Jorge Ricardo E, Acion Laura, Starkstein Sergio E, Magnotta Vincent
Department of Psychiatry, University of Iowa, Iowa City, IA 52242-1000, USA.
Biol Psychiatry. 2007 Aug 15;62(4):332-8. doi: 10.1016/j.biopsych.2006.07.024. Epub 2006 Nov 21.
Recent evidence from clinical studies and animal models of traumatic brain injury (TBI) suggest that neuronal and glial loss might progress after the initial insult in selectively vulnerable regions of the brain such as the hippocampus. There is also evidence that hippocampal dysfunction plays a role in the pathogenesis of mood disorders. We examined the relationship between hippocampal damage and mood disorders after TBI and the effect of hippocampal atrophy on the outcome of TBI patients.
The study group consisted of 37 patients with closed head injury who were evaluated at baseline and at 3, 6, and 12 months after trauma. Psychiatric diagnosis was made with a structured clinical interview and DSM-IV criteria. Quantitative magnetic resonance imaging scans were obtained at 3-months follow-up.
Patients with moderate to severe head injury had significantly lower hippocampal volumes than patients with mild TBI. Patients who developed mood disorders had significantly lower hippocampal volumes than patients without mood disturbance. Furthermore, there was a significant interaction between mood disorders diagnosis and severity of TBI, by which patients with moderate to severe TBI who developed mood disorders had significantly smaller hippocampal volumes than patients with equivalent severe TBI who did not develop mood disturbance. Finally, reduced hippocampal volumes were associated with poor vocational outcome at 1-year follow-up.
Our findings are consistent with a "double-hit" mechanism by which neural and glial elements already affected by trauma are further compromised by the functional changes associated with mood disorders (e.g., the neurotoxic effects of increased levels of cortisol or excitotoxic damage resulting from overactivation of glutaminergic pathways). Finally, patients with greater hippocampal damage were less likely to return to a productive life 1 year after trauma.
创伤性脑损伤(TBI)的临床研究和动物模型的最新证据表明,在脑的选择性易损区域,如海马体,神经元和神经胶质细胞的损失可能在初始损伤后仍会进展。也有证据表明海马体功能障碍在情绪障碍的发病机制中起作用。我们研究了TBI后海马体损伤与情绪障碍之间的关系,以及海马体萎缩对TBI患者预后的影响。
研究组由37例闭合性颅脑损伤患者组成,在基线以及创伤后3个月、6个月和12个月进行评估。采用结构化临床访谈和DSM-IV标准进行精神科诊断。在3个月随访时进行定量磁共振成像扫描。
中度至重度颅脑损伤患者的海马体体积明显低于轻度TBI患者。发生情绪障碍的患者海马体体积明显低于无情绪障碍的患者。此外,情绪障碍诊断与TBI严重程度之间存在显著交互作用,即发生情绪障碍的中度至重度TBI患者的海马体体积明显小于同等严重程度但未发生情绪障碍的TBI患者。最后,海马体体积减小与1年随访时职业预后不良相关。
我们的研究结果与“双重打击”机制一致,即已经受到创伤影响的神经和神经胶质成分会因与情绪障碍相关的功能变化(例如,皮质醇水平升高的神经毒性作用或谷氨酸能通路过度激活导致的兴奋性毒性损伤)而进一步受损。最后,海马体损伤更严重的患者在创伤后1年恢复正常生活的可能性较小。