In the realm of mental health, depression often stands as a formidable opponent, casting a shadow over millions of lives worldwide. Understanding the intricate mechanisms underlying this condition is not just an academic pursuit but a crucial step towards effective treatment and support. Join us as we embark on a journey through the science of depression, unraveling the mysteries of the brain's inner workings.

Traditionally, the narrative surrounding depression revolved around the concept of chemical imbalances in the brain, specifically implicating neurotransmitters like serotonin, dopamine, and norepinephrine. This model suggested that deficiencies in these chemicals led to the onset of depressive symptoms, paving the way for pharmacological interventions such as selective serotonin reuptake inhibitors (SSRIs) like Lexapro.

However, as our understanding deepened, so too did our realization that the story was far more complex than initially envisioned. Research has shown that the temporary increase in serotonin levels induced by medications like Lexapro does not correlate with immediate symptom relief. In fact, the peak in serotonin often coincides with the onset of adverse side effects, underscoring the inadequacy of the simplistic chemical imbalance hypothesis.

Enter the era of circuit dysfunction—a paradigm shift that redirected our focus towards the intricate neural circuits governing mood regulation. Within the labyrinth of the brain, specific circuits, including those involving the striatum and frontal lobes, emerged as key players in the emotional landscape. Brain imaging studies provided tangible evidence of disrupted circuitry in individuals grappling with depression, shedding light on the underlying neurological substrates of the disorder.

Yet, our journey did not end there. As scientific inquiry delved deeper, a new concept emerged—one that heralded a paradigmatic shift in our understanding of depression: neurotropism. At its core, neurotropism speaks to the vitality of brain cells, specifically the intricate network of dendrites that facilitate neural communication and information processing.

Imagine a neuron as a barren tree, its sparse branches unable to forge meaningful connections—a visual metaphor akin to the depressive state. However, with the introduction of antidepressant medications, a remarkable transformation occurs. Like a dormant sapling springing to life, neurons burgeon with newfound vigor, sprouting dendritic branches and fostering the growth of fresh connections. This phenomenon, known as neurogenesis, challenges previous dogmas surrounding the brain's plasticity, affirming its capacity for regeneration and renewal.

In essence, our journey through the science of depression reveals a narrative far more nuanced and profound than the simplistic narratives of yesteryears. It speaks to the resilience of the human brain, the intricate dance of molecules and circuits, and the profound impact of interventions aimed not merely at rectifying imbalances but at nurturing the very essence of neural vitality.

As we navigate the complexities of mental health, let us remember that behind every diagnosis lies a rich tapestry of biological narratives waiting to be understood and embraced. Through science, compassion, and collective understanding, we embark on a journey of healing—one neuron at a time.

In this episode, you'll discover:

• Depression's narrative has evolved beyond simplistic notions of chemical imbalances to encompass the intricate interplay of neural circuits and neurotropism.
• Brain imaging studies highlight disrupted circuitry in depression, while neurotropism underscores the importance of dendritic vitality in neural communication.
• Antidepressant medications stimulate neurogenesis, challenging previous beliefs about the brain's plasticity and offering hope for renewal in the face of depression.

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Transcription

Dr. Latt Mansor:

So let's talk a little bit about depression. Cause so you mentioned, how your brain is just not able to be in that happy state. Is that just a matter of the chemicals that the brain is secreting? Can you dive deeper into the science? Cause our audience do when all our experts like dive deep into the science and explain, I think a lot of people can also relate with, depression, given how common it is and how much people go through it. It'll be great for you to explain to us like what exactly is happening in our brain during depression.

Dr. Daniel Z. Lieberman

There's really been an evolution of thought about that. Years ago, we talked about chemical imbalances and it's still very common to hear about that.

For example, maybe somebody would say if you have depression, you don't have enough serotonin. So you take a medication, let's say like Lexapro, also known as escitalopram. and that blocks the reuptake of serotonin, which we can get into in more detail if you like. But anyways, you have more serotonin available in the brain.

Turns out that's not true. That's really overly simplistic. During the first few days that you take a medication like Lexapro and SSRI, serotonin levels do indeed go up. But what's curious is that improvement in symptoms doesn't happen for a few weeks. And by that time, The temporary rise in serotonin has gone back down again.

In fact, during those few days, when your serotonin is abnormally high, that's when you have the worst side effects to the medication. And it's only when the body adjusts and brings them back down that the side effects go away. So this idea of a deficiency of serotonin or dopamine or norepinephrine or any of these others really didn't hold up to further research.

So they moved on, they talk about circuit dysfunction. There's different circuits in your brain that are responsible for different behaviors and experiences. And there's a circuit that goes through a part of the brain called the striatum, which seems to be important for mood. Other areas important to mood too, goes through the frontal lobes and different places.

We said, all right, that circuit is not functioning well. And that is true to some degree. We can actually measure that on brain scans. But we've evolved even further than that to a very exciting place. And that's a place of looking at something called neurotropism. Neurotropism in some ways is a fancy word for How healthy brain cells are brain cells have a cell body where the nucleus is and where chemicals are produced.

And on that cell body is a whole bunch of branches called dendrites, and that's where other brain cells connect. And the more dendrites you have, the more connections you have that allows the brain cell to gather information from many other neurons, essentially getting their perspective on whatever's going on and making a more sophisticated decision about how to process that information.

When people get depressed they actually lose those dendrites. I don't know if you ever saw the Charlie Brown Christmas special. No, I have not. Anyway, Charlie Brown is a loser of a guy. Gets a Christmas tree and it's a pathetic tree. It's just got a few branches, it's half dead. That's what a depressed neuron looks like.

When you treat with antidepressants it reverses that course and it gets all bushy. Not only that, it creates places For new connections to occur, you can even get the growth of new neurons called neurogenesis, which not too long ago, we didn't think the adult brain was capable of.

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