Kendler Kenneth S, Abrahamsson Linda, Sundquist Jan, Sundquist Kristina
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Psychol Med. 2025 Mar 5;55:e72. doi: 10.1017/S0033291725000327.
We seek to clarify how changes in the prevalence of drug use disorder (DUD) in Sweden in the 1950-1990 birth cohort impact the aggregation and co-aggregation in siblings of DUD and alcohol use disorder (AUD).
We examined risk for DUD and AUD in siblings of 102,624 DUD cases and matched control probands and 123,837 AUD case and matched control probands identified using Swedish registries. Flexible parametric survival models assessed the difference in disorder risk in siblings of case versus control probands.
Over birthyears 1950-1990, rates of DUD increased substantially in the Swedish population. In siblings of DUD cases versus controls, the risk for DUD increased dramatically starting in birthyear 1965 while their risk for AUD fell moderately. A similar, but less pronounced pattern, was seen in the siblings of AUD versus control probands. These differences were much larger in male than in female siblings.
The factors that drove upward population rates of DUD in Sweden (e.g. increased availability, reduced stigma) produced much stronger effects in high-risk subjects (siblings of DUD and AUD probands) than in normal risk groups (siblings of controls), thereby increasing familial aggregation of DUD. However, parallel declines in AUD rates in high-risk versus normal-risk siblings were observed, likely due to 'competitive effects' reducing coaggregation of DUD and AUD. Results of genetic studies of substance use disorders can be substantially impacted by changes in availability and stigma of psychoactive substance use and indirectly by 'competition' as predicted by behavioral economic models, between abusable substances.
我们试图阐明1950 - 1990年出生队列中瑞典药物使用障碍（DUD）患病率的变化如何影响DUD与酒精使用障碍（AUD）在兄弟姐妹中的聚集及共同聚集情况。
我们研究了102,624例DUD病例及匹配对照先证者的兄弟姐妹以及123,837例AUD病例及匹配对照先证者的DUD和AUD风险，这些数据通过瑞典登记系统确定。灵活的参数生存模型评估了病例组与对照组先证者的兄弟姐妹中疾病风险的差异。
在1950 - 1990年出生年份中，瑞典人群的DUD患病率大幅上升。在DUD病例的兄弟姐妹与对照组中，从1965年出生年份开始，DUD风险急剧增加，而他们的AUD风险适度下降。在AUD病例与对照先证者的兄弟姐妹中也观察到类似但不太明显的模式。这些差异在男性兄弟姐妹中比在女性兄弟姐妹中要大得多。
在瑞典导致人群DUD患病率上升的因素（例如可及性增加、耻辱感降低）在高风险人群（DUD和AUD先证者的兄弟姐妹）中产生的影响比在正常风险组（对照组的兄弟姐妹）中要强得多，从而增加了DUD的家族聚集性。然而，观察到高风险与正常风险兄弟姐妹中AUD患病率同时下降，这可能是由于“竞争效应”减少了DUD和AUD的共同聚集。物质使用障碍的基因研究结果可能会受到精神活性物质使用的可及性和耻辱感变化的显著影响，并间接受到行为经济模型所预测的可滥用物质之间“竞争”的影响。
