Lifetime substance use disorder and suicidal behaviour: a population-based familial co-aggregation register study

Introduction Suicide is the most common cause of death among individuals aged 15 - 24 worldwide, and each year approximately 800,000 people die by suicide globally. Substance use disorders (SUD) are associated with suicidal behaviour, but less is known regarding the extent to which familial factors influence these associations across different types of SUD. The aim of the current study was two-fold: First, to investigate lifetime association between SUD across different substances (alcohol, opioids, cannabis, sedatives, stimulants etc) and suicidal behaviour at the population level using large scale national register data with 47 years of coverage. Second, to investigate familial co-aggregation of SUD and suicidal behaviour, to assess whether familial factors, including genetics and shared environment, contribute to the association in a similar fashion across different forms of SUD

Methods We performed a national register study including 4,209,615 individuals born in Sweden 1958–1999 and followed 1973-2020. Exposure was life-time SUD diagnosis, including alcohol use disorder (AUD), drug use disorder (DUD) or dual diagnosis (AUD+DUD). DUD was further classified into substance type (e.g., cannabis, opioids, sedatives or stimulants). Outcome was life-time suicidal event, operationalized as either suicide attempt or death by suicide. Log-linear regression models estimating risk ratios (RR) were fitted with adjustment for sex, birth year, socioeconomic factors and psychiatric co-morbidity. To investigate familial co-aggregation of SUD and suicidal behaviour, each individual was linked to their relatives with different degree of genetic relatedness. This generated seven new cohorts (genetic relatedness in parentheses) consisting of monozygotic twins (100%), dizygotic twins (50%), full siblings (50%), half siblings (25%), maternal half siblings (25%), paternal half siblings (25%) and cousins (12.5%). The exposure was defined as having a relative with SUD, and the outcome was any suicidal events.

Results Of 258,046 individuals with SUD, 23.0% (n=59,436) had any life-time suicidal event compared to 1.5% (n=59,784) in 3,951,569 persons without SUD. SUD was associated with increased risk of any suicidal event (Adjusted RR: 6.4 [6.3-6.5]), suicide attempt (6.9 [6.8-7.0]) and suicide death (3.3 [3.2-3.5]). Elevated suicide risk was observed across all SUD, with greatest risk in those with AUD+DUD. Larger RR suicidal events were observed in relatives of individuals with SUD as genetic similarity increased (e.g., full siblings: 2.6 [2.6-2.7]; half siblings: 1.5 [1.5-1.6]). This pattern was observed for all types of SUD, with highest RR in individuals with AUD+DUD relatives (e.g., full siblings: 3.5 [3.4-3.6]; half siblings: 1.7 [1.7-1.8]).

Conclusions The current study found a high rate of suicidal behaviour in individuals with SUD across all substances, and this association may be explained in part by familial factors including genetic and possibly shared environmental factors. These results have clinical implications for somatic, psychiatric and addiction treatment services in relation to suicide risk assessment and prevention, as well as highlighting the need for clinical research to include suicide related outcomes when designing treatment trials in SUD patients.

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