The neurobiology of suicide - A Review of post-mortem studies

Furczyk, Karolina; Schutová, Barbora; Michel, Tanja Maria; Thome, Johannes; Büttner, Andreas

doi:10.1186/2049-9256-1-2

Cited by 44 publications

(22 citation statements)

References 210 publications

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“…Results are less consistent in relation to suicide attempts: some researchers reported an association between suicide attempts and DST nonsuppression [5,6] and others did not [7]. It was hypothesized that HPA axis dysfunction might be more strongly correlated with completed suicide than suicide attempt [8]. …”

Section: Introductionmentioning

confidence: 79%

Association between FKBP5 Functional Polymorphisms and Completed Suicide

Fudalej¹,

Kopera²,

Wołyńczyk-Gmaj³

et al. 2015

Neuropsychobiology

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Objectives: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis leads to impaired stress response. FK506-binding protein 51 (FKBP5), which influences HPA axis activity via glucocorticoid receptors, is supposed to play an important role in the regulation of negative feedback and glucocorticoid resistance. Since ineffective stress response mechanisms are considered as a biological background of suicide behavior, we aimed to analyze a possible association between FKBP5 functional polymorphisms and completed suicide. Methods: The selected FKBP5 polymorphisms rs1360780 and rs3800373 were genotyped in a sample of 563 suicide victims and 475 controls. Results: A significant association between the high-induction rs3800373 C allele and completed suicide was detected (OR = 1.36, p = 0.007). In this polymorphism, genotype distribution supported a codominant model of inheritance. The analyzed SNPs were in strong linkage disequilibrium (D' = 0.916 and r² = 0.826) with the rs1360780 (T)-rs3800373 (C) haplotype apparently responsible for the observed association (OR = 1.34, p = 0.010). Conclusion: The results of the present study indicate that genetic alterations in FKBP5 may influence vulnerability to suicide.

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Section: Introductionmentioning

confidence: 79%

Association between FKBP5 Functional Polymorphisms and Completed Suicide

Fudalej¹,

Kopera²,

Wołyńczyk-Gmaj³

et al. 2015

Neuropsychobiology

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“…The consensus that there is a serotonin system abnormality is a lot stronger than which brain areas are involved and the direction of the difference in binding [15][16][17][18] and explanations for discrepancies include heterogeneity of the patient population, small group sizes, small effect sizes and variability in outcome measures due to demographic variables including sex and age in live cases and also postmortem interval and brain pH in in vitro studies.…”

Section: H]8-oh-dpat Binding To 5-ht1a Receptorsmentioning

confidence: 99%

Disconnect Between Brainstem Serotonin Neurons And Prefrontal Cortex Serotonin Receptors In Suicide

Underwood¹,

Arango²

2018

Acta Psychopathol

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Serotonin neurotransmission is widely reported as reduced in suicide attempt and completion. Evidence suggests reduced serotonin innervation of the prefrontal cortex and homeostatic upregulation of postsynaptic 5-HT 1A and perhaps 5-HT 2A receptors in suicide. However, in the brainstem, we have previously found more tryptophan hydroxylase serotonin biosynthetic enzyme and more serotonin in suicide decedents suggesting serotonergic hyperfunction, but also more autoreceptor binding that could result in reduced neuronal firing. We sought evidence of a disconnect between the brainstem and prefrontal cortex examining the serotonin transporter (SERT) and 5-HT 1A receptor in the dorsal and median raphe nucleus and SERT, 5-HT 1A and 5-HT 2A receptor binding in prefrontal cortex and in anterior cingulate cortex postmortem.Suicide decedents (n=11) and controls (n=18) died suddenly minimizing agonal effects and had a postmortem interval ≤ 24 hour. Autoradiography was performed in right hemisphere coronal sections at a pre-genual level and in transverse sections through the brainstem.In controls, there were correlations between DRN and MRN SERT and 5-HT 2A receptor binding throughout prefrontal cortex, and between DRN and MRN 5-HT 1A receptor binding and medial and ventral prefrontal cortex. In suicide decedents there were no such relationships.The absence of correlations between brainstem source serotonergic neuron function and receptors on target neurons in prefrontal cortex in suicides suggests a disconnect that may contribute to suicide neuropathology.

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“…However, a close examination of suicide prefrontal cortex with special reference to area BA46, mostly involved in affective disorders of altered mood, has been shown to be overrepresented in suicide behavior (Hoptman et al, 2002; Kamali et al, 2001; Keilp et al, 2001; Mann, 2003; Raine et al, 1998; Raust et al, 2007). The brain’s inability to respond properly to environmental stimuli due to impaired structural and neural plasticity has been well-established to cause suicide pathogenicity (Dwivedi, 2009, 2010; Furczyk et al, 2013). Recent neuroimaging identification of orbitofrontal and dorsolateral prefrontal cortex based structural abnormalities in suicide victims further reinforces the importance of impaired neuronal plasticity (Ding et al, 2015; van Heeringen et al, 2011).…”

Section: Influence Of Dna Methylation Based (5mc) Epigenetic Modifmentioning

confidence: 99%

Understanding epigenetic architecture of suicide neurobiology: A critical perspective

Roy

Dwivedi

2017

Neuroscience & Biobehavioral Reviews

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Current understanding of environmental cross-talk with genetic makeup is found to be mediated through an epigenetic interface which is associated with prominent reversible and heritable changes at gene expression level. Recent emergence of epigenetic modulation in shaping the genetic information has become a key regulatory factor in answering the underlying complexities associated with several mental disorders. A comprehensive understanding of the pertinent changes in the epigenetic makeup of suicide phenotype exhibits a characteristic signature with the possibility of using it as a biomarker to help predict the risk factors associated with suicide. Within the scope of this current review, the most sought after epigenetic changes of DNA methylation and histone modification are thoroughly scrutinized to understand their close functional association with the broad spectrum of suicide phenotype.

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The neurobiology of suicide - A Review of post-mortem studies

Cited by 44 publications

References 210 publications

Association between <b><i>FKBP5</i></b> Functional Polymorphisms and Completed Suicide

Association between <b><i>FKBP5</i></b> Functional Polymorphisms and Completed Suicide

Disconnect Between Brainstem Serotonin Neurons And Prefrontal Cortex Serotonin Receptors In Suicide

Understanding epigenetic architecture of suicide neurobiology: A critical perspective

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