The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies?
paper
Cited
Public
- Authors
- Courtet, P; Gottesman, I I; Jollant, F; Gould, T D
- Year
- 2011
- Journal
- Translational psychiatry
- PMID
- 21761009
- DOI
- 10.1038/tp.2011.6
- PMCID
- PMC3134241
Vulnerability to suicidal behavior (SB) is likely mediated by an underlying genetic predisposition interacting with environmental and probable epigenetic factors throughout the lifespan to modify the function of neuronal circuits, thus rendering an individual more likely to engage in a suicidal act. Improving our understanding of the neuroscience underlying SBs, both attempts and completions, at all developmental stages is crucial for more effective preventive treatments and for better identification of vulnerable individuals. Recent studies have characterized SB using an endophenotype strategy, which aims to identify quantitative measures that reflect genetically influenced stable changes in brain function. In addition to aiding in the functional characterization of susceptibility genes, endophenotypic research strategies may have a wider impact in determining vulnerability to SB, as well as the translation of human findings to animal models, and vice versa. Endophenotypes associated with vulnerability to SB include impulsive/aggressive personality traits and disadvantageous decision making. Deficits in realistic risk evaluation represent key processes in vulnerability to SB. Serotonin dysfunction, indicated by neuroendocrine responses and neuroimaging, is also strongly implicated as a potential endophenotype and is linked with impulsive aggression and disadvantageous decision making. Specific endophenotypes may represent heritable markers for the identification of vulnerable patients and may be relevant targets for successful suicide prevention and treatments.
Figure 1
Candidate gene regions, genes and endophenotypes implicated in suicide research. The upper portion of the figure indicates the dynamic interplay among genetic, epigenetic and environmental factors that produce cumulative liability to suicidal behaviors. Although attempted suicide does not always predate a completed suicide as suggested on the reaction surface, it is a significant risk factor.4 None of the sections of this figure can be definitive; many more gene loci, genes, candidate endophenotypes and links among the three remain to be discovered. Environment, protective and harmful, includes a substantial number of environmental events (for example, drug exposure) unmentioned here because of our focus on genetic and neurobiological correlates. Similarly, there are many gene loci, genes and candidate endophenotypes that were not included because of the conceptual limitations of this Figure. Modified from Kovacsics et al.28 See the following reviews for additional discussion: refs 7, 12, 14, 25, 28, 96, 97, 98. Β© II Gottesman and TD Gould and used with permission.
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| Name | Type |
|---|---|
| 5-HIAA local | drug |
| 5HT2A receptor local | drug |
| 5-HTT | gene |
| 5HTTLPR | variant |
| addiction | phenotype |
| adolescents | cohort |
| adults | cohort |
| age | phenotype |
| aggression | phenotype |
| alcoholism | phenotype |
| Alcohol Use Disorder | phenotype |
| amygdala | anatomy |
| amygdalaβprefrontal coupling local | anatomy |
| Animal disease model local | cohort |
| anterior cingulate cortex | anatomy |
| At risk individuals local | cohort |
| behavior | phenotype |
| Biochemistry local | drug |
| biological marker | phenotype |
| bipolar disorder | phenotype |
| bipolar patients with a history of suicide attempts local | cohort |
| bipolar patients without a past history of attempts local | cohort |
| borderline personality disorder | phenotype |
| brain | anatomy |
| Brain imaging local | drug |
| clinical illness local | phenotype |
| Coexisting psychiatric diagnoses local | phenotype |
| cognition | phenotype |
| Cognitive and emotional alterations local | phenotype |
| COMT | gene |
| Co-occurring psychopathology local | phenotype |
| craving | phenotype |
| decision making | phenotype |
| Depressed male non-attempters local | cohort |
| Depressed male suicide attempters local | cohort |
| depression | phenotype |
| Disadvantageous decision making local | phenotype |
| disease | phenotype |
| dorsolateral prefrontal cortex | anatomy |
| Early onset major depressive disorder local | phenotype |
| Elderly suicide attempters local | cohort |
| Elderly suicide ideators local | cohort |
| Elderly suicide ideators local | phenotype |
| Electrodermal hyporeactivity local | phenotype |
| Emotion | phenotype |
| Emotional functions local | phenotype |
| endophenotype | phenotype |
| fenfluramine local | drug |
| Functional changes in circuit activity local | phenotype |
| Future suicide local | phenotype |
| gene | gene |
| genes | gene |
| genetic factors | cohort |
| Genetic polymorphism local | gene |
| Genetic susceptibility factors local | gene |
| genetic variants | cohort |
| healthy controls | cohort |
| Healthy individuals local | phenotype |
| Healthy twins local | cohort |
| high lethality suicide attempters local | cohort |
| high-lethality suicide attempts local | phenotype |
| hopelessness | phenotype |
| human | cohort |
| Hypothalamicβpituitaryβadrenal axis hyperfunction local | phenotype |
| impulsive aggressive behavior local | phenotype |
| Impulsiveβaggressive behaviors local | phenotype |
| Impulsive/aggressive personality traits local | phenotype |
| impulsivity | phenotype |
| intent local | phenotype |
| intermediate phenotypes | phenotype |
| Iowa gambling task impairment local | phenotype |
| lateral prefrontal cortex | anatomy |
| left lateral orbitofrontal cortex local | anatomy |
| lethal phenotype | phenotype |
| Ligands | drug |
| lithium | drug |
| long-term decision making local | phenotype |
| low lethality suicide attempters local | cohort |
| Main metabolite of serotonin local | drug |
| major depressive disorder | phenotype |
| MAOA | gene |
| MATRICS local | cohort |
| medial prefrontal cortex | anatomy |
| Medical lethality local | phenotype |
| men | cohort |
| mice | cohort |
| mood disorders | phenotype |
| Neuroanatomical dysfunctions local | phenotype |
| Neuroimaging alterations local | phenotype |
| Neurophysiological alterations local | phenotype |
| Neurophysiological responses local | phenotype |
| Neuropsychological alterations local | phenotype |
| Neuropsychological responses local | phenotype |
| neuroticism | phenotype |
| new compound local | drug |
| Non-depressed subjects local | cohort |
| Non-depressed subjects local | phenotype |
| Non-suicidal depressed local | phenotype |
| Non-suicidal depressed subjects local | cohort |
| Obsessive-compulsive disorder population local | phenotype |
| older adults | cohort |
| orbitofrontal cortex | anatomy |
| pathological gamblers | cohort |
| Patients with addiction local | cohort |
| Patients with history of suicide behavior local | cohort |
| Patients without suicide behavior history local | cohort |
| personality traits | phenotype |
| pharmacological treatment | drug |
| Phenotypic syndrome local | phenotype |
| prefrontal cortex | anatomy |
| prepulse inhibition | phenotype |
| Previous suicide attempt local | phenotype |
| prolactin response local | phenotype |
| psychiatric disorders | phenotype |
| Psychological pain local | phenotype |
| rat chronic pain model local | cohort |
| rats | cohort |
| repetitive transcranial magnetic stimulation | drug |
| right orbitofrontal cortex | anatomy |
| risk allele | cohort |
| rodents | cohort |
| schizophrenia | phenotype |
| self-harm | phenotype |
| serotonin | drug |
| serotonin transporter local | drug |
| sex | phenotype |
| siblings | cohort |
| SLC6A4 | gene |
| Suicidal acts local | phenotype |
| suicide | phenotype |
| Suicide attempters local | cohort |
| Suicide behavior local | phenotype |
| Suicide endophenotype local | phenotype |
| suicide vulnerability local | phenotype |
| Suicide vulnerability local | phenotype |
| susceptibility genes | cohort |
| Therapeutic target local | drug |
| TPH1 | gene |
| Twin cohort | cohort |
| Unaffected relatives of alcoholics local | cohort |
| Valproic acid | drug |
| ventral prefrontal cortex | anatomy |
| ventromedial prefrontal cortex | anatomy |
| Vulnerable patient local | phenotype |
| women | cohort |
| working memory | phenotype |
| Ξ±-[11C]methyl-tryptophan local | drug |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | 2015 | 26236574 |
| Dissecting impulsivity and its relationships to drug addictions. | 2014 | 24654857 |
External
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| MicroRNAs as novel peripheral markers for suicidality in patients with major depressive disorder. | Stapel B et al. | β | 2022 | β |
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| SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans. | Sadeh N et al. | β | 2016 | β |
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