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Background To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. Methods Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). Results We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. Conclusions The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

ImportanceThe nature of the genetic relationship between major depression and bipolar disorder remains unclear and might be clarified by considering disorders outside of the mood spectrum.ObjectiveTo better understand the relationship between genetic liabilities for major depression (MD) and bipolar disorder (BD).Design, Setting, and ParticipantsA cohort study was conducted with data for individuals born in Sweden to Swedish parents from 1960 to 1990, with follow-up through December 31, 2018. The data included family genetic risk scores for MD and BD and International Classification of Diseases codes for a range of disorders as reported in primary care, specialist, and hospital registries. Data analysis was conducted from April 2022 to July 2022.ExposuresHigh and low genetic liability were defined as being in the upper and lower 2 risk deciles. Risk was compared in individuals at high genetic liability to (1) MD only, (2) BD only, and (3) both MD and BD and those at (4) high genetic liability to BD and low genetic liability to MD and (5) high genetic liability to MD and low genetic liability to BD.Main Outcomes and MeasuresRisk for nonpsychotic MD and BD, psychotic MD and BD, anxiety disorders, obsessive-compulsive disorder, schizoaffective disorder (SAD), schizophrenia, and other nonaffective psychosis.ResultsData were included for 2 736 950 individuals with a mean (SD) age at follow-up of 43.9 (9.1) years. High genetic liability to only BD increased risk for nonpsychotic BD, psychotic BD, and SAD. High genetic liability to only MD augmented risk for nonpsychotic MD, anxiety disorders, and nonpsychotic BD. High genetic liability to both BD and MD had the strongest association with risk for nonpsychotic BD, anxiety disorders, and nonpsychotic MD. High genetic liability to BD and low genetic liability to MD increased risk for psychotic BD, nonpsychotic BD, and SAD with no increased risk for nonpsychotic MD or anxiety disorders. High genetic liability to MD and low genetic liability to BD increased risk for nonpsychotic MD, nonpsychotic BD, and anxiety disorders with no increased risk for psychotic BD.Conclusions and RelevanceIn this study, hypotheses that BD and MD are either genetically distinct or genetically closely interrelated were not supported. Both BD and MD were associated with a genetic vulnerability to mood disorders, but even that liability was partially selective. However, compared with individuals at high liability to MD, those at elevated genetic liability for BD had a substantially increased risk for psychosis. Compared with individuals at elevated genetic liability to BD, those at high genetic risk for MD had a considerably augmented risk for anxiety disorders. Clarifying genetic relationships between psychiatric syndromes can be substantially aided by the consideration of profiles of risk for a range of disorders.

Few, if any, prior studies have considered whether undetermined intent (UDI) deaths and suicide deaths differ with respect to genetic liability for suicidal behavior or psychopathology.The authors used Swedish national registry data to identify suicide deaths (N = 31,835) and UDI deaths (N = 10,623); sociodemographic covariates; and registrations for psychopathology. Family genetic risk scores (FGRS) were derived for each form of psychopathology. The authors used LASSO models to assess genetic and phenotypic differences across outcomes.In the multivariate LASSO regressions, higher FGRS for major depression, bipolar disorder, and suicide death were associated with lower odds of UDI relative to unambiguous suicide (OR = 0.91-0.95), while those for alcohol and drug use disorders, ADHD, and criminal behavior were associated with higher odds of UDI relative to unambiguous suicide (OR = 1.04-1.12). When the corresponding phenotypic registration status for these outcomes was included in a subsequent model, the associations were attenuated and of small magnitude, but many remained different from OR = 1.Aggregate genetic differences between unambiguous suicide decedents and UDI deaths are small, particularly when accounting for psychiatric comorbidity, but in some cases, statistically significant. These findings suggest that different analytic treatment of UDI deaths may be warranted depending on the research question. Replication in other samples, and using molecular genetic data, is necessary.

The purpose of this study was to clarify the clinical heterogeneity of alcohol use disorder (AUD) in a national Swedish sample of affected individuals using latent class analysis.Using a Swedish population-based sample of AUD cases ascertained from medical, criminal, and pharmacy registries (in/i= 217,071), we applied latent class analysis to sex, externalizing and internalizing syndromes before first registration, and age at first registration. The resulting types were evaluated against 15 diverse validators and degree of resemblance in relative pairs concordant for AUD.A three-class solution was preferred by fit indices. The three classes were as follows: type 1 (male preponderant, externalizing; 32%), type 2 (minimal prior psychopathology; 46%), and type 3 (mixed-sex internalizing; 23%). Repeated split-half analyses revealed the statistical stability of these solutions. Meaningful differences emerged between the classes on many validators. Type 1 had the greatest family disruption, lowest educational levels, most AUD registrations, highest rates of criminal registration, and highest genetic risk for externalizing disorders and AUD. Type 2 had the least social dysfunction. Type 3 had the highest educational attainment, genetic liability to internalizing disorders, and proportion of women. All types significantly aggregated in affected pairs of relatives.Meaningful and reproducible subtypes of AUD, consistent with prior typological results, can be obtained from national registry-based samples. Using a range of external validators and patterns of familial aggregation, our results suggest that our three-class solution captured a meaningful proportion of the clinical heterogeneity of AUD.

To clarify, using an extended adoption design, the sources of parent-offspring transmission for anxiety disorder (AD) and its major subforms and their familial cross-generational relationship with major depression (MD).Offspring (born 1960-1992) and their parents, from six family types (intact, not-lived-with biological father or mother, lived-with step-father or step-mother, and adoptive), were ascertained from Swedish national samples. Diagnoses were obtained from national medical registers. We assessed three sources of parent-child resemblance: genes plus rearing, genes only, and rearing only. To test comorbidity effects, single diagnoses were assigned in comorbid cases based on frequency and recency.For AD to AD parent-child transmission, best-estimate tetrachoric correlations for the three types of parent-offspring relationships genes plus rearing, genes only, and rearing only-equaled +0.16 (95% CI=0.16, 0.16), +0.12 (95% CI=0.10, 0.13), and +0.06 (95% CI=0.04, 0.07), respectively, with broadly similar results for MD to MD transmission. Cross-disorder cross-generation correlations were modestly lower, with genetic and rearing correlations for AD and MD estimated at +0.83 (95% CI=0.76, 0.90) and +0.83 (95% CI=0.69, 0.96), respectively. Analyses for panic disorder and generalized anxiety disorder (GAD) produced comparable findings, with the genetic correlation with MD modestly higher for generalized anxiety disorder than panic disorder. Applying a diagnostic hierarchy to comorbid cases resulted in a decline in cross-disorder cross-generation transmission with the estimated genetic correlation equaling +0.46 (95% CI=0.30, 0.62).For AD and its major subforms, cross-generational transmission includes both genetic and rearing effects. In traditional analyses, AD and MD demonstrate highly correlated genetic and rearing effects. The genetic correlation weakened when applying a diagnostic hierarchy.

Background Among individuals with alcohol use disorder (AUD) and drug use disorder (DUD), is their genetic liability and its specificity moderated by substance availability? Methods Offspring (born 1960–1995) and their biological parents from three family types [not-lived-with (NLW) biological father, mother and adoptive] and their AUD and DUD diagnoses were ascertained from Swedish national registers. Parent–offspring resemblance was calculated by tetrachoric correlation. Results In Swedes born from 1960 to 1995, prevalence rates of AUD were stable while DUD rates increased substantially. Best-estimate tetrachoric correlations (±95% confidence intervals) between AUD in biological parents and AUD and DUD in their offspring were, respectively, +0.19 (0.18–0.20) and +0.18 (0.17–0.20). Parallel results from DUD in parents to AUD and DUD in children were +0.12 (0.10–0.13) and +0.27 (0.26–0.28). When divided into older and younger cohorts, the specificity of DUD transmission increased substantially over time, while the genetic correlation between AUD and DUD significantly decreased. Conclusions Raised when alcohol was the preferred substance of abuse and illicit drugs highly stigmatized, AUD in parents reflected a general liability to substance use disorders, as they transmitted similar genetic risk for AUD and DUD to their children raised when both substances were widely available and relatively acceptable. DUD in parents, by contrast, reflected a more specific liability to DUD and, when transmitted to offspring, produced a considerably stronger risk for DUD than for AUD that increased over time. The magnitude and specificity of the genetic liability to psychoactive substances can be influenced by the availability of that substance.

Substance use disorder (SUD) is related to widespread adverse consequences, including higher suicidality. Shared genetic liability has been demonstrated between SUD and suicidality. Here, we measured the factors that contribute to increased risk of non-fatal suicide attempt among individuals with SUD by focusing upon aggregate genetic risks and both childhood and past-year environmental factors.Longitudinal study. Family genetic risk scores and environmental factors (childhood, aged from 0 to 15 years, and the year preceding SUD registration) were used to predict the relative risk of non-fatal suicide attempt using Cox proportional hazards models. Additional analyses employed a co-relative design, accounting for genetic factors and shared familial environment, to test for potential causality.Based on longitudinal Swedish registry data, 228 617 individuals with SUD registrations from 1991 to 2015 were included.SUD and suicide attempts were identified using medical records (International Classification of Diseases codes). SUD was also identified using pharmacy and criminal registries.In multivariable analyses that jointly accounted for all the selected potential predictors, individuals with SUD were at higher risk for non-fatal suicide attempt if they had experienced a parental death [hazard ratio (HR) = 1.58; 95% confidence interval (CI) = 1.30, 1.93], were female (HR = 1.53, 95% CI = 1.49, 1.57), had low educational attainment (HR = 1.50, 95% CI = 1.46, 1.55), received social welfare (HR = 1.21, 95% CI = 1.17, 1.25) or had lived in a non-intact family (HR = 1.11, 95% CI = 1.08, 1.14). In co-relative analyses, low education was supported as a possible causal factor for suicide attempt. Aggregate genetic risks interacted with low education and being raised in a non-intact family, with increased prevalence of suicide attempt in people with high genetic risks and unfavorable environmental exposures.Aggregate genetic liability, childhood environmental experiences and specific socio-economic indicators are important risk factors for non-fatal suicide attempt among individuals with substance use disorder.

Background Despite a large descriptive literature linking creativity and risk for psychiatric illness, the magnitude and specificity of this relationship remain controversial. Methods We examined, in 1 137 354 native Swedes with one of 59 3-digit official and objective occupational codes in managerial and educated classes, their familial genetic risk score (FGRS) for ten major disorders, calculated from 1st through 5th degree relatives. Mean FGRS across disorders were calculated, in 3- and 4-digit occupational groups, and then controlled for those whose disorder onset preceded occupational choice. Using sequential analyses, p values were evaluated using Bonferroni correction. Results 3-digit professions considered to reflect creativity (e.g. ‘artists’ and ‘authors’) were among those with statistically significant elevations of FGRS. Among more specific 4-digit codes, visual artists, actors, and authors stood out with elevated genetic risks, highest for major depression (MD), anxiety disorders (AD) and OCD, more modest for bipolar disorders (BD) and schizophrenia and, for authors, for drug and alcohol use disorders. However, equal or greater elevations in FGRS across disorders were seen for religious (e.g. ministers), helping (e.g. psychologists, social workers), and teaching/academic occupations (e.g. professors). The potential pathway from FGRS → Disorder → Occupation accounts for a modest proportion of the signal, largely for MD and AD risk. Conclusions While traditional creative occupations were associated with elevated genetic risk for a range of psychiatric disorders, this association was not unique, as similar, or greater elevations were seen for religious, helping and teaching professions and was stronger for internalizing than psychotic disorders.

Background Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders. Methods This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric – major depression (MD) – and a somatic/autoimmune disorder: rheumatoid arthritis (RA). Results Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions. Conclusion Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.

Background Does the genetic aptitude for educational attainment (GAEA) moderate the genetic risk for alcohol use disorder (AUD) and drug use disorder (DUD)? Methods In the native Swedish population, born 1960–1980 and followed through 2017 (n = 1 862 435), the family genetic risk score (FGRS) for AUD and DUD and GAEA were calculated from, respectively, the educational attainment and risk for AUD and DUD, of 1st through 5th degree relatives from Swedish national registers. Analyses utilized Aalen's linear hazards models. Results Risk for AUD was robustly predicted by the main effects of FGRSAUD [b = 6.32 (95% CI 6.21–6.43), z = 64.9, p < 0.001) and GAEA [b = −2.90 (2.83–2.97), z = 44.1, p < 0.001] and their interaction [b = −1.93 (1.83–2.03), z = 32.9, p < 0.001]. Results were similar for the prediction of DUD by the main effects of FGRSDUD [b = 4.65 (CI 4.56–4.74), z = 59.4, p < 0.001] and GAEA [−2.08 (2.03–2.13), z = 46.4, p < 0.001] and their interaction [b = −1.58 (1.50–1.66)), z = 30.2, p < 0.001]. The magnitude of the interactions between GAEA and FGRSAUD and FGRSDUD in the prediction of, respectively, AUD and DUD was attenuated only slightly by the addition of educational attainment to the model. Conclusions and relevance The genetic propensity to high educational attainment robustly moderates the genetic risk for both AUD and DUD such that the impact of the genetic liability to AUD and DUD on the risk of illness is substantially attenuated in those with high v. low GAEA. This effect is not appreciably mediated by the actual level of educational attainment. These naturalistic findings could form the basis of prevention efforts in high-risk youth.

Background– Comorbidity between psychiatric disorders is extensive but, from a genetic perspective, still poorly understood. Modern molecular genetic approaches to this problem are limited by a reliance on case–control designs.Methods– In 5 828 760 individuals born in Sweden from 1932–1995 with a mean (s.d.) age at follow-up of 54.4 (18.1), we examined family genetic risk score (FGRS) profiles including internalizing, psychotic, substance use and developmental disorders in 10 pairs of psychiatric and substance use disorders diagnosed from population registries. We examined these profiles in three groups of patients: disorder A only, disorder B only and comorbid cases with both disorders.Results– The most common pattern of findings, seen in five pairings, was simple and quantitative. Comorbid cases had higher FGRS than both non-comorbid cases for all (or nearly all) disorders. However, the pattern was more complex in the remaining five pairings and included qualitative changes where the comorbid cases showed no increases in FGRS for certain disorders and in a few cases significant decreases. Several comparisons showed an asymmetric pattern of findings with increases, in comorbidity compared to single disorder cases, of the FGRS for only one of the two disorders.Conclusions– The examination of FGRS profiles in general population samples where all disorders are assessed in all subjects provides a fruitful line of inquiry to understand the origins of psychiatric comorbidity. Further work will be needed, with an expansion of analytic approaches, to gain deeper insights into the complex mechanisms likely involved.

BackgroundPrevious studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death.MethodsThe authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960–1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex.ResultsGenetic correlations between SA and SUD ranged from rA = 0.60–0.88; corresponding shared environmental correlations were rC = 0.42–0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42–0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48–0.72, rC = 0.92–1.00), but were attenuated for unique environmental factors (rE = −0.01 to 0.31).ConclusionsThese findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.

BackgroundAlcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment.MethodsIn the Swedish population born 1932–1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants.ResultsFGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders.ConclusionsFrom a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.

BACKGROUND: This study aimed to determine the robustness of the impact of immigration on risk for alcohol use disorder (AUD) using different measures, designs, and immigrant regional cohorts. METHODS: The analytic sample included all individuals born between 1950 and 1990 and registered in Sweden from 1973 to 2017. Using Cox regression models, we examined the risk for AUD from Swedish nationwide registries in immigrants to Sweden from seven geographical regions: Africa, Asia and Oceania, Eastern Europe, Finland, Latin America and the Caribbean, Middle East/North Africa, and Western countries. We assessed greater exposure to Swedish culture, which we interpreted as increasing acculturation, by (i) comparing first-generation immigrants and their children with no and one native Swedish parent and (ii) examining age at immigration. The baseline comparison group was the native Swedish population. We also examined AUD risk in first-generation sibling pairs discordant for their age at immigration. RESULTS: In nearly all immigrant cohorts in Sweden, increasing degrees of acculturation, as assessed by both our variables, were associated with rates of AUD that approached those of the Swedish population. These findings occurred in both men and women and both regional cohorts whose first-generation immigrants had lower and higher levels of AUD than native-born Swedes. For most cohorts, the rates of change with acculturation were greater in women than in men. In sibling pairs from most regions, the sibling who was younger at immigration had a higher rate of AUD. CONCLUSIONS: An examination of both sexes and two different proxies for acculturation provides consistent support for socio-cultural influences on AUD risk. Our cosibling analyses suggest that a meaningful proportion of this effect is likely to be causal in nature.

Background Suicidal behavior and substance use disorders (SUDs) are important public health concerns. Prior suicide attempts and SUDs are two of the most consistent predictors of suicide death, and clarifying the role of SUDs in the transition from suicide attempt to suicide death could inform prevention efforts. Methods We used national Swedish registry data to identify individuals born 1960–1985, with an index suicide attempt in 1997–2017 (N = 74 873; 46.7% female). We assessed risk of suicide death as a function of registration for a range of individual SUDs. We further examined whether the impact of SUDs varied as a function of (i) aggregate genetic liability to suicidal behavior, or (ii) age at index suicide attempt. Results In univariate models, risk of suicide death was higher among individuals with any SUD registration [hazard ratios (HRs) = 2.68–3.86]. In multivariate models, effects of specific SUDs were attenuated, but remained elevated for AUD (HR = 1.86 95% confidence intervals 1.68–2.05), opiates [HR = 1.58 (1.37–1.82)], sedatives [HR = 1.93 (1.70–2.18)], and multiple substances [HR = 2.09 (1.86–2.35)]. In secondary analyses, the effects of most, but not all, SUD were exacerbated by higher levels of genetic liability to suicide death, and among individuals who were younger at their index suicide attempt. Conclusions In the presence of a strong predictor of suicide death – a prior attempt – substantial predictive power is still attributable to SUDs. Individuals with SUDs may warrant additional suicide screening and prevention efforts, particularly in the context of a family history of suicidal behavior or early onset of suicide attempt.

Sweden has witnessed a significant increase in the rate of firearm-related homicide. We therefore aimed to study the characteristics of individuals suspected of homicide, attempted homicide, preparation to commit homicide as well as conspiracy to commit homicide with a firearm in Sweden. By using information from different registers, suspected individuals between 2000 and 2017 and aged 15 to 60 were included in the study. A total of 889 individuals were evaluated. A notable part were females (5.1%). Latent Class Analysis identified three classes, where two classes were high-offending-classes, and one class was a low-offending-class. The identification of these classes may be used for more effective preventive measures.

BackgroundHow does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD?MethodsIn the Swedish general population born 1932–1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers.ResultsIn univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD.ConclusionsFGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.