Can Lyme Disease Cause Depression? When Symptoms Are Misdiagnosed

Depression may not explain every symptom
Lyme disease can affect mood, energy, and cognition
A missed diagnosis can delay treatment

Can Lyme disease cause depression? Lyme disease has been associated with depression, anxiety, cognitive dysfunction, sleep disturbance, and other neuropsychiatric symptoms in some patients.

The following story is based on one of my own patients. Identifying details have been changed to protect patient privacy.

I want to share the story of a patient who almost fell through the cracks—not because people didn’t care, but because they stopped looking too soon.

She came to my office after seeing three different doctors. Each time, she heard the same thing: “You’re probably just depressed.”

But something did not sit right with her—and it did not sit right with me either.

When depression does not tell the whole story

Depression is real. It is serious. But it is not the explanation for every symptom a patient experiences.

By the time this patient found me, her fatigue was overwhelming.

• Her joints ached unpredictably.
• Her thoughts were cloudy.
• Her memory was slipping in ways that felt frightening.
• Sleep did not restore her energy.

She was not just sad or withdrawn. She was physically sick—and she knew it. Still, because she had a history of depression, her new symptoms were brushed aside.

• Nobody asked about the pattern of her pain.
• Nobody noticed how it migrated from joint to joint.
• Nobody questioned why sleep did not restore her energy.
• Nobody considered that something more could be going on.

Why Lyme disease is sometimes mistaken for depression

Lyme disease may be mistaken for depression because several symptoms overlap with mood disorders, including:

• Fatigue
• Loss of motivation
• Poor concentration
• Sleep disturbance
• Memory problems
• Reduced physical activity because of pain

Because these symptoms overlap with depression, the underlying cause may not be recognized immediately, particularly if physical symptoms receive less attention than mood symptoms.

Lyme Disease and Depression: Can Lyme Mimic Mental Health Conditions?

Yes. Lyme disease can sometimes mimic or overlap with depression, anxiety, chronic fatigue, cognitive dysfunction, sleep disturbance, and other mental health symptoms. A 2025 literature review noted that Lyme disease may be associated with neuropsychiatric symptoms such as depression, anxiety, sleep disturbance, and cognitive complaints, although the strength of evidence varies across studies.

This distinction matters. A patient may have depression and Lyme disease at the same time. Or a patient may be labeled with depression when an underlying infection, inflammation, pain syndrome, or neurologic illness has not been fully evaluated.

Psychiatric symptoms should not automatically end the diagnostic evaluation. When patients present with unexplained fatigue, migrating musculoskeletal pain, neuropathy, sleep disruption, cognitive changes, or other neurologic findings, clinicians should continue considering medical conditions that could contribute to the presentation.

What happens when we stop asking questions?

I see this happen more often than I would like to admit.

Once a label like “depression”—or any mental health diagnosis—is placed on a patient’s chart, everything that follows can get filtered through that lens.

• Headaches? Probably stress.
• Fatigue? Probably depression.
• Brain fog? Probably anxiety.

But medicine—and healing—require curiosity. They require us to ask:

“What else could be going on?”

When I sat down and listened to her full story, it was clear her symptoms did not fit neatly into a mental health box. They fluctuated, migrated, and worsened unpredictably—patterns often seen with infection, inflammation, autonomic dysfunction, or neurologic illness, not simply mood disorders.

So we dug deeper.

I ordered testing for Lyme disease.

Her clinical evaluation and testing supported a diagnosis of Lyme disease.

Lyme disease does not always look the way we expect

One reason Lyme disease is often missed is that it does not always look the way doctors are trained to recognize it.

• No obvious tick bite
• No bull’s-eye rash
• No early flu-like illness

Instead, it may present with symptoms that overlap with mental health conditions, including:

• Depression
• Anxiety
• Chronic fatigue
• Cognitive decline
• Mood swings
• Brain fog
• Panic episodes
• Sleep disturbance

Because Lyme disease can affect the immune system, nervous system, joints, sleep, and cognition, it can create a complicated picture that is easy to misread—especially when clinicians stop asking questions too soon.

Lyme disease and mental health symptoms

The relationship between Lyme disease and mental health is complex. Some studies report increased rates of depression, anxiety, sleep disturbance, cognitive complaints, or reduced quality of life in patients with Lyme disease, while other studies find weaker or inconsistent long-term associations.

Fallon and Nields reported that up to 40% of patients with Lyme disease may develop neurologic involvement, which may contribute to cognitive and psychiatric symptoms in some cases.

A large Danish cohort study found that individuals diagnosed with Lyme borreliosis in a hospital setting had higher rates of mental disorders, affective disorders, suicide attempts, and suicide compared with individuals without Lyme borreliosis. The absolute population risk remained low, but the authors emphasized that clinicians should be aware of possible psychiatric sequelae.

Because this was an observational study, it cannot determine whether Lyme disease directly caused these psychiatric outcomes, but it highlights the importance of considering mental health symptoms during evaluation and follow-up.

Another study of 252 Lyme disease patients reported lower quality of life, poorer sleep, attention and memory complaints, and depressive symptoms compared with controls. In that cohort, patients reported seeing an average of nearly eight physicians before receiving a diagnosis, with an average delay of approximately eight years.

These findings do not mean that Lyme disease explains every case of depression or anxiety. They do show that mood, cognition, sleep, and infection can intersect—and that patients with new or unexplained symptoms deserve a careful medical evaluation.

It is not just depression

Depression is not the only diagnosis that can mask an underlying Lyme infection or other medical illness.

I have seen patients misdiagnosed with:

• Anxiety disorders
• Panic attacks
• Bipolar disorder
• Obsessive-compulsive disorder (OCD)
• Somatic symptom disorder
• Post-traumatic stress disorder (PTSD)

These are real conditions—and they deserve real attention. But Lyme disease can mimic or overlap with many symptoms that are commonly attributed to mental health disorders, including:

• Emotional instability
• Irritability
• Panic episodes
• Severe fatigue
• Cognitive slowing
• Poor memory
• Sleep disruption
• Difficulty concentrating

When we anchor too quickly to a psychiatric explanation, we can miss a medical illness that may still be active—and still treatable.

Treatment changed everything

When we treated my patient’s Lyme disease, her health started to return.

• Her energy came back.
• Her brain fog lifted.
• Her joint pain improved.
• Her mood stabilized—not because she changed psychiatric medications, but because her infection was finally being treated.

She began feeling like herself again—regaining not just her physical strength, but her mental clarity and emotional resilience too.

It confirmed what she had known deep down all along: This was not just depression. This was Lyme disease.

If symptoms do not add up, keep asking

If you are struggling with symptoms that do not feel fully explained—fatigue, brain fog, pain, sleep disruption, mood changes—and you have been told it is “just depression” or another mental health diagnosis, keep asking questions.

• Trust your observations.
• Ask whether your symptoms fit one diagnosis or a broader pattern.
• Look for a clinician willing to consider medical, neurologic, infectious, and psychiatric explanations together.

Sometimes the real diagnosis is still waiting to be found.

Frequently Asked Questions

Can Lyme disease cause depression?

Lyme disease has been associated with depression in some patients, especially when symptoms involve fatigue, pain, sleep disruption, neurologic complaints, or prolonged illness. Depression can also occur as a reaction to chronic illness, delayed diagnosis, and reduced quality of life.

Can Lyme disease cause anxiety and depression?

Yes. Some patients with Lyme disease report anxiety, depression, panic symptoms, mood changes, irritability, sleep problems, and cognitive symptoms. These symptoms should be evaluated carefully rather than assumed to be purely psychiatric or purely infectious.

What mental symptoms can occur with Lyme disease?

Reported mental and cognitive symptoms include depression, anxiety, mood swings, irritability, brain fog, poor memory, difficulty concentrating, sleep disturbance, panic episodes, and emotional instability. Not every patient develops these symptoms, and other causes should also be considered.

Can Lyme disease be misdiagnosed as depression?

Yes. Lyme disease may be mistaken for depression when fatigue, brain fog, pain, and reduced function are interpreted only through a psychiatric lens. A broader evaluation is important when symptoms fluctuate, migrate, or occur with physical complaints.

Does treating Lyme disease improve depression?

Some patients report improvement in mood, energy, cognition, and sleep after Lyme disease treatment, especially when infection or inflammation is contributing to symptoms. However, depression may also require direct mental health care, and treatment decisions should be individualized.

Can Lyme disease cause mood swings?

Yes. Mood swings, irritability, emotional instability, anxiety, and depressive symptoms have been reported in some patients with Lyme disease, particularly when neurologic, sleep, pain, or inflammatory symptoms are also present.

Can Lyme disease affect the brain?

Lyme disease can affect the nervous system in some patients. Neurologic Lyme disease may involve the brain, cranial nerves, spinal cord, or peripheral nerves and can contribute to cognitive symptoms, headaches, sleep disturbance, mood changes, or other neurologic findings. Other medical conditions can cause similar symptoms, so careful evaluation is important.

Clinical Takeaway

Depression, anxiety, and other mental health conditions are real and deserve careful treatment. But when mood symptoms occur with fatigue, brain fog, migrating pain, sleep disturbance, neurologic complaints, or unexplained physical decline, clinicians should avoid stopping the evaluation too soon.

A psychiatric diagnosis should not prevent clinicians from continuing to evaluate new, progressive, or unexplained physical symptoms, including Lyme disease and other medical conditions that may contribute to depression, anxiety, cognitive symptoms, or mood changes.

Related Articles

These related articles explore psychiatric symptoms, neurologic Lyme disease, depression, and delayed diagnosis.

Suicidal behaviors in patients with Lyme disease
16-year-old boy with Lyme disease presenting as depression
Neuropsychiatric Lyme disease
Brain fog and Lyme disease
Lyme disease misdiagnosis

References

1. Šegždaitė G, Aliukonytė O, Pociūtė K. Neuropsychiatric Manifestations of Lyme Disease: A Literature Review of Psychiatric and Cognitive Impacts. Acta Med Litu. 2025;32(1):6-21. doi:10.15388/Amed.2025.32.1.17.
2. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151(11):1571-1583. doi:10.1176/ajp.151.11.1571.
3. Fallon BA, Madsen T, Erlangsen A, Benros ME. Lyme Borreliosis and Associations With Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Study. Am J Psychiatry. 2021;178(10):921-931. doi:10.1176/appi.ajp.2021.20091347.
4. Hündersen F, Forst S, Kasten E. Neuropsychiatric and Psychological Symptoms in Patients with Lyme Disease: A Study of 252 Patients. Healthcare (Basel). 2021;9(6):733. doi:10.3390/healthcare9060733.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention