Depression and Immunity: Inflammation and Depressive Symptoms in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic neurodegenerative and autoimmune disease. Motor, sensory and cognitive deficits in MS are commonly accompanied by psychiatric disorders. Depression and anxiety affect the quality of life of MS patients, and the treatment is still not well-established. Prevalence rates in MS patients for depression and anxiety vary widely between studies. However, the prevalence of these psychiatric disorders in the subgroups of MS patients and their association with a disability has not been studied yet. Therefore, this systematic review and meta-analysis proposes to estimate the prevalence of depression and anxiety in MS and to perform subgroup analyses (study type, Extended Disability Status Scale/EDSS, duration of MS, region, type of MS) on observational studies. The protocol was registered in PROSPERO (4202125033). A computerized search on PubMed, EMBASE and Scopus for studies on depression and anxiety in MS was performed from 2015 to 2021, and 12 articles were included. Most of the studies in the meta-analysis had a low risk of bias. The prevalence of depression was 27.01% (MS), 15.78% (relapsing-remitting multiple sclerosis/RRMS), and 19.13% (progressive multiple sclerosis/PMS). For anxiety the prevalence was 35.19% (MS), 21.40% (RRMS), and 24.07% (PMS). The prevalence of depression/anxiety for patients with EDSS <3 was 26.69/45.56% and for EDSS >3 was 22.96/26.70%. Using HADS-A (8) the prevalence was 38.5% and for depression was 22.4%. Then, our study brought together current data regarding psychiatric disorders in MS patients, which are comorbidities that affect the quality of life of these patients.

Multiple sclerosis (MS) is associated with a high prevalence of emotional and mood disorders. Emotional disorders may worsen during illness progression and affect the quality of life of patients and their families. MS is often associated with depression, with an increased risk of suicide, poor adherence to treatment, decreased functional status, and quality of life. The diagnosis and treatment of emotional and mood disorders in these patients is often challenging since several symptoms of these disorders overlap with those of MS. Other prevalent emotional disorders in MS include bipolar disorder, anxiety disorders, emotional blunting (apathy), and pseudobulbar affect. Early recognition and treatment of these comorbidities could contribute to the reduction of disability and even to decreased mortality. The aim of this chapter is to provide an up-to-date review of mood and emotional disorders that are often associated with MS, focusing on their epidemiology, clinical features, pathogenesis, assessment, and treatment. The interplay between the psychosocial impact of the chronic disability and the demyelinating structural lesions of the brain in precipitating emotional and mood disorders is discussed, as well as its implications for diagnosis and treatment.

Sickness behavior represents a centrally organized suite of behaviors – depression, inactivity, anorexia, sleepiness, and reduction of grooming – that evolved in animals living in nature to conserve body resources for the high energetic costs of fever in fighting infections. The domestic scene reveals that sickness behaviors can be an early marker of infections such as mastitis in cows. Aspects of sickness behavior are markers of stressful situations such as separating a young animal from its mother. In husbandry of animals that are pets, farm animals or in zoos, markers of sickness behavior are indications of infection, or stress and impaired welfare.

Sickness behavior represents a centrally organized suite of behaviors – depression, inactivity, anorexia, sleepiness, and reduction of grooming – that evolved in animals living in nature to conserve body resources for the high energetic costs of fever in fighting infections. The domestic scene reveals that sickness behaviors can be an early marker of infections such as mastitis in cows. Aspects of sickness behavior are markers of stressful situations such as separating a young animal from its mother. In husbandry of animals that are pets, farm animals or in zoos, markers of sickness behavior are indications of infection, or stress and impaired welfare.

Prevalence rates of depression and anxiety in patients with Multiple Sclerosis (MS) vary widely across studies. Aim of this systematic review and meta-analysis was to a) estimate the prevalence of depression and anxiety in MS, and specifically b) explore sources of heterogeneity (assessment method, prevalence period, study quality, recruitment resource, region) by extensive analyses.

A computerized search in PubMed, EMBASE, and PsycINFO for studies on depression and anxiety in MS was performed up to December 2014.

Fifty-eight articles with a total sample size of 87,756 MS patients were selected. Pooled mean prevalence was 30.5% (95% CI = 26.3%–35.1%) for depression, and 22.1% (95% CI = 15.2%–31.0%) for anxiety. Prevalence of clinically significant depressive or anxiety symptoms was higher (35% and 34%) compared with disorders (21%; p = 0.001 and 10%; p < 0.001). Prevalence of a depressive disorder was relatively lower in studies from Europe. Anxiety disorder was more prevalent in community-based samples. Sources of high heterogeneity were not revealed.

Data of a large number of patients indicate increased prevalence of depression and anxiety in MS. Further research is needed to identify sources of heterogeneity. Issues to consider are the definition of depression and anxiety, patient recruitment, and patient characteristics.

Depression is one of the leading causes of disability and a significant health-concern worldwide. Much of our current understanding on the pathogenesis of depression and the pharmacology of antidepressant drugs is based on pre-clinical models. Three of the most popular stress-based rodent models are the forced swimming test, the chronic mild stress paradigm and the learned helplessness model. Despite their recognizable advantages and limitations, they are associated with an immense variability due to the high number of design parameters that define them. Only few studies have reported how minor modifications of these parameters affect the model phenotype. Thus, the existing variability in how these models are used has been a strong barrier for drug development as well as benchmark and evaluation of these pre-clinical models of depression. It also has been the source of confusing variability in the experimental outcomes between research groups using the same models. In this review, we summarize the known variability in the experimental protocols, identify the main and relevant parameters for each model and describe the variable values using characteristic examples. Our view of depression and our efforts to discover novel and effective antidepressants is largely based on our detailed knowledge of these testing paradigms, and requires a sound understanding around the importance of individual parameters to optimize and improve these pre-clinical models.