Podcasts 12

Takahashi’s article also tells us that when an alcohol dependence is concomitant with depression, it increases the rate of suicide. And that many who attempt suicide are under the influence of alcohol even where the diagnostic criteria for alcoholism is not met.

And a 2010 study by Cabra, the article identifies risk factors for children and adolescents. In children, the personality of the parents are a suicidal risk factor, because in cases of suffering a disorder of the same, such as antisocial or emotionally instability, the upbringing would be mediated by these traits. In the same way, parents with psychiatric illnesses, such as maternal depression, alcoholism, or schizophrenia, are predisposing factors in their children. A dysfunctional home in which there are frequent arguments between parents and other members, associated with physical or psychological abuse or a home without rules, can predispose to a suicidal act. Nemeroff (2020) also states that there is a vast body of evidence that poverty, as one form of child mistreatment, is associated with poor health outcomes and with increases in both major medical and psychiatric disorders, and, not surprisingly, suicide rates. 

For adolescents, among the risk factors described are the presence of mental disorders, especially major depression, bipolar disorder, or psychosis, abuse of psychoactive substances, family history of suicide, sexual abuse, delinquency, parental divorce, poor interpersonal relationships, and a history of family abuse.

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Now I would like to talk about the neurobiology of suicidal behavior, beginning with the genetics of Suicide. 

An article called “Insights into Suicide and Depression” written in 2020 by Kalin references an article by Docherty et al. (2020) in which new genetic leads from a genome-wide association study or a GWAS identified 22 genes potentially related to suicide death with a heritability, this was based on single-nucleotide polymorphisms, of 25%. The study also found that a number of the implicated genes overlapped with genes associated with schizophrenia and bipolar disorder. A polygenic risk scores (PRSs) computed from the suicide GWAS data was predictive of suicide in an independent sample. But another article by Mann & Rizk mentions that there can be as many as 40 genes associated with suicidal behavior, independently of psychiatric diagnoses. And that further combining GWASs with transcriptome data reveals suicide-related genes associated with inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, GABA, which is the Ɣ-aminobutyric acid, and glutamate transmission, and finally, neurogenesis.

In another article called “Predicting suicide” by David Goldman, he also references Docherty et. al and is able to continue with the premise of how to predict suicide as the article clearly mentions. Now in the article, he said that the identification of genes that are significantly associated with suicide, and the implication of a much larger number of other genes in the genomic statistical threshold, was what enabled Docherty et al. to derive a polygenic risk score accounting for a substantial portion of the risk of suicide. The GWAS study done by Dochety et. al, was of more than 3,400 suicide victims from the state of Utah and several times that number of ethnically matched comparison subjects from outside the state, and although more studies on the genetics of suicide need to be done, a hypothesis that Goldman mentions is “a hypothesis that never dies” is that depletions of brain serotonin and, as reflected in low levels of the metabolite 5-HIAA (or 5-Hydroxyindoleacetic acid, which is the main metabolite of serotonin) in Cerebrospinal fluid, serotonin receptor binding potential, as well as serotonin itself, predict suicide. Goldman concludes with the ability of geneticists to capture increasing portions of the heritability of suicide may enable psychiatrists to better help people at risk, combining genetic predictors of innate (trait) vulnerability with such state and trait measures.

Continuing with another article on the genetics of suicide called “The Promise and Limits of Suicide Genetics” by Lopes & McMahon (2019) tells us that in people with bipolar disorder, suicide attempts were associated in a small but significant way with a common genetic marker on chromosome 4, although even when this marker does not immediately implicate any particular gene, the marker was also associated with genome-wide significance in a meta-analysis of suicide attempts in mood disorder, suggesting that bipolar disorder and major depression have something in common. In references to an article by Mullins et al (2019), PSR analysis showed that genetic risk for major depression increases risk for suicide attempts in people with major depression. However, results also showed that genetic risk for major depression also increased risk for suicide in people diagnosed with bipolar disorder or schizophrenia. 

Continuing forward, I want to talk about an explanatory model for suicidal acts written by Carballo et al. (2008), in which he references Gottesman & Gould, 2003, which talks about endophenotypes, which are “measurable components along the pathway between disease and distal genotype”. These can be characteristics that often accompany psychiatric illness including abnormal neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological findings. In Carballo’s model, the endophenotypic models for suicide behavior are deemed clinical, neurochemical, and neuroendocrine. 

The clinical endophenotypes include impulsivity, aggression, neuroticism, and hopelessness which can also be regarded as intermediary phenotypes, which can possibly predispose individuals to suicidal behavior.

Beginning with Impulsivity it’s a personality trait or cognitive style that can be characterized by disinhibition and a tendency to act quickly on urges or in response to stimuli. An association between impulsivity and suicidal/self-destructive behaviors has been reported in various adult psychiatric populations

Continuing, pessimism has also been implicated in suicidal behavior. With studies showing that compared to non-attempters, suicide attempters tend to experience more pessimism as reflected in more suicidal ideation, fewer perceived reasons for living in response to illness or social adversity, and higher subjective ratings of the severity of depression and hopelessness. 

Elevated neuroticism has also been linked to negative affect and may constitute a vulnerability factor for suicidal behavior. Carballo references Roy (2002) when he mentions that differences in neuroticism scores between those with and without a family history of suicide which were significant when personal histories of suicide attempts were taken into account, with patients with a positive family history for suicide and who had themselves attempted suicide having had higher neuroticism scores. 

Another clinical endophenotype is hopelessness, which can be associated with suicidal behavior. Pollock and Williams (2004) propose that suicidal behavior is associated more with hopelessness than with the severity of depression. And hopelessness was the principal predictor of suicidality in a study conducted among schizophrenic patients.