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7 Things We Now Know About Depression

It’s a complicated illness, with no exact cause, but there is still a lot we now understand about depression, thanks to the work of dedicated scientists. For World Mental Health Day, we look at the facts, common misconceptions and research that’s underway.

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Despite how often you hear the term, depression is still a largely misunderstood—and stigmatized—disease.

Perhaps for this reason, depression is the #1 cause of disability around the world, since many people may not seek the treatment they need. In fact, an estimated 300 million people around the world are living with depression. That’s an increase of more than 18% between 2005 and 2015, according to the World Health Organization.

But there’s reason to have hope—and it starts with understanding what the disease is really about, which can help reduce stigma.

Depression is a mental disorder that affects how you feel, think and act. And it can strike anyone.

“It is characterized by a combination of symptoms, including low mood, loss of positivity, feeling guilty or worthless, sleep disturbances, fatigue, lack of energy, changes in appetite, loss of interest in activities you once enjoyed and thoughts of death or suicide,” says Wayne Drevets, M.D., Vice President, Disease Area Leader in Mood Disorders, Janssen Pharmaceutical Companies of Johnson & Johnson.

The exact cause of depression is unknown. However, a family history of depression, chemical imbalances in the brain, stressful life events such as the death of a loved one and certain medications or illnesses may increase a person’s chances of becoming depressed.

For World Mental Health Day, we sat down with leading experts in the field to learn more about the illness, plus what’s on the treatment horizon.

Depression Doesn’t Have to Define You

As part of the GoBoldly campaign, Janssen Pharmaceuticals researcher Wayne Drevets, M.D., uses science to banish stigma.


“Depression” isn’t a blanket term.

When people think of the term “depression,” they’re usually thinking of clinical depression, which is also known as major depressive disorder (MDD) and is characterized by a persistently depressed mood that affects quality of life. But there are actually many different forms of the illness.

Man sitting on outdoor steps with his head in his hands

Because depression isn’t a single entity, we should actually be using the term “depressions,” says John Greden, M.D., Executive Director of the University of Michigan Comprehensive Depression Center.

Episodes of major depression can occur in the course of other types of depression, such as perinatal depression, bipolar disorder, seasonal affective disorder (SAD), psychotic depression, premenstrual dysphoric disorder (PMDD) and a short list of others.

And each form of depression can have different causes and treatments.

For example, SAD, which is triggered by changes in the season, may be treated with light therapy, psychotherapy, medication or vitamin D. For bipolar disorder, which is characterized by episodes of depression and mania, patients are usually encouraged to pursue mood-balancing medication and psychotherapy.


Some forms of depression present especially unique challenges.

Just as people can feel depressed for a number of different reasons, MDD can have a variety of subtypes.

MDD is diagnosed by the presence of a number of varied symptoms over a specified period of time, such as anxiety, apathy or feelings of hopelessness. Because these symptoms can be present in a variety of combinations, people can experience MDD in distinct ways and respond differently to medications. Depending upon these variables, some forms of MDD can be especially challenging to treat.

For example, some people may experience the symptom of suicidal ideation or behavior, in which someone thinks about death or dying often, contemplates suicide or has attempted suicide, explains Abigail Nash, M.D., Ph.D., Medical Director, Janssen Pharmaceutical Companies of Johnson & Johnson.

And some people with MDD have what’s known as treatment-resistant depression (TRD), she adds, which is generally defined as depression that has failed to respond adequately to two or more different antidepressants taken for a proper duration, usually four to six weeks.

Anyone can develop TRD. However, women, seniors, people with anxiety disorders and those with severe depression (having many and severe symptoms) can be at higher risk for developing treatment resistance. Some health issues, such as thyroid disease, chronic pain, substance abuse and eating and sleeping disorders can also make a person more susceptible to TRD.

Treating these forms of depression can be difficult. For MDD with suicidal thoughts or actions, symptoms need to be addressed quickly to keep the individual safe, and antidepressants can take up to four to six weeks to relieve symptoms, Dr. Nash explains. In addition, people with TRD tend to cycle through multiple antidepressants and may not experience symptom relief.*


Family history and genes play a significant role.

Has someone in your family suffered from depression? It’s an important question to ask yourself.

Illustration of DNA strand

A DNA strand

“The odds of developing depression are about 17% in the total population—20% for women and 12% for men,” Greden says. “However, if someone has a family history of clinical depression, those odds go up. If a male has a mother or father who has a depression, that 12% may jump to 30%. And if there’s a family history of bipolar illness, those odds are even higher at about 50 to 60%.”

Genes are another factor, although determining exactly which ones influence the risk for depression and how they do so has proven difficult for researchers.

“What’s thought to be the case is that some genetic mutations increase vulnerability to depression, while others increase resilience,” Dr. Drevets says. “It appears that some complex combination of these genetic mutations, along with interactive environmental factors, ultimately determines whether an individual develops the illness or not.”

Because genetic patterns are so complicated, Dr. Drevets says it’s still challenging to accurately predict how to define who will develop major depression. Nevertheless, identifying the vulnerability and resilience factors that can influence the risk for developing depression may lead to new treatments.


Major depression can lead to physical changes in the brain.

Although depression is a brain disorder, it also affects the body in tangible ways. In addition to sleep problems and fatigue, depression can cause changes in a person’s speech patterns, explains Greden, and many people have aches and pains in different areas of the body.

In fact, in a survey of adults with a mood disorder, about half reported experiencing chronic pain, according to results published this year in the Journal of Affective Disorders.

Depression can cause physical changes to the brain, too.

Studies have shown that the quality and volume of white matter that connects neurons and transports information was reduced in people who reported symptoms indicative of depression. It’s also been found that some patients with depression have a smaller hippocampus—an area of the brain that plays a major role in learning and memory—compared to patients who had one or no episodes of depression.

We’ve seen that chronic, low-grade inflammation in the brain, which occurs in a subgroup of people with depression, can return to normal levels once the patient responds favorably to treatment with an antidepressant.
Wayne Drevets, M.D.

But with the right treatment, Greden says, some brain changes can be reversed.

“We’ve seen that chronic, low-grade inflammation in the brain, which occurs in a subgroup of people with depression, can return to normal levels once the patient responds favorably to treatment with an antidepressant,” Dr. Drevets adds.

But not all depression is related to inflammation. There are other brain abnormalities that can play a role—like changes in the thickness of gray matter, where synapses are located—but that may also respond to medication.

“Although currently available antidepressants won’t correct this abnormality, lithium, which is widely used as a mood stabilizer in bipolar disorder, is able to reverse these gray matter changes,” Dr. Drevets explains. “Moreover, early research with experimental compounds that regulate glutamate pathways, which are linked to neurotransmitters, may restore synaptic health.”

He adds that the mood-stabilizing effect of lithium appears to be related to its ability to change the gene expression of many types of neuroprotective factors in the brain that are thought to help restore synaptic connections.


Depression is more common in women.

According to Greden, the risk of depression for boys and girls is almost identical, but after puberty, the risk for girls is about double that of boys.

Could this possibly mean hormones are to blame?

Woman with her hand to her head holding her baby in a nursery

“We don’t know the answer to that, but it seems that when people reach puberty, biological changes place girls at greater risk for depression,” Greden says, adding that those increased odds persist until menopause. Some women who have clinical depression are prone to have their worst episodes at premenstrual times, Greden notes.

Women are also more vulnerable to depression during and after pregnancy, says Dr. Drevets, who attributes this phenomenon to fluctuations in estrogen and progesterone. “These hormones have a major effect on brain function,” he notes.

“Janssen is actually studying perinatal depression, which is defined as depression during pregnancy and up to six months afterward, as part of our Disease Interception Accelerator program, which investigates how to identify and address root causes of certain diseases,” Dr. Drevets says.

According to the Maternal Health Task Force at the Harvard Chan School Center of Excellence in Maternal and Child Health, perinatal depression is a major health concern, with a prevalence of around 10 to 20%. Currently, Janssen researchers, in collaboration with the University of North Carolina, are trying to figure out who is most at risk of developing perinatal depression by looking at specific biomarkers and clinical features.

The hope: offer mothers solutions before they and their babies are affected.


Depression can increase the risk of developing other health issues.

Untreated depression has been linked to a number of additional health problems, like heart disease.

People who are depressed are two to three times more likely to develop cardiovascular disease than people who aren’t, according to the National Heart, Lung, and Blood Institute.

“And once they have cardiovascular disease, they show an accelerated risk of dying of it than those who don’t have depression,” Dr. Drevets adds.

One theory, explains Dr. Drevets, has to do with how depression creates an imbalance in the autonomic nervous system (which unconsciously regulates bodily functions) that makes you prone to heart-rhythm disturbances, which can increase mortality risk.

Another has to do with inflammation. “Depression is associated with chronic, low-grade inflammation, which may contribute to an increased vulnerability for developing coronary artery disease,” he says. “So some of the treatments we’re researching focus on directly targeting primary immune mechanisms to reduce inflammation in patients with depression.”


There are effective ways to help manage depression and its symptoms.

Many studies have shown that regular exercise can decrease depression symptoms, says Dr. Drevets. Aerobic exercise has been associated with the release of endorphins—the body’s own “feel-good” chemicals—as well as with a reduction in inflammation.

But, he adds, exercise on its own is unlikely to be sufficient in helping manage symptoms in someone who has severe or treatment-resistant depression.

Illustration of the brain with the hippocampus highlighted in red

The brain’s hippocampus, which can be affected by depression

Cognitive behavioral therapy (known as psychotherapy or talk therapy) is also effective, says Dr. Drevets, especially in cases where depression is mild or in the earlier stages.

Sometimes, though, depression requires antidepressant medications or a combination of treatments. “It’s more common to need medication as depression becomes more severe, chronic or recurrent in the course of the illness,” Dr. Drevets explains.

“Currently, Janssen is working to develop new treatments that act on different pathways in the brain for people who don’t respond to antidepressants,” he says. Some 30% of the depressed population falls into this camp.

“All of the available antidepressants work through increasing the availability of neurotransmitters, like serotonin and norepinephrine, which play key roles in emotional processing and behavior,” Dr. Drevets explains. “However, this means that, right now, the available antidepressant medications offer a very limited number of mechanisms of action that physicians can use to help people with depression.”

And that kind of work—finding solutions for people usually left behind—is helping to change the future of depression, hopefully creating a world in which fewer people suffer from the illness.

* This story was updated on October 5, 2020

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