Psychiatric traits and intracerebral hemorrhage: A Mendelian randomization study

Abstract

BackgroundPsychiatric traits have been associated with intracerebral hemorrhage (ICH) in observational studies, although their causal relationships remain uncertain. We used Mendelian randomization analyses to infer causality between psychiatric traits and ICH.MethodsWe collected data from genome-wide association studies of ICH (n = 361,194) and eight psychiatric traits among Europeans, including mood swings (n = 451,619), major depressive disorder (n = 480,359), attention-deficit/hyperactivity disorder (n = 53,293), anxiety (n = 459,560), insomnia (n = 462,341), schizophrenia (n = 77,096), neuroticism (n = 374,323), and bipolar disorder (n = 51,710). We performed a series of bidirectional two-sample Mendelian randomization and related sensitivity analyses. A Bonferroni corrected threshold of p < 0.00625 (0.05/8) was considered to be significant, and p < 0.05 was considered suggestive of evidence for a potential association.ResultsMendelian randomization analyses revealed suggestive positive causality of mood swings on ICH (odds ratio = 1.006, 95% confidence interval = 1.001–1.012, p = 0.046), and the result was consistent after sensitivity analysis. However, major depressive disorder (p = 0.415), attention-deficit/hyperactivity disorder (p = 0.456), anxiety (p = 0.664), insomnia (p = 0.699), schizophrenia (p = 0.799), neuroticism (p = 0.140), and bipolar disorder (p = 0.443) are not significantly associated with the incidence of ICH. In the reverse Mendelian randomization analyses, no causal effects of ICH on mood swings (p = 0.565), major depressive disorder (p = 0.630), attention-deficit/hyperactivity disorder (p = 0.346), anxiety (p = 0.266), insomnia (p = 0.102), schizophrenia (p = 0.463), neuroticism (p = 0.261), or bipolar disorder (p = 0.985) were found.ConclusionOur study revealed that mood swings are suggestively causal of ICH and increase the risk of ICH. These results suggest the clinical significance of controlling mood swings for ICH prevention.

Schizophrenia and Types of Stroke: A Mendelian Randomization Study

“…Previous evidence for intracerebral hemorrhage is also limited. One MR study has suggested a lack of association between schizophrenia and intracerebral hemorrhage, 42 and another study found little association between second‐generation antipsychotic drugs and intracerebral hemorrhage among patients with schizophrenia. 36 If there exists an explanation in favor of our finding, it may be the more common use of anticoagulant drugs due to cardiac problems (eg, atrial fibrillation) among patients with schizophrenia.…”

Association Between Major Depressive Disorder and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study

“…In contrast, we used a more stringent threshold of p < 5E-08 when examining the three pairwise associations between MDD and CSVD clinical phenotypes. Furthermore, a recent MR in 2023 examined the risk association between MDD and ICH and found no causal relationship (Wang et al, 2022). Because we used larger and more comprehensive GWAS datasets for both MDD and CSVD clinical phenotypes, our findings may provide more reliable evidence of an association between the two.…”

Mood swings are causally associated with intracranial aneurysm subarachnoid hemorrhage: A Mendelian randomization study

“…In addition, positive psychological health could reduce the incidence of stroke (Lambiase et al., 2015 ). A recent MR analysis demonstrated that genetically determined mood swings were causally related to the risk of intracerebral hemorrhage (ICH) (Wang et al., 2022 ). IA and aSAH share up to 50% genetic characteristics with ICH (Bakker et al., 2020 ; Mayerhofer et al., 2022 ; Tromp et al., 2014 ; Wahab et al., 2019 ; Yamada et al., 2018 ).…”