The Boy Missing an Entire Type of Brain Cell

Author Article

MRIs of the boy's brain
MRIs of the boy’s brain showed structural abnormalities.OOSTERHOF ET AL / AMERICAN JOURNAL OF HUMAN GENETICS

Even before he was born, it was clear that the boy’s brain was unusual—so much so that his expecting parents flew from rural Alaska to Seattle, where specialists could attend to their son from birth. That is how James Bennett first met the boy, then a days-old infant struggling to breathe. The baby’s head was too big. The structures in his brain looked wrong. Bennett, a pediatric geneticist at Seattle Children’s, was tasked with figuring out why.

The answer was ultimately stranger than doctors could have imagined: The boy’s brain was missing an entire type of cell, called microglia, the result of mutations in a single gene, called CSF1R. Doctors had never seen anything like it.

Microglia make up 10 percent of the brain’s cells, but they are not neurons and therefore have long been overlooked. The boy’s case makes their importance unmistakable. In the absence of microglia, the boy’s neurons still grew to fill his skull, but they ended up in the wrong places and made the wrong connections. Microglia, scientists have started to realize, guide the development of the brain.

“There wasn’t any part of the brain that wasn’t involved and affected in this child,” Bennett says. A part of the baby’s cerebellum jutted at an odd angle. His ventricles, normally small fluid-filled cavities in the brain, were too large. And a dense bundle of nerves that is supposed to connect the brain’s left and right hemispheres, called the corpus callosum, had entirely failed to develop.

In petri dishes and in animals, scientists had previously observed how microglia guide developing neurons to the right locations, creating the highly organized layers that make up the brain. They also prune connections between neurons. “Things get off track pretty quickly when you start manipulating the functions of microglia,” says Stephen Noctor, a developmental neurobiologist at the University of California at Davis who was not involved in examining the boy. To better understand the CSF1R gene, Bennett teamed up with zebra-fish biologists. In fish, turning off the gene disrupts a cellular pathway necessary for corpus-callosum neurons to grow in humans.

Kim Green, a neurobiologist at the University of California at Irvine, notes that mutant mice lacking microglia have broadly similar patterns of disorganization in their brains. These mice models essentially predicted what would happen in a human. Green had just never expected to see a person without microglia. “It’s absolutely remarkable,” he says.

The boy’s brain helped unlock these scientific mysteries. But he was ultimately still a boy, a very sick one with worried young parents. Their son’s condition was so severe, it turns out, because he had inherited two faulty copies of the CSF1R gene—one from each parent. His parents happened to carry the same rare mutation because they are cousins.

In adults, just one copy of a CSF1R mutation can lead to a brain disorder called adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, which causes memory loss and eventually dementia beginning in one’s 40s. When the boy’s DNA-sequencing results came back, Bennett realized that he had to explain to the parents their own CSF1R mutation and their risks of developing the disorder. They were relieved, he says, to understand what was wrong with their child, but perhaps too overwhelmed to fully take in what it meant for their lives. The couple spoke with a genetic counselor before their son’s DNA sequencing, and Bennett says he arranged to have them meet with another genetic counselor back in Alaska, where they returned home.

This story has no miracle cure or happy ending. The boy died in Alaska at 10 months old of likely related causes, and Bennett says the family agreed to an autopsy. They have since lost touch. The phone numbers he has for them no longer work. He told me that he recently got hold of the mother’s sister, in an attempt to tell the family about the research made possible by their child. It’s a delicate balance: He feels a duty to inform, but he understands that the parents might not want to be reminded of their dead son.

A pediatric geneticist’s job, Bennett said, is often to diagnose extremely rare conditions, which push up against the limits of the human body. “On any day, you can find a patient you spend the rest of your career thinking about,” he said. The boy is one of them.

We want to hear what you think about this article. Submit a letter to the editor or write to

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

How Does Music Affect Your Brain? Every Imaginable Way

Author Article

*Video in link above

WAKING UP. WORKING out. Riding the bus. Music is an ever-present companion for many of us, and its impact is undeniable. You know music makes you move and triggers emotional responses, but how and why? What changes when you play music, rather than simply listen? In the latest episode of Tech Effects, we tried to find out. Our first stop was USC’s Brain & Creativity Institute, where I headed into the fMRI to see how my brain responded to musical cues—and how my body did, too. (If you’re someone who experiences frisson, that spine-tingling, hair-raising reaction to music, you know what I’m talking about.) We also talked to researchers who have studied how learning to play music can help kids become better problem-solvers, and to author Dan Levitin, who helped break down how the entire brain gets involved when you hear music.

From there, we dove into music’s potential as a therapeutic tool—something Gabrielle Giffords can attest to. When the onetime congresswoman was shot in 2011, her brain injuries led to aphasia, a neurological condition that affects speech. Through the use of treatments that include melodic intonation therapy, music helped retrain her brain’s pathways to access language again. “I compare it to being in traffic,” says music therapist Maegan Morrow, who worked with Giffords. “Music is basically like [taking a] feeder road to the new destination.”

But singing or playing something you know is different from composing on the fly. We also wanted to get to the bottom of improvisation and creativity, so we linked up with Xavier Dephrepaulezz—who you might know as two-time Grammy winner Fantastic Negrito. At UCSF, he went into an fMRI machine as well, though he brought a (plastic) keyboard so he could riff along and sing to a backing track. Neuroscientist Charles Limb, who studies musical creativity, helped take us through the results and explain why the prefrontal cortex shuts down during improvisation. “It’s not just something that happens in clubs and jazz bars,” he says. “It’s actually maybe the most fundamental form of what it means to be human to come up with a new idea.”

If you’re interested in digging into the research from the experts in the video, here you go:

• Matthew Sachs’ research on music and frisson

• Assal Habibi, “Music training and child development: a review of recent findings from a longitudinal study.”

• Daniel Levitin’s research on music and the brain’s internal opioid system, and on music and stress

• Levitin’s book, This is Your Brain on Music

• Charles Limb, “Your Brain on Improv” (TED Talk) and “Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation”

• ABC News’ report on Gabrielle Giffords’ music therapy

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.

What Being Excluded Does To Your Brain

Author Article

We are want to be included, to belong to the tribe. Our brains are constantly scanning our environment and our interactions to determine if we “fit in” or not. That’s why the “like me” bias is so prevalent—because we feel most comfortable (most safety and belonging) with people that are similar to us.


Who’s Special–And Thus Included?

I’m not going to talk about diversity here, as I’ve done so before. Instead, I want to urge you to look at your organization, and to notice who is being excluded and why. Sometimes it’s easiest to first look at who is included, or who’s in the “in group” (yes, just like in High School!). Ask yourself:

  • Who receives the high profile assignments/projects?
  • Who receives frequent public praise/is held up as an example of positive performance, attitude, etc?
  • Who receives promotions?
  • Who has lunch/is invited to play golf with the key leaders?

Chances are really good that you thought of a smallish group of people. And I’ll bet they all have things in common with the leaders that offer them the above benefits. We’ll call them the “in group”. That’s the “like me” cognitive bias at work, and beneath it, we’re subconsciously just trying to mitigate risk. Everyone else is the “out-group”.

Your brain has three to four times as much real estate devoted to identifying threats versus identifying opportunities and rewards. Since we are all naturally biased, there’s no need to feel ashamed of it. However, there’s a very profound business case for becoming more aware of exclusion and how it damages our performance, emotional engagement, health and happiness at work and in life overall.

Your Brain On Exclusion

You’ve been left out of a group before (think back to Junior High or High School, or the last round of promotions you weren’t part of or the special meeting/project you weren’t included in, you get the idea). You know how emotionally painful it feels. Our belonging is threatened when we are ostracized or excluded, and we dive into Critter State (fight, flight, freeze). Now our brain literally cannot function the way it does when it feels safe and is in Smart State.

When we’re excluded, our brain will release an enzyme that attacks the hippocampus, which is responsible for regulating synapses. As a result, our brain does the following:

  • Reduces the field of view and focuses only on a narrow span of what it must do to survive. Myelin sheathing increases on existing neural pathways, and we are less likely to consider or try new solutions.
  • Shrinks its working memory, so that it is not distracted by other ideas, bits of information, or stray thoughts. This means we can’t problem solve optimally. Think of students panicked by a pop quiz: the information is there, but they cannot access it.
  • Is less creative. With less gray matter and modified synapses, we experience fewer ideas, thoughts, and information available to “bump into each other,” so our capacity to create is reduced.
  • Increases cell density in the amygdala, the area of the brain responsible for fear processing and threat perception, making us more likely to be reactive rather than self-controlled.
  • Is less likely to connect with others. Fight, flight, freeze, or faint is not a “sharing” type of activity. When the synapses have been modified in this way, we appear grumpy and unsociable.

Bring The “Out” Group “In”

What would change if you started including the “out-group” members more? You’d witness:

As leaders, we must promote everyone’s Smart State by not just hiring diverse team members but including them. If your not-like-you team members don’t feel included, they’ll end up in Critter State, where no one wins.

The Net-Net

  • The brain is profoundly impacted when a person feels excluded—and the person, their performance, their emotional engagement, and the organization overall suffers as a result
  • Leaders must raise their awareness to identify who’s being excluded and why—then include them
  • The ROI of inclusion is high

Christine Comaford is a leadership and culture coach who helps businesses achieve growth. Learn more at SmartTribes Institute and see Power Your Tribe: Create Resilient Teams in Turbulent Times and SmartTribes: How Teams Become Brilliant Together.