Some People Can Thrive After Depression, Study Finds

Author Article
We may think of depression as a recurring condition with a gloomy prognosis, but findings from one study indicate that nearly 10% of adults in the United States with major depression were thriving ten years later. The findings, which appear in Clinical Psychological Science, suggest that some people with depression experience more than a reduction in depressive symptoms over time – they can achieve optimal psychological well-being.

Writing for The Conversation, lead investigator Jonathan Rottenberg, a researcher at the University of South Florida, discusses how clinical scientists often neglect the potential for positive outcomes among individuals with depression.

“Depression can be a lifelong problem. Yet as we dug deeper into the epidemiological findings, we also saw signs of better outcomes – an aspect that we found is rarely investigated,” he says.

Although current clinical practice emphasizes symptom reduction and achieving an absence of stress, evidence indicates that patients prioritize other measures of well-being.

“They want to love and be loved, be engaged in the present moment, extract joy and meaning, and do something that matters – something that makes the pain and setbacks of daily life worthwhile,” says Rottenberg.

Rottenberg and his colleagues found that a substantial percentage of those with depression can achieve just that.

Using data from the Midlife Development in the United Stated (MIDUS) study, the researchers examined outcomes in a nationally representative sample of middle-aged adults. The participants completed phone interviews and questionnaires, including a measure of depression and a battery of nine facets of well-being including autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, self-acceptance, life satisfaction, and negative and positive affect.

A total of 239 participants in the sample met the criteria for depression, meaning that they experienced depressed mood most of the day or every day, as well as additional symptoms, for at least 2 weeks out of the previous 12 months. The researchers reviewed data from the initial screening and a follow-up survey completed 10 years later.

At the 10-year follow-up, half of the participants reported experiencing no major symptoms of depression in the past 12 months, and almost 10% of the participants with a history of depression were thriving. To count as thriving, a participant had to show no evidence of depression and score higher than 75% of nondepressed MIDUS participants on the nine factors of psychological well-being.

Higher well-being at beginning of the study predicted thriving 10 years later, but severity of depression did not. Specifically, depressed adults who reported higher well-being at the beginning of the study had a 30% chance of thriving, compared with a 1% chance for participants who had low well-being when they began the study. Depressed participants with higher well-being at the beginning of the study and who were thriving at the end of the study had larger increases in well-being over time than did other depressed participants.

These findings could influence how mental health professionals think about the prognosis associated with depression, as well as how they communicate this prognosis to patients. The study suggests that treatment could focus on strategies for optimizing well-being optimization that go beyond just managing symptoms.

“The task now for researchers is to follow these encouraging signs with systematic data collection on how people thrive after depression,” says Rottenberg.


Rottenberg, J., Devendorf, A. R., Panaite, V., Disabato, D. J., & Kashdan, T. B. (2019). Optimal well-being after major depression. Clinical Psychological Science.

The Powerful Link Between Insomnia and Depression

Author Article

When one has difficulty sleeping, the waking world seems opaque. On top of feeling tired and fatigued, those who experience sleep disturbances can be irritable and have difficulty concentrating. When one has more severe cases of insomnia, one also faces a higher risk of developing heart disease, chronic pain, hypertension, and respiratory disorders. It can also cause some to gain weight.

Sleep disruptions can also have a major impact on one’s emotional well-being. A growing body of research has found that sleep disturbances and depression have an extremely high rate of concurrence, and many researchers are convinced that the two are biconditional—meaning that one can give rise to the other, and vice-versa. A paper that was published in Dialogues in Clinical Neuroscience concluded, “The link between the two is so fundamental that some researchers have suggested that a diagnosis of depression in the absence of sleep complaints should be made with caution.” The paper’s lead author, David Nutt—the Edmond J. Safra Chair in Neuropsychopharmacology at Imperial College London—found that 83 percent of depressed patients experienced some form of insomnia, which was more than double the amount (36 percent) of those without depression.

Bei Bei, Dpsych, PhD, from the Monash School of Psychological Sciences in Clayton, Australia, said the inverse was true, as well: “If a person does not currently have depression but goes through extended periods of time with sleep disturbances or insomnia, the sleep disturbances can potentially contribute to a mood disturbance or to even more severe depression.”

The Mechanisms Behind the Two Diseases

The sleep-wake cycle is regulated by what is known as the circadian process. When working properly, the circadian process operates in rhythm with the typical cycle of a day. One gets tired as the light of the day fades and the body prepares for sleep. One awakes as it becomes light again. The internal mechanisms behind the circadian cycle involve a complex orchestration of the neurochemical and the nuerophysiological presided over by the hypothalamus.

Depression, meanwhile, is a medical condition and a mood disorder. While there are several possible antecedents to depression, as genetic and environmental factors can lead to a depressive episode, the neurophysiological causes of depression pertain to a deficiency of chemicals in the brain that regulate mood: serotonin, dopamine, and norepinephrine.

However, these neurotransmitters do far more than just regulate mood. They have also been found to be integral to sleep efficiency. Disruptions in these brain chemicals can lead to disturbances in sleep, particularly REMsleep, and can also lead to more restlessness during typical times when one should be in bed. This can create a vicious cycle wherein the more severe one’s depression becomes, the more severe one’s insomnia becomes. The inverse can also true: The more severe one’s insomnia becomes, the more severe one’s depression becomes.

Evaluation and Treatment

Because these concurrent afflictions reinforce one another, medical professionals need to address both simultaneously for optimal treatment. However, there is not one cookie-cutter response that can eliminate both depression and insomnia. Many variables, including improper medication, can contribute to insomnia and different symptoms indicate different causes, which is why it is important to provide your mental health professional with any information that can give them with more insight about your condition. Describing your symptoms to your doctor allows them to narrow down the list of likely culprits and prescribe medications with greater precision. For example, letting your doctor know that you wake up in the middle of the night, and then have difficulties falling back to sleep is a distinct symptom from having difficulties falling asleep in the first place.

Though depression and insomnia are commonly linked, they can be independent of one another. Then again, they may be part of a larger array of comorbid disorders that require specific treatment plans to resolve. To determine the best course of action, your doctor may recommend a sleep study, medication, or a behavioral therapy.

Sleep Study

A sleep study is a test that measures how much and how well you sleep. During this test, you will be monitored by a team of sleep specialists who will be able to determine if there are any other disorders, such as restless leg syndrome or sleep apnea, that may be causing your insomnia. Even if the study does not reveal a definitive culprit, the sleep study will also allow your doctor to get a better picture about what is behind your insomnia.


Sleeping pills may help you fall asleep, but they are not long-term solutions to mental health. If you are suffering from a bout of insomnia that is related to a psychiatric disorder, you need to address that disorder to address your insomnia. Oftentimes, this will require a treatment plan that includes a pharmaceutical component. This component will be unique to each patient, as there is not a one-size-fits-all regimen of medication for optimal mental health. Furthermore, there are numerous comorbidities with depression, such as anxiety, that may be contributing to your insomnia and that may not be resolved by certain types of anti-depressants alone.

Another potential treatment involves a combination of medication, light treatment, and melatonin, a hormone that helps regulate the circadian process. The conditions of patients who receive light therapy in conjunction with antidepressant therapy tend to show more improvement than those who are prescribed antidepressants alone. This is true for patients with seasonal and nonseasonal depression.

Cognitive Behavioral Therapy for Insomnia

In other cases, some mental health professionals may recommend you see a sleep specialist to receive cognitive behavioral therapy for insomnia. Cognitive behavioral therapy for insomnia (CBTI) involves numerous non-drug techniques to induce sleep and it can be utilized before resorting to the use of pharmacological sleep aids with surprisingly good results.

Several studies have shown CBTI to be quite effective in treating insomnia and some forms of depression. A paper published in the Journal of Clinical Sleep Medicine in 2006 concluded that “The benefits of CBTI extend beyond insomnia and include improvements in non-sleep outcomes, such as overall well-being and depressive symptom severity, including suicidalideation, among patients with baseline elevations.” A paper published in the International Review of Psychiatry in 2014 found that CBTI may help with other comorbidities beyond depression. These include anxiety, PTSD, and substance abuse issues.

The National Sleep Foundation notes that this type of therapy can still be quite intensive. CBTI requires regular visits to a clinician for assessment, keeping a sleep diary, and, perhaps most importantly, the changing of behaviors that may be felt as though they are firmly part of one’s routine. CBTI may also include some sleep hygiene education, where patients learn how different settings and actions can inhibit or promote sleep. It may also rely on relaxation training, where patients learn methods of calming their bodies and minds.

Concluding Thoughts

If you are struggling with either depression, insomnia, or both, treatments are available. The above studies demonstrate that there are holistic approaches, as well as pharmaceutical remedies, that can help induce sleep without the aid of sleeping pills. It is also a reminder that the most effective treatment plans are tailored to both the individual patient and the patient’s concurrent illnesses.

LinkedIn Image Credit: Kleber Cordeiro/Shutterstock

Child Abuse May Change Brain Structure And Make Depression Worse

Author Article

A study of over a hundred people’s brains suggests that abuse during childhood is linked to changes in brain structure that may make depression more severe in later life.

Nils Opel at the University of Münster, Germany, and his colleagues scanned the brains of 110 adults hospitalised for major depressive disorder and asked them about the severity of their depression and whether they had experienced neglect or emotional, sexual or physical abuse during childhood.

Statistical analysis revealed that those who experienced childhood abuse were more likely to have a smaller insular cortex – a brain region involved in emotional awareness.

Over the following two years, 75 of the adults experienced another bout of depression. The team found that those who had both a history of childhood abuse and a smaller insular cortex were more likely to have a relapse.

“This is pointing to a mechanism: that childhood trauma leads to brain structure alterations, and these lead to recurrence of depression and worse outcomes,” says Opel.

The findings suggest that people with depression who experienced abuse as children could need specialised treatment, he says.

Brain changes can be reversible, says Opel, and the team is planning to test which types of therapies might work best for this group.

Journal reference: Lancet Psychiatry, DOI: 10.1016/S2215-0366(19)30044-6

Why Do Antidepressants Fail For Some?

Author Article

Serotonin is the chemical messenger that has a major impact on feelings of happiness and wellbeing.

Scientists have long suspected that disruption in serotonin brain circuits is a key factor in major depressive disorder. Selective serotonin reuptake inhibitors (SSRIs) are a significant class of drug that seeks to remedy this disruption by increasing serotonin levels at nerve junctions.

However, for reasons that have been unclear, SSRIs do not work for around 30 percent of people with major depression. Now, researchers from the Salk Institute for Biological Studies in La Jolla, CA, and the Mayo Clinic in Rochester, MN, may have solved the mystery.

A Molecular Psychiatry paper describes how, by studying cells from hundreds of people with major depression, the team uncovered differences that could explain resistance to SSRIs.

“These results,” says senior study author Fred H. Gage, who is president of the Salk Institute and also a professor in their Laboratory of Genetics, “contribute to a new way of examining, understanding, and addressing depression.”

He and his colleagues believe that their findings also offer insights into other psychiatric illnesses that involve disruption of the brain’s serotonin system, such as schizophrenia and bipolar disorder.

Depression and nerve cell response to SSRIs
Depression is a leading cause of disability that affects all ages and contributes in a major way to the “global burden of disease,” according to the World Health Organization (WHO). The United Nations agency estimate that there are around 300 million people worldwide living with this widespread psychiatric condition.

In the United States, the National Institutes of Health (NIH) suggest that in 2017 around 17.3 million adults, or 7.1 percent of all adults, reported having “at least one major depressive episode” in the previous 12 months.

The FDA approve esketamine nasal spray for severe depression
The FDA approve esketamine nasal spray for severe depression
U.S. regulators have approved a prescription nasal spray for the treatment of depression that does not respond to other drugs.
For the recent study, the scientists took skin cells from more than 800 people with major depression and turned the cells into stem cells.

They then coaxed the stem cells to mature into “serotonergic neurons,” which are the nerve cells that make up the brain circuitry for producing and using serotonin.

The team compared serotonergic neurons of “SSRI non-responders” with those of “SSRI responders.” The non-responders were those individuals with depression whose symptoms showed no improvement, while the responders were those whose symptoms showed the most dramatic improvement to treatment with SSRIs.

In previous work, the researchers had demonstrated that cells from SSRI non-responders had more serotonin receptors, causing them to overreact to the chemical messenger.

Structural differences in nerve cells
The new study explored a different facet of SSRI non-response at the cell level. It found no differences between SSRI responder and non-responder cells in terms of the biochemistry of serotonin. However, it did reveal some fundamental structural differences in the cells.

These differences were in the shape and growth of neurites — or projections — that carry signals to and from nerve cells.

The development of the nervous system relies on tight control of neurite growth. Disruption of this process, according to a 2018 study, can lead to “developmental and neurological disorders.”

The team found that the nerve cells of SSRI non-responders had much longer neurites than those of SSRI responders. Genetic analysis also uncovered much weaker expression of the genes PCDHA6 and PCDHA8 in the non-responder cells.

These two genes belong to the protocadherin family and play a key role in the growth and formation of nerve cells and brain circuits.

When they silenced PCDHA6 and PCDHA8 in healthy serotonergic neurons, the researchers found that these also grew unusually long neurites, just like the nerve cells of SSRI non-responders.

Having neurites of the wrong length can disrupt communication in serotonin brain circuits with some regions having too much traffic and others not enough. This could explain, says the team, why SSRIs sometimes fail to treat major depression.

“This paper,” Prof. Gage concludes, “along with another we recently published, not only provides insights into this common treatment but also suggests that other drugs, such as serotonergic antagonists, could be additional options for some patients.”

The team now intends to take a closer look at the role of the two protocadherin genes in SSRI non-responders.

“With each new study, we move closer to a fuller understanding of the complex, neural circuitry underlying neuropsychiatric diseases, including major depression.”

Prof. Fred H. Gage

What You Need to Know if You’re Dating Someone With Depression

Author Article


When my boyfriend and I first started dating, he told me that he struggled with depression. In retrospect, I think I was naive. I didn’t realize how much it would impact me and our relationship. What can I do to help him? What can I do do help our relationship when he’s struggling? —Down (Not Out)


You are not alone and neither is your boyfriend: According to the American Psychological Association, as many as 17 million adults in this country suffer from depression. Depression does not discriminate based on age, socioeconomics, fame or success. In fact, many celebrities have spoken openly about their own difficulties with depression, including Lady GagaKristen Bell. Most recently, reports have come out that the newly married Justin Bieber, while thrilled with his marriage to Hailey Baldwin, has been struggling with depression and has undergone treatment for it. This really speaks to depression being an underlying issue and not a reflection of someone’s relationship. That said, it impacts a relationship enormously. Studies have shown that relationships where at least one partner suffers from depression have a divorce rate that’s nine times higher than the average. Understanding the signs and difficulties that depression can bring, and exactly how to get help, are crucial to keeping yourself — and your partnership — on an even keel when tides get rough.

The symptoms of depression can vary from upsetting and concerning to debilitating, and it’s obvious how this would impact a relationship. It is common to see sufferers struggle with apathy, hopelessness, loss of joy or interest in things that once brought pleasure, mood swings, exhaustion, obsessive thinking, sadness and anxiety. And in terms of lifestyle or behavior, depression can impact sleep (insomnia or sleeping too much), eating (loss of appetite or overeating), energy (low energy or restlessness), and cognitive ability.

Often, depression in men shows up up differently, in the form of agitation, irritability or anger. While anyone can experience depression related to a life event — a death of a loved one, loss of a job, traumadivorce, e.g. — certain people are more prone to general depression. People who have one or both parents who struggle with depression, have experienced abuse, suffered from neglect growing up, and people who have drug or alcohol issues are among those who can be predisposed to depression. Whether your partner is dealing with a-once-in-a-while down mood, or has been diagnosed with a mental illness that will be part of your lives for good, here’s what you need to know.

It’s Not About You

Depression greatly impacts the way a person thinks. It creates a lot of negative filters when it comes to how a person views the world. Someone who is depressed tends to see the glass as half-empty and anticipate the worst a situation or person can offer. They typically do not feel worthy of love, kindness and care. They may appear lethargic or lazy when in fact they are just too physically exhausted from the depression to do much of anything. Many people who are depressed feel emotionally numb or sad much of the time.

RELATED: I Thought I Needed Klonopin — Turns Out I Needed a Divorce

Keep in mind that his depression is not a reflection of you or your relationship. (Think of Justin Bieber and how over the moon he is for Hailey, even while he says he’s “struggling a lot” and asking for prayers and healing.) While it impacts you, this is your partner’s own struggle and it is important not to take it personally. Separating yourself from the “cause” or reason your partner is depressed can help you better support him. Understand that even if it’s hard for him to take action against depression, he does not want to be depressed. Depression is not a choice. Do not feel blamed or attacked for it “happening to” you or your relationship; and speak about it with empathy. Getting mad at someone for suffering from depression is like getting angry at someone for having cancer.

View Getting Help as a Sign of Strength

The single most important thing you can do to help your boyfriend is to encourage him to get treatment. In a more general sense, creating a judgment-free zone where he can be vulnerable and talk about his struggle can be very healing. Anything you can do to help reduce his stress and lighten the load while he is struggling can be helpful.

In order for you to help your partner, it is very important that he be open to help. Too many people who struggle with depression mistakenly think that getting help is a weakness. A woman recently wrote to me on Instagram saying that she had been “so weak” that she started therapy. The opposite is true. Getting help shows enormous strength. It is brave to be willing to face your pain, work on making things better, and be honest about your emotional state. Many people are too afraid to do the work. It is important that your boyfriend knows that you view this as a strength.

And the “work” shouldn’t be seen as insurmountable. Depression is extremely treatable. It is the common cold of psychotherapy, and something every licensed therapist knows how to handle. Psychotherapy can be very helpful treatment. For those who are experiencing depression that is more resistant to psychotherapy, the combination of antidepressants along with talk therapy can be extremely effective. Helping your boyfriend to utilize whatever support system he has is important. People who are depressed tend to isolate from those who love them, which only feeds their depression. In addition, encouraging him to take good care of himself is an important component of treating depression and even preventing it. Encouraging him to get enough sleep, eat healthy, get sunlight, exercise, and utilize stress reduction techniques can help.

RELATED: How to Salvage Your Sexless Marriage

De-Stress Your Sex Life

Depression will impact your sex life together. It can kill a person’s libido, or simply challenge intimacy as it makes your boyfriend struggle to connect. If he is pulling away from you in bed, it does not mean he is not sexually attracted to you, it is the result of a chemical imbalance. And unfortunately, some antidepressant medications can lower libido, too. Do your best to work together to address these issues. You won’t want to put pressure on him to perform, as that could exacerbate the problem. Each person should have space to express their wants and needs, and the safety to know their boundaries will be respected. Proceed with care.

Look Out for You, Too

Men who suffer from depression often experience it as anger, meaning they have a short fuse and can be very moody. It is also not uncommon for them to self-medicate with drugs or alcohol which can have terrible results in terms of mood and temperament with their partner. It is important that you have good boundaries and self-care when it comes to how he treats you. If his illness manifests in poor treatment of you, or abuse of any kind, you may not be able to stay together. If someone is unwilling to get help and is consistently mistreating you — as hard as it can be to leave someone you love — sometimes you have to leave for your own well-being. You are allowed to do this, even if the other person is suffering from mental illness. You are not expected to endanger or harm yourself out of a sense of guilt for what the other is going through.

Call for Help

In some severe cases, people with depression may become suicidal. If your boyfriend expresses anything along those lines it should be taken very seriously. It is important to share with his therapist if he has one, family and support system, especially if it seems as if he isn’t addressing it how he needs to. Sometimes it is necessary to call authorities so they can determine if he’s a danger to himself, and needs to be checked into a hospital where they can monitor and treat him. (This is called “50150,” and can be a life-saving measure.) Another resource if you are concerned about suicidality is the Suicide Prevention Hotline (there’s a web chat, or you can call 1-800-273-8255). That can be a resource for you, for him, or for anyone else who is concerned.

Clinical Depression: What Does That Mean?

Author Article

Depression ranges in seriousness from mild, temporary episodes of sadness to severe, persistent depression. Clinical depression is the more-severe form of depression, also known as major depression or major depressive disorder. It isn’t the same as depression caused by a loss, such as the death of a loved one, or a medical condition, such as a thyroid disorder.

To diagnose clinical depression, many doctors use the symptom criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association.

Signs and symptoms of clinical depression may include:

  • Feelings of sadness, tearfulness, emptiness, or hopelessness
  • Angry outbursts, irritability, or frustration, even over small matters
  • Loss of interest or pleasure in most or all normal activities, such as sex, hobbies, or sports
  • Sleep disturbances, including insomnia or sleeping too much
  • Tiredness and lack of energy, so even small tasks take extra effort
  • Reduced appetite and weight loss or increased cravings for food and weight gain
  • Anxiety, agitation, or restlessness
  • Slowed thinking, speaking, or body movements
  • Feelings of worthlessness or guilt, fixating on past failures, or self-blame
  • Trouble thinking, concentrating, making decisions, and remembering things
  • Frequent or recurrent thoughts of death, suicidal thoughts, suicide attempts, or suicide
  • Unexplained physical problems, such as back pain or headaches

Symptoms are usually severe enough to cause noticeable problems in relationships with others or in day-to-day activities, such as work, school, or social activities.

Clinical depression can affect people of any age, including children. However, clinical depression symptoms, even if severe, usually improve with psychological counseling, antidepressant medications or a combination of the two.

Updated: 2017-05-13

Publication Date: 2017-05-13

How New Ketamine Drug Helps with Depression

Author Article

An illustration of a woman suffering from depression who might be helped by esketamine

The FDA approval of esketamine gives doctors another valuable tool in their arsenal against depression—and offers new hope for patients no one had been able to help before. “This is a game changer,” says John Krystal, MD, chief psychiatrist at Yale Medicine and one of the pioneers of ketamine research in the country.

On March 5, the Food and Drug Administration (FDA) approved the first truly new medication for major depression in decades. The drug is a nasal spray called esketamine, derived from ketamine—an anesthetic that has made waves for its surprising antidepressant effect.

Because treatment with esketamine might be so helpful to patients with treatment-resistant depression (meaning standard treatments had not helped them), the FDA expedited the approval process to make it more quickly available. In one study, 70 percent of patients with treatment-resistant depression who were started on an oral antidepressant and intranasal esketamine improved, compared to just over half in the group that did not receive the medication (called the placebo group).

“This is a game changer,” says John Krystal, MD, chief psychiatrist at Yale Medicine and one of the pioneers of ketamine research in the country. The drug works differently than those used previously, he notes, calling ketamine “the anti-medication” medication. “With most medications, like valium, the anti-anxiety effect you get only lasts when it is in your system. When the valium goes away, you can get rebound anxiety. When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It’s the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects,” he says.

And this is exactly what makes ketamine unique as an antidepressant, says Dr. Krystal.

However, as the nasal spray becomes available via prescription, patients have questions: How does it work? Is it safe? And who should get it? Read on for answers.

How do antidepressants work?

Research into ketamine as an antidepressant began in the 1990s with Dr. Krystal and his colleagues Dennis Charney, MD, and Ronald Duman, PhD, at the Yale School of Medicine. At the time (as is still mostly true today) depression was considered a “black box” disease, meaning that little was known about its cause.

One popular theory was the serotonin hypothesis, which asserted that people with depression had low levels of a neurotransmitter called serotonin. This hypothesis came about by accident—certain drugs given to treat other diseases like high blood pressure and tuberculosis seemed to drastically affect people’s moods. Those that lowered serotonin levels caused depression-like symptoms; others that raised serotonin levels created euphoric-like feelings in depressed patients. This discovery ushered in a new class of drugs meant to treat depression, known as selective serotonin reuptake inhibitors (SSRIs). The first one developed for the mass market was Prozac.

But eventually it became clear that the serotonin hypothesis didn’t fully explain depression. Not only were SSRIs of limited help to more than one-third of people given them for depression, but growing research showed that the neurotransmitters these drugs target (like serotonin) account for less than 20 percent of the neurotransmitters in a person’s brain. The other 80 percent are neurotransmitters called GABA and glutamate.

GABA and glutamate were known to play a role in seizure disorders and schizophrenia. Together, the two neurotransmitters form a complex push-and-pull response, sparking and stopping electrical activity in the brain. Researchers believe they may be responsible for regulating the majority of brain activity, including mood.

What’s more, intense stress can alter glutamate signaling in the brain and have effects on the neurons that make them less adaptable and less able to communicate with other neurons.

This means stress and depression themselves make it harder to deal with negative events, a cycle that can make matters even worse for people struggling with difficult life events.

Ketamine—from anesthetic to depression “miracle drug”

Interestingly, studies from Yale research labs showed that the drug ketamine, which was widely used as anesthesia during surgeries, triggers glutamate production, which, in a complex, cascading series of events, prompts the brain to form new neural connections. This makes the brain more adaptable and able to create new pathways, and gives patients the opportunity to develop more positive thoughts and behaviors. This was an effect that had not been seen before, even with traditional antidepressants.

“I think the interesting and exciting part of this discovery is that it came largely out of basic neuroscience research, instead of by chance,” says Gerard Sanacora, MD, PhD, a psychiatrist at Yale Medicine who was also involved in many of the ketamine studies. “It wasn’t just, ‘let’s try this drug and see what happens.’ There was increasing evidence suggesting that there was some abnormality within the glutamatergic system in the brains of people suffering from depression, and this prompted the idea of using a drug that targets this system.”

For the last two decades, researchers at Yale have led ketamine research by experimenting with using subanesthetic doses of ketamine delivered intravenously in controlled clinic settings for patients with severe depression who have not improved with standard antidepressant treatments. The results have been dramatic: In several studies, more than half of participants show a significant decrease in depression symptoms after just 24 hours. These are patients who felt no meaningful improvement on other antidepressant medications.

Most important for people to know, however, is that ketamine needs to be part of a more comprehensive treatment plan for depression. “Patients will call me up and say they don’t want any other medication or psychotherapy, they just want ketamine, and I have to explain to them that it is very unlikely that a single dose, or even several doses of ketamine alone, will cure their depression,” says Dr. Sanacora. Instead, he explains, “I tell them it may provide rapid benefits that can be sustained with comprehensive treatment plans that could include ongoing treatments with ketamine.  Additionally, it appears to help facilitate the creation new neural pathways that can help them develop resiliency and protect against the return of the depression.”

This is why Dr. Sanacora believes that ketamine may be most effective when combined with cognitive behavioral therapy (CBT). CBT is a type of psychotherapy that helps patients learn more productive attitudes and behaviors. Ongoing research, including clinical trials, addressing this idea are currently underway here at Yale.

A more patient-friendly version

The FDA-approved drug esketamine is one version of the ketamine molecule, and makes up half of what is found in the commonly used anesthetic form of the drug. It works similarly, but its chemical makeup allows it to bind more tightly to the NMDA glutamate receptors, making it two to five times more potent. This means that patients need a lower dose of esketamine than they do ketamine. The nasal spray allows the drug to be taken more easily in an outpatient treatment setting (under the supervision of a doctor), making it more accessible for patients than the IV treatments currently required to deliver ketamine.

But like any new drug, this one comes with its cautions. Side effects, including dizziness, a rise in blood pressure, and feelings of detachment or disconnection from reality may arise. In addition, the research is still relatively new. Studies have only followed patients for one year, which means doctors don’t yet know how it might affect patients over longer periods of time. Others worry that since ketamine is sometimes abused (as a club drug called Special K), there may be a downside to making it more readily available—it might increase the likelihood that it will end up in the wrong hands.

Also, esketamine is only part of the treatment for a person with depression. To date, it has only been shown to be effective when taken in combination with an oral antidepressant. For these reasons, esketamine is not considered a first-line treatment option for depression. It’s only prescribed for people with moderate to severe major depressive disorder who haven’t been helped by at least two other depression medications.

In the end, though, the FDA approval of esketamine gives doctors another valuable tool in their arsenal against depression—and offers new hope for patients no one had been able to help before.

To learn more, visit

Should We Look at Depression as More Than Just a ‘Chemical Imbalance’?

Author Article

Two years ago, a piece argued that depression isn’t simply about chemical imbalances. In no equivocal terms, it stated that depression’s link to being this kind of an imbalance is a lie. This report, of course, is not the only one. Another piece in the Harvard medical journal reiterates the same point.

Research suggests that depression doesn’t spring from simply having too much or too little of certain brain chemicals. Rather, there are many possible causes of depression, including faulty mood regulation by the brain, genetic vulnerability, stressful life events, medications, and medical problems. It’s believed that several of these forces interact to bring on depression.
Harvard Health Publishing

Both reports suggest that yes, chemicals are involved in the process of being depressed, but that comes later.

Also Read : Eating Junk Food Can Raise Risk of Bipolar Disorder, Depression

First come several other factors like trauma, stressful surroundings, emotional triggers and so on and so forth. Depression simply does not exist in isolation or a vacuum and is not the first step, several factors lead to it, claim the reports.

If depression indeed is a chemical imbalance, the next logical step is to take a pill that counterbalances it.
If depression indeed is a chemical imbalance, the next logical step is to take a pill that counterbalances it.
(Photo: iStockphoto)

If depression indeed is a chemical imbalance, the next logical step is to take a pill that counterbalances it and voila! You’re cured. Not so easy. People sometimes take pills for years without being recovered.

To be sure, chemicals are involved in this process, but it is not a simple matter of one chemical being too low and another too high. Rather, many chemicals are involved, working both inside and outside nerve cells. There are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.
Harvard Health Publishing

This also goes to explain why two people with similar symptoms of depression might respond entirely differently to the same medication. Additionally, there is no concrete or definite data on the direct link of antidepressants to mental health and depression. Consequently, we don’t know for sure what Prozac, one of the most widely used medication used for depression in the US, is really doing to a depressed person.

Also Read : These Negative Social Media Behaviours Are Linked to Depression

Depression: A Complex Illness

Dr Achal Bhagat, Senior Consultant Psychiatrist and Psychotherapist at Apollo Hospital, comments on this and says that depression is a complex illness which cannot be explained in definite terms.

There are a number of factors that may increase its chances. These include abuse, certain medicines, interpersonal conflict, death or a loss, genetics, major events – both positive and negative, serious illnesses and substance abuse (nearly 30 percent people with substance abuse problems also have major or clinical depression).
Dr Achal Bhagat
So, what is the role of medication and hormones in all this?
So, what is the role of medication and hormones in all this?
(Photo: iStockphoto)

So, what is the role of medication and hormones in all this?

Also Read : Are Creativity and Mental Disorders Connected?

Depression and Hormones

According to Dr Bhagat, there are two hormones that have primarily been associated with depression – serotonin and cortisol.

The commonest explanation is an imbalance of serotonin. This is supported by imaging studies where it has been found that the size of the hippocampus (a part of the brain) in those with depression is relatively smaller than those who do not have depression. The serotonin receptors in smaller hippocampus are also low. Some people have also proposed that cortisol levels are higher in those with depression and this may lead to shrinking of the hippocampus.
Dr Achal Bhagat

Also Read : I’m Mad Because My Heart Has Been Broken: Diary of a Schizophrenic

Can This Hormonal Imbalance be Treated with Medication?

Following the thought expressed in the studies which don’t see depression as linked to chemical imbalances, Reshma Valliappan, a mental health activist who has been very vocal in the past about her struggle with schizophrenia, agrees that medication doesn’t help deal with mental disorders.

How does she look at depression at depression and its links with medication?

Many of us know for certain that once medication is given, we are also suggested therapy. It is in that room, that I uncover the layers of causes to my said disorder and this mostly points to a dysfunctional upbringing of some sort. I’ve had many therapists and counsellors who have worked with those like myself and we’ve all uncovered areas of parenting that messed us up.
Reshma Valliappan
 Reshma agrees that medication doesn’t help deal with mental disorders.
Reshma agrees that medication doesn’t help deal with mental disorders.
(Photo: iStockphoto)

However, in her case even therapy hasn’t been the solution. Reshma adds that different experts seem to have different views which impede her recovery.

The politics in the practice here contradicts each other where the practitioner who is prescribing these medications only look at a possible imbalance that needs to be fixed. Yet in the same school of practice – a different practitioner is suggesting that we’ve had bad experiences and require family therapy to enable us confront our past issues. Practitioners tend to override each other on our expense and unfortunately we are caught in the chaos of their practice being more important than our actualities.
Reshma Valliappan

Also Read : All in the Head: Alarming Rise of Psychosomatic Disorders in India

How Does Reshma Look at Her Depression?

Reshma has lived with depression since 1995 and has a non-traditional approach to it. It should be noted that this is a very personal approach and should not be looked at as medical advice. Each person’s treatment differs and only a trained medical professional can guide you with that.

Reshma has lives with depression since 1995 and was diagnosed with schizophrenia in 2002. Her hallucinations were auditory, olfactory, tactile and visual in nature.
Reshma has lives with depression since 1995 and was diagnosed with schizophrenia in 2002. Her hallucinations were auditory, olfactory, tactile and visual in nature.
(Photo: Saumya Pankaj/The Quint)

For Reshma, emotions often become overwhelming to the point of leaving her unable to function or in her own words:

The minute my body faces a ‘crash on energy’, I notice how I am overwhelmed by the simplest of emotions and situations and fall into weeping spells, fatigue and the lack of interest to do anything in life.
Reshma Valliappan

She adds her life experiences have a huge role to play in her depression, but pinpointing them helps her find a solution which she didn’t otherwise find in medication.

As a human, I am bound to get affected by them (life experiences). Where my expectations and what I want is not met, I also observe a slow dip in me which further builds up into a ball of depression… I’ve noticed unrealistic expectations with myself, owing to the lifestyle I lead, and often it can make it difficult to know where and when must I stop and simply let go of what I can’t achieve. When I can pinpoint these reasons and see how they are affecting or even causing my depression, it makes me feel that I do have control over what is happening with me and that there are solutions I can find.
Reshma Valliappan

Also Read : What’s a ‘Happiness Class’? Enter a Delhi Govt School to Find Out

Depression – a Quicksand of Uncertainty

With depression, as both Dr Bhagat and Reshma suggest, we have only scraped a little of the tip of the iceberg. While data and research continues to remain sketchy on what really works, both people FIT reached out to are in disagreement about what truly works when it comes to mental illness.

Reducing depression to simply a chemical imbalance gives a very bleak perspective of the illness to the one suffering with it.
Reducing depression to simply a chemical imbalance gives a very bleak perspective of the illness to the one suffering with it.
(Photo: iStockphoto)

Dr Bhagat comments about the potency of antidepressants in treating severe depression, Reshma feels that it reduces her agency and gives her a pessimistic view of her illness when we reduce it to chemicals. In fact, she’s not the only one in feeling this manner. According to this study, reducing depression to simply a chemical imbalance gives a very bleak perspective of the illness to the one suffering with it.

If someone were to merely tell me it’s a chemical imbalance, it suggests that there is nothing I can ever do to help myself. It kills any hope one can have to help oneself. It puts help in a material process instead which also depends on my bank account, thereby adding more struggle to my pain.
Reshma Valliappan

On the other hand, Dr Bhagat points out the role of antidepressants in addressing this very chemical imbalance. In fact, they have been proven to perform better than placebo, he further says.

Severe depression responds well to treatment with anti depressants which seem to have a long term neurotrophic impact on neurons. The two main meta analysis of many studies on effectivity of antidepressants conclude that antidepressants do work well in severe depression. A recent studywhich brought together the information regarding 1,00,000 patients concluded the antidepressants work significantly better than placebo.
Dr Achal Bhagat

Yet, he adds:

It does not mean that psychotherapy does not work for depression. However the availability of trained psychotherapists in a country like India is limited. Where access to therapy is available, a combination of both medicines and psychotherapy works well.

Anything related to the mind is still overwhelming beyond comprehension. While people located at different points of the spectrum would disagree on several aspects, we can all agree that there definitely isn’t any one single way to address or treat depression.

More American Millennials Are Experiencing Depression and Suicide

Author Article


More young adults in the U.S. are experiencing mental health issues, and digital media usage might be partly to blame, said a new study.

Between 2005 and 2017, the rate of adolescents reporting symptoms consistent with major depression in the last 12 months jumped 52 percent, according to the study published Thursday in the peer-reviewed Journal of Abnormal Psychology, run by the American Psychological Association.

The study found a 63 percent increase in young adults between the ages of 18 and 25 reporting symptoms of depression between 2009 and 2017. It also showed significant increases in the rates of young adults who reported serious psychological distress and suicidal thoughts or suicide-related outcomes during similar time periods.

Researchers also note there is no similar increase among older adults during corresponding time periods.

Jean Twenge, lead author of the study and professor of psychology at San Diego State University, said digital media might play a role in the increase among young adults.

“Cultural trends in the last 10 years may have had a larger effect on mood disorders and suicide-related outcomes among younger generations compared with older generations,” Twenge said in a statement.

Ian Gotlib, a professor of psychology at Stanford University and director of the Stanford Neurodevelopment, Affect, and Psychopathology (SNAP) Laboratory, said genetics can be ruled out as a potential factor because the increase in reports of mental health issues happens too quickly.

“It’s correlational, but what’s increased with depression is the use of social media with kids,” said Gotlib, who was not affiliated with the study. “And I don’t think that should be underestimated.”

A Pew Research survey released last month revealed 70 percent of teens believe anxiety and depression are critical issues among peers, even more than bullying or drug and alcohol use.

Several other studies have found a rise in depression among teens and young adults, leaving many experts to wonder how big a role social media might contribute.

“These results suggest a need for more research to understand how digital communication versus face-to-face social interaction influences mood disorders and suicide-related outcomes and to develop specialized interventions for younger age groups,” Twenge said.

Gotlib said having conversations with your kids is a good starting point, as well as paying attention to their digital media habits. “I would just watch for what looks to be an inability to not be with your phone,” he said. “It doesn’t necessarily mean depression but it has that potential.”


One Counterintuitive Way to Forget Unwanted Memories

Author Article

“Try to pose for yourself this task: not to think of a polar bear, and you will see that the cursed thing will come to mind every minute.”
— Fyodor Dostoevsky, (Winter Notes on Summer Impressions, 1863)

You can try Daniel Wegner’s famous “white bear” experiment on successful though suppression right now: As you’re reading this post, try NOT to think about this polar bear image.
Source: cocoparisienne/Pixabay

In the 1980s, Daniel Wegner (1948-2013)—who was a pioneering social psychologist at Harvard University best known for his groundbreaking research on thought suppression—stumbled upon the above-mentioned Dostoevsky “polar bear” quote, which inspired him to dedicate the rest of his life to deconstructing the best way to deliberately forget about something.

As Dostoevsky writes in Winter Notes on Summer Impressions, “Try to pose for yourself this task: not to think of a polar bear, and you will see that the cursed thing will come to mind every minute.” We all know from daily life experience that Dostoevsky is right: The more you try to forget about something or suppress a visual image in your mind, the more you think about that topic or conjure up the ‘vetoed’ image in your mind’s eye.

Daniel Wegner was so intrigued by Dostoevsky’s “polar bear” hypothesis that he designed a psychological experiment to test this 19th-century observation in a 20th-century laboratory setting.

During Wegner’s first thought-suppression study, participants were explicitly instructed not to think about a white bear for five minutes as they verbalized stream of consciousness thoughts. Throughout these five minutes, every time someone (who had been told, “don’t think about white bears!“) thought about a white bear, he or she was instructed to ring a bell. Most study participants rang the bell multiple times during the five-minute test.

In a follow-up experiment, Wegner and colleagues instructed another group of participants to only think about white bears for five minutes. When the researchers compared the number of “thought tokens” relating to white bears from both groups, Wegner et al. found that being told not to think about white bears made the unwanted thought more omnipresent in people’s minds.

The main takeaway from the initial “white bear” thought-suppression experiments: The more people tried not to think about white bears; the more they thought about white bears. In 1987, Wegner published these findings in a paper, “Paradoxical Effects of Thought Suppression,” which is credited with kickstarting the modern-day field of thought-suppression research.

Wegner and co-authors summed up their findings on the paradox of trying to suppress thoughts about white bears: “These observations suggest that attempted thought suppression has paradoxical effects as a self-controlstrategy, perhaps even producing the very obsession or preoccupation that it is directed against.”

A Million-Dollar Thought Suppression Question: What Is the Best Way to Stop Thinking Unwanted Thoughts?

Throughout the late-20th century, Wegner fine-tuned his “Ironic Process of Mental Control” theory. By the dawn of this century, it became clear to Wegner that people were hungry for some take-home advice based on the paradoxical findings of his “white bear” experiments. I am one of these people. Anecdotally, everyone reading this probably has a specific unwanted memory or something you tend to ruminate about that you’d like to think about less via successful thought suppression.

In 2011, Wegner gave a presentation at the American Psychological Association’s annual convention that laid out five specific strategies he recommended for helping to “suppress the white bears.” These include:

  1. Pick an absorbing distractor and focus on that instead
  2. Try to postpone the thought
  3. Cut back on multitasking
  4. Meditation and mindfulness
  5. Exposure

Wegner’s fifth recommendation of “exposure” is based on the counterintuitive hypothesis that if you force yourself to consciously focus attention (for a brief period) on thinking about something you’re ultimately trying to forget, the unwanted thought is less likely to pop into your mind at a later date. “This [exposure] is painful,” Wegner said in a 2011 APA statement, “but it can work.”

Although Wegner’s work on thought suppression wasn’t neuroscience-based, recently 21st-century, state-of-the-art fMRI research from the University of Texas at Austin reaffirmed that exposure (purposely thinking about unwanted memories) may, in fact, be the most effective way for someone’s brain to forget about proverbial “white bears.”

Successful Thought Suppression May Require More (Not Less) Attention to Unwanted Memories

A new fMRI-based study on successful thought suppression, “More Is Less: Increased Processing of Unwanted Memories Facilitates Forgetting,” was published today in the Journal of Neuroscience. This research was conducted by first author Tracy Wang of UT Austin along with senior author Jarrod Lewis-Peacock.

Notably, Wang and her colleagues found that successfully discarding specific information or unwanted memories from the brain takes moremental effort than trying to retain visual images.

 Wang et al., JNeurosci (2019)
Figure 2. GLM results for forgetting success (greater activity for successful intentional forgetting relative to successful intentional remembering, P < .001, k = 237). See Table 2 for complete univariate results.
Source: Wang et al., JNeurosci (2019)

A press release from the Society of Neuroscience summed up the latest findings on successful intentional forgetting from Jarrod Lewis-Peacock’s cognitive neuroscience laboratory (The LewPeaLab) at UT Austin:

“Tracy Wang and colleagues instructed healthy young adults to remember or forget images of scenes and neutral faces. An analysis of functional resonance imaging data revealed forgotten images were associated with stronger activation of the visual cortex than remembered images. But not too strong – forgetting was most successful when this brain region was activated at moderate levels. The research provides evidence for a forgetting strategy that involves activation, rather than suppression, of unwanted information. This provides a new link between the voluntary control of visual attention and the long-term fate of memories.”

“We found a perhaps counterintuitive result that the intention to forget a memory is associated with increased memory activation of that memory as compared to the intention to remember a memory,” Wang and her co-authors stated in their paper’s conclusion. “We found that forgetting occurs more often when a memory has a moderate degree of activation (vs. too high or too low) following the instruction to forget. This highlights the contribution of an automatic memory weakening mechanism to deliberate forgetting, and it suggests an alternative strategy for successful forgetting: to weaken an unwanted memory, raise (rather than suppress) its level of activation.”

The recent fMRI-based discovery that increased processing may be required to forget unwanted memories (Wang et al., 2019) from the LewPeaLab at UT Austin advances our neuroscience-based understanding of Wegner’s ‘white bear’ observations and his iconic, “ironic process of mental control” (1994), thought suppression theory.

Now that they know there’s a sweet spot (e.g., not too much, not too little mental attention) for optimal thought suppression, future research from the LewPeaLab will focus on best practices for successfully forgetting unwanted memories. Jarrod Lewis-Peacock’s team at UT Austin recently began a neurofeedback-based study that tracks how much attention someone is giving to various types of memories

“This will make way for future studies on how we process, and hopefully get rid of, those really strong, sticky emotional memories, which can have a powerful impact on our health and well-being,” Lewis-Peacock said in a statement. “We’re learning how these mechanisms in our brain respond to different types of information, and it will take a lot of further research and replication of this work before we understand how to harness our ability to forget.”

%d bloggers like this: