskat)abstract
- Treatment resistant depression (TRD) and suicidal behavior are among the most important public health problems and are commonly associated with significant disability and psychosocial impairment. Although there have been recent advances in identifying neurobiological correlates of these complex conditions, their pathophysiology still remains unclear. Although the recent advances concerning the neurobiological determinants underlying these complex conditions, their pathophysiology still remains unclear. Compared to non-suicidal subjects, higher mean concentrations of inflammatory mediators have been found in both the periphery and brain of individuals at risk for suicide. Several lines of evidence suggest that neuroinflammation is accompanied by a dysregulation of the kynurenine pathway (KP) in both TRD and suicidal individuals, resulting in an imbalance of neuroactive metabolites. In particular, neuroinflammation may trigger an increased production of the N-Methyl-D-aspartate (NMDA) receptor agonist quinolinic acid and a concomitant reduction of neuroprotective metabolites, potentially causing downstream effects in glutamatergic systems resulting in depressive symptoms and suicidal behavior. This systematic review of the current literature is mainly aimed at summarizing the most important evidence pertaining to KP metabolism abnormalities in TRD and suicidal behavior. Targeting the KP enzymes may provide innovative approaches in the management of both TRD and suicidality.
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| 2. |
- Serafini, Gianluca, et al.
(författare)
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Neuropeptides : Active neuromodulators involved in the pathophysiology of suicidal behavior and major affective disorders
- 2015
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Ingår i: Bioactive Natural Products: Chemistry and Biology. - Weinheim, Germany : Wiley-VCH Verlag GmbH & Co. KGaA. - 9783527337941 - 9783527684403 ; , s. 409-442
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Bokkapitel (refereegranskat)abstract
- Neuropeptides, protein-like molecules used for direct communication between neurons, may play a critical role in the pathophysiology of mood disorders and suicidal behavior. This chapter aims to critically review the current literature on associations between neuropeptides, major affective disorders, and suicidal behavior. Most studies included in this overview reported an association between suicidality and corticotropin-releasing factor (CRF), VGF nerve growth factor inducible (VGF), cholecystokinin (CCK), orexin, substance P, and neuropeptide Y (NPY). It has been suggested that these molecules play a key role in many biological functions and act as important neuromodulators of emotional processing. The majority of the studies reviewed in this chapter found that suicidal subjects display higher mean concentrations of various neuropeptides compared to control subjects although depressed patients and suicide completers may also display lower NPY levels throughout the brain compared to healthy controls or individuals deceased from causes other than suicide. In addition, some studies have reported that orexin and corticotropin-releasing hormone (CRH) levels are lower in suicidal patients. In spite of these cross-sectional reports, a causal link between neuropeptide dysregulation and suicidality cannot be determined. The main implications of the studies that are included in the present chapter are critically analyzed and discussed.
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