Why it’s Important to Recognize Signs of Depression in People with Neurologic Disorders

Jordan Dorfman's life changed unexpectedly in 2019, the year she turned 18. While visiting her older sister at the University of Michigan, the high school senior experienced her first tonic-clonic seizure (loss of consciousness, stiffening of muscles, and jerking of limbs) in front of 200 people at a fraternity party.The aftermath was overwhelming. At the emergency department (ED), she was confused and had no memory of the seizure. And she felt humiliated when the doctors initially dismissed her symptoms as alcohol-related, even though she hadn't been drinking. Eventually, an assessment by a neurologist at NYU Langone Health, in New York City, determined that Dorfman had epilepsy. Treating the condition required a strict regimen of medication, getting more sleep, avoiding alcohol, and giving up her driver's license for at least a year. (New York State law requires that drivers with epilepsy go 12 months without a seizure that involves loss of consciousness.)Her public seizure, misdiagnosis by the doctors at the ED, and loss of her license triggered serious depression. After she enrolled as a freshman at Michigan, she felt isolated, and socializing became complicated, especially in places involving drinking.The stress of managing a chronic illness and the anxiety and unpredictability associated with it affected her motivation, academic performance, and self-esteem. She struggled to adapt. A natural extrovert, she began to withdraw, skipping classes and gaining weight. Dorfman finally got help by talking to a therapist, attending support groups, and adopting mindfulness-based therapies. She learned to accept the reality of her new life in a supportive environment with people who were experiencing similar challenges. She also benefited from taking lamotrigine (Lamictal), an antiseizure medication that can have a positive impact on mood.Now 23, Dorfman is a research data associate and graduate student, pursuing a master's degree in clinical psychology at NYU. “I balance a heavy workload with rest and self-care.”TJ Griffin's life was similarly upended when he dislocated his fourth and fifth vertebrae due to a high school football injury in 1990. Paralyzed from the shoulders down, Griffin, who lives in Euless, TX, spent six months in an acute rehabilitation facility learning how to feed himself, drive a modified car, and figure out his new life. By night, he attended high school to graduate with his classmates. The emotional impact of his injury was difficult, he says. “It took me months to accept my new life.”The loss of his former self continued to hit hard in unexpected moments even as he attended college and began a career in sales for a major technology company. Seeking help from a therapist and talking to other people with similar injuries at Baylor University Medical Center in Waco, TX, sparked a new sense of purpose. “I learned to use my injury to help others cope, set goals, and overcome hurdles,” he says.Griffin's volunteer work at Baylor eventually led him to his current role working remotely as coordinator of the peer and family support program at the Christopher & Dana Reeve Foundation, which is based in Short Hills, NJ. Griffin, now 52, counsels newly injured individuals and those struggling to accept their circumstances. His mantra is, “You can have a bad day. Just don't let it turn into a bad week.”Experiences such as Dorfman's and Griffin's are common, says Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program in New Haven, CT. “Anxiety, social withdrawal, and pain stemming from neurologic conditions may trigger stress-related changes in brain regions that regulate emotions and cognition,” he says. “It is also possible that the primary neurologic illness indirectly affects the brain circuits and networks associated with depressive symptoms.”

Depression Defined

The mood disorder is characterized by persistent feelings of sadness or hopelessness that often disrupt sleep, appetite, energy levels, and concentration and, in severe cases, can lead to thoughts of self-harm, suicide, or harming others. Depression differs from normal periods of sadness, grief, or apathy in that it is prolonged and interferes with daily life.Researchers have identified several types of depression. Each has a distinct duration and set of symptoms, and some have clearly identified causes. The most common is major depressive disorder, which is marked by chronic sadness, loss of interest in normal activities, and physical symptoms such as fatigue or changes in appetite, lasting at least two weeks, says Nada Kais El Husseini, MD, FAAN, associate professor of neurology at Duke University School of Medicine in Durham, NC.Persistent depressive disorder is a chronic, low-grade depression that lasts for two years or more, often with less severe symptoms. People who have bipolar depression experience alternating periods of elevated, excitable moods known as mania and dark, depressive moods. After giving birth, women may have postpartum depression, likely triggered by hormonal changes, stress, and sleep deprivation.In late fall and early winter, when daylight hours are short, some people experience seasonal affective disorder. Another type of depression is situational, triggered by specific events, such as job loss, financial woes, or a traumatic experience. Similarly, grief-related depression is a response to loss, but unlike normal grief, it involves prolonged or intense symptoms that interfere with daily living.The biological relationship between neurologic conditions and depression is not yet fully understood, but a potential link is inflammation, the body's natural response to injuries and infection, which is often present in conditions like stroke, brain trauma, and spinal cord injury, says Scott E. Hirsch, MD, a neuropsychiatrist at Contemporary Care of America in Greenwich, CT. Chronic stress and inflammation in the brain can damage neurons and impair their ability to communicate, contributing to depressive symptoms. The largest-ever study linking depression and inflammation, with data from 86,000 participants, was published in the American Journal of Psychiatry in 2021 and found that people with depression had higher levels of C-reactive protein (CRP), a marker of inflammation.Other mechanisms in the brain that may contribute to depression include disruptions in brain chemicals such as serotonin, dopamine, and norepinephrine, which help regulate mood, motivation, and pleasure. And the body's response to stress is often hyperactive in people with depression, leading to excessive cortisol levels that can affect mood and cognition.Recognizing depression in people with neurologic disorders can be challenging because some of its symptoms—such as fatigue, emotional distress, and cognitive changes—mimic those of epilepsy, spinal cord injury, stroke, multiple sclerosis, and Parkinson's disease, says Dr. El Husseini. For this reason, she recommends routine screening for depression in all patients with neurologic conditions. In addition to tools such as the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire-9, which identify at-risk individuals, a clinical interview is necessary to confirm the diagnosis. Physicians rely on criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, which require at least five depressive symptoms over two weeks, including either a depressed mood or loss of interest, says Dr. El Husseini.

Research Breakthroughs

Antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which increase levels of serotonin in the brain and improve mood, are standard treatment for depression. These drugs are often combined with cognitive behavioral therapy (CBT) to help people identify, address, and modify negative thought patterns and behaviors. A more recent treatment is dialectical behavioral therapy, which teaches strategies that help patients accept their challenges and manage intense emotions, and offers them coping skills for a better quality of life.The potential drawbacks of SSRIs, which can often take weeks to be effective, include weight gain and a risk of increased suicidal thoughts. Researchers continue to study alternatives. The stakes are high, as untreated depression poses risks to cognitive function. A study of more than 64,000 older adults, published in Translational Psychiatry in 2024, suggested that depression significantly increases the risk of developing dementia. The mechanisms include changes in areas of the brain responsible for memory, decision-making, and learning.A promising fast-acting therapy for people with serious depressive episodes is esketamine, an FDA-approved medication administered at certified treatment centers as a nasal spray, says Dr. Hirsch. But esketamine's side effects can include sedation, dissociation, and the risk of addiction. However, a recent study funded by the NIH Blueprint Neurotherapeutics Network for Small Molecules and published in Clinical Pharmacology & Therapeutics in 2024 examined RR-HNK, an esketamine-related medication known as a “metabolite,” and found that it had the fast-acting antidepressant effects of esketamine without its potential undesirable side effects.Scientists are making advances in blood work, gene tests, and brain imaging that could help personalize SSRI prescriptions to better match patients with the most appropriate drugs rather than following the current trial-and-error process that even the most experienced psychiatrists use.

Complementary Therapies

Nondrug options such as CBT can help people manage stress, foster independence, and encourage exercise and social interaction, says Dr. Sanacora.Physical and occupational therapy also can make a difference, says Dr. Hirsch. They can impart a sense of control and progress that can improve outcomes, he says. “The feeling of achievement during rehabilitation can significantly alleviate depressive symptoms,” he says. Physical therapy can include strength training and neurodevelopmental exercises that improve physical and psychological well-being, while occupational therapy focuses on regaining independence and improving quality of life.Dr. Hirsch says repetitive trans-cranial magnetic stimulation (rTMS) also may be helpful, although more research is needed. The noninvasive procedure uses magnetic pulses to stimulate specific areas of the brain involved in mood regulation and appears to alleviate symptoms of depression, he says. In a study published in Nature Mental Health in 2023, researchers at the University of Pennsylvania Perelman School of Medicine in Philadelphia used MRI scans to target regions of the brain that are less active in people with depression. In aiming to “reset” these areas, the researchers saw improvement in mood.Neurologists also recommend support groups. Gathering in a communal environment helps patients share and learn from others in similar situations, says Dr. El Husseini. They're also safe places in which to practice new coping and communication skills.Maintaining healthy habits is an important part of managing depression, Dr. Sanacora says. Moderate exercise boosts mood-enhancing endorphins, and balanced meals enhance brain health. Quality sleep, building and maintaining social connections, and practicing mindfulness techniques such as yoga or meditation all can help reduce stress.

Volunteer Boost

People with neurologic conditions who are diagnosed with depression should look for therapists who understand their unique challenges, such as grieving the old self, having anxiety about the illness progressing, and accepting new physical and/or cognitive limitations and possibly changes in interpersonal relationships, says Dr. El Husseini.Reaching out to others with the same condition was healing for both Jordan Dorfman and TJ Griffin. Through his work with the Christopher & Dana Reeve Foundation, Griffin has shared his story of resilience and determination with school groups and organizations and demonstrated that it's possible to find purpose and thrive. “My approach to life has been shaped by my gratitude. Family, friends, and mentors have all played a role,” he says. It hasn't always been easy, he admits. “I still have bad days, but I remind myself that things could be worse.”As a psychology student at NYU, Dorfman has been active in FACES (Finding a Cure for Epilepsy and Seizures), a nonprofit organization that's part of NYU Langone Health's Comprehensive Epilepsy Center. The group funds epilepsy research, raises awareness, and provides education and community support for people with epilepsy and their families. Recently, Dorfman was a speaker at the annual FACES gala.“Invisible illnesses like epilepsy are hard. I appear to be a normal 23-year-old living in New York City who works remotely and goes to graduate school, but there's so much more beneath the surface,” she says. She's learned how to advocate for herself by speaking openly with doctors about her physical and emotional symptoms, given the overlapping nature of epilepsy and depression.And Dorfman is not afraid to ask for help. “Whether it's requesting an extra day from professors or leaning on friends for support, I've found that openness fosters understanding and connection.” Source: brainandlife.org, Robert Firpo-Cappiello