Dataset Information

The Life Span Model of Suicide and Its Neurobiological Foundation.

ABSTRACT: 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.

SUBMITTER: Ludwig B

PROVIDER: S-EPMC5306400 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Life Span Model of Suicide and Its Neurobiological Foundation.

Ludwig Birgit B Roy Bhaskar B Wang Qingzhong Q Birur Badari B Dwivedi Yogesh Y

Frontiers in neuroscience 20170214

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 h ...[more]

PMID: 28261051

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Project description:ImportanceAlthough adults with schizophrenia have an increased risk of suicide, sample size limitations of previous research have hindered characterizations of suicide risk across the life span.ObjectiveTo describe suicide mortality rates and correlates among adults with schizophrenia across the life span and standardized mortality ratios (SMRs) for suicide compared with the general US population.Design, setting, and participantsFive national retrospective longitudinal cohorts of patients with schizophrenia in the Medicare program from January 1, 2007, to December 31, 2016, were identified by age: 18 to 34, 35 to 44, 45 to 54, 55 to 64, and 65 years or older. Death record information was obtained from the National Death Index. The total cohort included 668 836 Medicare patients with schizophrenia, 2 997 308 years of follow-up, and 2218 suicide deaths. Data were analyzed from September 30, 2020, to March 10, 2021.Main outcomes and measuresFor each age group, suicide mortality rates per 100 000 person-years and adjusted hazard ratios (aHRs) with 95% CIs of suicide were determined. Suicide SMRs were estimated for the total cohort and by sex and age cohorts standardized to the general US population by age, sex, and race/ethnicity.ResultsThe study population of adults 18 years and older included 668 836 Medicare recipients with schizophrenia (52.5% men, 47.5% women). The total suicide rate per 100 000 person-years was 74.00, which is 4.5 times higher than that for the general US population (SMR, 4.54; 95% CI, 4.35-4.73) and included a rate of 88.96 for men and 56.33 for women, which are 3.4 (SMR, 3.39; 95% CI, 3.22-3.57) and 8.2 (SMR, 8.16; 95% CI, 7.60-8.75) times higher, respectively, than the rates for the general US population. Suicide rates were significantly higher for men (aHR, 1.44; 95% CI, 1.29-1.61) and those with depressive (aHR, 1.32; 95% CI, 1.17-1.50), anxiety (aHR, 1.15; 95% CI, 1.02-1.30), drug use (aHR, 1.55; 95% CI, 1.36-1.76), and sleep disorders (aHR, 1.22; 95% CI, 1.07-1.39), suicidal ideation (aHR, 1.41; 95% CI, 1.22-1.63), and suicide attempts or self-injury (aHR, 2.48; 95% CI, 2.06-2.98). The adjusted hazards of suicide were lower for Hispanic patients (aHR, 0.66; 95% CI, 0.54-0.80) or Black patients (aHR, 0.29; 95% CI, 0.24-0.35) than White patients. The suicide rate declined with age, from 141.95 (SMR, 10.19; 95% CI, 9.29-11.18) for patients aged 18 to 34 years to 24.01 (SMR, 1.53; 95% CI, 1.32-1.77) for patients 65 years or older. The corresponding declines per 100 000 person-years were from 153.80 (18-34 years of age) to 34.17 (65 years or older) for men and from 115.70 (18-34 years of age) to 18.66 (65 years or older) for women. In the group aged 18 to 34 years, the adjusted hazards of suicide risk were significantly increased for patients with suicide attempt or self-injury (aHR, 2.57; 95% CI, 18.20-2.04) and with comorbid drug use disorders (aHR, 1.48; 95% CI, 1.17-1.88), but not with comorbid depressive disorders (aHR, 0.99; 95% CI, 0.38-1.26) during the year before the start of follow-up.Conclusions and relevanceIn this cohort study of adult Medicare patients with schizophrenia, suicide risk was elevated, with the highest absolute and relative risk among young adults. These patterns support suicide prevention efforts with a focus on young adults with schizophrenia, especially those with suicidal symptoms and substance use.

Project description:ABSTRACT MAGWIRE, MICHAEL MAHLON. Mutations Increasing Drosophila melanogaster Life Span. (Under the direction of Trudy F. C. Mackay.) Better living conditions and advances in medicine have made it possible for humans to live considerably longer than before. This has uncovered many health problems associated with age. By identifying genes involved in the limitation of life span, we may better understand the processes that lead to aging. In model organisms, we can use mutagenesis to discover mutations that increase life span, and hence infer that the wild-type allele limits life span by some means. We have assessed longevity in a collection of 1332 co-isogenic gene-trap P-element insertion lines and determined changes in life span of each insert line relative to the corresponding control line. Significant lines were determined via two different methods of analysis: A 95% confidence interval was established based on deviations of the mutant life spans from the controls and Dunnett’s two tailed t-tests were used to examine differences between mutant and control in each individual block. Based on the 95% confidence interval, 139 inserts displayed an increase in life span and 194 inserts a decrease. Using Dunnett’s, 70 lines increased in life span, while 270 decreased in life span. An additional 48 increased longevity lines were close enough to meeting Dunnett’s criteria to be considered for additional investigation. Combining these two analyses, we chose 83 inserts associated with increased life span for a secondary screen using an additional twelve replicates. 58 of these lines remained significant. We have determined the P-element insertion site for 50 of these lines. Starvation resistance, chill coma recovery time and climbing activity were measured on the lines remaining significant after the the secondary screen to identify pleiotropic effects. A positive correlation was found for males between life span and starvation resistance as well as between life span and chill coma recovery. Females only displayed a correlation between life span and chill coma recovery, which was negative. None of the lines indicated increased fitness for all phenotypes, indicating there may be some type of trade-off. There also appears to be a lot of pleiotropic variation depending on background and sex. Ten of the lines, all with the same parental background, were chosen for a half-diallel cross to identify epistasis between the mutants. There were substantial epistatic interactions between all ten lines. Furthermore, males and females displayed vastly different patterns of epistasis, again indicating major differences in life span regulation between the sexes. Finally, a subset of seven of the lines used in the epistatic study, in addition to the corresponding parental control, were chosen for microarray analysis to look for possible pathways and novel genes involved in increasing life span. 1,996 probe sets were significant at a false discovery rate q-value threshold of q < 0.0001. Tukeys tests were carried out for these probe sets to determine how each of the seven mutant backgrounds differed compared to the control and each other. In addition, each mutant background was compared individually with the control to identify any changes in expression. Gene ontologies were determined for each of the lines to identify over-represented biological functions which would indicate possible longevity pathways. Dozens of pathways were suggested, including several novel pathways. Keywords: Genetic (P-element insertion) modification and comparison to control line

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The Life Span Model of Suicide and Its Neurobiological Foundation.

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The Life Span Model of Suicide and Its Neurobiological Foundation.

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