Post-traumatic stress disorder in patients with amyotrophic lateral sclerosis and its correlation with clinical symptoms

Abstract

Background:Patients with amyotrophic lateral sclerosis (ALS) also exhibit non-motor symptoms; however, the relationship between the disease and post-traumatic stress disorder (PTSD) is unclear.
Objective:This study aimed to determine the frequency of PTSD and its correlation with motor disability and cognitive impairment in patients with ALS.
Methods:PTSD was diagnosed according to the Diagnostic and Statistical Manual V (DSM-V), and its severity was quantified using the PTSD Checklist for DSM-5 (PCL-5) in 106 patients with ALS and 55 healthy controls (HCs). Patients were assessed for clinical symptom severity by the revised ALS Functional Rating Scale (ALSFRS-R). Cognitive and behavioral functioning were assessed by the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Frontal Behavioral Inventory (FBI), the Hamilton Anxiety Rating Scale (HARS), and the Hamilton Depression Rating Scale (HDRS) scales.
Results:PTSD was diagnosed in 32 (30.2 %) patients with ALS. Compared to patients with ALS and without PTSD (ALS-NP), patients with ALS and PTSD (ALS-P) had significantly lower ALSFRS-R and higher FBI scores (P < 0.05). Moreover, in the ALS-P patients, the PCL-5 scores significantly correlated with the ALSFRS-R scores (r = − 0.302; P = 0.03) and FBI scores (r = 0.421; P = 0.02).
Conclusion:Our findings suggest that PTSD is a common condition in patients with ALS.

Keywords

Amyotrophic lateral sclerosis / Post-traumatic stress disorder / DSM-V / ALSFRS-R

Ethics approval

The study followed the principles of the Declaration of Helsinki as revised in 2013. This study was approved by the Research Ethics Committee of the School of Medicine of Shandong University. The ethics committee approval number is KYLL-202310-016-2. Participant information was collected only after all the patients and HCs were made aware of the purpose of the study and provided their written informed consent.

Funding

This work was supported by the China Postdoctoral Science Foundation (Grant no.: 2020M672067) and National Natural Science Foundation of China (Grant no.: NSFC82001354).

CRediT authorship contribution statement

Shuangwu Liu: Conceptualization, Data curation, Validation, Writing-original draft. Tianrui Wena: Conceptualization, Validation, Writing-review and editing. Jun Zhua: Conceptualization, Validation, Writing-review and editing. Pengfei Lin: Data curation, Writing-review and editing. Xiaohan Sun: Investigation, Writing-review and editing. Lejin Yang: Conceptualization, Investigation. All the authors have read and approved the final version of this manuscript.

Declaration of Competing Interest

The authors declared none conflicts of interest.

Acknowledgements

We thank the ALS patients and health controls for them participate in this study.

Data availability

The anonymized data presented in this article are available upon request from a qualified investigator after review by the corresponding author. Final approval will be granted by the Research Ethics Committee of the School of Medicine at Shandong University.

References

[1] Swinnen B, Robberecht W. The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol. 2014; 10(11):661-670. https://doi.org/10.1038/nrneurol.2014.184

[2] Taylor JP, Brown Jr RH, Cleveland DW. Decoding ALS: from genes to mechanism. Nature. 2016; 539(7628):197-206. https://doi.org/10.1038/nature20413

[3] Feldman EL, Goutman SA, Petri S, et al. Amyotrophic lateral sclerosis. Lancet. 2022; 400(10360):1363-1380. https://doi.org/10.1016/S0140-6736(22)01272-7

[4] Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014; 17(1):17-23. https://doi.org/10.1038/nn.3584

[5] Miller TM, Cudkowicz ME, Genge A, et al. Trial of Antisense Oligonucleotide Tofersen for SOD1ALS. N Engl J Med. 2022; 387(12):1099-1110. https://doi.org/10.1056/NEJMoa2204705

[6] Niedermeyer S, Murn M, Choi PJ. Respiratory Failure in Amyotrophic Lateral Sclerosis. Chest. 2019; 155(2):401-408. https://doi.org/10.1016/j.chest.2018.06.035

[7] Eisen A, Braak H, Del Tredici K, Lemon R, Ludolph AC, Kiernan MC. Cortical influences drive amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017; 88(11):917-924. https://doi.org/10.1136/jnnp-2017-315573

[8] Pitman RK, Rasmusson AM, Koenen KC, et al. Biological studies of post-traumatic stress disorder. Nat Rev Neurosci. 2012; 13(11):769-787. https://doi.org/10.1038/nrn3339

[9] Kunimatsu A, Yasaka K, Akai H, Kunimatsu N, Abe O. MRI findings in posttraumatic stress disorder. J Magn Reson Imaging. 2020; 52(2):380-396. https://doi.org/10.1002/jmri.26929

[10] Cordova MJ, Riba MB, Spiegel D. Post-traumatic stress disorder and cancer. Lancet Psychiatry. 2017; 4(4):330-338. https://doi.org/10.1016/S2215-0366(17)30014-7

[11] Ben Assayag E, Tene O, Korczyn AD, et al. Posttraumatic Stress Symptoms After Stroke: The Effects of Anatomy and Coping Style. Stroke. 2022; 53(6):1924-1933. https://doi.org/10.1161/STROKEAHA.121.036635

[12] Brewin CR, Andrews B, Valentine JD. Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. J Consult Clin Psychol. 2000; 68(5):748-766. https://doi.org/10.1037//0022-006x.68.5.748

[13] Rajkumar RP. Biomarkers of Neurodegeneration in Post-Traumatic Stress Disorder: An Integrative Review. Biomedicines. 2023; 11(5):1465. https://doi.org/10.3390/biomedicines11051465

[14] Gupta R, Advani D, Yadav D, Ambasta RK, Kumar P. Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders. Mol Neurobiol. 2023; 60(11):6476-6529. https://doi.org/10.1007/s12035-023-03502-9

[15] Song H, Sieurin J, Wirdefeldt K, et al. Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases. JAMA Neurol. 2020; 77(6):700-709. https://doi.org/10.1001/jamaneurol.2020.0117

[16] Ostacoli L, Carletto S, Borghi M, et al. Prevalence and significant determinants of post-traumatic stress disorder in a large sample of patients with multiple sclerosis. J Clin Psychol Med Settings. 2013; 20(2):240-246. https://doi.org/10.1007/s10880-012-9323-2

[17] Herringa RJ. Trauma, PTSD, and the Developing Brain. Curr Psychiatry Rep. 2017; 19(10):69. doi:10.1007/s11920-017-0825-3.

[18] Schrader C, Ross A. A Review of PTSD and Current Treatment Strategies. Mo Med. 2021; 118(6):546-551.

[19] Liu S, Ren Q, Gong G, et al. Hippocampal subfield and anterior-posterior segment volumes in patients with sporadic amyotrophic lateral sclerosis. Neuroimage Clin. 2021; 32. https://doi.org/10.1016/j.nicl.2021.102816

[20] Liu S, Sun X, Ren Q, et al. Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis. Brain. 2024; 147(1):100-108. https://doi.org/10.1093/brain/awad274

[21] Hunt JC, Chesney SA, Jorgensen TD, Schumann NR, deRoon-Cassini TA. Exploring the gold-standard: Evidence for a two-factor model of the Clinician Administered PTSD Scale for the DSM-5. Psychol Trauma. 2018; 10(5):551-558. https://doi.org/10.1037/tra0000310

[22] Eisma MC, Schmitt LO. ICD-11 and DSM-5-TR prolonged grief symptoms and quality of life: A criterion validity test. Aust N Z J Psychiatry. 2024; 58(8):693-701. https://doi.org/10.1177/00048674241249601

[23] Goldstein LH, Abrahams S. Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol. 2013; 12(4):368-380. https://doi.org/10.1016/S1474-4422(13)70026-7

[24] Chatterjee M, Özdemir S, Fritz C, et al. Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS. Nat Med. 2024; 30(6):1771-1783. https://doi.org/10.1038/s41591-024-02937-4

[25] Magen I, Yacovzada NS, Yanowski E, et al. Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis. Nat Neurosci. 2021; 24(11):1534-1541. https://doi.org/10.1038/s41593-021-00936-z

[26] Oudman E, Baert JCM.Eye movement desensitization and reprocessing (EMDR) and mediative behavioral therapy for the treatment of suffocation related post-traumatic stress disorder (PTSD) in amyotrophic lateral sclerosis (ALS): A case report. Palliat Support Care. 2023; 21(1):181-183. https://doi.org/10.1017/S1478951522000542