Anderson Chloe, Carmichael Jai, Hicks Amelia J, Burke Richard, Ponsford Jennie
Monash-Epworth Rehabilitation Research Centre, Epworth HealthCare, Melbourne, Australia; Turner Institutes for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
School of Biological Sciences, Monash University, Clayton, Victoria, Australia.
J Neurotrauma. 2023 Feb;40(3-4):326-336. doi: 10.1089/neu.2022.0226. Epub 2022 Sep 27.
Emotional distress is common following moderate-severe traumatic brain injury (TBI) and is associated with poorer post-injury outcomes. Previously investigated sociodemographic, psychological, and injury-related factors account for only a small proportion of variance in post-TBI emotional distress, highlighting a need to consider other factors such as genetic factors. The apolipoprotein E gene (APOE) has been commonly studied in the TBI literature, with the ɛ4 allele linked to worse neuronal repair and recovery. Few studies have investigated the potential relationship between APOE ɛ4 and emotional distress after moderate-severe TBI, and results have been varied. We examined whether APOE ɛ4 was associated with emotional distress 1 year following moderate-severe TBI, and whether this relationship was moderated by age, sex, and TBI severity (as indexed by the duration of post-traumatic amnesia [PTA]). Moderate-severe TBI survivors provided saliva samples following inpatient admission to a TBI rehabilitation hospital. They completed a self-report measure of emotional distress, the Hospital Anxiety and Depression Scale (HADS), at a follow-up interview ∼1 year post-injury. Complete genetic and follow-up data were available for 441 moderate-severe TBI survivors (mean age = 39.42 years; 75% male). We constructed a linear regression model that included APOE ɛ4 carriage status (carrier vs. non-carrier) and interactions with age, sex, and TBI severity (APOE × age, APOE × sex, APOE × age × sex, and APOE × PTA duration) to predict total score on the HADS, while covarying for the main effects of age, sex, PTA duration, and previous head injury. There was a significant main effect of APOE ɛ4, whereby ɛ4 carriers reported emotional distress than non-carriers ( = 0.04). However, we also found a significant interaction with age such that APOE ɛ4 carriers reported increasingly emotional distress with age compared with non-carriers ( = 0.01). A sensitivity analysis ( = 306) suggested that the APOE × age interaction, and main effects of age and previous head injury, were not unique to individuals with pre-injury mental health problems ( = 136). However, the main effect of APOE ɛ4 was no longer significant when individuals with pre-injury mental health problems were removed. Our findings highlight the importance of considering moderation of genetic associations, suggesting that APOE ɛ4 may be a risk factor for emotional distress specifically among older survivors of moderate-severe TBI. If these findings can be independently replicated, APOE ɛ4 carriage status, interpreted in the context of age, could be incorporated into risk prediction models of emotional distress after moderate-severe TBI, enhancing targeted early detection and intervention efforts.
中重度创伤性脑损伤（TBI）后，情绪困扰很常见，且与伤后较差的预后相关。先前研究的社会人口统计学、心理和损伤相关因素仅占TBI后情绪困扰变异的一小部分，这凸显了考虑其他因素（如遗传因素）的必要性。载脂蛋白E基因（APOE）在TBI文献中已得到广泛研究，其中ɛ4等位基因与较差的神经元修复和恢复相关。很少有研究调查中重度TBI后APOEɛ4与情绪困扰之间的潜在关系，结果也各不相同。我们研究了APOEɛ4是否与中重度TBI后1年的情绪困扰相关，以及这种关系是否受到年龄、性别和TBI严重程度（以创伤后遗忘症[PTA]持续时间为指标）的调节。中重度TBI幸存者在入住TBI康复医院后提供唾液样本。他们在伤后约1年的随访访谈中完成了一项情绪困扰的自我报告测量，即医院焦虑抑郁量表（HADS）。441名中重度TBI幸存者（平均年龄=39.42岁；75%为男性）有完整的基因和随访数据。我们构建了一个线性回归模型，该模型包括APOEɛ4携带状态（携带者与非携带者）以及与年龄、性别和TBI严重程度的相互作用（APOE×年龄、APOE×性别、APOE×年龄×性别和APOE×PTA持续时间），以预测HADS的总分，同时对年龄、性别、PTA持续时间和既往头部损伤的主要影响进行协变量调整。APOEɛ4有显著的主效应，即ɛ4携带者报告的情绪困扰比非携带者更多（=0.04）。然而，我们还发现与年龄有显著的相互作用，即与非携带者相比，APOEɛ4携带者随着年龄增长报告的情绪困扰越来越多（=0.01）。一项敏感性分析（=306）表明，APOE×年龄的相互作用以及年龄和既往头部损伤的主效应并非伤前有心理健康问题的个体所特有（=136）。然而，当去除伤前有心理健康问题的个体时，APOEɛ4的主效应不再显著。我们的研究结果强调了考虑基因关联调节作用的重要性，表明APOEɛ4可能是中重度TBI老年幸存者情绪困扰的一个风险因素。如果这些发现能够独立复制，在年龄背景下解释的APOEɛ4携带状态可以纳入中重度TBI后情绪困扰的风险预测模型，加强有针对性的早期检测和干预措施。
