Psychological Well-Being and Spinal Cord Injury Recovery: A Two-Way Street?

Abstract

Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease psychological well-being remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in well-being. We used a battery of established behavioral tests to assess depression and anxiety in contused rats and (1) characterized psychological well-being as a function of SCI severity, (2) examined peripheral (serum) and central (hippocampi and spinal cord) inflammation in relation to psychological well-being post SCI, and (3) explored whether social enrichment, as a modulator of psychological well-being, could improve overall recovery post SCI, by housing contused animals either alone, or with an injured or an intact cagemate. Following SCI, the contused subjects showed one of three profiles: depression-like, depression- and anxiety-like, or no signs of decreased psychological well-being. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. Social enrichment, in the form of group housing, did not improve psychological well-being post SCI. Depression- and anxiety-like signs were found in all group housing conditions. Unexpectedly, we found that the intact animals housed with contused subjects showed depression- and anxiety-like signs similar to those of contused subjects, indicating that their psychological well-being was affected by the presence of an injured cagemate. This is reminiscent of the caregiver effect in humans, specifically the manifestation of symptoms of depression in individuals who care for patients suffering with a chronic illness, such as SCI. These experiments demonstrate that the depression and anxiety patients experience following spinal cord injury is not due solely to psychosocial factors, but may also, in part, result from increased immune activation following the injury.