Approximately 8.3 percent of U.S. adults experienced at least one major depressive episode in 2021. Remarkably, that rate more than tripled during the COVID-19 pandemic among participants of one study; the prevalence of depression increased to approximately 27.8 percent of U.S. adults by mid-April 2020.

It is estimated that 21 percent of women and 11 percent to 13 percent of men in the United States have dealt with major depression at some point. However, depression is not limited to adults.

The Substance Abuse and Mental Health Services Administration did an extensive U.S. survey in 2021 (pdf) and found that just over 20 percent of individuals aged 12 to 17 years old had a major depressive episode, and 3.4 percent of individuals in this same age category attempted suicide within the past year of the study.

The American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) classifies depressive disorders into the following categories.

Major Depressive Disorder

Also known as clinical depression, this is the most severe form. It is also one of the most common. To be diagnosed with major depressive disorder (MDD), you would have experienced sadness or feeling low or worthless most days for at least two weeks, along with changes in sleep, appetite, and interest in activities.

Specific forms of MDD include:

• Seasonal affective disorder: This form of depression typically starts in the fall, continues through winter, and goes away in the spring.
• Prenatal and postpartum depression: Prenatal depression occurs during pregnancy; postpartum depression begins within four weeks after delivering a baby.
• Atypical depression: This is referred to as MDD with atypical features. One of the key differences between MDD and atypical depression is that a person with this type of depression feels a temporary improvement in mood following a positive event. Individuals in this category also experience rejection sensitivity and increased appetite.

Other

• Persistent depressive disorder (dysthymia): This is mild or moderate depression that persists for at least two years. The symptoms are less severe than MDD but are chronic.
• Premenstrual dysphoric disorder: With this type of depressive disorder, you have premenstrual (PMS) symptoms and debilitating mood symptoms of anxiety, extreme irritability, or depression. While these symptoms may improve a few days after a woman’s period begins, their severity is great enough to impact her life adversely.
• Disruptive mood dysregulation disorder: This childhood disorder was added to the DSM-5 in 2013. Symptoms include ongoing and extreme irritability and frequent, angry outbursts. Symptoms typically begin by age 10.
• Depressive disorder due to another medical condition: Several medical conditions can affect the body in ways that cause depression symptoms.

Symptoms of depression can include any number of the following:

• Feelings of sadness or emptiness.
• Outbursts of anger, irritability, or agitation over minor matters.
• Feeling worthless or hopeless.
• Guilt and fixation on past failures.
• Disturbed sleep, whether insomnia or sleeping excessively.
• Loss of pleasure or interest in most (or all) normal activities.
• Lack of energy, tiredness, and being overwhelmed by even small chores.
• Disturbed appetite, including decreased appetite and weight loss, or increased appetite and weight gain.
• Trouble concentrating and remembering things.
• Unexplained pain in different parts of the body.
• Sexual dysfunction.
• Frequent thoughts of death.
• Suicidal ideation and possible suicide attempts.

Symptoms of depression in children and teenagers are similar to those in adults, with some differences. Younger children may exhibit sadness, clinginess, worry, complain of aches and pain, or refuse to go to school.

Teens may exhibit the same symptoms as adults, but also:

• Use recreational drugs.
• Drink alcohol.
• Perform poorly in school.
• Engage in self-harm.
• Avoid social interactions.
• Feel sensitive or insecure.

The causes of depression can be divided into two categories: congenital and acquired environmental.

1. Congenital

Congenital factors are things a person is born with, whether those factors are influenced by genetics or pregnancy conditions (i.e., smoking during pregnancy, exposure to toxins, etc.).

Researchers have identified more than 100 genetic risk loci for depression, confirming that depressive disorder has a strong polygenicity—meaning many genes may contribute to risk. A locus (plural loci) is a unique chromosomal location identifying a particular gene or DNA sequence.

In a large systematic review published in the international journal Medicina, researchers performed an in-depth analysis of genetic risk for MDD. They found that the GRIA, GRIN, GRIK, and SLC6A family genes seem to be the most crucial in conferring risk for MDD.

The SLC6A family of genes codes for transporters that mediate the reuptake of neurotransmitters such as serotonin, norepinephrine, dopamine, gamma-aminobutyric acid (GABA), and glycine.

Of particular interest, SLC6A4—one of the most widely studied genes—codes for the serotonin transporter, which is responsible for the reuptake of serotonin after it has completed sending its message.

Only a few gene families are implicated in conferring an increased risk for depressive disorders. For further research, this review article has summarized many research findings on genetic and epigenetic influences on depression.

Epigenetic

Epigenetic events occur when your DNA is biochemically modified, often due to environmental influences, including pollution exposure and diet habits. This can cause a change in the information obtained from the gene. Often this reduces gene expression, which can, in turn, reduce the amount of protein that the gene was coding for. This can significantly affect the individual’s biochemistry—and, therefore, physiology.

2. Acquired Environmental

Acquired environmental factors include factors not in your genome but in your environment, such as your childhood experiences, diet, exercise, use of certain substances, and life events.

Hypotheses on Mechanisms Behind Depression

How does a specific genetic background or environmental event “trigger” depression? What is happening in the individual, on a biochemical level, to cause this mood disorder?

These questions have been the focus of many studies, and in general, there are several hypotheses for how depression develops.

Neurotransmitter Abnormality

This hypothesis suggests depression is a deficiency in the brain’s serotonergic and/or noradrenergic systems. The idea is that too little serotonin and/or norepinephrine exists in certain brain regions, leading to depression. Though this hypothesis does make sense given that SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been proven very effective for many cases of depression, questions remain about the actual mechanism of these types of drugs. For instance, not all pharmaceuticals that enhance signaling in the serotonergic or noradrenergic systems alleviate depression symptoms.

Cytokine Abnormality

Studies have revealed a relationship between the immune and endocrine systems and neurotransmitters. A powerful presence of inflammatory factors has been discovered in some depressed patients. Studies indicate increased numbers of circulating white blood cells and proinflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-12 (IL-12), and IL-6, are linked to depression and also reveal a connection between tumor necrosis factor alpha (TNF-alpha), inflammation, and depression.

Impaired Gut–Brain Axis

The gut–brain axis is a bidirectional pathway essential to physiological balance. Enteroendocrine cells are found throughout the lining of the gut. These cells respond to nutrient and mechanical stimuli by releasing neurotransmitters and hormones such as serotonin, cholecystokinin, and ghrelin. Metabolites from bacteria in the gut, such as short-chain fatty acids, play a role in modulating the release of these neurotransmitters and hormones.

Several studies have revealed reduced microbiota diversity in depressed patients.

Impaired HPA Axis

The hypothalamic-pituitary-adrenal (HPA) axis is a pathway between a portion of the brain and the adrenal glands adjacent to the kidneys. This axis regulates the stress response. The thinking here is that stressful stimuli trigger hyperactivity of the HPA axis, resulting in abnormal amounts of cortisol being released from the adrenal glands in depressed patients.

One study found patients with depression symptoms exhibited heightened cortisol response to a test designed to cause stress. In a research article published in Frontiers in Psychiatry, researchers state, “It appears that cortisol dysregulation, specifically in response to stress, is reliably associated with severe and acute presentations of MDD.”

Anyone can develop depression, but there are certain individuals more at risk:

• Women: Depression is approximately 50 percent more common in women than men.
• People who have experienced traumatic life events: A childhood adverse event, death of a loved one, divorce, or other traumatic event can cause an individual to cross the threshold into depression.
• People with certain medical conditions: Certain conditions are associated with a higher likelihood of depression. Patients with cardiovascular disease have a greater incidence of clinical depression. Other conditions linked to depression include: hypothyroidism, Parkinson’s disease, Alzheimer’s disease, stroke, fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome.
• People with chronic pain: It is noteworthy that chronic pain has a significant link to depression. Chronic pain often causes depression, as up to 85 percent of patients with it suffer from depression. Researchers at the University of California, San Francisco, performed a systematic review to determine nervous system connections for psychological pain. They suggested a possible network that includes several portions of the brain, including the thalamus and prefrontal cortex. There is evidence that the development of pain and depression may share some identical nervous system changes, which could be an important route for initiating and exacerbating both conditions.
• People taking certain medications: Some medications can trigger depression, such as medications used to treat Parkinson’s disease, some cancer medicines, oral contraceptives, and corticosteroids like prednisone.
• People who consume excessive alcohol: Alcohol-induced depressive disorder occurs during and shortly after alcohol consumption or withdrawal. It typically goes away three to four weeks after the individual begins abstaining from alcohol.

Your health care provider should carefully assess your symptoms, medical history, and mental health history. To be diagnosed with a major depression episode, you must experience five or more depression symptoms for at least two weeks, with one of the symptoms being anhedonia or depressed mood. Anhedonia is a loss of interest or pleasure in things you previously enjoyed.

Your health care provider may give you a series of tests to assess your mental well-being. Your provider may also order bloodwork to determine if any underlying medical conditions are causing your depression.

Treatment for depression should be tailored to your individual needs. There are several effective ways to treat depression.

Psychotherapy

Psychotherapy is talk therapy with a mental health professional. Cognitive behavioral therapy (CBT) is one of the most common types of psychotherapy. It is known to be valuable for mild, moderate, and severe major depression, and studies show it is equally as effective as medication.

Medication

Various medications treat depression. Each person responds differently, and you may need to try more than one to find the right fit.

SSRIs are the most commonly prescribed class of antidepressants. These include the following:

• Citalopram.
• Escitalopram.
• Fluoxetine.
• Fluvoxamine.
• Paroxetine.
• Sertraline.

Monoamine oxidase inhibitors (MAOIs): These are the oldest antidepressants and often are reserved for depression that has been resistant to other medications. They require careful diet monitoring so you don’t have a medicine-induced hypertensive event.

Tricyclic antidepressants (TCAs): These are also an older class of antidepressants and often are reserved for depression resistant to other medications. They can have many unpleasant side effects, such as dizziness, constipation, dry mouth, blurred vision, confusion, increased appetite, weight gain, and cardiovascular complications such as irregular heartbeat.

SNRIs are another class of antidepressants, including:

• Desvenlafaxine.
• Duloxetine.
• Venlafaxine.

While antidepressant medications can be very effective in alleviating symptoms of depression for some individuals, they can have unpleasant side effects such as anxiety, tiredness, diarrhea or constipation, weight gain or weight loss, and sexual dysfunction. In addition, about half of depressed patients do not respond to SSRIs.

Fortunately, there are effective natural remedies that can help alleviate symptoms of depression.

1. Botanicals

• Saffron: Saffron, derived from the Crocus sativus flower, is used in South Asia and the Middle East as a spice and medicine. Studies reveal ingesting this spice can relieve depression with the same degree of effectiveness as the SSRI fluoxetine and the tricyclic imipramine.
• Green tea: The results of one systematic review and meta-analysis suggest consumption of green tea decreases the risk of depression symptoms. In a large study of 7,524 Chinese participants, researchers found that frequent green tea consumption was associated with a reduced risk of depressive symptoms.
• Lavender: In a meta-analysis of 17 articles, researchers found lavender has significant antidepressant effects. They found that oral administration gave the most effective results.
• St. John’s wort: Studies on St. John’s wort and its role in reducing depression have been conflicting. One meta-analysis of 27 clinical trials (3,808 patients) found St. John’s wort had a comparable response and remission rate of mild-to-moderate depressive symptoms compared to standard SSRIs. Authors noted that most of the studies were short-term (four to 12 weeks), so longer studies need to be done to ensure safety and long-term efficacy. They also noted the results apply to mild-to-moderate depression, so it is unclear whether St. John’s wort is effective for severe depression. Don’t take St. John’s wort if you take an SSRI because it could raise your serotonin levels to dangerously high. This herb can also weaken the effectiveness of birth control pills.
• Turmeric (Curcuma longa): Curcumin is the principal curcuminoid of turmeric. Several possible mechanisms of action for its antidepressant effects have been identified. In one randomized, double-blind study, 56 patients with MDD were given either curcumin (500 milligrams twice daily) or placebo. The study was eight weeks long. During weeks 4 through 8, the curcumin was significantly more effective than the placebo in improving mood-related symptoms as measured by the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). Further, curcumin seemed to show even greater efficacy in individuals with atypical depression.

2. Exercise 

Exercise has a significant antidepressant effect on those suffering from depression. Exercise is beneficial in numerous ways, including the following:

• Increased endorphin release: Endorphins are the “feel-good” chemicals in the brain. They act as natural painkillers and help elevate mood.
• Neurotransmitter regulation: Exercise can help modulate neurotransmitters like dopamine, serotonin, and norepinephrine.
• Self-esteem and confidence: Exercise can help you build confidence and healthy self-esteem. You develop a sense of pride and accomplishment as you set and achieve fitness goals.

3. Acupuncture 

In one eight-week controlled trial assessing the efficacy of electroacupuncture in MDD, scientists found no significant difference between the electroacupuncture-treated cohort and the SSRI treatment group regarding response rates in the 24-item Hamilton depression rating scale. Further, electroacupuncture showed more substantial improvement in patients’ feelings of despair than SSRIs.

It should be noted that this study was small (60 patients), and patients were allowed to choose which cohort they wanted to be part of at the onset, so it was not randomized. Regardless, the results are promising and warrant further study.

4. Light Therapy

Light therapy (LT or phototherapy) involves daily exposure to a specialized light source. In one meta-analysis of controlled trials, light therapy significantly reduced the severity of depression symptoms in patients with seasonal affective disorder (SAD). Further, the aforementioned meta-analysis also found light therapy significantly reduced the severity of depression symptoms in patients with nonseasonal depression. Effect sizes were equivalent to those in most pharmacotherapy trials for antidepressant medications, meaning the depression-relieving effects of light therapy are similar to the depression-relieving effects of antidepressants.

5. Psychedelics: MDMA and Psilocybin

MDMA is short for 3,4-methylene-dioxymethamphetamine, the active component of the drug ecstasy. MDMA quickly increases the amount of serotonin in the synapse, similar to SSRIs; however, SSRIs can take up to six weeks to change the brain’s neuronal signaling to produce the serotonin level needed to ease depression symptoms. With MDMA, relief from depressive symptoms could be instantaneous.

There are currently clinical trials testing the efficacy and safety of MDMA for the treatment of depression. The Multidisciplinary Association for Psychedelic Studies (MAPS) allows volunteers to participate in research studies on MDMA and other substances.

There has also been a recent exploration into treating MDD with psilocybin, the active compound in psychedelic mushrooms. A study published in 2022 in the Journal of Psychopharmacology found that participants’ symptoms of depression were significantly reduced for up to a full year after they received two doses of psilocybin in a research setting.

Research into the use of psychedelic substances is still in its infancy, and legality varies among states. However, preliminary research offers promise.

Mindset can have a huge impact on mood. A positive mindset involves purposefully reframing negative thoughts into positive ones. This can help you escape the rut of pessimism or self-criticism that can keep you in a negative state of mind.

Think about who you want to be and set attainable goals to get there. It may start as just having the goal of getting out of bed and showering each day. Start small, and you’ll feel a sense of accomplishment for each goal you accomplish, giving you momentum to keep moving forward to become the healthy, productive person you want to be.

You cannot necessarily prevent depression, but you can reduce your risk of developing it by following a healthy lifestyle. Consider implementing the following strategies:

• Eat a healthy diet: A healthy diet can significantly support mental well-being and decrease the risk of developing depression. Nutrient-rich foods such as vegetables, fruits, lean proteins, and healthy fats provide phytonutrients, fiber, vitamins, and minerals. Limiting sugar and processed foods will decrease inflammation and help your body function optimally.
• Exercise regularly: Exercise is a very effective way to elevate mood. Aim to get 20 to 30 minutes of activity at least five times weekly. It doesn’t need to be intense exercise—even a 20-minute walk can make a huge difference in your mental well-being.
• Get enough sleep: Getting the right amount of sleep (seven to eight hours) is crucial for healthy mental functioning. Don’t drink caffeine late in the afternoon. Try putting away your devices, such as phones or tablets, an hour before bed. Make sure you get to bed on time to get adequate sleep.
• Limit social media and screen time: Social media can cause some individuals to feel depressed, anxious, and lonely. Comparing yourself to others and reading negative news online can bring your mood down. Conversely, limiting your time on social media can help you focus on those around you and strengthen real-life relationships, greatly benefiting your emotional well-being.
• Reduce stress: Consider the areas in your life that are causing you stress. If you can do something about those things, consider setting goals to attain healthy boundaries in those areas. If you cannot change the circumstances, you can work to reframe your thinking to see how you can grow through those challenges.
• Evaluate medications: Some medications can contribute to feelings of depression. Consider whether you can stop your medication or switch to one not associated with causing or exacerbating depression. Be sure to consult your health provider before going off any medications.
• Limit alcohol: Alcohol is a known depressant and should be limited to protect your mental well-being.
• Avoid smoking: Smoking is very hard on the body and can lead to several health issues, such as cancer, respiratory problems, and cardiovascular disease. Dealing with these health issues can take a toll on your mental health and may trigger some individuals to become depressed.