Egyptian Journal of Psychiatry

: 2018  |  Volume : 39  |  Issue : 3  |  Page : 133--139

Depression and unexplained somatic symptoms in multiple sclerosis: MRI and quality of life correlates

Yahia A.A.El Aziz1, Wardaa Aboelez2, Ashraf El-Mitwalli3, Wafaa El Bahaey2,  
1 Mansoura International Hospital, Mansoura, Egypt
2 Department of Psychiatry, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
3 Department of Neurology, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt

Correspondence Address:
Wardaa Aboelez
Department of Psychiatry, Mansoura Faculty of Medicine, Mansoura University, Mansoura


Background Medically unexplained symptoms (MUSs) are considered a huge burden on both physicians and patients alike and can be regarded as a form of multiple sclerosis (MS) mimic, which should be carefully investigated together with other psychiatric comorbidity-like depression and anxiety in MS patients to overcome its negative influence on patients’ quality of life. Aim The aim of our thesis research was to determine the rate of comorbidity between MS, the unexplained somatic symptoms and depression, and correlation with MRI findings, and to study the impact of the unexplained somatic symptoms, depression and disabilities on quality of life in patients with MS. Patients and methods This study was conducted on 30 patients and 30 controls. All patients were evaluated by clinical assessment and radiological assessment using MRI of brain and spine. Both patients and controls were evaluated by Patient Health Questionnaire-15 for unexplained somatic symptoms, Beck Depression Inventory for depression and 36-item Short Form Health Survey for health-related quality of life. Conclusion MS patients had an increased incidence of medically unexplained somatic symptoms and depression versus the matched normal participants, which in turn was responsible for the decline of their quality of life. Most MUS in MS patients resulted from the burden of the primary disease. However, the probability of whether these MUS could be a relapse could not be confirmed or excluded.

How to cite this article:
Aziz YA, Aboelez W, El-Mitwalli A, Bahaey WE. Depression and unexplained somatic symptoms in multiple sclerosis: MRI and quality of life correlates.Egypt J Psychiatr 2018;39:133-139

How to cite this URL:
Aziz YA, Aboelez W, El-Mitwalli A, Bahaey WE. Depression and unexplained somatic symptoms in multiple sclerosis: MRI and quality of life correlates. Egypt J Psychiatr [serial online] 2018 [cited 2022 Oct 1 ];39:133-139
Available from:

Full Text


Multiple sclerosis (MS) is considered as an inflammatory disease where the insulating covers of all nerve cells in the brain and spinal cord are destroyed. This insult affects their ability to communicate, resulting in a wide range of signs and symptoms (Compston and Coles, 2008).

Patients usually present with unexplained somatic symptoms that are commonly encountered in various medical settings where those patients are usually disabled and distressed. Symptoms are given different diagnoses such as functional symptoms’ disorders, somatization, medically unexplained symptoms (MUSs), and somatoform symptoms (Carson et al., 2015).

The clinical picture of MS is diverse and includes physical and neuropsychiatry symptoms where prevalence of comorbid major depression is about 50% (Feinstein, 2005). However, the source of depression in MS still remains an important question (Santoro et al., 2016).

MS is usually associated with poor health quality of life (HQOL), which may be due to fatigue, progressive course, physical disability, long duration of illness, and depression (Glanz et al., 2010).

The diagnosis of MS is usually based on the recurrent occurrence of neurological symptoms that characterize the disease, supported by neuroimaging, evoked potential, together with cerebrospinal fluid (CSF) analysis (McDonald et al., 2001). MS is associated with greater utilization of health services together with subjective distress and impaired functioning (Heinrich, 2004).

This study was performed over 6 months with the aim to assess the comorbidity between MS, unexplained somatic symptoms, and depression, and correlate it with MRI findings. In addition, we also aimed to study its impact on quality of life in this group of patients.

 Patients and methods

This study was a case–control study that was conducted on the following. Ethical considerations: Study protocol will be submitted for approval by Mansoura Faculty of Medicine - Institutional Research Board. Written consent will be obtained from each participant in the study after assuring confidentiality.

Patient group

This group consisted of patients who were diagnosed with MS and fulfilled the inclusion and exclusion criteria of the study, and who were recruited from the Neurology Outpatient Clinic and Inpatient Department of both Mansoura University Hospitals and Mansoura New General Hospital, within a period of 6 months with a minimum of 30 patients. The total number of patients was 39; six patients refused to join the study, and three had severe disability; only 30 patients fulfilled the inclusion criteria.

Inclusion criteria were as follows: patients of both sexes; aged 20–40 years, and diagnosed with MS. Exclusion criteria were as follows: major psychiatric disorders; mental retardation; comorbid general medical or neurological conditions.

Control group

A total of 30 healthy persons with no apparent psychiatric or medical disease were recruited from the relatives of patients and the workers in the neurology and psychiatry outpatient clinics in Mansoura University Hospital. The control group was matched with the patient sample of the study with regard to age and sex.

Ethical aspect

A written consent was obtained from the patients after explaining the aim and procedures of the study.


The methodology used in this study consisted of the following steps: (a) detailed history taking, and general and neurological examination was carried out; (b) medically unexplained somatic symptoms’ assessment was performed using the Patient Health Questionnaire (PHQ), in which the scores ranged from 0 to 30 (minimal, low, medium, and high; Kroenke et al., 2002); (c) depression assessment was carried out using Beck Depression Inventory-II (Beck et al., 1961); (d) quality of life assessment was performed using the 36-item Short Form Health Survey (SF36) (McHorney et al., 1993); (e) radiological assessment was performed using MRI brain and cervical spine.

Statistical analysis

Statistical analysis was performed using SPSS version 22 (statistical package for social sciences; SPSS Inc., Chicago, Illinois, USA). Both parametric and nonparametric data were expressed in mean, median, and range. Normality of data was first tested by the Shapiro test. Mann–Whitney test was used to compare nonparametric continuous variables.


[Table 1] shows that there is no statistically significant difference between the case and control groups as regards age, sex, residence, and educational level (P>0.05).{Table 1}

With respect to [Table 2], more than half of patients were polysymptomatic, with the relapsing remitting course being the highest.{Table 2}

[Table 3] shows highly significant statistical differences were observed in the patient group with regard to pain in the arms, shortness of breath, constipation and diarrhea, feeling tired and trouble during sleep (P<0.05), while menstrual cramps were significantly higher in the control group (P<0.05). The total score showed no significant difference between the two groups (P>0.05).{Table 3}

As observed, the total score showed high significant statistical difference between both groups (P<0.05; [Table 4]).{Table 4}

[Table 5] shows that all items were statistically significantly lower in patients than in the control group (P<0.05), except for pain, which revealed no statistical difference (P>0.05).{Table 5}

As observed, most of the patients had periventricular, parietal and juxtacortical plaques; the least were in the corpus callosum and in the brain stem ([Table 6] and [Figure 1]).{Table 6}{Figure 1}

[Table 7] shows that the only significant statistical difference in the depression score was among patients having frontal and temporal plaques (P<0.05).{Table 7}

[Table 8] shows no significant statistical difference in MRI findings among low and high MUS scores (P>0.05).{Table 8}

As observed, highly significant negative correlations were found between quality of life (SF36) and depression score, (PHQ0.7–0.8 <0.001) with statistical significance (P<0.05; [Table 9]).{Table 9}


MS is a chronic and debilitating disease that can have many devastating effects physically and psychologically. Although clinical features are characteristic for MS, its presentation varies widely in symptoms as well as in pace and progression (Files et al., 2015).

Psychiatric comorbidity with MS include anxiety, depression, and bipolar disorder. They are associated with frequent hospitalizations, lower quality of life with increased mortality. Thus it needs better understanding of its risk factors (Marrie et al., 2016).

Hence, we tried to evaluate MUS and the related depression and disability in patients with MS as well as its influence on the quality of life of these patients, and predict the possibility of MUS to be a sort of relapse or just a psychiatric manifestation associated with MS as with any chronic disease.

The mean age of MS patients was 30.4 years, which was matched with Galeazzi et al. (2005), whereas Sundgren et al. (2013) found the mean age of the MS group to be 37.9 years, which may be due to different sampling.

A lot of studies reported that female individuals are affected more than male individuals among MS patients. This study found slight predominance of female to male 1.14:1, respectively. Galeazzi et al. (2005) found the same results in the MS group, also with predominance of female individuals and there was slight predominance of married MS patients, which was in agreement with Al Jumah et al. (2013). A reasonable hypothesis related increased incidence of MS leading to the growing female: male ratio to environmental, biological, socioeconomic, genetic, and autoimmune factors, as most autoimmune diseases show female predominance, because female individuals show stronger immune responses (Cendrowski, 2014).

With regard to residence, the higher ratio of urban to rural MS patients was due to refusal of rural cases to participate in this study, which may be due to customs and traditions or lack of awareness of the importance of such studies.

First presentation was polysymptomatic in 56.7% of MS patients in our study, whereas 43.3% were monosymptomatic; this matched with the definition of MS itself as the ‘MS’ (Ashtari et al., 2016).

The mean of age at onset was 25.3 years, which was supported by studies by Kargarfard et al. (2012) and Al Jumah et al. (2013). The median of the first attack duration was 6 weeks (range: 2–12 weeks). The degree of improvement from first attack was complete in 50%, and there was partial improvement in 46.7% of cases, with a predominance of complete improvement, whereas one patient did not get any improvement from the first attack, which was classified as primary progressive MS. Toledano et al. (2015), stated that the earlier the age at onset of illness, the more increased was the likelihood of complete recovery from an initial relapse.

In this study 3.3% of MS patients had a primary progressive course, 13.3% had a secondary progressive and 85% are still having a relapsing remitting course. Most of the studies revealed that relapsing remitting course is the most common type.

As regards depression it was found to be higher in patients having MS than in control subjects. This was supported by studies of Benedict et al. (2005), Galeazzi et al. (2005), Sundgren et al. (2013), and Klevan et al. (2014) which could be explained by the uncertainty that patients have about their future, lost hope, defensive strategies for coping with emotion, changed life style and the stigma of having a chronic disease. Together with high cost of treatment and the need of regular follow up are difficulties and challenges facing MS patients.

Bakshi et al. (2000) observed that T1 lesion load in superior parietal, temporal regions can predict the presence of depression, while depression severity was predicted through T1 lesions in these regions with enlarged third and lateral ventricles, and frontal atrophy.

Bonavita et al., (2013) mentioned that depression could result from interrupted connections between brain areas regulating mood, specifically, the frontal, temporal, and fronto limbic regions, through affecting serotoninergic pathways, as the pathology of MS involves hypocellularity, demyelination, and axonal loss.

Patients with MS had reduced HQOL even with limited disability, while bodily pain was related to disease duration. This was supported by Gottberg et al. (2006) and Klevan et al. (2014). Moreover, fatigue, depression, and disability could contribute to the impaired HQOL, together with the presence of comorbidity (Marrie et al., 2012).

The negative correlation between HQOL, depression and MUS is supported by the study carried out by Kargarfard et al. (2012) and Papuć and Stelmasiak (2012). Furthermore, Fricska-Nagy et al. (2016), demonstrated that depression significantly influences HQOL and affects greatly all aspects of the quality of life. Rolak and Fleming (2007) concluded that MUSs may mimic MS.The only difference between patients and controls with regard to PHQ-15 was in pain in the arms, shortness of breath, constipation and diarrhea, feeling tired and trouble during sleep, as it bothered a lot more MS patients than normal controls.

Many patients with MUS have either anxiety or depression, and some have longstanding somatic symptoms; hence, physical and psychological factors lead to MUS (Creed, 2016).

With regard to the correlation between MUS and SF36, we found that, in this study, there was a negative correlation between PHQ-15 and all domains of SF36, which was in agreement with Reuber et al. (2007).

Patients with MUS often have some psychiatric disorders, mostly anxiety and depression, which often coexist with each other with more utilization of healthcare services with economic overload (Bener et al., 2013).

MS is usually expressed somatically, which might not have a clear explanation (MUS), and is associated with neuropsychological manifestations and objective cognitive abnormalities. MUS might not be caused by traditionally defined neurological disease. Instead, it might result from a complex interaction between psychological and biological factors.

To sum up, we assume that most MUS in MS patients resulted from the burden of the primary disease. However, the probability that these MUS can be a subclinical form of MS or a relapse could not be confirmed or excluded because of two reasons. First, is that our sample included already diagnosed MS patients. Second, the confirmatory answer of the nature of these symptoms can only be determined through MRI, which was difficult to be performed again for all patients (cost limitations).


This study was conducted on 30 MS patients and 30 controls. There was no significant age, sex, marital status, residence, and educational level differences between both groups.

We concluded that MS patients had an increased incidence of depression, and medically unexplained somatic symptoms versus the matched normal participants, which in turn was responsible for the decline of their quality of life.

Depressive symptoms were associated mainly with lesions located in both the frontal and temporal lobes by using MRI, which could be attributed to disturbed connection between the frontal and limbic circuits regulating the mood, thus affecting serotoninergic pathways with irreversible damage to critical pathways.

Frequent associations were found between somatic symptoms, physical disability and depression in patients having MS with low related quality of life.

This study draw our attention to the importance of through psychiatric follow-up for both medically unexplained somatic symptoms and patients having multiple sclerosis.


This study had the following limitations:One important limitation is the small sample size that limits generalizations.Patients could freely report their somatic symptoms rather than reveal any depressive feelings, as we obtain objective assessment for patients’ symptoms by special questionnaires.

Another limitation was the radiological investigations, as there were more recent methods for detection of relation between MS lesions and depression, such as diffusion tensor imaging.[30]

Conflicts of interest

There are no conflicts of interest.


1Ashtari F, Valiani M, Mansourian M, Mohammadi S, Sodouri M (2016). Prevalence, severity of pain in patients with multiple sclerosis (MS). Biomed Pharmacol J 9:49–54.
2Bakshi R, Czarnecki D, Shaikh ZA, Priore RL, Janardhan V, Kaliszky Z, Kinkel PR (2000). Brain MRI lesions and atrophy are related to depression in multiple sclerosis. Neuroreport 11:1153–1158.
3Beck AT, Ward C, Mendelson M (1961). Beck depression inventory (BDI). Arch Gen Psychiatry 4:561–571.
4Benedict RH, Wahlig E, Bakshi R, Fishman I, Munschauer F, Zivadinov R, Weinstock-Guttman B (2005). Predicting quality of life in multiple sclerosis: accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change. J Neurol Sci 231:29–34.
5Bener A, Dafeeah EE, Chaturvedi SK, Bhugra D (2013). Somatic symptoms in primary care and psychological comorbidities in Qatar: neglected burden of disease. Int Rev Psychiatry 25:100–106.
6Bonavita S, Tedeschi G, Gallo A (2013). Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis. Mult Scler Int 2013:104254.
7Carson AJ, Stone J, Hansen CH, Duncan R, Cavanagh J, Matthews K et al. (2015). Somatic symptom count scores do not identify patients with symptoms unexplained by disease: a prospective cohort study of neurology outpatients. J Neurol Neurosurg Psychiatry 86:295–301.
8Cendrowski W (2014). Increasing occurrence of multiple sclerosis in women correlates to hygiene level. Aktualn Neurol 14:245–249.
9Compston A, Coles A (2008). Multiple sclerosis. Lancet 372:1502–1517.
10Creed F (2016). Exploding myths about medically unexplained symptoms. J Psychosom Res 85:91–93.
11Feinstein A (2005). The clinical neuropsychiatry of multiple sclerosis. CNS Spectr 10:362.
12Files DK, Jausurawong T, Katrajian R, Danoff R (2015). Multiple sclerosis. Prim Care 42:159–175.
13Fricska-Nagy Z, Füvesi J, Rózsa C, Komoly S, Jakab G, Csépány T et al. (2016). The effects of fatigue, depression and the level of disability on the health-related quality of life of glatiramer acetate-treated relapsing-remitting patients with multiple sclerosis in Hungary. Mult Scler Relat Disord 7:26–32.
14Galeazzi GM, Ferrari S, Giaroli G, Mackinnon A, Merelli E, Motti L, Rigatelli M (2005). Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon beta therapy. Neurol Sci 26:255–262.
15Glanz BI, Healy BC, Rintell DJ, Jaffin SK, Bakshi R, Weiner HL (2010). The association between cognitive impairment and quality of life in patients with early multiple sclerosis. J Neurol Sci 290:75–79.
16Gottberg K, Einarsson U, Ytterberg C, de Pedro Cuesta J, Fredrikson S, Von Koch L, Holmqvist LW (2006). Health-related quality of life in a population-based sample of people with multiple sclerosis in Stockholm County. Mult Scler 12:605–612.
17Heinrich TW (2004). Medically unexplained symptoms and the concept of somatization. WMJ 103:83–87.
18Kargarfard M, Eetemadifar M, Mehrabi M, Maghzi A, Hayatbakhsh M (2012). Fatigue, depression, and health‐related quality of life in patients with multiple sclerosis in Isfahan, Iran. Europ J Neurol 19:431–437.
19Klevan G, Jacobsen C, Aarseth J, Myhr KM, Nyland H, Glad S et al. (2014). Health related quality of life in patients recently diagnosed with multiple sclerosis. Acta Neurol Scand 129:21–26.
20Kroenke K, Spitzer RL, Williams JB (2002). The PHQ15: validity of a new measure for evaluating the severity of somatic symptoms. Psychosom Med 64:258–266.
21Marrie RA, Horwitz R, Cutter G, Tyry T (2012). Cumulative impact of comorbidity on quality of life in MS. Acta Neurol Scand 125:180–186.
22Marrie RA, Patten SB, Greenfield J, Svenson LW, Jette N, Tremlett H et al. (2016). Physical comorbidities increase the risk of psychiatric comorbidity in multiple sclerosis. Brain Behav 6:e 00493.
23McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al. (2001). Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127.
24McHorney CA, Ware JE Jr, Raczek AE (1993). The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 31:247–263.
25Papuć E, Stelmasiak Z (2012). Factors predicting quality of life in a group of Polish subjects with multiple sclerosis: accounting for functional state, socio-demographic and clinical factors. Clin Neurol Neurosurg 114:341–346.
26Reuber M, Burness C, Howlett S, Brazier J, Grünewald R (2007). Tailored psychotherapy for patients with functional neurological symptoms: a pilot study. J Psychosom Res 63:625–632.
27Rolak LA, Fleming JO (2007). The differential diagnosis of multiple sclerosis. Neurologist 13:57–72.
28Santoro M, Nociti V, De Fino C, Caprara A, Giordano R, Palomba N et al. (2016). Depression in multiple sclerosis: effect of brain derived neurotrophic factor Val66Met polymorphism and disease perception. Eur J Neurol 23:630–640.
29Sundgren M, Maurex L, Wahlin A, Piehl F, Brismar T (2013). Cognitive impairment has a strong relation to nonsomatic symptoms of depression in relapsing-remitting multiple sclerosis. Arch Clin Neuropsychol 28:144–155.
30Toledano M, Weinshenker BG, Solomon AJ (2015). A clinical approach to the differential diagnosis of multiple sclerosis. Curr Neurol Neurosci Rep 15:1–13.