Recent molecular genetic studies and methodological issues in suicide research

Tsai, Shih‐Jen; Hong, Chien Tai; Liou, Ying‐Jay

doi:10.1016/j.pnpbp.2010.10.014

Cited by 45 publications

(33 citation statements)

References 123 publications

(127 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, a significant increase of MAOA has been found in the hypotalamus of suicide victims [3]. However, polymorphisms that increase MAOA expression are defined risk factors for suicide [1][2][3]. Moreover, in recent years MAOA gene is a site of high biological plausibility in antisocial spectrum disorders and psychopathy [12].…”

Section: To the Editormentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Lombardo¹,

Zarrilli²,

Ceglia

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

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

show abstract

Section: To the Editormentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

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

Lombardo¹,

Zarrilli²,

Ceglia

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

show abstract

“…Postmortem studies of suicide attempters have shown decreased presynaptic 5-HT 2 receptor binding in ventromedial prefrontal cortex (VMPFC) (60). Polymorphisms in different genes of the serotonin system have been associated with suicide including serotonin, serotonin transporter (5-HTTLPR), serotonin receptors, and tryptophan hydroxylase (TPH2) (62,63 vulnerability to suicide behavior, independent of psychiatric diagnosis (61). Lastly, low serotonergic tone has also been associated with cognitive factors predisposing to suicide (64,65).…”

Section: Serotonin (5-ht)mentioning

confidence: 99%

“…The DA receptor variant DRD2 has been similarly linked to suicide attempts (62). A single nucleotide polymorphism (SNP) within a coding region of the α 2A -adrenergic receptor gene (ADRA2A) may confer susceptibility to suicide, but this finding has not been replicated (63).…”

Section: Noradrenergic and Dopaminergic Systemsmentioning

confidence: 99%

Conducta suicida: factores de riesgo y protección.

Cáceda

2014

Rev Neuropsiquiatr

View full text Add to dashboard Cite

RESUMENAproximadamente un millón de personas mueren cada año debido a suicidio. Poblaciones de alto riesgo de suicidio incluyen militares, adolescentes, ancianos, y pacientes con enfermedades crónicas mentales o médicas. Más de 90% de suicidios ocurren en personas que sufren de alguna enfermedad psiquiátrica. Prácticamente todas las enfermedades psiquiátricas aumentan el riesgo de suicidio, sin embargo la depresión está asociada a más de la mitad de los casos de suicidio. Hallazgos clínicos, epidemiológicos, autopsias psicológicas, en genética, neuroquímica, y neuroimágenes han incrementado significativamente nuestro conocimiento sobre el suicidio. El factor biológico más consistentemente asociado a suicidio es la disminución en la neurotransmisión serotoninérgica, particularmente en la zona ventral de la corteza prefrontal. Déficits en la función de la zona ventral de la corteza prefrontal están asociadas a impulsividad y a subóptima toma de decisiones. Las otras aminas biogénicas y el eje hipotalámico-pituitaria-adrenal (HPA) también parecen estar involucrados en la proclividad al suicidio. Los factores cognitivos y psicológicos involucrados en suicidio incluyen desesperanza, dolor psicológico o mental, impulsividad, pobre habilidad para solucionar problemas, perfeccionismo y pobre autoestima. Los factores de protección contra el suicidio más estudiados son: acceso y utilización de servicios de salud, conexión significativa con familia y la comunidad, y creencias religiosas y culturales que se oponen al suicidio. A pesar de la abundancia de estudios realizados, aun carecemos de factores fidedignos de predicción de riesgo de suicidio y debemos basarnos en el reporte del individuo y emplear el juicio clínico. Por eso continúa siendo tremendamente difícil predecir quién morirá por suicidio. Dada esta dramática carencia, continúa siendo una alta prioridad el desarrollo de estrategias de detección y prevención de suicidio, especialmente en poblaciones de alto riesgo.PALABRAS CLAVE: Suicidio, depresión, neuroimágenes, genética, neurotransmisores. SUMMARYApproximately one million people worldwide die from suicide every year. High risk populations include active military, adolescents, the elderly and the chronically mentally and physically ill. More than 90% of suicides are in individuals with a diagnosable psychiatric disorder. Practically all of the major psychiatric disorders are associated with an increased risk for suicide, but depression accounts for more than half of the cases. Clinical observation, epidemiological studies, psychological autopsies, genetics, neurochemistry and brain imaging have yielded important findings that have contributed to our increased understanding of suicide. The strongest biological factor associated with suicide is decreased serotonergic neurotransmission, particularly in the ventral prefrontal cortex. Deficits in ventromedial prefrontal cortex function are associated with impulsivity and impaired decision making. Additionally, a burgeoning body of evidence supports a central role o...

show abstract

“…Previous twin studies have estimated that the heritability of suicide attempt is between ∼17 and 55% [3,4,5]. Despite the evidence from previous family-based studies, molecular genetic approaches have failed to elucidate any robust associations between candidate genes and suicide attempt [6]. …”

Section: Introductionmentioning

confidence: 99%

Interaction between Methylation and CpG Single-Nucleotide Polymorphisms in the HTR2A Gene: Association Analysis with Suicide Attempt in Schizophrenia

Bani‐Fatemi

Howe²,

Matmari³

et al. 2016

Neuropsychobiology

View full text Add to dashboard Cite

Dysfunctional mechanisms in the serotonergic system have been implicated in suicidal behavior among patients with schizophrenia. However, previous association analyses of major serotonin genes have provided inconsistent findings regarding their role in suicidal behavior. The goal of the current study was to identify single-nucleotide polymorphisms (SNP) within HTR2A that directly affect CpG methylation sites in schizophrenic patients with suicidal behavior. Furthermore, direct methylation analysis was performed using genomic DNA from peripheral leukocytes employing bisulfite pyrosequencing to assess the contributions of six CpG sites in HTR2A exon I in 67 schizophrenia patients assessed for lifetime suicide attempt. Potential methylation in 25 CpG SNPs across the entire HTR2A gene was analyzed considering their direct contribution to methylation. When we compared direct methylation between attempters and nonattempters, we found that only the polymorphic T102C (rs6313) was significantly different between the two groups (p = 0.02). Furthermore, in the potential methylation analysis, we found a nominal association with suicide attempt for six of the 25 SNPs analyzed, i.e. rs2770293 (p = 0.045), rs6313 (p = 0.033), rs17068986 (p = 0.029), rs4942578 (p = 0.024), rs1728872 (p = 0.014), and rs9534511 (p = 0.003). The results of this investigation provide preliminary evidence that the combined analysis of CpG SNPs and methylation may be useful for investigating the genetic and epigenetic factors involved in suicidal behavior.

show abstract

Recent molecular genetic studies and methodological issues in suicide research

Cited by 45 publications

References 123 publications

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

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

Conducta suicida: factores de riesgo y protección.

Interaction between Methylation and CpG Single-Nucleotide Polymorphisms in the HTR2A Gene: Association Analysis with Suicide Attempt in Schizophrenia

Contact Info

Product

Resources

About