Medical Conditions As a Cause of Depression

Some disease processes can cause physical changes in the brain structure and function. These, in turn, can cause depression because of their effect on neurotransmitters and neurons. In some cases, the meaning of the disease itself causes depression, especially if it is chronic: It can cause grief and perceived loss and control in an affected person. In other cases, there is actual irreversible damage to the brain, the neurons, and neurotransmission, which causes depression.

It is a vicious cycle: Illness causes depression, and studies show that depression lowers immunity, which...causes more susceptibility to illness.

Struggling With Depression

What Kinds of Medical Conditions Can Cause Depression? Common examples of these include:

• Infections (like Epstein-Barr virus, long-COVID, HIV/AIDS, syphilis), most of which can cause inflammatory changes in the brain and subsequent damage.

• Hyperglycemia of uncontrolled diabetes can lead to neurovascular destruction (neuronal and vascular destruction in the brain), leading to gray matter attrition and changes in neurotransmission (see Depression: Overview). These processes cause a change in mood. In fact, according to NIH publications,10-15 percent of those with diabetes experience depression.

• Hypothyroidism

• Chronic kidney disease tends to cause neurologic damage and concomitant mood changes like depression

• Autoimmune diseases like Guillain-Barré and multiple sclerosis (MS) often cause destruction and alteration of brain structure and function

• Cancer/alteration or loss of a body part can also cause neurochemical changes within the brain, often causing depression.

• Being diagnosed with a chronic condition

• Painful conditions

• Experiencing a heart attack or receiving a terminal diagnosis often forces people to confront their own mortality, which may trigger depression.

  
  

This is not to say that depression is only caused by physical neurologic changes, but a good deal of it is.

At this point, MRIs can discern certain patterns of neurologic changes in a depressed person's brain; however, there are so many more complex patterns in the brain that it is difficult to use as a diagnostic tool specific for depression. 

In the case of illness-related depression, a multidisciplinary approach would be optimal in treating depression. Treating the underlying medical disorder (to decrease physical symptoms and fight the progression of the disease) combined with the use of antidepressants (to help increase neurotransmitters like serotonin, norepinephrine, dopamine, and others) along with therapy (to form new neuronal transmission pathways) could, perhaps, minimize depression through repair and possibly reversal within areas of the brain.

Presumably, if some illnesses can be recognized and managed early on, there is less likelihood of permanent neurologic damage and permanent changes within the brain. Some examples include debilitating diseases like chronic pain (such as rheumatoid arthritis [RA], osteoarthritis and fibromyalgia), migraine headaches, irritable bowel syndrome [IBS], insomnia and some acute metabolic disorders like hyponatremia and hypercalcemia, hypothyroidism, and adrenal disorders, hypothyroidism (thyroid hormones can change serotonin levels) and insulin resistance. Treating the underlying disorder and symptoms early might prevent chronic depression.

When there has been extensive damage to brain structure and function, depression is likely more difficult to treat. For example, a major cerebrovascular accident (stroke), epilepsy, Parkinson’s disease (Parkinson's patients require very specific antidepressants), Alzheimer’s (especially during the early and middle stages when there is damage to gray matter, neurons, and neurotransmission), and other forms of dementia. We can "fix" some chemicals and form new patterns of thinking, but we cannot generate new neurons in the brain: we don't make gray matter. 

So, there is a promise, but remember, it sometimes takes a LOT of work. No one ever said it would be easy.

Medical Conditions As a Cause of Depression-

Other Medical Causes of Depression

Environmental Toxin Exposure as a Cause of Depression

Exposure to various toxic substances in the environment can cause neurotoxicity, endocrine changes, and changes in neurotransmitter function. Frequent exposures to substances heavy metals (especially cadmium and lead), chronic pesticide use, and particulates in air pollution, among others) can cause neurologic changes resulting in depression. They do this by various mechanisms (discussion in each link).

A blood sample can be tested for lead and cadmium if there is a question of overexposure.

Treatment: The best answer to this is, of course, avoidance of - or minimal exposure to - these substances in addition to other recommendations to treat depression, if necessary.

Vitamin and Mineral Deficiencies as a Cause of Depression​

Nutrition, as well as vitamin and mineral deficiencies, can cause depression (long-term deficiency can actually cause permanent brain damage).

Vitamin deficiencies: Vitamin A, B6, B12, thiamine (B1), folate (B9), vitamin C, vitamin D, E, and K can cause physical and neurologic changes that cause depression. This is especially true of the B vitamins, which are, in part, responsible for the production and structure of neurotransmitters serotonin, dopamine, and GABA. Sometimes, when there is a deficiency, neurons can atrophy and die, and neurotransmitters fail to function properly, potentially causing depression.

Mineral deficiencies: Deficiencies in iron, calcium, magnesium, selenium, zinc, and iron can cause depression as well. Most of these are responsible for some degree of nerve transmission in the brain and elsewhere in the body.

Vitamin and mineral deficiencies are primarily caused by an inadequate dietary intake or by decreased gastrointestinal absorption. Gastrointestinal problems can be caused by a number of things. Among these are cystic fibrosis, alcoholism, physiologic changes of aging, chronic pancreatitis, celiac disease, Crohn's disease, lactose intolerance, surgeries (gastric bypass, resection), pernicious anemia (inability to absorb vitamin B12), various medications, some gastrointestinal infections, and others.

Although long-term deficiencies can cause damage to the neuronal systems of the brain, most short-term deficiencies can be treated, in turn, treating the manifestation of depression. Initially, blood levels should be checked and a good nutrition/vitamin and mineral supplementation program initiated accordingly. If levels are stabilized and depression persists, it would be time to consider other potential causes, remedies, and  treatments for depression. In many cases, it will not hurt to take a reputable multivitamin anyway - particularly of you drink alcohol which depletes many vitamins and minerals.

Medications as a Cause of Depression

Besides straightforward medical conditions that can cause depression, some medications can inadvertently cause these mood changes . If you areon a quest to find the unknown cause of your depression, consider checking your medicine cabinet. Some medications can cause depression by changing neurotransmitter levels. Some of these include:

• Sedatives

  • Ambien (zolpidem)

  • Barbiturates

  • Benzodiazepines: Xanax (alprazolam), Ativan (lorazepam)

• Acne Treatment

  • Isotretinoin

• Allergy & Respiratory Medications

  • Antihistamines: Zyrtec (cetirizine)

  • Singulair (montelukast)

  • Anticholinergics: Benadryl (diphenhydramine), oxybutynin

• Corticosteroids

  • Prednisone

• Pain Relievers

  • Ibuprofen

  • Opioids (listed under multiple categories)

• GERD & Acid Reflux Medications (Proton Pump Inhibitors)

  • Omeprazole (Prilosec)

  • Lansoprazole (Prevacid)

• Antiseizure Medications

  • Lamotrigine

  • Gabapentin

  • Dilantin

  • Topiramate

• Antibiotics

  • Gentamicin

  • Ciprofloxacin (“Cipro”)

• Blood Pressure Medications

  • Beta blockers (often end in “-olol”)

• Cholesterol-Lowering Drugs (Statins)

  • Atorvastatin (Lipitor)

  • Pravastatin (Pravacol)

  • Rosuvastatin (Crestor)

• Thyroid Medications

  • Levothyroxine

• Hormones

  • Birth control pills

  • Estradiol

  • Finasteride (Propecia)

• Mental Health Medications

  • Antidepressants: amitriptyline, SSRIs

  • Anti-anxiety meds: benzodiazepines (Xanax, Ativan)

So many people respond differently to medication.

If taking a certain medication is the only cause of your depression, that would be an easy answer. If you think this may be the cause, discuss it with your healthcare provider. They may help to find a substitute. (Reminder: Don’t just come off your medication without discussing it with a healthcare provider first).​

Genetics/Heredity as a Cause of Depression

Children of parents with major depression often ask: Am I going to suffer from depression the way my parent does?

Genes passed on from generation to generation wire your brain function. According to a publication from Stanford if a parent or sibling has major depression, the possibility that it is inherited is from 30% to 50%. Inheritance is also responsible for other mental health concerns.

Genes can affect the development and processing mechanism of many brain features: From neuron structure and neurotransmission to, presumably, some processes involved in neuroplasticity. Because of this, it is important to consider family history when looking into a person’s depression (or any mental health problems for that matter) because there can be a strong association. If a parent is successfully on a particular psychiatric medication, it sometimes helps to consider that the same medication will work on the child, or even a sibling because of the possibility of genetics.

If you are worried about having inherited genes for depression, you can rest assured that genetic traits do not always manifest in relatives: That means, family members will not always develop symptoms. Often, the genes are simply not expressed. And, in consideration of nature versus nurture, the environment can play a great role in whether or not the genes are expressed in a negative or dysfunctional fashion. It is also important (and promising) to note that some genes are inherited for "resilience," which is the ability to adapt to challenging life circumstances.

Environmental Conditions Can Cause Depression-

Neurological Changes From Physical, Mental, and Social Conditions

​As mentioned earlier, the environment can affect our mental health. If a person is exposed to trauma, stress, socioeconomic shortcomings, or ruminations about these things, they can trigger neurochemical changes to a point of not just sadness, but other, more severe forms of depression. No, our current environment does not help. Think of how many negative news stories we hear (click-bait) from the media every day. Even the number of "likes" a person gets on Facebook can affect serotonin levels. Kids get bullied, but did you know that, according to Psychology Today, 31% of adults get "bullied" as well?. We get hit with negative punches from the left and the right, and we have to learn to dodge them, challenge them, or totally bypass them. We need to learn to be resilient. Throughout history, there have been challenges.

If environmental factors seem to be causing your depression, remove yourself from your negative environment, if only for a while. Make time for yourself; take care of yourself. After all, what you perceive of your life is the life you are living at the time. You can change perceptions.

General Approaches to Help Depression

Depression triggered by underlying medical or environmental factors is best managed through optimized care focused on the primary condition. At the same time, the depression can be treated as well, either concurrently or alone. There are numerous approaches to this:

• Reduce stress

• Exercise or walk

• Try techniques such as yoga, tai chi,

• Meditation:

  -Deep breathing exercises - This helps release endorphins in your brain, which are"feel good" hormones. This technique is practiced by taking a deep breath through your mouth using your diaphragm muscle located just beneath your lower ribs (instead of using neck, shoulder and upper chest muscles), pausing and then releasing the breath through the mouth. Repeat this several times.

  -Guided Imagery - Think of a relaxing situation or a place you have been and focus on only that - focusing on texture, smells and visuals.

  -Use Mindfulness - This is when a person focuses on the present moment, feeling and experiencing the moment with awareness and acceptance, not judgment. This reportedly helps the fronto-limbic area of the brain, which is responsible, in great part, for emotional regulation and processing.

  -Try Progressive Muscle Relaxation Exercises: This is done by tightening muscle groups for eight seconds then relaxing them for several seconds: Begin with facial muscles, with the face, moving to the scalp - tighten muscles eight seconds, then relax; then the neck, doing with each muscle group of the chest, back, pelvis, extremities and so on. This releases some tension and stress. If you do not have time to move through all of your muscle groups, do this with those muscles you believe have the most tension.

  -Analytical Meditation - This meditation involves focus on an object or a concept and focusing on only that.

  -Body Scanning-Focus on a part of your body and feel relaxation, warmth, release of tension

  -Reiki, where a person connects with a universal positive energy. There are quite a few online sources with instructions and many live instructors who teach these methods.

• Journal: Write your thoughts in a journal 

• Talk to someone about your problem - friends, family: Don't worry, people who care about you are commonly concerned and want to help

• Practice affirmations - saying good things about yourself

• Listen to good music

• Set realistic goals and work toward them

• Recognize and celebrate even small successes

• Humor therapy - laugh or just make yourself smile (usually used as an adjunct to other therapies).

• Light therapy - May help non-seasonal depression in conjunction with serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

  
  
  
  

​Counseling often helps: Sometimes, just being able to talk to someone helps more than you know. The best therapies all have one common bond: establishing a trusting relationship. If a counselor is good, they can work with you on different ways to cope and provide therapy that will suit your needs. Some of the more popular of these are mentioned in the following:

Therapies and Other Treatments for Depression

Cognitive Behavioral Therapy (CBT) - This is currently considered one of the best, if not the best, forms of therapy. There are several subtypes of CBTs, but they all work on the same premise: to help recognize and challenge dysfunctional thought patterns that underly a person's depression. 

​CBT is a way in which people promote neuroplasticity to improve. Through this kind of therapy, neurons can be trained to send impulses down different, new pathways instead of using the old negative pathways. The brain changes and adapts by forming new neural connections (or strengthening existing "good" ones) based on purposeful learning, recitation, and practicing more constructive thought patterns and positive experiences: Essentially "rewiring".  This implies that you can train your brain to think differently and more positively. It makes sense.

​ Types of CBT:

           -Cognitive Restructuring - Cognitive restructuring can help a person change their way of thinking about a situation. Using this therapy, a person learns to identify and challenge negative or irrational thought patterns and develop new patterns of thinking.

          ​ -Dialectic Behavioral Therapy (DBT) - Similar to CBT, but with DBT a person works on validating or accepting uncomfortable thoughts, feelings, and behaviors instead of fighting them.

           -Mindfulness-Based Stress Reduction Therapy (MBSR) - Helps people change their response to depressing and intrusive thoughts.

           -Motivational Interviewing (MI) helps people identify positive goals and factors that might motivate them to work toward those goals. 

           -Acceptance and Commitment Therapy (ACT) - This also helps direct a person to accept feelings and develop some tolerance to those feelings through the use of new coping mechanisms.

             Note: CBT is also effective for those with other mental health problems.

• Psychoanalysis is an interpersonal therapy that delves into a person's past, exploring possible roots of depression and working through the thoughts and feelings. It aims to help a person develop alternative, more effective coping mechanisms.

• ​Eye Movement Desensitization and Reprocessing (EMDR) - This therapeutic technique deals with traumatic memories and, in this case, depression due to trauma. The therapist guides the client to focus their eyes on an object as it moves repetitively from side to side. At the same time, they process through the negative traumatic memories and transition to positive ones. This is effective for many people. This treatment entails "rewiring" of the brain.

• Transcranial Magnetic Stimulation (TMS) This treatment is sometimes used when other conventional treatments have not worked. An electrical coil is placed on your scalp, through which electrical stimulation occurs. Current is sent to the area of the brain responsible for mood/depression, which results in "rewiring" of that area. Transcranial Magnetic Stimulation (TMS)

• TMS is typically well tolerated, usually with little or no discomfort. It is often given as an adjunct to medication. Interestingly, some of these devices are available online but the electrical charge is lower, so they may not be as effective as those at a clinic and their safety cannot be assured (not FDA approved). I'm not sure I would go this route.

       ​TMS is a time-consuming therapy. Treatments are, on average, 30 minutes long, five times a week for about six weeks (this is variable). According to PubMed, about 36% of people experience improvement (many other resources say more), and sometimes a relapse occurs, but a person can undergo more than one course.

• Electroconvulsive Therapy (ECT) is often portrayed as an intrusive maniacal treatment straight out of One Flew OVER the Cuckoo's Nest. But the fact is that it can work as a last resort when therapy and medication are not working. It is another type of electrical stimulation to the brain, more powerful than TMS, eliciting a small seizure under general anesthesia. The remission rate is higher than 50% and is best used in conjunction with and followed by antidepressant medications to avoid relapse, which can occur.

      Immediately after the procedure, there may be some brief disorientation, nausea, headaches, fatigue, muscle aches, and a brief episode of memory loss, but this usually passes quickly. Very occasionally, some of these side effects last days to weeks, maybe longer. The question is, do the benefits outweigh the risks? For a person with severe depression, they may.

​​Over-the-Counter Medications

There are no reliable over-the-counter medications that treat major depression. You can try to do it by lifestyle changes, like getting enough sleep, eating a truly nutritional diet, and taking multivitamins (especially B12). While those things may support your health, and to a small degree your mood, they are not reliable avenues to treating major depression.

Considered Natural and Herbal Remedies

• Kava Kava

• Lemon Balm

• St Johns Wort

• SAMe

• 5HTP

• ​​DHEA (dehydroepiandrosterone) is a substance produced by the adrenal gland. It is a      prohormone or precursor to certain hormones including estrogen and progesterone  (among others). It also has neuroprotective effects and increases serotonin and dopamine levels in the brain. It has some medication interactions and quite a few potentially unwanted side effects however may help with depression. As a mood enhancer in depression, DHEA usually takes up to six months for optimal effects  Because it does increase estrogen, there is a potential risk of taking in those who have hormone-receptive cancer.

• Chamomile

• Ginseng

• Lavender

• Omega 3 - Fish oil/krill oil - has a lot of beneficial properties for the brain (and possibly for depression): Decreases inflammation of the brain tissue, thereby protecting neurons from damaging effects. It reportedly has neuroplasticity benefits, and because it enhances communication between neurons, it promotes neuroplasticity. In general, Omega-3 protects the gray matter and white matter of the brain from some degeneration.

  Omega 3s can take up to six months to work, so you may want to use it to supplement a prescription antidepressant medication.

Prescriptive Medications for the Treatment of Depression

In general, medication works better when given as an adjunct to counseling. However, if a person really doesn't want to engage in counseling, just taking medication is better than nothing. 

Regarding medication: Some people are concerned about not being able to "feel" their emotions when taking an antidepressant. This is called "blunting" and is a reason why patients sometimes come off their medications. It is important that you speak to the person prescribing the medication if you feel this is occurring (there are many types of medications for depression on the market, and with these, it's like a shoe that fits. You sometimes have to try on several before you find the one that fits the best. In some cases, there is no such shoe; in which case, you may want or need to try some of the other approaches discussed here.

• SSRIs (serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) are widely used antidepressants. These medications increase concentrations of the neurotransmitters in the brain responsible for elevating a person's mood: Serotonin, dopamine, and norepinephrine in the brain. These neurotransmitters are responsible for elevating a person's mood. Common antidepressant medications here include escitalopram (Lexapro), citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil, Pexeva), sertraline (Zoloft), and vilazodone (Viibryd).

• Tricyclic Antidepressants also increase levels of available neurotransmitters, serotonin and norepinephrine. The best-known of these is Amitriptyline (Elavil). Because of their propensity for side effects, they are not prescribed as much as the SSRIs and SNRIs mentioned above. Sometimes tricyclics are also used off-label to help decrease neuropathic pain.​

• MAO inhibitors are the oldest class of antidepressants, developed in the 1950s. ​They have a lot of interactions with foods, drinks, other medications and herbs so these are not used a lot anymore.

• ​Lithium is occasionally  used off-label (that is, not approved for depression by the FDA) in treatment-resistant depression when other means fail but people need to be closely monitored for side effects and lithium levels need to be monitored.

Some newer potential treatments are in the early stages of testing and development. Interestingly, some good results with depression are coming from these but, since they are known as illicit drugs, they are controversial. These include:

• Ketamine (esketamine) was originally used as an anesthetic during the Vietnam War and has been used for that purpose ever since. It is a relatively new off-label approach to treatment-resistant depression. The benefit of ketamine is that, if it is going to work for depression (about 50%), it works fast, within two to four hours, and the effects last for several days. So if there is a person with severe acute depression and suicidality, this may help. The downside is that it can cause some psychiatric/dissociative (i.e. disconnectedness, hallucinations) characteristics and also has the potential for addiction, and it should not be used by people with substance abuse issues.

Exactly how ketamine works in the brain is not yet clear. There are several theories; the primary premise is that Ketamine decreases glutamate (an excitatory neurotransmitter) and increases GABA (a "calming" neurotransmitter) activity in the brain. This essentially repairs and enhances neurotransmission in the prefrontal cortex, in turn, reducing depression. Because it works on different brain receptors than SSIs and SNRIs, it may be a good option when a person does not respond to conventional antidepressants. Ketamine is also considered an adjunct in creating greater neuroplasticity-helping to create new neuronal channels, transformational in depressive thinking patterns.

​There are other theories that are far beyond the scope of this site. For more detailed information, see the NIH publication: Ketamine Treatment for Depression: A Review. There is a good deal of ongoing research and emerging information on Ketamine. It is approved by the FDA for the treatment of major depression. For those interested (especially for those who cannot afford it), there are clinical trials in several states.

Ketamine (esketamine) is a controlled substance. It is given under close monitoring in a ketamine clinic or, in some cases, at home. It is administered intravenously or intranasally  (Spravato). While dosing is different for many people, it is generally given three to six times over the course of a few weeks.

• Psilocybin mushrooms are another novel approach to treatment-resistant depression. It is similar to ketamine in that it enhances the effects of neurotransmitters and neuroplasticity. These rapidly produce a reduction in depressive symptoms almost immediately, and the antidepressant effects last for several weeks, sometimes even longer. More research is currently being done on psilocybin and depression, and although it has been shown to decrease depression in many people, it has not been approved by the FDA for the treatment of depression.

Because of some of the potential side effects of psilocybin (sometimes anxiety, confusion, paranoia, and others), it is not for everyone, and because of the hallucinations and the "high" some people feel it is considered an "illicit drug". When used for depression, counseling is used as an adjunct. It is administered under controlled conditions, and the only clinics where it is administered at this time are in Oregon (as of November 2024). Colorado is reportedly planning to open psilocybin clinics in 2025.

Hopefully, the above symptoms and approaches to major depression will help you understand depression and the many strategies that can be used to help deal with it successfully. If one does not work, try another. If you believe you are depressed, you need to do something about it ; otherwise you just remain your old "dumpy" self. The answer rarely comes to you; you need to seek it out.

If you are depressed, remember: Things really can and do change. Take out a pen and paper. You have strengths, potential, capabilities, and resources. Dig deep if you have to. Think of what worked for you in the past on your better days. Then, write them down and start working on optimizing them.

Remember: If you are severely depressed or are considering suicide, call the suicide hotline:

9-8-8

You can make it another day. Life is dynamic. Ever-changing. And that may be a good thing