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.
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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
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:
• 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”
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.
Both reports suggest that yes, chemicals are involved in the process of being depressed, but that comes later.
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 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.
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.
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?
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
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
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
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.
For Reshma, emotions often become overwhelming to the point of leaving her unable to function or in her own words:
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
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.
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:
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.
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.
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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.
- 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”
- Increased safety, belonging, and mattering
- Increased collective intelligence
- Greater innovation from diverse points of view
- Easier and more diverse recruiting
- A culture of meritocracy that creates empowerment
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 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.