The Psychology and Neurobiology of Suicidal Behavior

Joiner, Thomas E.; Brown, Jessica; Wingate, LaRicka R.

doi:10.1146/annurev.psych.56.091103.070320

Cited by 380 publications

(291 citation statements)

References 181 publications

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“…Since the demonstration of decreased levels of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT), in the cerebrospinal fluid of a subgroup of depressed suicide attempters 30 years ago, 7 substantial additional evidence has accumulated that implicates the serotonergic system in both depression and suicide. 3,4,[8][9][10][11] Despite some inconsistencies across these studies and their inability to distinguish between neurobiological factors associated with suicide from those associated with the comorbid mental illness, these findings have raised the possibility of specific suicide-associated differences in various aspects of serotonergic function (for example, receptors, transporters, metabolic enzymes and their functional regulation). Recent studies have suggested abnormalities in mRNA editing of one of the serotonin receptors-2C (5-HT 2C R)-in depressed suicide victims.…”

Section: Introductionmentioning

confidence: 99%

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

et al. 2007

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Suicide is a major public health problem with B1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2C R mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.

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Section: Introductionmentioning

confidence: 99%

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

et al. 2007

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“…Social interactions influence a wide array of affective behaviours. In humans, social isolation is a risk factor for suicide [19]. In rhesus monkeys (Macaca mulatta), anxietyand depressive-like behaviours increase in response to social isolation [24].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing

Workman¹,

Trainor²,

Finy³

et al. 2008

Behavioural Brain Research

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Many psychological disorders are characterized by anxiety and alterations in social interactions. Recent studies demonstrate that the chemical messenger nitric oxide (NO) can regulate both anxiety and social behaviours. We tested whether an enzyme that produces NO in the brain, neuronal nitric oxide synthase (nNOS), serves as an interface between social interactions and anxiety-like behaviour. Several investigators have observed that mice increase anxiety-like responses in the elevated plusmaze after pair housing. nNOS gene deletion and 3-Bromo-7-Nitroindazole were used to inhibit the production of neuronal NO. Similar to previous studies, pair housing reduced open arm exploration in the elevated plus-maze. Pair housing also increased corticotropin-releasing hormone (CRH) immunoreactive cells in the paraventricular nucleus (PVN) of the hypothalamus. Inhibition of NO production increased open arm exploration in pair-housed mice but decreased open arm exploration in individually-housed mice. These results suggest that the effect of nNOS inhibition on anxiety-like responses is context dependent and that behavioural responses to social housing are altered after nNOS inhibition. This research suggests that NO may play an important role in mediating the effect social interactions have on anxiety.

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“…[1][2][3][4] Disturbances in serotonergic systems in brain have been implicated in mental illness, including schizophrenia, 5,6 anxiety disorders, 7 obsessivecompulsive disorders, 8 addiction, 9-12 depression [13][14][15][16] and suicide. 15,17 After release from axonal terminals of serotonergic neurons, synaptic effects of serotonin are terminated by reuptake into the nerve endings. 18 The serotonin transporter mediating this reuptake, SERT, belongs to the Na þ and C1 À -dependent family of neurotransporters.…”

Section: Introductionmentioning

confidence: 99%

Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of correlation with the polymorphism SERTLPR

Papp

Pinsonneault

et al. 2006

Mol Psychiatry

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An insertion/deletion polymorphism in the SERT linked promoter region (SERTLPR), previously reported to regulate mRNA expression in vitro, has been associated with mental disorders and response to psychotropic drugs. Contradictory evidence, however, has raised questions about the role of SERTLPR in regulating mRNA expression in vivo. We have used analysis of allelic expression imbalance (AEI) of SERT mRNA to assess quantitatively the contribution of SERTLPR to mRNA expression in human post-mortem pons tissue sections containing serotonergic neurons of the dorsal and median raphe nuclei. Any difference in the expression of one allele over the other indicates the presence of cis-acting elements that differentially affect transcription and/or mRNA processing and turnover. Using a marker SNP in the 3 0 untranslated region of SERT mRNA, statistically significant differences in allelic mRNA levels were detected in nine out of 29 samples heterozygous for the marker SNP. While the allelic expression differences were relatively small (15-25%), they could nevertheless be physiologically relevant. Although previous results had suggested that the long form of SERTLPR yields higher mRNA levels than the short form, we did not observe a correlation between SERTLPR and allelic expression ratios. Also in contrast to previous results, we found no correlation between SERTLPR and allelic expression ratios or SERT mRNA levels in Blymphocytes. This study demonstrates that regulation of SERT mRNA is independent of SERTLPR, but could be associated with polymorphisms in partial linkage disequilibrium with SERTLPR.

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The Psychology and Neurobiology of Suicidal Behavior

Cited by 380 publications

References 181 publications

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing

Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of correlation with the polymorphism SERTLPR

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