Tropomyosin-related kinase B receptor polymorphisms and isoforms expression in suicide victims

Zarrilli, Federica; Amato, Felice; Keller, Simona; Florio, Ermanno; Carli, Vladimir; Stuppia, Liborio; Sarchiapone, Marco; Chiariotti, Lorenzo; Castaldo, Giuseppe; Tomaiuolo, Rossella

doi:10.1016/j.psychres.2014.07.036

Cited by 4 publications

(4 citation statements)

References 11 publications

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“…Reduced neurotrophins (BDNF and NGF) as well as reduced receptor (TRKB, TRKA) mRNA and protein expression were found in the hippocampus of a sample of suicide victims, compared with a sample of controls who died of other causes (Banerjee et al, 2013 ). Decreased receptor expression of TRKB in suicide victims has also been reported in several other studies in hippocampus (Dwivedi et al, 2003a ) and prefrontal cortex (Dwivedi et al, 2003a ; Ernst et al, 2009 ), incongruent results have been reported for the Wernicke area (Keller et al, 2011 ; Zarrilli et al, 2014 ). In line with the above mentioned findings, phosphoinositide 3 (PI 3)-kinase, a key enzyme in the neurotrophin pathway, was found to be decreased in PFC and hippocampus of suicide victims (both mRNA and protein levels; Dwivedi et al, 2008 ).…”

Section: The Life Span Model Of Suicide and Its Neurobiological Foundsupporting

confidence: 55%

The Life Span Model of Suicide and Its Neurobiological Foundation

et al. 2017

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The very incomprehensibility of the suicidal act has been occupying the minds of researchers and health professionals for a long time. Several theories of suicide have been proposed since the beginning of the past century, and a myriad of neurobiological studies have been conducted over the past two decades in order to elucidate its pathophysiology. Both neurobiology and psychological theories tend to work in parallel lines that need behavioral and empirical data respectively, to confirm their hypotheses. In this review, we are proposing a “Life Span Model of Suicide” with an attempt to integrate the “Stress-Diathesis Model” and the “Interpersonal Model of Suicide” into a neurobiological narrative and support it by providing a thorough compilation of related genetic, epigenetic, and gene expression findings. This proposed model comprises three layers, forming the capability of suicide: genetic factors as the predisposing Diathesis on one side and Stress, characterized by epigenetic marks on the other side, and in between gene expression and gene function which are thought to be influenced by Diathesis and Stress components. The empirical evidence of this model is yet to be confirmed and further research, specifically epigenetic studies in particular, are needed to support the presence of a life-long, evolving capability of suicide and identify its neurobiological correlates.

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Section: The Life Span Model Of Suicide and Its Neurobiological Foundsupporting

confidence: 55%

The Life Span Model of Suicide and Its Neurobiological Foundation

et al. 2017

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“…Similar results were found in the Caucasian subgroup (n = 521) with an association between the rs2289656 and acute SA (bivariate: p = 0.002 and adjusted p = 0.005). The CC genotype of the rs2289656 was associated with higher acute SA rates (CC: 29%, CT: 16.1%, TT: 12%) as compared respectively to CT (OR = 2.1, CI95% [1.3–3.5], adjusted OR = 2.1, CI95% [1.3–3.5]) and TT (OR = 3.0, CI95% [1.0–12.9], adjusted OR = 3, CI95% [ 1 – 13 ]) genotypes. There was no association between rs2289656 and past SA.…”

Section: Resultsmentioning

confidence: 99%

“…The study performed by Ropret and colleagues did not find any association between 5 TRKB SNPs and suicide [ 12 ]. However, another one reported that 2 out of 17 TRKB SNPs (rs10868235 and rs1867283) were associated with suicide [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The TRKB rs2289656 genetic polymorphism is associated with acute suicide attempts in depressed patients: A transversal case control study

et al. 2018

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IntroductionSuicide Attempts (SA) are the main complications of Major Depressive Episodes (MDE) and are difficult to predict. Suicide is associated with the expression of Receptor Tyrosin-Kinase B (TRKB), the receptor of the Brain Derived Neurotrophic Factor (BDNF) involved in MDE. However, the impact of its genetic polymorphisms as predictive factors of SA should be clarified. Our main aim is to assess the association of 8 TRKB genetic polymorphisms and SA in depressed patients.Material and methodsIn 624 patients currently experiencing an MDE in the context of Major Depressive Disorder (MDD) (METADAP study), we assessed the association between 8 TRKB genetic polymorphisms (rs1778933, rs1187352, rs2289658, rs2289657, rs2289656, rs3824519, rs56142442 and rs1439050) and acute (previous month) or past (older than one month) SA. Bonferroni corrections and multivariate analysis adjusted for age, sex, level of education, marital status, Hamilton Depression Rating Scale score and previous MDE were used.ResultsThe rs2289656 was associated with acute SA (CC = 28.5%, CT = 15.0% and TT = 11.5%, p = 0.0008). However, the other SNPs were not. Patients with the CC genotype had a higher rate of acute SA (28.5%) as compared to T carriers (14.6%) (adjusted OR = 2.2, CI95% [1.4; 3.5], p<0.0001).ConclusionThe TRKB rs2289656 CC genotype is associated with a 2.2 fold higher risk of acute SA in depressed patients. If this result could be confirmed, this TRKB SNP may be assessed to contribute to the prediction of SA in depressed patients.

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“…In addition, we evaluated NTRK2 expression of the main TrkB isoforms on Wernicke's area, i.e., Brodmann's area 22, that have relevant function in understanding and language [5]. Finally, we demonstrated that some NTRK2 polymorphisms predispose to SB modulating the expression of the different isoforms of the receptor in Wernicke area [7]. All studies performed so far focused on point mutations in candidate genes.…”

mentioning

confidence: 97%

Two novel genomic rearrangements identified in suicide subjects using a-CGH array

Lombardo¹,

Zarrilli²,

Ceglia

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Many genes expressed in the central nervous system are candidates for the susceptibility to suicidal behavior (SB) including serotonergic, noradrenergic, and dopaminergic systems [1][2][3]. We studied the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) system that plays a critical role in neuronal survival and morphogenesis and in brain plasticity. We ruled out the association between polymorphisms G196A and -281 C/A of the BDNF gene and suicide [4]. Thus, we demonstrated a decreased BDNF expression in Wernicke area of brain of suicide subjects, due to BDNF promoter hypermethylation [5] revealing, for the first time, an association between epigenetics and suicide. Furthermore, we investigated the other component of the system, i.e., the neurotrophic tyrosine receptor kinase (NTRK) 2 gene, that encodes the TrkB receptor, excluding correlations between NTRK2 gene methylation in Wernicke area and suicide [6]. In addition, we evaluated NTRK2 expression of the main TrkB isoforms on Wernicke's area, i.e., Brodmann's area 22, that have relevant function in understanding and language [5]. Finally, we demonstrated that some NTRK2 polymorphisms predispose to SB modulating the expression of the different isoforms of the receptor in Wernicke area [7]. All studies performed so far focused on point mutations in candidate genes. Recently, array-comparative genomic hybridization (a-CGH) has allowed the identification of gains and losses of DNA as small as few kilobases enabling a large number of genomic alterations associated with neurological disorders to be identified [8]. However, at present, no studies have been performed to identify genomic alterations in subjects with SB; in order to identify alterations that could be correlated to SB we analyzed by a-CGH DNA samples of brain tissue extracted postmortem from the Wernicke area obtained from 34 suicides (23 females and 11 males) and 34 non-suicide control subjects (21 females and 13

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Tropomyosin-related kinase B receptor polymorphisms and isoforms expression in suicide victims

Cited by 4 publications

References 11 publications

The Life Span Model of Suicide and Its Neurobiological Foundation

The Life Span Model of Suicide and Its Neurobiological Foundation

The TRKB rs2289656 genetic polymorphism is associated with acute suicide attempts in depressed patients: A transversal case control study

Two novel genomic rearrangements identified in suicide subjects using a-CGH array

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