Giordano G N, Ohlsson H, Sundquist K, Sundquist J, Kendler K S
Center for Primary Health Care Research,Lund University,Malmö,Sweden.
Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University,Richmond, VA,USA.
Psychol Med. 2015 Jan;45(2):407-14. doi: 10.1017/S0033291714001524. Epub 2014 Jul 3.
Although cannabis abuse (CA) is known to be associated with schizophrenia, the causal nature of this association is unclear, with prodromal effects complicating its interpretation.
From Swedish national registry databases, we used a co-relative case-control design with full-sibling, half-sibling and first-cousin comparisons, alongside a general Swedish population sample. Using ICD codes, 5456 individuals with an initial diagnosis of schizophrenia (2000-2010) were matched with five schizophrenia-free controls. We further identified first-cousin, half-sibling and full-sibling pairs discordant for CA and statistically extrapolated results for discordant monozygotic (MZ) twins.
Within the general Swedish population, CA was strongly associated with later schizophrenia [odds ratio (OR) 10.44, 95% confidence interval (CI) 8.99-12.11]. This association was substantially attenuated both by increasing temporal delays between CA exposure and schizophrenia diagnosis and by controlling for increasing degrees of familial confounding. Extrapolated discordant MZ pairs suggested that fully controlling for confounding familial factors reduced the association between CA and later schizophrenia to more modest levels (ORs of approximately 3.3 and 1.6 with 3- and 7-year temporal delays respectively). Opiate, sedative, cocaine/stimulant and hallucinogen abuse were also strongly associated with subsequent schizophrenia in the general population. After controlling for familial confounding, only cocaine/stimulant exposure remained associated.
CA has an appreciable causal impact on future risk for schizophrenia. However, population-based estimates of cannabis-schizophrenia co-morbidity substantially overestimate their causal association. Predictions of the cases of schizophrenia that might be prevented by reduced cannabis consumption based on population associations are therefore likely to be considerably overestimated.
尽管已知大麻滥用（CA）与精神分裂症有关，但这种关联的因果性质尚不清楚，前驱效应使其解释变得复杂。
我们从瑞典国家登记数据库中，采用了一种同胞、半同胞和一级表亲比较的相关病例对照设计，并与瑞典普通人群样本进行了对比。使用国际疾病分类代码，将5456例初始诊断为精神分裂症（2000 - 2010年）的个体与5名无精神分裂症的对照进行匹配。我们进一步确定了在大麻滥用方面不一致的一级表亲、半同胞和同胞对，并对不一致的同卵双胞胎（MZ）的结果进行了统计推断。
在瑞典普通人群中，大麻滥用与后期精神分裂症密切相关[比值比（OR）为10.44，95%置信区间（CI）为8.99 - 12.11]。随着大麻滥用暴露与精神分裂症诊断之间时间间隔的增加以及对家族混杂程度控制的增加，这种关联显著减弱。推断出的不一致MZ对表明，完全控制混杂的家族因素会使大麻滥用与后期精神分裂症之间的关联降至更适度的水平（分别有3年和7年时间间隔时，OR约为3.3和1.6）。阿片类、镇静剂、可卡因/兴奋剂和致幻剂滥用在普通人群中也与随后的精神分裂症密切相关。在控制家族混杂因素后，只有可卡因/兴奋剂暴露仍有关联。
大麻滥用对未来患精神分裂症的风险有明显的因果影响。然而，基于人群的大麻 - 精神分裂症共病估计大大高估了它们的因果关联。因此，基于人群关联来预测通过减少大麻消费可能预防的精神分裂症病例很可能被大幅高估。
