Anxiety and Depression Could be Early Indicators of Multiple Sclerosis


Summary: A study has found that people are nearly twice as likely to experience mental illness in the years leading up to the onset of multiple sclerosis (MS). The occurrence of psychiatric comorbidity is common following an MS diagnosis. However, little is known about psychiatric morbidity prior to the onset of MS. The research suggests that psychiatric conditions like anxiety and depression may be part of a prodromal phase of MS, a set of preliminary symptoms and clues that arise before classic MS symptoms.

According to new research from the University of British Columbia, people are nearly twice as likely to experience mental illness in the years preceding the onset of multiple sclerosis (MS).

The study, published in Neurology, suggests that psychiatric conditions such as anxiety and depression may be part of a prodromal phase of MS — a set of preliminary symptoms and clues that appear before classic MS symptoms.

“For a long time, it was thought that MS only really began clinically when a person experienced their first demyelinating event, such as in the form of vision problems. But we’ve come to understand there is a whole period preceding those events where the disease presents itself in more indirect ways,”

said senior author Dr. Helen Tremlett, professor of neurology at UBC.

Difficult to Diagnose

Multiple sclerosis is an autoimmune disease in which the immune system assaults the protective sheath (myelin) that covers nerve fibers, thereby interfering with brain-to-body communication. MS is frequently difficult to diagnose because its symptoms are diverse and easily confused with those of other conditions. This means that the path to a diagnosis can be lengthy and uncertain for many patients.

Working to provide a more accurate description of the early phases of MS, Dr. Tremlett and her colleagues seek to enable earlier detection and potential intervention. In some well-known disorders like Parkinson’s, where symptoms like constipation occur years before the onset of conventional motor impairments, prodromal periods are well-established.

“If we can recognize MS earlier, treatment could begin sooner. That has tremendous potential to slow disease progression and improve quality of life for people,”

said Dr. Tremlett.

A Widening Gap

The researchers reviewed the health records of 6,863 MS patients in British Columbia for the study. They investigated the prevalence of mental health problems such as depression, anxiety, bipolar disorder, and schizophrenia in the five years preceding the onset of classical, medically recognized symptoms of multiple sclerosis. These MS patients were compared to 31,865 non-MS patients.

The data showed that MS patients had approximately twice the rate of mental illness as the general population, at 28.0% and 14.9%, respectively. Healthcare utilization for psychiatric symptoms was also consistently greater among MS patients, including physician and psychiatrist visits, medications, and hospitalizations.

Notably, the gap increased in each of the five years preceding the onset of the disease.

“We see higher and higher rates of psychiatric conditions that peak in the final year before MS onset. While we’re not suggesting that these conditions alone can be a predictor of MS, they may be one piece of the MS prodrome puzzle and a potential signal when combined with other factors,”

said first author Dr. Anibal Chertcoff. Chertcoff, a postdoctoral associate in Dr. Tremlett’s lab who is now an assistant professor at the University of Manitoba, led the work.

Multiple Sclerosis Prodrome

Dr. Tremlett’s lab has demonstrated that other symptoms such as fatigue, sleep difficulties, irritable bowel syndrome, anemia, and pain may potentially be part of the multiple sclerosis prodrome.

Sharon Roman, who has lived with multiple sclerosis for 25 years, believes that better defining the prodromal phase could have enormous benefits for patients.

“We take many things in life for granted — walking, balance, vision, speech, even the simple act of swallowing — until one day it’s taken from us by MS,”

Roman said.

“The better we can identify the early signs and symptoms of MS, the earlier we can recognize, diagnose and treat it. We can help prevent people from being diagnosed the way I was, with a massive attack and hospitalization, and prevent the losses I’ve experienced. Earlier treatment may help slow progression,”

she added.


Background: Psychiatric morbidity is common after an MS diagnosis. However, little is known about psychiatric morbidity during the prodromal phase (before MS onset).

Objectives: To compare the prevalence and relative burden of psychiatric morbidity in individuals with MS versus matched controls before MS onset.

Methods: Using linked administrative and clinical data from British Columbia, Canada, we identified MS cases via a validated algorithm or from neurologist-diagnosed MS clinic attendees. Cases were matched by age, sex, and geographical location with up to 5 general population controls. We identified psychiatric morbidity through a validated definition and determined its prevalence in cases/controls in the 5 years before MS cases’ first demyelinating claim (‘administrative cohort’) or symptom onset (‘clinical cohort’), and estimated case/control prevalence ratios with 95%CIs. We also compared the yearly number of physician visits for psychiatric morbidity, visits to psychiatrists, psychiatric-related admissions, and psychotropic dispensations pre-MS onset in cases/controls regardless of whether psychiatric morbidity algorithm was fulfilled using negative binomial regression fitted via generalised estimating equations; results reported as adjusted rate ratios with 95%CIs. We assessed yearly trends via interaction terms between cases/controls and each year pre-MS onset.

Results: The administrative cohort comprised 6,863/31,865 cases/controls; the clinical cohort 966/4,534 cases/controls. Over the entire 5-year period pre-MS onset, 28.0% (1,920/6,863) of cases and 14.9% (4,738/31,865) of controls (administrative cohort) had psychiatric morbidity, as did 22.0% (213/966) of clinical cases and 14.1% (638/4,534) controls. Psychiatric morbidity prevalence ratios ranged from 1.58; 95%CI:1.38-1.81 (clinical cohort) to 1.91; 95%CI:1.83-2.00 (administrative cohort). In the administrative cohort, healthcare use was higher for cases in each year pre-MS onset (all 95%CIs >1); physician visits were 78% higher in year 5 pre-MS onset and 124% 1 year prior; visits to psychiatrists were 132% higher in year 5 and 146% in year 1; hospitalizations were 129% higher in year 5 and 197% in year 1; and prescription dispensations were 72% higher in year 5 and 100% in year 1. Results were not significant in the clinical cohort.

Conclusion: Psychiatric morbidity represents a significant burden before MS onset and may be a feature of the MS prodrome.

  1. Anibal S Chertcoff, Fardowsa Yusuf, Feng Zhu, Charity Evans, John D. Fisk, Yinshan Zhao, Ruth Ann Marrie, Helen Tremlett. Psychiatric Comorbidity During the Prodromal Period in Patients With Multiple Sclerosis. Neurology Sep 2023, 10.1212/WNL.0000000000207843

Last Updated on March 4, 2024