Abstract
Abstract
Objectives
Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy manifested by progressive limb weakness. Anxiety and depression are significant yet under-recognised complications of GBS, particularly in low- and middle-income countries (LMICs). This study examined the proportion and progression of anxiety and depression in Bangladeshi GBS patients and their associations with clinical features, outcomes and quality of life (QoL).
Design
A prospective cohort study.
Settings
National Institute of Neurosciences and Hospital, Dhaka, Bangladesh.
Participants
A total of 148 GBS patients aged ≥18 years diagnosed by National Institute of Neurological Disorders and Stroke criteria for GBS, were recruited within 2 weeks of symptom onset.
Primary and secondary outcome measures
Anxiety and depression were evaluated as the primary outcome using the Hospital Anxiety and Depression Scale (HADS) at week 13 and week 26 post-GBS. Secondary outcomes included Medical Research Council sum score, GBS Disability Score, fatigue severity, pain intensity and EuroQol 5-Dimension 5-Level. Statistical analyses involved descriptive summaries, group comparisons, correlation tests and longitudinal assessments by analysis of variance.
Results
A total of 111 patients with complete HADS data were analysed (median age 36 years; 71% male). At week 13, 45% had anxiety reducing to 36% at week 26. Depression was 53% at week 13 and 41% at week 26. Baseline bulbar involvement was significantly associated with week 13 depression and week 26 anxiety. Between week 13 and week 26, 27%–30% of patients had persistent symptoms and 13%–16% experienced worsening. Anxiety and depression mostly followed concordant patterns, though 28 patients showed discordant patterns. Elevated mood symptoms were associated with greater fatigue, pain and reduced QoL.
Conclusions
Anxiety and depression are common and persistent in GBS adversely affecting recovery and QoL. Mental health monitoring and targeted support should be integrated into GBS management, especially in LMIC settings.
Keywords: Anxiety disorders, Depression & mood disorders, MENTAL HEALTH, Quality of Life
STRENGTHS AND LIMITATIONS OF THIS STUDY.
First prospective cohort study from low- and middle-income country to evaluate anxiety and depression in Guillain-Barré syndrome (GBS) patients.
Validated tools (Hospital Anxiety and Depression Scale, EuroQol 5-Dimension 5-Level) were used to ensure standardised outcome measurement.
Single-centre setting and selectively recruited hospital-based cohort may limit generalisability.
No baseline mental health data and small subgroups limit causal inference.
Long-term mental health outcome beyond week 26 of GBS onset remained unknown.
Introduction
Guillain-Barré syndrome (GBS) is an acute postinfectious autoimmune polyneuropathy with a global incidence rate ranging from 0.16 to 3.0 cases/100 000 individuals/year.1 2 GBS is manifested through progressive, symmetrical limb weakness that may involve cranial and respiratory muscles.1–3 The clinical outcomes present along a wide spectrum, ranging from mild motor impairment to severe manifestations such as complete paralysis, respiratory failure, and, in some cases, death.3 Clinical management of GBS has focused largely on restoring physical function.4 Along with motor impairment, GBS patients experience several mental health conditions, which often remain underrecognised during routine care.5 The prevalence of mental health conditions in GBS patients varies across patient populations with anxiety affecting 21%–82% of patients, depression 18%–67% and stress-related disorders 20%–65%.5 These mental health symptoms can occur independently of disease severity and may persist even after apparent physical recovery.6 If not adequately managed, early symptoms may evolve into long-term psychiatric morbidity, leading to reduced quality of life (QoL), impaired daily functioning, job loss and disrupted social relationships.7 8
Most data on mental health outcomes in GBS patients came from studies conducted in the Northern Hemisphere, primarily in high-income countries. These studies largely focused on acute phase of GBS, particularly during hospital admission. There is limited research from low- and middle-income countries (LMICs), and a notable gap exists in understanding the longitudinal pattern of post-GBS mental health outcomes. In Bangladesh, incidence of GBS, mostly observed in young adults, is reported to be higher (~3.0 cases/100 000/year) than global averages reflecting a significant disease burden.1 Additionally, ~85% of patients in Bangladesh cannot afford standard immunotherapies like intravenous immunoglobulin (IVIg) or plasmapheresis (PE).1 Patients’ recovery is negatively impacted by inadequate rehabilitation services and fragmented mental health infrastructure.9 10 Therefore, many patients in Bangladesh lack proper mental health evaluation, leading to underreporting, misdiagnosis and poor management. The scenario from Bangladesh is representative of many LMICs, emphasising the urgent need for further research and improved mental healthcare in these settings. We therefore aimed to characterise the proportion and longitudinal patterns of anxiety and depression from early to later recovery phase in GBS patients in Bangladesh using a prospective cohort study. The study also aimed to identify baseline demographic, clinical factors and functional outcome parameters, for example, motor function, fatigue, pain and QoL associated with the anxiety and depression in GBS patients in Bangladesh.
Methods and materials
Study design and study subjects
Patients diagnosed with GBS were recruited through a prospective cohort study conducted by icddr,b. The parent cohort consists of patients from four different prospective studies.11 Among these studies, only the most recent study (2022–2024) collected data on anxiety and depression using the Hospital Anxiety and Depression Scale (HADS)12 in 148 patients (online supplemental figure 1). Among the 148 patients, a total of 111 patients had complete HADS data and patients with incomplete HADS data were excluded (n=37) from analysis. To assess potential selection bias, baseline characteristics of the included and excluded patients were compared (online supplemental table 1).
A post hoc power analysis (α=0.05) indicated that a sample of approximately 109 participants would provide more than 90% power to detect moderate effect sizes (eg, Cohen’s d≈0.5 or correlation r≈0.33). Therefore, the achieved sample size was considered adequate to assess longitudinal physical and psychosocial outcomes in GBS patients. Furthermore, existing studies examining psychosocial outcomes in GBS have generally been based on smaller sample sizes, thereby supporting the adequacy of the current study sample.13
All patients were enrolled from the National Institute of Neurosciences and Hospital, Dhaka, between August 2022 and May 2024. GBS patients aged ≥18 years, diagnosed by the National Institute of Neurological Disorders and Stroke (NINDS) criteria for GBS,14 were recruited within 2 weeks of symptom onset. Patients unable to provide informed consent were excluded. Baseline data included demographics, preceding infections, disease progression, neurological findings and treatment. Nerve conduction study was performed within 7 days of enrolment and the subtype classification was performed as per Hadden criteria.15 Patients were followed up at week 2, week 4, week 13 and week 26 (figure 1).
Figure 1. Study flow chart outlining patient enrolment, data collection time points and mental health outcome grouping in GBS patients. Mental health, functional outcome and QoL were assessed at weeks 13 and 26. Based on HADS-Anxiety and HADS-Depression scores at these two time points, patients were categorised into four mood pattern groups (persistent disorder, recovered, worsened and persistent normal) and further classified into concordant (same trend in anxiety and depression) or discordant (opposing trends) mood patterns. EQ-5D-5L, EuroQol 5-Dimension 5-Level; FSS, Fatigue Severity Scale; GBS-DS, Guillain-Barré syndrome Disability Score; HADS, Hospital Anxiety and Depression Scale; MRC, Medical Research Council; NINDS, National Institute of Neurological Disorders and Stroke; NRS, Numeric Rating Scale; QoL, quality of life.
Assessment of mental health status
Anxiety and depression were assessed by dedicated study physicians at week 13 and week 26 post-enrolment using the HADS.12 The HADS is a validated and widely used instrument to measure symptoms of anxiety and depression in patients or at-risk populations across the world including Bangladesh.16 17 It includes two subscales: HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D), each comprising 7 items scored on a 4-point Likert scale (0 to 3), yielding subscale scores ranging from 0 to 21. According to established cut-offs, scores of 0–7 are considered normal, 8–10 borderline and ≥11 indicates clinically significant anxiety or depression.12 For analysis purposes, patients were recategorised into two groups based on subscale scores: 0–10 (no clinically significant anxiety or depression) and 11–21 (clinically significant anxiety or depression). We selected a cut-off of ≥11 as this threshold has been shown to provide high specificity (>95%) for identifying probable cases of anxiety or depression, minimising false-positive classifications.18
Patients were categorised into four distinct mood patterns to analyse changes in anxiety and depression symptoms over time. The grouping was based on HADS-A and HADS-D scores at week 13 and week 26. For each subscale, the following patterns were defined: (1) Persistent disorder (scores remained ≥11 at both time points); (2) Recovered (scores were ≥11 at week 13 but dropped <11 by week 26); (3) Worsened (scores were <11 at week 13 but increased to ≥11 at week 26) and (4) Persistent normal (scores remained <11 at both assessments). Using these individual anxiety and depression patterns, patients were further classified into two overall mood patterns: (1) Concordant when both anxiety and depression have the same trend (eg, both recovered, worsened or remained normal) and (2) Discordant when anxiety and depression changed in opposite directions (eg, anxiety worsened but depression recovered, or vice versa). The aim of developing the concordance/discordance framework was to examine whether anxiety and depression symptoms evolved together or independently, helping to identify distinct symptom trajectories and inform tailored psychological monitoring.
Assessment of functional outcome
Functional outcomes were measured across multiple domains. Motor function was assessed by Medical Research Council (MRC) sum score, which quantifies muscle strength across key muscle groups to provide a measure of motor impairment.19 Disability was evaluated using GBS Disability Score (GBS-DS), which classifies patients according to their functional independence and mobility status.20 Poor outcome was defined as GBS disability score >2. Fatigue severity was assessed with Fatigue Severity Scale (FSS), an instrument designed to measure the impact and intensity of fatigue on daily functioning.21 Pain severity was recorded using Pain Numeric Rating Scale (NRS), using a scale from 0 (no pain) to 10 (worst possible pain).22 If patients reported pain at multiple body parts with varying intensities, the highest reported NRS score was used for analysis.
Assessment of QoL
The QoL of patients was assessed at weeks 13 and 26 using EuroQol 5-Dimension 5-Level (EQ-5D-5L), a standardised self-reporting measure with two components.23 The descriptive part covers five areas: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is rated on five levels, from ‘no problems’ (level 1) to ‘extreme problems/unable to perform’ (level 5). For analysis, responses were grouped into two categories: no or slight problems (levels 1–2) and moderate to extreme problems (levels 3–5).24
Each patient’s responses across five dimensions generated a 5-digit health profile, which is converted into a single EQ-5D index value.25 This value ranges from −0.594 (states worse than death) to 1.0 (perfect health), with 0.0 representing death.26 Due to absence of a Bangladesh-specific value set, we used value set from India (the neighbouring country of Bangladesh) for index calculation.27 The EQ-5D also includes a Visual Analogue Scale, where patients rated their overall health from 0 (worst) to 100 (best).
Statistical analysis
Statistical tests were conducted using ‘IBM SPSS Statistics V.20’, ‘GraphPad Prism V.9 (GraphPad Software, San Diego, California, USA)’ and ‘R V.4.2.1’. Descriptive analyses were conducted to summarise demographic and clinical data. Categorical variables were summarised as frequencies and percentages, while continuous variables following a normal distribution were expressed using means with SD. For variables that were not normally distributed, medians with IQRs were reported. Differences in proportions between groups (eg, patients with or without anxiety/depression and concordant vs discordant mood) were assessed using χ² test or Fisher’s exact test, as appropriate. Spearman’s rank correlation coefficients (rs) were used to assess associations between anxiety and/or depression scores with functional outcome measures (MRC sum score, FSS, pain NRS and EQ-5D index).
A heatmap (where individual values are graphically represented as colours) was generated to identify patterns and concordance of anxiety and depression over time. Longitudinal outcome changes from week 13 to 26 were analysed using repeated measures analysis of variance, with time (week 13 and week 26) as the within-subject factor and mood pattern group (concordant vs discordant) as the between-subject factor. This approach allowed assessment of changes in mean outcomes over time, as well as the interaction between time and mood pattern group. Estimated marginal means with Bonferroni-adjusted pairwise comparisons were used to explore group differences at each time point. Line graphs were generated to illustrate trends in mean outcome trajectories by mood pattern group. A two-tailed p<0.05 was considered significant.
Patient and public involvement
Patient and public were not directly involved in the design, conduct or reporting of the particular study.
Results
Clinical characteristics of study participants
Median age of the patients was 36 years (IQR: 25–49), with 71% male (table 1). The majority presented with severe motor weakness at baseline, with 52% having an MRC sum score ≤20. Nearly half of the patients (49%) required mechanical ventilation (GBS-DS=5) at study entry which increased to 51% within 7 days of enrolment. Cranial nerve involvement was observed in 56% of patients, including 38% with bulbar dysfunction, while 38% experienced autonomic disturbances. A total of 47% of patients received IVIg treatment. Nerve conduction study was performed among 88 patients, and axonal subtype was most common (63%). Poor outcomes (GBS-DS>2) were observed among 27% and 13% of patients at week 13 and week 26, respectively.
Table 1. Characteristics of the patients.
| Variables at study entry | All patients N=111 n (%) |
|---|---|
| Age (years) | 36 (25, 49)* |
| ≤40 | 70 (63) |
| 41–60 | 35 (32) |
| >60 | 6 (5) |
| Sex | |
| Male | 79 (71) |
| Female | 32 (29) |
| Preceding diarrhoea† | 32/109 (29) |
| Preceding RTI† | 18/109 (17) |
| MRC sum score total | |
| 41–60 | 6 (5) |
| 21–40 | 48 (43) |
| 0–20 | 57 (52) |
| GBS disability score | |
| 1 | 0 |
| 2 | 5 (5) |
| 3 | 24 (21) |
| 4 | 28 (25) |
| 5 | 54 (49) |
| Mechanical ventilation within 7 days of study entry | 56(51) |
| Cranial nerve involvement | 62 (56) |
| Facial involvement | 31 (28) |
| Bulbar involvement | 42 (38) |
| Autonomic dysfunction‡ | 42 (38) |
| Treatment | |
| Intravenous immunoglobulin | 51 (47) |
| Plasma exchange | 31 (28) |
| Supportive care only§ | 29 (25) |
| Nerve conduction study | |
| Axonal | 55/88 (63) |
| Acute inflammatory demyelinating polyneuropathy | 29/88 (33) |
| Normal | 2/88 (2) |
| Miller Fisher syndrome | 2/88 (2) |
| Poor outcome¶ week 4 | 61 (55) |
| Poor outcome¶ week 13 | 28/105 (27) |
| Poor outcome¶ week 26 | 14/107 (13) |
Median (IQR).
Within 4 weeks prior to the onset of weakness.
Defined as any abnormalities in cardiac features (tachycardia/bradycardia/arrhythmia); blood pressure (hypertension/hypotension/fluctuation), bowel-bladder involvement and pupillary-dysfunction.
Mostly due to unavailability or unaffordability of immunotherapy.
Defined as GBS disability score >2.
GBS, Guillain-Barré syndrome; MRC sum score, Medical Research Council Sum Score; RTI, respiratory tract infection.
Proportion and factors associated with anxiety and depression
At week 13, 45% of patients had clinically significant anxiety which went down to 36% at week 26 (figure 2). The proportion of depression was 53% at week 13 and 41% at week 26. Table 2 shows baseline factors associated with anxiety and depression. Only bulbar involvement was significantly associated with week 13 depression (p=0.045) and week 26 anxiety (p=0.036). Both anxiety and depression at week 13 were significantly associated with poor outcome (GBS-DS >2) at week 26.
Figure 2. Prevalence of anxiety and depression at 13 and 26 weeks. Bar diagram showing the proportion of anxiety and depression at different time points where x-axis represented time points of follow-up, and y-axis represented proportion of patients. Normal: 0–7; Borderline: 8–10; Abnormal: 11–21.
Table 2. Clinical factors associated with anxiety and depression at week 13 and week 26 post-GBS.
| Demographic and clinical characteristics | Anxiety (HADS-A ≥11) | Depression (HADS-D ≥11) | ||
|---|---|---|---|---|
| At week 13 N=93* n (%) |
At week 26 N=104† n (%) |
At week 13 N=93* n (%) |
At week 26 N=104† n (%) |
|
| Age (years) | ||||
| ≤40 | 28 (67) | 24 (63) | 31 (63) | 24 (56) |
| 41–60 | 12 (29) | 11 (29) | 16 (33) | 15 (35) |
| >60 | 2 (4) | 3 (8) | 2 (4) | 4 (9) |
| Sex | ||||
| Male | 31 (74) | 25 (66) | 36 (74) | 29 (67) |
| Female | 11 (26) | 13 (34) | 13 (26) | 14 (33) |
| Preceding diarrhoea‡ | 13/91 (33) | 11/102 (31) | 13/91 (28) | 13/102 (32) |
| Preceding RTI‡ | 8/91 (20) | 7/102 (19) | 8/91 (17) | 6/102 (15) |
| MRC sum score total | ||||
| 41–60 | 4 (9) | 2 (5) | 5 (10) | 1 (2) |
| 21–40 | 12 (29) | 15 (40) | 17 (35) | 17 (40) |
| 0–20 | 26 (62) | 21 (55) | 27 (55) | 25 (58) |
| GBS disability score | ||||
| 0–2 | 1 (2) | 1 (3) | 2 (4) | 0 |
| 3–5 | 41 (98) | 37 (97) | 47 (96) | 43 (100) |
| Mechanical ventilation within 7 days of study entry | 26(62) | 24(63) | 29(59) | 27(63) |
| Cranial nerve involvement | 25 (60) | 26 (68) | 32 (65)§¶ | 28 (65) |
| Facial involvement | 13 (31) | 13 (34) | 16 (33) | 15 (35) |
| Bulbar involvement | 17 (41) | 20 (53)§** | 22 (45)§†† | 20 (47) |
| Autonomic dysfunction | 18 (43) | 15 (40) | 21 (43) | 17 (40) |
| Treatment | ||||
| IVIg | 18 (43) | 20 (53) | 20 (41) | 21 (49) |
| Plasma exchange | 15 (36) | 13 (34) | 20 (41) | 15 (35) |
| Supportive care only | 9 (21) | 5 (13) | 9 (18) | 7 (16) |
| Nerve conduction study | ||||
| Axonal | 18/70 (56) | 14/78 (58) | 21/70 (58) | 14/78 (54) |
| AIDP | 14/70 (44) | 10/78 (42) | 15/70 (42) | 12/78 (46) |
| Poor outcome week 4‡‡ | 25(60) | 23 (61) | 28 (57) | 29 (67) |
| Poor outcome week 13‡‡ | 13 (31) | 11/98(30) | 14 (29) | 13/98 (32) |
| Poor outcome week 26‡‡ | 7/90 (18)§ §§ | 5/103 (14) | 8/90 (17)§ ¶¶ | 7/103 (17) |
*Significant p<0.05 (calculated using χ2 or Fisher’s exact test, comparing patients with and without anxiety or depression at the same time point); ap=0.034; bp=0.036; cp=0.018; d p=0.045; ep=0.024.
N=93 is the total number of patients assessed for anxiety and depression at week 13. The column of the table presents characteristics of patients with anxiety/depression; patients without anxiety/depression form the remaining group.
N=104 is the total number of patients assessed for anxiety and depression at week 26. The table presents characteristics of patients with anxiety/depression; patients without anxiety/depression form the remaining group.
Within 4 weeks prior to the onset of weakness.
Significant p-value < 0.05 (calculated using chi-square or Fisher’s exact test, comparing patients with and without anxiety or depression at the same time point).
p=0.018.
p=0.036.
p=0.045.
defined as GBS disability score >2.
p=0.03.
p=0.024.
AIDP, acute inflammatory demyelinating polyneuropathy; GBS, Guillain-Barré syndrome; HADS, Hospital Anxiety and Depression Scale; HADS-A, HADS-Anxiety; HADS-D, HADS-Depression; IVIg, intravenous immunoglobulin; RTI, respiratory tract infection; MRC sum score, Medical Research Council Sum Score.
Concordant and discordant patterns of anxiety and depression
Figure 3 illustrates the co-evolution of anxiety and depression patterns in GBS patients from week 13 to week 26. Persistent anxiety and depression were observed in 27% and 30% of patients, respectively. Within this period, symptoms worsened in 13% (anxiety) and 17% of patients (depression), while 19%–23% showed improvement.
Figure 3. Patterns and alignment of anxiety and depression in GBS patients from week 13 to week 26. (A) Stacked bar plots displaying the distribution of anxiety and depression patterns from week 13 to week 26. Each bar represents the proportion of patients classified into one of four categories: Persistent disorder (≥11 both times); recovered (≥11 at week 13, <11 at week 26); worsened (<11 at week 13, ≥11 at week 26); persistent normal (<11 both times). (B) Heatmap illustrating the concordance and discordance between anxiety and depression patterns in GBS patients from week 13 to week 26. The rows represent categories of anxiety pattern, and the columns represent categories of depression pattern. Cell values reflect row-wise percentages (% within anxiety pattern) to emphasise the distribution of depression outcomes within each anxiety pattern group. Darker shading indicates higher proportions. Concordant patterns (eg, persistent–persistent or recovered–recovered) appear along the diagonal (red circled area), while off-diagonal cells reflect discordant mood patterns. GBS, Guillain-Barré syndrome.
A strong alignment between anxiety and depression patterns was evident (figure 2B). Among those with persistent anxiety, 87% also had persistent depression. Similarly, 69% of those who recovered from anxiety also recovered from depression (p=0.000), indicating a concordant pattern. However, 28 patients showed discordant patterns. For example, 2 of 23 patients (8.7%) with persistent anxiety had worsening depression, and 1 of 11 with worsening anxiety (9.1%) showed improved depression. In summary, these demonstrated that most patients exhibited parallel trajectories of anxiety and depression. However, a smaller subgroup showed discordant patterns indicating heterogeneity in symptom progression.
Baseline characteristics were compared between patients with concordant (n=58) and discordant (n=28) groups and no significant differences in age, sex, severity or treatment could be found (online supplemental table 2).
Figure 4 and online supplemental table 3 illustrate the longitudinal changes of functional outcomes between week 13 and week 26, between concordant and discordant groups. Overall, the discordant group reported higher fatigue (p=0.038, η²=0.050) and lower muscle strength (p=0.008, η²=0.081) compared with the concordant group. Changes over time differed between concordant and discordant groups only for pain severity, with a moderate effect size (p=0.002, η²=0.116). At week 13, the discordant group reported lower pain than the concordant group, but pain in the discordant group increased by week 26, while pain in the concordant group decreased over time. No other measures, including fatigue, muscle strength or EQ-5D scores, showed significant longitudinal changes between groups.
Figure 4. Longitudinal changes in functional outcomes from week 13 to week 26 by mood pattern group. Line graphs illustrate mean values (±SD) of key outcome measures stratified by mood pattern group (concordant vs discordant anxiety–depression patterns): (A) EQ-5D index score; (B) Pain numerical rating scale; (C) Fatigue Severity Scale; (D) MRC sum score. EQ-5D, EuroQol 5-Dimension; MRC, Medical Research Council.
Relationships between anxiety and depression with QoL and functional outcome
Among the EQ-5D-5L domains, pain/discomfort was the only domain significantly associated with both anxiety and depression at weeks 13 and 26 (table 3). Additionally, self-care problems were higher in patients with depression at week 26 (31% vs 15%, p=0.049). Differences in mobility, usual activities and anxiety/depression domains were not statistically significant at either time point.
Table 3. Impact of anxiety and depression on the quality of life of the patients.
| Anxiety1 at 13 weeks (N=93) | Depression1 at 13 weeks (N=93) | |||||
|---|---|---|---|---|---|---|
| EuroQol-5D-5L week 13 | Patients with anxiety N (%) | Patients without anxiety N (%) | P value | Patients with depression N (%) | Patients without depression N (%) | P value |
| Mobility | ||||||
| No/slight problem | 27 (64) | 39 (76) | 0.253 | 34 (69) | 32 (73) | 0.820 |
| Moderate/severe/extreme problem | 15 (36) | 12 (23) | 15 (31) | 12 (27) | ||
| Self-care | ||||||
| No/slight problem | 24 (57) | 34 (67) | 0.394 | 28 (57) | 30 (68) | 0.292 |
| Moderate/severe/extreme problem | 18 (43) | 17 (33) | 21 (43) | 14 (32) | ||
| Usual activities | ||||||
| No/slight problem | 23 (55) | 34 (67) | 0.288 | 28 (57) | 29 (66) | 0.403 |
| Moderate/severe/extreme problem | 19 (45) | 17 (33) | 21 (43) | 15 (34) | ||
| Pain/discomfort | ||||||
| No/slight problem | 20 (48) | 48 (94) | 0.000* | 40 (91) | 40 (91) | 0.000* |
| Moderate/severe/extreme problem | 22 (52) | 3 (6) | 4 (9) | 4 (9) | ||
| Anxiety/depression | ||||||
| No/slight problem | 29 (69) | 43 (84) | 0.089 | 36 (73) | 36 (82) | 0.457 |
| Moderate/severe/extreme problem | 13 (31) | 8 (16) | 13 (26) | 8 (18) | ||
| Anxiety1 at 26 weeks (N=102) | Depression1 at 26 weeks (N=102) | |||||
|---|---|---|---|---|---|---|
| EuroQol-5D-5L at week 26 | Patients with anxiety (%) | Patients without anxiety N (%) | P value | Patients with depression N (%) | Patients without depression N (%) | P value |
| Mobility | ||||||
| No/slight problem | 36 (78) | 49 (87) | 0.287 | 32 (76) | 54 (88) | 0.112 |
| Moderate/severe/extreme problem | 10 (22) | 7 (12) | 10 (24) | 7 (11) | ||
| Self-care | ||||||
| No/slight problem | 33 (72) | 47 (84) | 0.154 | 29 (69) | 52 (85) | 0.049* |
| Moderate/severe/extreme problem | 13 (28) | 9 (16) | 13 (31) | 9 (15) | ||
| Usual activities | ||||||
| No/slight problem | 36 (78) | 42 (75) | 0.816 | 32 (76) | 46 (75) | 0.928 |
| Moderate/severe/extreme problem | 10 (22) | 14 (25) | 10 (24) | 15 (25) | ||
| Pain/discomfort | ||||||
| No/slight problem | 32 (70) | 48 (86) | 0.048* | 28 (67) | 52 (85) | 0.032* |
| Moderate/severe/extreme problem | 14 (30) | 8 (14) | 14 (33) | 9 (15) | ||
| Anxiety/depression | ||||||
| No/slight problem | 37 (80) | 48 (86) | 0.596 | 33 (79) | 53 (87) | 0.290 |
| Moderate/severe/extreme problem | 9 (20) | 8 (14) | 9 (21) | 8 (13) | ||
The bold text with * indicated statistical significance.
EuroQol-5D-5L, EuroQol-5-Dimension 5-Level.
Correlation analysis (table 4) showed, at week 13, both anxiety and depression score positively correlated with fatigue severity (rs=0.347 and 0.311, respectively; p≤0.002) and pain severity (rs=0.410 and 0.313; p≤0.002), and negatively correlated with EQ-5D index (rs=−0.358 and −0.305; p≤0.003). By week 26, only depression remained significantly correlated with higher pain severity (rs=0.279, p=0.004) and lower EQ-5D index (rs=−0.319, p=0.001).
Table 4. Correlation between anxiety and depression score with muscle power, GBS severity, FSS score and EQ-5D index.
| MRC sum score at week 13 | FSS score at week 13 | Pain NRS week 13 | EQ-5D index at week 13 | |||||
|---|---|---|---|---|---|---|---|---|
| rs | P value | rs | P value | rs | P value | rs | P value | |
| HADS Anxiety score at week 13 | −0.147 | 0.159 | 0.347 | 0.001 | 0.410 | 0.000 | −0.358 | 0.000 |
| HADS Depression score at week 13 | −0.150 | 0.151 | 0.311 | 0.002 | 0.313 | 0.002 | −0.305 | 0.003 |
| MRC sum score at week 26 | FSS score at week 26 | Pain NRS week 26 | EQ VAS index at week 26 | |||||
|---|---|---|---|---|---|---|---|---|
| rs | P value | rs | P value | rs | P value | rs | P value | |
| HADS Anxiety score at week 26 | 0.087 | 0.380 | −0.064 | 0.521 | 0.167 | 0.094 | −0.148 | 0.135 |
| HADS Depression score at week 26 | −0.053 | 0.592 | 0.092 | 0.354 | 0.279 | 0.004 | −0.319 | 0.001 |
The bold text indicated statistical significance.
EQ-5D, EuroQol 5-Dimension; FSS, Fatigue Severity Scale; GBS, Guillain-Barré syndrome; HADS, Hospital Anxiety and Depression Scale; NRS, Numeric Rating Scale; MRC sum score, Medical Research Council Sum Score; VAS, Visual Analogue Scale.
Discussion
Anxiety and depression are important yet underexplored complications of GBS, particularly in LMICs. This prospective cohort study found high prevalence of anxiety and depression at 13 and 26 weeks of disease onset in GBS patients in Bangladesh. Depression at week 13 and anxiety at week 26 were significantly associated with baseline bulbar involvement. Between weeks 13 and 26, one-third of patients had persistent anxiety or depression symptoms, and over 20% showed symptom worsening. Anxiety and depression often followed similar patterns (concordant), although few patients had differing symptom courses (discordant). The concordant group had significantly greater improvement of pain severity compared with the discordant group. Elevated mood symptoms were associated with greater fatigue, pain and reduced QoL.
Our findings were consistent with previous studies showing a high prevalence of anxiety and depression in GBS patients.13 Anxiety and depression are also highly prevalent in other neurological conditions that are characterised by similar physical disability and functional limitations like GBS. For example, 20%–40% of the post-stroke survivors report depressive symptoms and/or anxiety disorders.28–31 Similarly, mood disorders including both depressive and anxiety symptoms have been reported frequently in conditions such as multiple sclerosis and Parkinson’s disease.32
Most of the earlier GBS studies focus on acute phase, mainly in ventilated patients.33 However, the duration of persistence of mental health symptoms and predominant mood disturbance in GBS remains unclear. Most studies report anxiety tends to peak during acute or early phase of GBS and mostly link to sudden onset of symptoms, diagnostic uncertainty and fear of disease progression.33 Anxiety rates range from 20% at hospital admission to as high as 40%–80% during Intensive Care Unit (ICU) stays.34–36 In contrast, depression is reported more prominent during recovery, when patients face prolonged disability, fatigue, slow recovery and reduced independence.37 38 One Australian study reported depression, anxiety and stress in around 20% of patients at a median of 6 years after ICU discharge which represents a considerably longer follow-up than our 26-week endpoint.6 Compared with most of the existing literature, Bernsen et al showed a different pattern.39 They reported normal anxiety scores by 3 months post-onset, while depressive symptoms peaked at 3 months and returned to normal by 6 months. However, the authors suggested that lower rates of mood symptoms in their cohort might be influenced by improved ICU sedation and early anxiety management practices.39
In our study, age, sex, preceding infections, disease severity or treatment showed no significant association with anxiety and depression. These findings aligned with findings of a previous study reporting no direct impact of age or sex on patients with and without mental health symptoms.34 However, contrasting evidence was also reported in a Dutch study where age, gender, treatment, artificial respiration and specialised rehabilitation were reported as potential factors influencing anxiety and depression.6 39 Regarding the influence of treatment on anxiety and depression, some unexpected associations were reported by Witsch et al. They showed mental health symptoms had better outcomes after IVIg as compared with PE, but the reasons were unclear.40 We found baseline bulbar involvement to be associated with anxiety and depression. This also aligned with prior studies showing an association of cranial nerve dysfunction with acute anxiety in ICU-admitted GBS patients.34 35 Bulbar dysfunction impairs essential functions such as speech, swallowing and airway protection, which exacerbate psychological distress in neurological populations, including stroke, amyotrophic lateral sclerosis and neurodegenerative disorders.41 42 Furthermore, bulbar involvement often necessitates intensive monitoring or mechanical ventilation, which may itself be a source of psychological stress.43
Most previous studies have reported an association between mechanical ventilation and mental health conditions in GBS patients.33–36 However, we did not find a similar association in our cohort. This discrepancy might reflect several factors unique to our setting. First, in most LMICs, including Bangladesh, mental health symptoms are often underreported due to low awareness and cultural stigma.40 Additionally, the use of assessment tools not specifically validated for ICU survivors in these settings further complicated accurate diagnosis of mental disorders.44 Second, ICU survivors often view their recovery as a sign of divine favour or personal resilience. Therefore, strong religious beliefs or spiritual coping mechanisms common in Bangladesh may contribute to reduced mental health symptoms among ventilated patients.45 Third, regional variations in GBS were well recognised worldwide.1 46 Most previous studies on GBS and mental health have focused on older adults and acute inflammatory demyelinating polyneuropathy subtype. In contrast, our study population consisted mainly of younger patients with a predominance of axonal variants. These differences might contribute to distinct mental health outcomes between subtypes.
In this study, most patients had concordant patterns of anxiety and depression, while a smaller subgroup exhibited discordant patterns. Although there were no baseline differences between these groups, this heterogeneity in symptom progression suggested that anxiety and depression may not always share the same underlying mechanisms. Clinically, this distinction is important, as patients with concordant symptoms may benefit from integrated management approaches, whereas those with discordant patterns may require more individualised assessment and targeted interventions. These findings also emphasise the importance of longitudinal monitoring of mental health to better inform prognosis and optimise patient care.
Regarding the QoL, pain/discomfort was the only domain found to be associated with both anxiety and depression in our cohort. Additionally, individuals with depression at week 26 showed a higher likelihood of self-care difficulties. Correlation analysis showed that at week 13, both anxiety and depression were linked to greater fatigue, increased pain and lower EQ-5D index scores, while at week 26, only depression (rather than anxiety) remained significantly associated with these outcomes. In contrast, Ranjani et al showed fatigue correlated significantly with anxiety, but not with depression.47 However, the pattern we found was consistent with prior studies in other neurological disorders. For example, research in stroke, multiple sclerosis and Parkinson’s disease has demonstrated that depression (not anxiety) served as a stronger predictor of poor long-term outcomes and reduced QoL.48–50 This interplay between mood and somatic symptoms emphasised that mental health conditions among these patients were closely related to their physical experiences.
Our study has several limitations. First, it was conducted at a single centre. Additionally, the cohort was intentionally sampled to develop a prognostic model for mechanical ventilation in GBS patients, resulting in higher rates of mechanical ventilation and immunotherapy use compared with previous Bangladeshi studies,11 24 which might impact generalisability. Second, subgroup analyses such as mood pattern groups had small sample sizes to detect significant differences. Third, baseline mental health status of the patients prior to GBS onset was not available, making it difficult to distinguish pre-existing mood disorders from those caused by GBS. Different socioeconomic factors that could impact mental health outcomes were not collected or analysed. The follow-up period was limited to 26 weeks, so long-term mental health outcomes remained unknown. Fourth, the categorisation of HADS scores into two groups instead of three might have reduced sensitivity to detect more subtle gradations in symptom severity. Fifth, QoL was measured based on only EQ-5D, which is a relatively brief and generic measure that might not fully capture the complex and multidimensional nature of QoL. Finally, the statistically significant correlation tests were moderate in strength, indicating partial rather than strong relationships. Additionally, multiple statistical tests were performed to allow a comprehensive and transparent evaluation of the data, but this approach could potentially increase the risk of type I error. As this analysis was primarily exploratory, adjustments for multiple comparisons were not undertaken, and the findings should be interpreted with caution. Despite these limitations, to our knowledge, this is the first longitudinal study from an LMIC to comprehensively evaluate anxiety and depression in GBS patients.
In conclusion, the study provided valuable insights into the mental health burden in patients with GBS in Bangladesh, highlighting critical areas for clinical intervention and research. Clinicians should be trained to recognise and manage mood symptoms, even in patients with mild disability or complete recovery. Tools for assessing mental health should be validated specifically for GBS and LMICs to ensure accuracy and relevance. Qualitative studies are needed to better understand patient experiences and coping strategies with mental health complications along with sociocultural influences. Low-cost, culturally appropriate interventions such as counselling, caregiver support and psychoeducation may improve recovery outcomes. Routine mental health screening, follow-up and intervention particularly within the first 6 months, should be integrated into GBS management guidelines. Finally, further research is needed to understand how GBS subtype-specific neurological damage is linked to mental health and develop effective, scalable management for LMIC contexts.
Supplementary material
Acknowledgements
We thank all study personnel for their efforts in patient enrolment, data collection and management. We are grateful to the neurologists who referred patients, and to patients for generously providing valuable data. We acknowledge use of ChatGPT for minor grammar and language corrections. icddr,b gratefully acknowledges its core donors, including GoB and Canada, for providing unrestricted support for its operations and research. ZI received a restricted grant (5K43TW011447-04) from the Fogarty International Center and National Institute of Neurological Disorders and Stroke (NINDS), the National Institutes of Health (NIH), and support from Annexon Biosciences unrelated to the current manuscript. QDM received consulting honoraria from Annexon Biosciences for activities unrelated to this manuscript.
Footnotes
Funding: This research was funded by icddr,b with a matching grant from Government of Bangladesh (GoB) (GR-01945).
Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2025-111943).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Consent obtained directly from patient(s).
Ethics approval: The study protocol was reviewed and approved by Ethical Committees of icddr,b (PR-22005). Participants gave informed consent to participate in the study before taking part.
Data availability free text: Data used in the manuscript are not publicly available due to patient privacy and ethical restrictions. Therefore, no publicly available datasets were used, and dataset citations are not applicable. De-identified data may be made available from the corresponding author on reasonable request and with appropriate ethical approval, where applicable.
Patient and public involvement: Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Data availability statement
Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.
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