Association Between Traumatic Spinal Cord Injury and Psychiatric Disorders,Mental Illness and Dementia: A Systematic Review and Meta-Analysis

Abstract

Study Design

Systematic review and meta-analysis.

Objectives

Meta-analysis was used to evaluate the association between traumatic spinal cord injury and mental disorders, psychological disorders, and dementia onset, and to provide a scientific basis for the prevention of traumatic spinal cord injury.

Methods

A computerized search of English databases such as PubMed, Web of Science, Embase, and other English databases for retrospective studies on the associations between traumatic spinal cord injury and psychiatric disorders, mental illnesses, and dementia was carried out within a timeframe of from the creation of the databases to 7 April 2024, and two researchers independently carried out the screening of the literature, extracted and collated the baseline and endpoint indicators, and assessed the quality of the literature, before conducting meta-analysis by using the Stata 15.1 software for meta-analysis.

Results

Eleven papers were included, and meta-analysis showed that patients with traumatic spinal cord injury were at significantly higher risk of anxiety, depression, psychosis, dementia, insomnia, adjustment disorders, mood disorders, personality disorders, alcohol-related disorders, substance-use disorders, adjustment reactions, drug dependence, and central pain relative to patients with nontraumatic spinal cord injury (P < 0.05); there was no significant correlation between traumatic spinal cord injury and PTSD.

Conclusions

Traumatic spinal cord injury may increase the risk of developing anxiety, depression, psychiatric disorders, and dementia; with national regional differences in the risk of developing anxiety. Clinical staff should be alert to the possibility of co-existence of psychiatric disorders, psychological disorders and dementia when diagnosing patients with traumatic spinal cord injury.

Keywords

spinal cord injury psychiatric disorders mental illness dementia meta-analysis

Introduction

Traumatic spinal cord injury (TSCI) is an acute, life-threatening condition that affects health, physical functioning, social activities, and quality of life, causing irreversible physical damage, paraplegia, and even life-threatening injuries.¹ Spinal cord injuries resulting from traumatic events usually result in varying degrees of pain, disability, loss of function, and autonomic dysfunction with symptoms such as paralysis of the casual muscles below the level of the lesion and loss of sensation associated with reduced mobility and functional independence.² In addition, patients with TSCI may be prone to complications such as pneumonia, sepsis, urinary tract infections,^3,4 heart disease and chronic pain, this may increase the severity of their clinical symptoms. Although survival rates and life expectancy for TSCI patients have improved over the years as a result of improvements in care, rehabilitative medicine, and clinical research, the disabilities and dysfunctions that exist in the majority of patients continue to cause various types of emotional distress in their subsequent lives. After spinal cord injury, in addition to physical injury, there may also be psychological disorders.⁵ Psychiatric sequelae of TSCI include dementia, anxiety, depression, P osttraumatic stress disorders, sleep disorders and substance-related disorders et al.⁶

Le and Dorstyn⁷ noted that the prevalence of anxiety after SCI as estimated by self-report measures ranged from 15%–32%.Williams and Murry⁸ estimated the prevalence of post-SCI depression to be approximately 18.7%-26.3%. Craig et al⁹ conducted a longitudinal assessment of psychological disorders in patients with SCI 6 months after discharge from hospital. Studies have found that the incidence of psychological disorders is 17 to 25%. Thus, it is extremely important to analyse the mental and psychological characteristics of TSCI patients. Adults with TSCI have a higher prevalence of cardiometabolic¹⁰ and psychological disorders,¹¹ and both are considered major risk factors for dementia formation. To date, there are no large-scale national or international studies investigating the relationship between TSCI and dementia. Due to the different treatment modalities as well as the healthcare system, the association between the TSCI and mental disorders, mental illness and dementia varies considerably across countries. Therefore, this paper collects relevant literatures in recent years, For the first time, meta-analysis was used to demonstrate whether patients with TSCI were significantly associated with the risk of psychiatric disorders, mental illness and dementia. Informing the effective management of patients with psychiatric disorders, mental illness and dementia symptoms, and to provide higher level of evidence-based medicine evidence for clinical practice and prevention.

Methods

Search Strategy and Selection Criteria

This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews (number CRD42023445963). We selected relevant studies published between creation, and April 7, 2024, by searching PubMed, Web of Science, Embase, and other English databases. Collecting retrospective cohort study on the correlation between traumatic spinal cord injury and mental disorders, psychological disorders and dementia, Language limited to English. The complete search used for PubMed was: (see Annex A). We considered all potentially eligible studies for review, irrespective of the primary outcome or language. We also did a manual search, using the reference lists of key articles published in English.

Study Selection and Data Extraction

We regarded studies as eligible for inclusion: (1) The study group consisted of patients with traumatic spinal cord injury¹² and the control group consisted of patients with other health conditions without traumatic spinal cord injury; (2) retrospective cohort study; (3) The study analysed the difference in risk of psychiatric disorders, mental illness or dementia between TSCI and non-TSCI patients; It can provide sufficient data for evidence synthesis and statistical analysis. The age of the patient is not limited, and the language of publication is limited to English. Exclusion criteria were as follows: (1) The full text cannot be obtained or the original research data cannot be extracted; (2) Case reports, Article Summary, Conference papers, reviews, meta-analyses; (3) Duplicate published literature; (4) animal experimentation.

We use EndNote X9 for document management. The literature was independently screened by 2 researchers trained in evidence-based medicine methodology. Further discussion to resolve when screening results differ. Literature screening process: Exclude clearly irrelevant literature after reading the title and abstract, further strictly compare the inclusion and exclusion criteria to read through the full text and decide whether the relevant literature is included in the meta-analysis, the extracted data included author, country, age, publication time, sample size, study type, outcome indicators, follow-up time, etc.

The Newcastle-Ottawa Scale (NOS scale) was used independently by 2 investigators to score the quality of the retrospective cohort study, The evaluation included 3 aspects: selection, comparability and exposure, totalling 9 items. The total score of the scale ranges from 0 to 9, with 0 to 3 as low quality, 4 to 6 as medium quality, and 7 to 9 as high quality. The total score of the scale ranges from 0 to 9, with 0 to 3 being low quality, 4 to 6 being medium quality, and 7 to 9 being high quality. Each entry is evaluated by “Yes”, “No” and “Unclear”, with “Yes” scoring 1, “No” and “Unclear” scoring 0. A score of 1 is assigned to “Yes” and 0 to “No” and “Unclear”. Consult with a third person when evaluation results are not Agreement is reached.

Statistical Analysis

We used Stata15.1 software for meta-analysis. Using rate as the effect analysis statistic and providing its 95% CI. Information on dichotomous variables was expressed as ratio (OR or HR) and its 95% CI. Heterogeneity was tested by observing Q and I², when heterogeneity was small (I² ≤ 50% or P > 0.1) a fixed effects model was chosen for the analysis; Literature with large heterogeneity (I² > 50% or P ≤ 0.1) was analysed using a random effects model and the literature was re-read carefully to find and analyse sources of heterogeneity. If there is significant heterogeneity with statistically significant differences in phenomenon we analysed the sources of heterogeneity using subgroup analyses; Sensitivity analyses were used to observe the extent to which the exclusion of literature on the combined effect sizes after the merger, using sensitivity analyses to observe the extent to which the exclusion of literature; To further study heterogeneity, We performed sensitivity analyses, meta-regression, and subgroup analyses to evaluate the outcome data from standardized meta-analyses and associations. If the source of heterogeneity cannot be explained, descriptive analysis can be used to analyze.

Results

Literature Screening Results

Our first search yielded a total of 6553 articles, including 3075 articles in PubMed and 3305 articles in Web of Science, Embase 173 articles. Removing duplicates gives 5786 articles. Excluding 5694 articles after reading the title and abstract. The remaining 92 articles, after further reading the full text, were finally included in 11 literatures. Our process for screening 11 studies based on inclusion and exclusion criteria, See Figure 1.

Figure 1.

Literature screening process.

Characteristics and Quality Assessment of the Included Literature

Among the 11 studies,^6,13-22 3 were from Taiwan, 4 from the United States, 3 from Australia, and 1 from Switzerland; The maximum sample size was 9018/1474232 and the minimum sample size was 31/31; Age ≥17 years old, maximum age 79 years old; In 11 studies, follow-up was between 1 and 7 years. The basic characteristics of specific literatures are shown in Table 1. The quality evaluation results of included studies are shown in Table 2.

Table 1.

Information of Included Studies (n = 11).

Included in the Research	Year of Publication	Country/Area	Sample Size (TSCI/ Non-TSCI)	Type of Study	Age	Outcome Indicator	Follow-Up Time
Sher-Wei Lim¹³	2017	Taiwan	3556/3556	Cohort study	NA	Anxiety or depression	3
MarkD. Peterson¹⁴	2022	America	9018/1474232	Cohort study	>18	Psychological morbidity	5
Senior Lecturer¹⁵	1994	Australia	31/31	Cohort study	≥17	Anxiety or depression	2
KMHancock¹⁶	1993	Australia	41/41	Cohort study	≥17	Anxiety or depression	1
CE Migliorini¹⁷	2009	Australia	443/62	Cohort study	≥18	Anxiety or depression	…
M Kreuter¹⁸	1998	Switzerland	167/264	Retrospective study	19-79	Anxiety or depression	…
MarkD. Peterson¹⁹	2019	America	10006/779545	Cohort study	≥18	Psychological morbidity	…
MarkD. Peterson⁶	2020	America	6847/857245	Cohort study	≥18	Psychological morbidity	…
Elham Mahmoudi, PhD²⁰	2021	America	7019/916516	Cohort study	≥45	Dementia	4
Shih-Wei Huang²¹	2017	Taiwan	1038/5190	Cohort study	≥18	Dementia	7
Tian-Shin Yeh²²	2018	Taiwan	9527/555390	Cohort study	NA	Dementia	3

Table 2.

Quality Evaluation of the Included Qualitative Literature (n = 11).

Study	Selection				Comparability	Exposure			Scores
Study	Adequ-Ate definit-ion of Cases	Representativeness of the Cases	Selec-tion of Contr-ols	Defini-tion of Contro-ls	Control for Important Factor	Ascertai-nment of Exposure	Same Method of Ascertain-ment for Cases and Controls	Non- Responserate	Scores
Sher-Wei Lim	⭐	⭐	⭐	⭐	⭐⭐	⭐	…	⭐	8
MarkD. peterson	⭐	⭐	⭐	⭐	⭐	⭐	⭐	⭐	8
Senior lecturer	⭐	⭐	…	⭐	⭐⭐	⭐	…	⭐	7
KMHancock	⭐	⭐	⭐	⭐	⭐	⭐	…	⭐	7
CE Migliorini	⭐	⭐	⭐	⭐	⭐	⭐	…	…	6
MKreuter	⭐	⭐	⭐	⭐	⭐⭐	⭐	…	…	7
MarkD. peterson	⭐	⭐	⭐	⭐	⭐⭐	⭐	…	…	7
MarkD. peterson	⭐	⭐	⭐	⭐	⭐⭐	⭐	…	⭐	8
Elham Mahmoudi, PhD	⭐	⭐	⭐	⭐	⭐	⭐	⭐	⭐	8
Shih-Wei Huang	⭐	⭐	⭐	⭐	⭐	⭐	…	⭐	7
Tian-Shin Yeh	⭐	⭐	⭐	⭐	⭐⭐	⭐	…	…	7

A maximum of 2 stars can be allotted in this category, 1 for age, the other for other controlled factors.*

Meta-Analysis Results

Relationship Between TSCI Patients and Anxiety

We identified a total of 6 studies reporting dichotomous data analysing the association between TSCI patients and anxiety. There was significant heterogeneity among the references I² = 95.5%. The random effects model was used for analysis. The results showed that patients with TSCI had a significantly higher risk of anxiety relative to non-TSCI patients (OR = 1.77, 95 %CI: 1.512∼2.072), P < 0.001; The forest map is shown in Figure 2. Our sensitivity analysis of the data did not reveal sources of heterogeneity. By meta regression of age, country and other factors, it is found that age is the source of heterogeneity. Meta-analyses of risk data suggest the same results, (OR = 1.329, 95 %CI: 0.986∼1.790), P = 0.062.

Figure 2.

A meta-analysis of the association between TSCI and risk of anxiety.

We analyse countries in subgroups, The results show that in the Australian group, there was no significant difference in the risk of anxiety in TSCI patients relative to non-TSCI patients (P = 0.407); In the US group, results showed that TSCI patients had a significantly higher risk of anxiety relative to non-TSCI patients (P < 0.001). See Figure 3 for details. Subgroup analysis by age showed that patients with TSCI had a significantly higher risk of developing anxiety compared with non-TSCI patients in the age groups ≥17 years, >18 years, and ≥45 years. See Figure 4 for details.

Figure 3.

Subgroup analysis of country differences and risk of anxiety.

Figure 4.

Subgroup analysis of age vs risk of anxiety.

Relationship Between TSCI Patients and Depression

We identified a total of 5 studies that evaluated the correlation between patients with TSCI and depression. There was significant heterogeneity among literatures I² = 94.2%. The random effects model was used for analysis, The results showed that TSCI patients had a significantly higher risk of depression compared to non-TSCI patients. Patients with TSCI had a significantly higher risk of depression compared to non-TSCI patients (OR = 3.298,95 %CI: 2.622∼4.150), P < 0.001. We performed sensitivity analyses and found CE Migliorini¹⁷ to be a source of heterogeneity, We remove this piece of literature, The meta-analysis showed that I² = 53.8%, (OR = 4.219,95 %CI: 3.929∼4.530), P < 0.001. The forest map is shown in Figure S1.

Relationship Between TSCI Patients and Psychological Morbidity

We conclude that a total of 4 studies reporting dichotomous data. Assessing the association between TSCI patients and psychological morbidity, there was significant inter-reference heterogeneity I² = 99%. Analysed using a random effects model, The results showed that patients with TSCI had a significantly higher risk of developing psychological disorders relative to non-TSCI patients (OR = 2.736, 95 %CI: 2.166∼3.456), P < 0.001. The forest map is shown in Figure S2. The meta-analysis of the risk data suggested the same result, (OR = 2.190, 95 %CI: 1.218∼3.938), P = 0.009. If we performed subgroup analyses by one-way multifactorial, The results showed that in the multifactorial group, patients with TSCI had a significantly higher risk of developing psychological disorders relative to non-TSCI patients (OR = 2.369, 95 %CI: 1.115∼5.036), P = 0.02; In the univariate group, patients with TSCI had a significantly higher risk of mental illness relative to non-TSCI patients (OR = 1.73, 95 %CI: 1.600∼1.870), P < 0.001.

Relationship Between TSCI Patients and Dementia

It totalled 7 studies assessing the correlation between TSCI patients and dementia, There was significant inter-reference heterogeneity I² = 97.3%.Analysed using a random effects model, The results showed that TSCI patients had a significantly higher risk of dementia relative to non-TSCI patients (OR = 3.207, 95 %CI: 2.485∼4.137), P < 0.001,The forest map is shown in Figure S3. Our sensitivity analyses did not reveal sources of heterogeneity. By meta regression of age, country and other factors, no heterogeneity was found.

When we analyse subgroups by country, The results showed that the risk of dementia was significantly higher in TSCI patients relative to non-TSCI patients in both the Chinese and US patient groups (P < 0.001). See Figure S4 for details.

Relationship Between TSCI Patients and Other Outcome Measures

Our analysis of the results showed no significant difference between TSCI patients and PTSD; Patients with TSCI were significantly different from those with insomnia, adjustment disorders, mood disorders, personality disorders, alcohol-related disorders, substance-use disorders, adjustment reactions, drug dependence, and central pain. See Table 3 for details.

Table 3.

Association Between Patients With TSCI and Other Outcome Measures.

Outcome Indicator	Effect Model	OR (95 %CI)	P-Value	I² (%)
PTSD	Random effects model	1.615 (0.926, 2.818)	0.091^*	96.8
Insomnia	Random effects model	1.799 (1.473, 2.198)	0.000^*	96.8
Adjustment disorders	Fixed effects model	1.754 (1.632, 1.885)	0.000^*	0.0
Mood disorders	Random effects model	2.834 (2.422, 3.316)	0.000^*	95.8
Personality disorders	Random effects model	2.691 (2.022, 3.582)	0.000^*	76.3
Alcohol-related disorders	Random effects model	4.47 (1.594, 12.534)	0.004^*	99.6
Substance-use disorders	Random effects model	3.653 (2.020, 6.605)	0.000^*	98.2
Djustment reactions	Random effects model	1.881 (1.167, 3.033)	0.009^*	98.6
Drug dependence	Random effects model	3.59 (2.427, 5.309)	0.000^*	93.8
Central pain	Random effects model	19.573 (1.393,275.002)	0.027^*	97.3

Discussion

Correlation Between TSCI and Anxiety

This study assessed the correlation between TSCI patients and anxiety, The results of meta-analysis showed that the risk of anxiety in TSCI patients was significantly higher than that in control group, there was a significant correlation between TSCI and the risk of anxiety. This may be related to the fear of poor prognosis and affect the quality of life of patients, If TSCI can not be timely and effective treatment, Not only have a huge physical and mental burden on the patients themselves, but also cause a considerable degree of economic burden on the family and society, it causes patients to have different levels of anxiety. The present results are similar to the 27% hospital incidence and 29% community incidence that have been reported.⁷ Subgroup analysis showed that risk assessment results did not change significantly in most subgroups, It is suggested that the results of meta-analysis are stable and reliable. Studies have also shown that TSCI is associated with the risk of mood disorders and other psychiatric disorders, rehabilitation was associated with a reduced risk of these disorders in the TSCI cohort.²³

Correlation Between TSCI and Depression

The World Health Organization conducted a survey of 17 countries and found that: One in 20 people have been depressed at 1 time or another, It is estimated that 350 million people in the world suffer from depression²⁴ With the development of society and the acceleration of the pace of life, more and more people are stressed, tired and stressed at work, psychological and social problems are increasingly affecting the nation’s physical health. SCI patients, as a group of people who cannot return to social life in a short time, After injury, they are more likely to have a series of new problems such as physical, psychological, employment and social reintegration, The incidence of SCI varies from country to country, Among them, developed countries represented by the United States have the highest incidence, That’s 906 people per million.²⁵ Therefore, this study evaluated the association between TSCI patients and depression, The results showed that patients with TSCI had a significantly higher risk of anxiety than those in the control group, Some scholars have reported that patients with spinal cord injury have a higher incidence of depression, depressive mood is closely related to functional status.²⁶ At the same time, studies²⁷ have shown that individuals still have PTSD, depression and other mental disorders 8.5 years after experiencing sudden catastrophic events, It affects the social function of the individual. This is consistent with the results of this study.

Correlation Between TSCI and Mental Illness

This study evaluated the association between patients with TSCI and mental illness, The results showed that TSCI patients were at a significantly higher risk of developing psychological disorders than controls, It has been documented that adults with TSCI have a higher prevalence and risk of common psychological disorders compared to those without SCI.¹⁴ Patients with TSCI have poorer mental health compared to the general population. People with spinal cord injuries exhibit unique lifestyle and socio-economic factors that are associated with poorer mental health and increased suicidal thoughts.²⁸ Health professionals need to work to promote the development of early interventions to reduce the risk of chronic central and neuropathic pain as well as the risk of the onset or progression of psychological morbidity in this high-risk population. Due to the long duration of spinal cord injuries and the low rate of complete healing, Patients are more likely to have adverse psychological, Establishing effective nurse-patient communication, grasping the patient’s psychological state, mobilising the social support system, and giving timely and effective psychological care interventions can improve the patient’s adverse psychological.²⁹

Correlation Between TSCI and Dementia

The etiology and pathogenesis of dementia have not been elucidated, and the characteristic pathological changes can be classified into 3 types: neurofibrillary tangles, senile plaques, and granular vacuolated lesions.³⁰ Our review of the literature found no significant correlation between patients with SCI and Alzheimer’s disease, However, the risk of other types of dementia was higher in SCI patients than in controls. In conclusion, patients with SCI are at high risk of developing dementia, and effective dementia prevention strategies are recommended for comprehensive SCI care.²¹ This study evaluated the association between the TSCI patients and dementia, and the results showed that the TSCI patients have a significantly higher risk of developing dementia than the controls. Thus, adults with TSCI have a higher risk of dementia. We believe that improved clinical screening and early interventions aimed at maintaining cognitive function are critical for this patient.

Limitations and Perspectives of This Study

Most of the articles included in this study were rated around 7 out of 10, and the quality of the literature was high. This paper is 1 of the relatively few meta-analyses that have examined the association between the TSCI and psychiatric disorders, mental illness and dementia. However, many shortcomings remain, (1) Although the results of this study showed a significant correlation between the risk of psychiatric disorders, psychological disorders and dementia onset and the TSCI, there was significant heterogeneity between the findings of the included literature. (2) A portion of the original literature included in this study did not define and differentiate the severity of TSCI. Therefore, future high-quality, prospective studies are still needed to further elucidate the relationship between TSCI severity and the risk of developing dementia. (3) There is a lack of national and international studies on large samples exploring the TSCI and the risk of developing dementia, The number of papers included in this study that were able to extract data for analysis was small, and more studies are needed to validate the above factors. We recommend further large-sample, multi-centre, high-quality prospective cohort studies or clinical trials in the future, to explore in depth the relationship between TSCI and the risk of developing mental disorders, mental illnesses and dementia, and to provide more reliable evidence to support the early identification and effective management of psychological and psychiatric complications.

Brief Summary

Traumatic spinal cord injury may increase the risk of anxiety, depression, mental illness and dementia, with national differences in the risk of anxiety. Recommendations for this phenomenon: (1) Nursing staff need to communicate with patients frequently, psychological counselling for patients, explaining to patients the successful cases of treatment, which will help guide patients out of negative emotions, increase patients’ compliance with treatment, and thus enhance the treatment effect of patients.³¹ (2) We should assist patients to enhance their level of knowledge about TSCI and its rehabilitation, and motivate them to actively seek and accept support from all aspects of society. (3) Family members and healthcare professionals implement all-round supervision of the patient, which contributes to the patient’s functional recovery. Therefore, understanding the association between TSCI and mental disorders, mental illnesses and dementia in populations of all ages and in different regions of the world across countries, we can target prevention and control, which is of great significance in reducing the incidence of TSCI, lowering the rate of disability, and increasing the rate of social reintegration of patients.

Supplemental Material

Supplemental Material - Association Between Traumatic Spinal Cord Injury and Psychiatric Disorders, Mental Illness and Dementia: A Systematic Review and Meta-Analysis

Supplemental Material for Association Between Traumatic Spinal Cord Injury and Psychiatric Disorders, Mental Illness and Dementia: A Systematic Review and Meta-Analysis by Tiantian Wang, Mengjiao Bai, Huimin Du, and Yuantong Zang in Global Spine Journal.

Footnotes

Author Contributions

All authors contributed to the study conception and design. Writing - original draft preparation: Tiantian Wang ; Writing - review and editing: Yuantong Zang; Conceptualization: Mengjiao Bai; Methodology: Tiantian Wang; Formal analysis and investigation: Tiantian Wang; Funding acquisition: Yuantong Zang; Resources: Yuantong Zang; Supervision: Huimin Du, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by 2022 Autonomous Region Health Science and Technology Programme Project [Grant numbers 202202211].

ORCID iD

Yuantong Zang

Supplemental Material

Supplemental material for this article is available online.

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