Time-varying living arrangements and suicide death in the general population sample: 14-year causal survival analysis via pooled logistic regression.

AIMS: While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches. METHODS: Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation. RESULTS: A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3-2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83-7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2-10.5%; RR: 1.56, 95% CI: 1.38-1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2-11.3%; RR: 1.60, 95% CI: 1.42-1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses. CONCLUSIONS: Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

Association of sleep characteristics with suicidal ideation and suicide attempt among adults aged 50 and older with depressive symptoms in low- and middle-income countries.

OBJECTIVES: Investigate the association of sleep characteristics with suicidal ideation and suicide attempt among middle-aged and older adults with depressive symptoms in five low- and middle-income countries (LMICs). DESIGN: Cross-sectional. SETTING: China, Ghana, India, Russia, and South Africa. PARTICIPANTS: Adults aged ≥50 years with depressive symptoms from the World Health Organization (WHO) Study on Global AGEing and Adult Health (n=2,040). MEASUREMENTS: Predictors were self-reported average sleep duration for the past 2 nights (<7 hours (shorter), 7 to <9 hours (reference), ≥9 hours (longer)), sleep quality for the past 2 nights (moderate/good/very good [both nights], poor/very poor [≥1 night]), past-month insomnia symptoms (none/mild, moderate, severe/extreme), and past-day daytime sleepiness. Outcomes were past-year suicidal ideation and suicide attempt. Analyses were adjusted for age, sex, household wealth, marital status, self-rated health, cognitive performance, number of depressive symptoms, and country of residence. RESULTS: Participants with poor/very poor sleep quality ≥1 night had greater odds of suicidal ideation (vs. moderate/good/very good sleep quality both nights). Participants with moderate and severe/extreme insomnia symptoms had greater odds of suicidal ideation and suicide attempt (vs. none/mild insomnia symptoms). In moderation analyses, greater insomnia symptoms were associated with higher odds of suicidal ideation among women only and those aged 60-60 years and ≥80 years only. CONCLUSIONS: Among middle-aged and older adults with depressive symptoms in LMICs, sleep characteristics are markers of-and potential contributors to-suicidal ideation and suicide attempt, and there was evidence of moderation by age and sex. Interventions aimed at preventing suicide-related outcomes in these populations should consider the role of sleep.

Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder.

Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis abnormalities and an increased risk to both suicidal behaviors and post-traumatic stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA methylation associations with suicidal behavior in the blood and brain of multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior with ~80% accuracy. SKA2 is hypothesized to reduce the ability to suppress cortisol following stress, which is of potentially high relevance in traumatized populations. Our objective was to investigate the interaction of SKA2 and trauma exposure on HPA axis function, suicide attempt and PTSD. SKA2 DNA methylation at Illumina HM450 probe cg13989295 was assessed for association with suicidal behavior and PTSD metrics in the context of Child Trauma Questionnaire (CTQ) scores in 421 blood and 61 saliva samples from the Grady Trauma Project (GTP) cohort. Dexamethasone suppression test (DST) data were evaluated for a subset of 209 GTP subjects. SKA2 methylation interacted with CTQ scores to predict lifetime suicide attempt in saliva and blood with areas under the receiver operator characteristic curve (AUCs) of 0.76 and 0.73 (95% confidence interval (CI): 0.6-0.92, P = 0.003, and CI: 0.65-0.78, P < 0.0001) and to mediate the suppression of cortisol following DST (ß = 0.5 ± 0.19, F = 1.51, degrees of freedom (df) = 12/167, P = 0.0096). Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.

Latent classes of childhood trauma exposure predict the development of behavioral health outcomes in adolescence and young adulthood.

BACKGROUND: To develop latent classes of exposure to traumatic experiences before the age of 13 years in an urban community sample and to use these latent classes to predict the development of negative behavioral outcomes in adolescence and young adulthood. METHOD: A total of 1815 participants in an epidemiologically based, randomized field trial as children completed comprehensive psychiatric assessments as young adults. Reported experiences of nine traumatic experiences before age 13 years were used in a latent class analysis to create latent profiles of traumatic experiences. Latent classes were used to predict psychiatric outcomes at age ⩾13 years, criminal convictions, physical health problems and traumatic experiences reported in young adulthood. RESULTS: Three latent classes of childhood traumatic experiences were supported by the data. One class (8% of sample), primarily female, was characterized by experiences of sexual assault and reported significantly higher rates of a range of psychiatric outcomes by young adulthood. Another class (8%), primarily male, was characterized by experiences of violence exposure and reported higher levels of antisocial personality disorder and post-traumatic stress. The final class (84%) reported low levels of childhood traumatic experiences. Parental psychopathology was related to membership in the sexual assault group. CONCLUSIONS: Classes of childhood traumatic experiences predict specific psychiatric and behavioral outcomes in adolescence and young adulthood. The long-term adverse effects of childhood traumas are primarily concentrated in victims of sexual and non-sexual violence. Gender emerged as a key covariate in the classes of trauma exposure and outcomes.

Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity.

BACKGROUND: The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders. METHOD: A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998-2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA. RESULTS: The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives. CONCLUSIONS: The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.

Longitudinal predictors of past-year non-suicidal self-injury and motives among college students.

BACKGROUND: Non-suicidal self-injury (NSSI) is the deliberate and direct injuring of body tissue without suicidal intent for purposes not socially sanctioned. Few studies have examined the correlates of NSSI among young adults. This study aimed to identify predictors of lifetime and past-year NSSI, and describe motives for NSSI and disclosure of NSSI to others. METHOD: Interviews were conducted annually with 1081 students enrolled in the College Life Study, a prospective longitudinal study conducted at a large public mid-Atlantic university. NSSI characteristics were assessed at Year 4. Demographic and predictor variables were assessed during Years 1 to 4. Multivariate logistic regression models were used to identify correlates of lifetime NSSI and predictors of past-year NSSI. RESULTS: The prevalence of past-year and lifetime NSSI was 2% and 7% respectively (>70% were female for both lifetime and past-year NSSI). Seven percent of NSSI cases self-injured once, whereas almost half self-injured six or more times. Independent predictors of past-year NSSI were maternal depression, non-heterosexual orientation, affective dysregulation and depression. Independent predictors of lifetime NSSI were depression, non-heterosexual orientation, paternal depression and female sex. One in six participants with NSSI had attempted suicide by young adulthood. The three most commonly reported motives for NSSI were mental distress, coping and situational stressors. Most (89%) told someone about their NSSI, most commonly a friend (68%). CONCLUSIONS: This study identified unique predictors of NSSI, which should help to elucidate its etiology and has implications for early identification and interventions.

Prenatal drug exposure and child outcome. Past, present, future.

Scientific study of prenatal drug exposure and child outcome began a period of substantial growth in the 1970s with a focus on exposure to opiates. By the mid-1980s, attention shifted to cocaine. Most of this research has involved cohort studies in which groups of children are followed up longitudinally from birth. Significant progress has been made regarding the assessment of child outcome (greater range of outcome areas and greater specificity of measures) and regarding attention to and analysis of confounding factors that travel with prenatal exposure. As progress has been made, investigators are tackling new and continuing challenges inherent in these complex studies. Considerable effort is being devoted to determining the level of severity of exposure. Interest is increasing regarding the use of neuroimaging assessments as well as the identification of possible biologic and environmental mechanisms underlying associations between prenatal exposure and subtle child outcomes.

Relationships between fatty acid synthesis and lipid secretion in the isolated perfused rat liver: effects of hyperthyroidism, glucose and oleate.

Various studies on the effects of thyroid status on hepatic fatty acid synthesis have produced conflicting results. Several variables (e.g., plasma free fatty acid and glucose concentrations) are altered simultaneously by thyroid status and can affect fatty acid synthesis. To evaluate the effects of these variables, hepatic fatty acid synthesis (lipogenesis) was studied in isolated perfused livers from normal and triiodothyronine-treated rats. Livers were perfused with media containing either 5.5 or 25 mM glucose without fatty acid, or 5.5 mM glucose and 0.7 mM oleate. Rates of lipogenesis were determined by measurement of incorporation of 3H2O into fatty acids. Lipogenesis in livers from hyperthyroid animals exceeded that of controls, when perfused with 5.5 mM glucose with or without oleate. Perfusion with 25 mM glucose increased lipogenesis in both euthyroid and hyperthyroid groups to the same level, abolishing this difference between them. Perfusion with oleate reduced rates of lipogenesis by livers from euthyroid and hyperthyroid rats to a similar extent, but stimulated secretion of radioactive fatty acid in phospholipid and free fatty acid fractions. Oleate increased ketogenesis by livers from normal and triiodothyronine-treated rats, with higher rates of ketogenesis in the triiodothyronine-treated group. When oleate was omitted, ketogenesis in the presence of 5.5 mM glucose by the hyperthyroid group was similar to that of euthyroid controls, while ketogenesis was decreased in the hyperthyroid group relative to controls when perfused with 25 mM glucose. About 30% of the radioactivity incorporated into the total fatty acid of both groups was recovered in palmitate, with the remainder in longer chain saturated and unsaturated fatty acids. In both euthyroid and hyperthyroid groups, the ratio of triacylglycerol:phospholipid fatty acid radioactivity was not only less than predicted (based on synthetic rates of PL and TG) but also was decreased in perfusions with exogenous oleate compared to perfusions without oleate. In perfusions with oleate, both groups incorporated twice as much radioactivity into phospholipid as into triacylglycerol. The data suggest the following concepts: while hepatic fatty acid synthesis and oxidation are increased simultaneously in the hyperthyroid state, de novo synthesized fatty acids seem to be poorer substrates for oxidation than are exogenous fatty acids, and are preferentially incorporated into phospholipid, while exogenous fatty acids are better substrates for oxidation and esterification to triacylglycerol. The preferential utilization of de novo synthesized fatty acid for phospholipid synthesis may be an important physiologic adaptation insuring a constant source of fatty acid for membrane synthesis.