Understanding Depression: Causes, Complications, and Treatment

Written By Adama Diarra, DO, FACP

What is Depression?
Depression, also known as Major Depressive Disorder (MDD), is a mental health condition that affects not only mood but also the body, cognition, and behavior. It goes beyond occasional feelings of sadness or “the blues.” For many, depression manifests as a lack of interest or pleasure in life, fatigue, difficulty concentrating, changes in sleep and appetite, or feelings of worthlessness. These symptoms can persist for weeks, months, or even years without treatment. The mind and body are intricately linked, which makes untreated depression a significant risk factor for overall health.

Depression Without Sadness: The Hidden Symptoms

Not everyone with depression experiences sadness. Some people might feel emotionally numb or disconnected. Others might experience changes in cognitive function, such as memory issues or trouble making decisions. This can lead to depression being overlooked or misdiagnosed, as it doesn’t always fit the typical stereotype of sadness and crying.

In "The Body Keeps the Score" by Dr. Bessel van der Kolk, he explains how trauma and stress can manifest as physical symptoms like chronic pain or digestive issues. These symptoms are part of how the body responds to unresolved emotional and psychological stress, highlighting the deep connection between mental and physical health.

What Leads to Depression?

Depression can result from a variety of factors, often a combination of genetic, biological, environmental, and psychological contributors:

  • Biological Factors: An imbalance of neurotransmitters such as serotonin, dopamine, and norepinephrine in the brain plays a role in depression. Many therapies aim to restore balance by increasing or adjusting the levels of various neurotransmitters. More on this under “Treating Depression” below. Genetics also have a significant influence—those with a family history of depression are more prone to develop the condition.

  • Psychological and Social Factors: Trauma, prolonged stress, childhood neglect, and major life changes (such as loss or financial stress) can trigger or worsen depression. Dr. van der Kolk's research in "The Body Keeps the Score" emphasizes that trauma, even when it seems distant or dormant, can continue to affect brain function and mental health.

  • Medical Conditions and Substance Use: Chronic illnesses like diabetes, heart disease, and chronic pain disorders are linked to higher rates of depression. Additionally, substance abuse—either as a coping mechanism or due to chemical dependence—can lead to or exacerbate depression.

Potential Health Complications of Untreated Depression

Untreated depression can have serious consequences for both mental and physical health:

  • Cardiovascular Issues: Depression has been shown to increase the risk of heart disease, high blood pressure, and stroke. Studies from the Journal of the American Medical Association (JAMA) indicate that depression contributes to higher mortality rates in patients with heart disease.

  • Cognitive Decline: Depression, especially if untreated, has been associated with an increased risk of dementia and other cognitive disorders. Persistent depressive symptoms can damage parts of the brain responsible for memory and decision-making.

  • Substance Abuse and Self-Harm: Depression increases the likelihood of using drugs and alcohol as a way to self-medicate. This can lead to a vicious cycle of worsening mental health and physical complications, including overdose. The risk of suicide is also significantly higher among individuals suffering from untreated depression.

Treating Depression

Early Detection and Monitoring

Early diagnosis is essential in preventing the progression of depression and avoiding these severe complications. Regular check-ups with a primary care provider or a mental health professional, including depression screening tools like the Patient Health Questionnaire-9 (PHQ-9), can identify early signs of depression. This is especially important for patients with a family history of mental illness or those dealing with chronic health conditions.

Lifestyle-Based Management

Lifestyle changes can have a profound impact on managing depression, though they are often best used alongside other treatments.

  • Exercise: Physical activity is known to boost levels of endorphins, the body's natural mood enhancers. The American Journal of Psychiatry reports that regular exercise can significantly alleviate symptoms of depression. A systematic review and meta-analysis published in October 2024 examined 25 randomized clinical trials involving over 1,900 patients diagnosed with both cancer and depression. The study assessed the effects of aerobic exercise on depression severity over different timeframes: at 1 month (short-term), between 1 and 6 months (medium-term), and 6 to 12 months (long-term). Without diving into the detailed statistics, the findings consistently showed that patients in the exercise group reported significant improvements in their depressive symptoms at all time points.

    If I had absolute power, I'd mandate exercise for everyone—muhahaha!

  • Diet: Eating a balanced diet rich in omega-3 fatty acids (found in fish like salmon and walnuts) and whole grains can have mood-boosting effects. Nutrient deficiencies, particularly in B vitamins and magnesium, are linked to depression. The relationship between the gut microbiome and depression is an emerging area of research. Some studies suggest that an imbalance in gut bacteria (dysbiosis) can influence brain function and mood through various mechanisms, including inflammation, production of neurotransmitters like serotonin, and the modulation of the immune system. This connection suggests that maintaining a healthy gut microbiome with a healthy diet may play a role in managing or reducing depression symptoms.

  • Sleep Hygiene: Lack of sleep or poor-quality sleep can worsen depression. Establishing good sleep habits, such as maintaining a consistent sleep schedule and limiting screen time before bed, can be helpful.

  • Mindfulness and Meditation: Techniques like meditation, yoga (one of my favorites), or mindfulness practices help to manage stress, improve mood, and reduce symptoms of anxiety and depression. Studies from Psychiatry Research have shown that mindfulness-based cognitive therapy (MBCT) can reduce the recurrence of depressive episodes.

  • Social Connections and Support Systems: I’m referring to real life social connections here. Having a solid support system and meaningful social connections is vital for managing depression. Whether through friends, family, support groups, or mental health professionals, regular interactions with others provide emotional support and a sense of belonging, both of which are protective factors against depression. Social isolation, on the other hand, can worsen symptoms. The COVID-19 pandemic highlighted the critical role of social connection. When a close-knit unit lost a member, this often cascaded into more losses and emotional struggles. In my practice, I witnessed many cases where, after a couple lost one spouse, the surviving partner would struggle and frequently experience a decline in both physical and mental health. This illustrates the powerful and sometimes fragile nature of social bonds and their impact on overall well-being.

    Sense of Purpose: Cultivating a sense of purpose and meaning in life is a powerful tool in combating depression. Engaging in activities that align with one’s values, such as hobbies, work, volunteering, or creative pursuits, can foster a sense of fulfillment and direction. Studies suggest that people with a strong sense of purpose often report better mental health and lower levels of depression. Feeling that one's life has meaning can provide a buffer against the emotional toll of depression and contribute to overall well-being.

    For me, practicing medicine has been a significant part of my purpose, but I’ve also realized that I’m not as happy when I’m not doing other things that bring me joy and balance. Coaching soccer, gardening when the weather is nice, running a few times a week (usually toward a slow half marathon or 10K), taking a walk, practicing yoga weekly, learning a new topic or skill, or playing a board game with my family are just a few of the activities that lower my stress and keep me grounded. These pursuits help reduce my stress hormone levels and give me the sense of purpose and balance I need to stay mentally and physically healthy.

Medication for Depression

When lifestyle interventions are not enough to manage depression, medication is often necessary. Here are the most common types of medications prescribed for depression:

  1. Selective Serotonin Reuptake Inhibitors (SSRIs)
    Examples: Fluoxetine (Prozac), Sertraline (Zoloft), and Escitalopram (Lexapro). These are the most common I have prescribed for lifestyle resistant depression.
    How They Work: SSRIs increase serotonin levels in the brain, which can improve mood, energy levels, and emotional regulation.
    Pros: Generally well-tolerated with fewer side effects.
    Cons: Side effects may include nausea, headaches, or sexual dysfunction. It may take several weeks to see improvement.

  2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
    Examples: Venlafaxine (Effexor), Duloxetine (Cymbalta).
    How They Work: SNRIs increase both serotonin and norepinephrine levels to help improve mood and energy levels.
    Pros: Effective for patients who do not respond to SSRIs, also used for chronic pain management.
    Cons: Side effects may include increased blood pressure and sleep disturbances.

  3. Tricyclic Antidepressants (TCAs)
    Examples: Amitriptyline (Elavil), Nortriptyline (Pamelor).
    How They Work: TCAs work by increasing the levels of norepinephrine and serotonin.
    Pros: Effective for more severe forms of depression.
    Cons: More side effects (drowsiness, weight gain, dry mouth) and are often used when SSRIs/SNRIs are not effective.

  4. Monoamine Oxidase Inhibitors (MAOIs)
    Examples: Phenelzine (Nardil), Tranylcypromine (Parnate).
    How They Work: MAOIs block the enzyme monoamine oxidase, which breaks down serotonin, norepinephrine, and dopamine.
    Pros: Effective for treatment-resistant depression.
    Cons: Strict dietary restrictions (e.g., avoiding aged cheeses, wine) and potential for significant drug interactions.

  5. Atypical Antidepressants
    Examples: Bupropion (Wellbutrin), Mirtazapine (Remeron).
    How They Work: These medications work on different neurotransmitters. Bupropion, for example, increases dopamine and norepinephrine, helping improve focus and energy.
    Pros: Bupropion may aid in smoking cessation and does not cause sexual side effects like SSRIs.
    Cons: May cause anxiety or insomnia in some patients.

Combined Treatment Approach: A Marathon, Not a Sprint

Depression treatment is often most effective when multiple approaches are combined. Medication can be crucial for stabilizing mood, while lifestyle changes and therapy address the underlying causes of depression and help prevent relapse. It’s important to remember that depression treatment can take time. Results aren’t immediate, and finding the right combination of therapies is often a process of trial and error. Like a marathon, treating depression requires endurance, patience, and persistence.

Every patient is unique, and the best treatment plan will depend on their personal history, symptoms, and health status. A healthcare provider can work with each individual to design a comprehensive, personalized plan to manage and eventually overcome depression.

References:

  1. American Psychiatric Association. (n.d.). Practice guidelines for the treatment of patients with major depressive disorder.

  2. Kulchycki, M., Halder, H. R., Askin, N., Rabbani, R., Schulte, F., Jeyaraman, M. M., Sung, L., Louis, D., Lix, L., Garland, A., Mahar, A. L., Abou-Setta, A., & Oberoi, S. (2024). Aerobic physical activity and depression among patients with cancer: A systematic review and meta-analysis. JAMA Network Open, 7(10), e2437964. https://doi.org/10.1001/jamanetworkopen.2024.37964

  3. Mayo Clinic. (n.d.). Depression (major depressive disorder). Retrieved from https://www.mayoclinic.org

  4. Van Der Kolk, B. (2015). The body keeps the score: Brain, mind, and body in the healing of trauma. Penguin Books.

  5. The Journal of the American Medical Association (JAMA). (n.d.). Depression and heart disease: The link and management.

  6. World Journal of Psychiatry. (n.d.). The role of exercise in treating depression: A review of clinical studies.