Yin and yang of serotonin neurons in mood regulation



More nuanced view of brainstem neurons could lead to better drugs for depression, anxiety

Low levels of serotonin in the brain are known to play a role in depression and anxiety, and it is customary to treat these disorders with medications that increase the amount of this neurotransmitter. However, a new study carried out by researchers at Columbia University Medical Center (CUMC) suggests that this approach may be too simple. It appears that neighboring serotonin-producing brainstem regions exert different and sometimes opposing effects on behavior.

The findings, published in the online edition of Cell Reports, provide new insights into the development of mood disorders and may aid in designing improved therapies.

“Our study breaks with the simplistic view that ‘more is good and less is bad,’ when it comes to serotonin for mood regulation,” said study leader Mark S. Ansorge, Ph.D., assistant professor of psychiatry at CUMC and research scientist at New York State Psychiatric Institute. “Rather, it tells us that a more nuanced view is necessary.”

From anatomical studies, researchers knew that the brainstem contains two distinct clusters of serotonergic neurons: one in dorsal raphe nucleus (DRN) and another in the median raphe nucleus (MRN). Together both regions harbor the vast majority of neurons that supply serotonin to the rest of the brain, but it was unclear how neuronal activity within these clusters controls behavior.

To learn more, the CUMC team used a technique called pharmacogenetics to control the activity of serotonergic neurons in the DRN and MRN in both normal mice and in a mouse model of depression- and anxiety-like behavior. (The model was created by giving mice the drug fluoxetine shortly after birth, which produces long-lasting behavioral changes.)

The experiments revealed that alterations in serotonergic neuronal activity in the DRN and MRN produce markedly different behavioral consequences.

“Going into the study, our hypothesis was that reduced activity of serotonergic neurons is what drives these mood behaviors,” said Dr. Ansorge. “But what we found was more complicated. First, it appears that hyperactivity of the MRN drives anxiety-like behavior. We also observed that decreased DRN activity increases depression-like behavior, while decreased MRN activity reduces it. This led us to conclude that an imbalance between DRN and MRN activity is what leads to depression-like behavior.”

“This new understanding of the raphe nuclei should help us better understand why certain medications are effective in treating depression and anxiety, and aid in designing new drugs,” Dr. Ansorge added. “In the future, it may be possible to find treatments that selectively target the DRN or the MRN, or that correct any imbalance between the two.”

Jeffrey Lieberman, M.D., chair of the department of psychiatry at CUMC, observed that “Neurobiological studies such as this are essential to elucidate the molecular mechanisms of antidepressant treatments and to develop more effective therapies.”

The study also demonstrated, in experiments using the fluoxetine-treated mice, that inhibition of serotonin reuptake early in life leads to long-lasting imbalances between the DRN and MRN. “This raises possible concerns about exposure to serotonin-specific reuptake inhibitors during gestation,” said Dr. Ansorge. “SSRIs cross the blood-brain barrier as well as the placenta, and bind maternal and fetal serotonin transporters alike. It’s too early to say whether this has any effect on behavior in humans, but it’s certainly something worth looking into.”

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The above post is reprinted from materials provided byColumbia University Medical Center. Note: Materials may be edited for content and length.

I do feel slightly over medicated, under stimulated…


Sort of blah, sort of bored. Is this what normal feels like?

On loads of lithium, well actually on 900 mg one day and 600 mg the next day, so not loads, perhaps a bit of a hyperbole, yes, every now and then. Helps keep boredom at bay…

Wanted to go out dancing, but no one would go with me… There’s a band every Sunday, at a park a stone’s throw away from my house, people dance. I can hear the music playing, my feet eager and impatient to dance, but no partner… well if this is the worst problem I have then I can complain of nothing at all.

Nothing dramatic, sort of addicted to drama I think, are all people with mood disorders addicted to drama? Must have ups and downs or the steady, non fluctuating rhythm of life seems to get boring and then a boredom anxiety sets in, haha, damned if you do, damned if you don’t. Well, the dancing would have helped, I’m sure, moving my feet makes me happy, hence Zumba, hence dancing for 4 hours at weddings.

Very hot outside, have a bad case of allergies, the gym is closed today. So I’m going to exercise at home, inside, away from the ragweed allergens swirling outside.

Don’t have much to say, feel dull and bored. Time to reduce the lithium? At my own risk, but I do feel slightly over medicated, under stimulated… Time to call the doctor, oh never mind, I have an appointment with him soon.

Perhaps a cup of coffee!

Love, Empty Nest Syndrome, and From kind of a meltdown to Almost back to normal

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At least Fluff still lives at home. And a picnic below.

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I still miss my Aral tons. I really think we were meant to live as family units all our lives. This nuclear family bs is just that, bs!

Anyway, I sort of had a meltdown, crying all the way here from Buffalo, and this morning was no cake and ice cream walk either.

They say love is what a mother feels for her newborn, I mean the emotion of love is based totally on what a mother feels when she sees her newborn. Romantic love is just that feeling transferred to your romantic partner. So of course, when a mother is separated from her child, she is going to experience heartbreak, elementary my dear Watson. The first time I felt that awful, sickening heartbreak was when Aral went to college. I didn’t get out of bed for a week, could not stop crying for the Kohinoor diamond, and just felt, in the pit of my stomach, that nothing was ever going to be right again. Not ever. And I know other moms who felt the same way as me. Just today, at a picnic, a friend who is a mom said she is planning on buying three lots of land adjacent to each other, to build three houses, one for herself and her husband, one for her son, and one for her daughter, so they cal always live close to one another and never be separated. Yesterday, on the plane, the woman seated next to me and I were talking, and she said that when her first son went to college, she basically went to bed for four days and couldn’t even talk to her son for weeks because her emotions were so raw, that she was afraid she was going to upset him. Another friend used the exact same phrase as I did, “Nothing will ever be ok again” when her daughter went off to college.

This is what we women have to go through. Maybe mine is a little more extreme because I have a mood disorder, but not much more extreme. Or more likely, at this extremely stressful time, all moms “develop” mood disorders, temporarily. These are extremely powerful emotions, maybe the most powerful emotion in the world, the love of a mother for her child. It is a survival of the species thing, if mothers didn’t love and adore their children, they would not take care of them, if they didn’t take care of them, the babies would not survive, and if the babies didn’t survive, the human race would die out. Therefore, this love a mother feels for her child has to be so powerful that it leads to the survival of the human species. And when that bond is broken, then the strength of the pain is proportional to the strength of the powerful love. And so we have empty nest syndrome. Awful, awful, awful, heartbreaking, most horrible feeling in the world. I sort of go through that every time I leave Aral in Buffalo after my visit. If love is a drug, and as I have hypothesized, maternal love is the most powerful of loves, then we mothers experience the most powerful of withdrawal symptoms when our babies leave the nest. Aaaah! So not fair. And so awful.

Well anyway, I am getting over my Aral withdrawals, and becoming a person again instead of a human water (tear) producing system.

I have to learn my lines! My play practice is in a day, and I have to learn my lines. I’m taking today off for empty nest, and tomorrow, back to business and learning lines.

Sleep Cycle Alarm Clock.

helps.https://itunes.apple.com/us/app/sleep-cycle-alarm-clock/id320606217?mt=8sleep cycle 1 sleep cycle 2 Sleep Cycle 3slepp cycle 4

Sleep is one of the most important elements in managing a mood disorder. Sleep deprivation happens when you are manic, you don’t need sleep then at all. You can go all day, all night, like a zombie, without any sleep. Your brain is working full throttle, you can’t turn it off.

In a depression, you sleep all the time. You don’t want to wake up. You have no drive, seemingly no reason to do anything. Your mind is not working at all, you and your brain are sluggish, you have no energy. Getting out of bed is actually a Herculean task.

When your mood is normal, you are sleeping the 6-8 hours a night and getting up in the morning with a smile and going to bed at a good hour.

If your sleep gets disturbed, it can throw your mood off. Conversely, when your mood is off, it can affect your sleep cycle. It’s the proverbial vicious cycle. As someone who suffers from mood disorders, you have to be extra vigilant about getting the right amount of sleep consistently.

Lately, I have been having a dickens of a time waking up every morning. I simply don’t want to get out of bed. I wish someone would invent an intravenous coffee machine that I could hook up to every night, which will deliver the right dose of coffee to me every morning so I can open my eyes. Haha. Barring that, I just read about Sleep Cycle alarm clock. It’s an App for iPhones. Just got it to help wake me up, lets see if it works.

You put it on your bed, close enough so it can detect your movement. And it wakes you up in the correct phase of your sleep, the lightest phase of your sleep cycle. According to the description and it makes sense, this is the natural way to wake up, rested, refreshed and relaxed. And Wow! since you move differently in bed in different sleep states, it can monitor your movement in bed to determine which phase you’re in. I hope big brother isn’t watching this, haha.

I’ll keep you posted. Starting tonight. Good night, y’all

NO to suicide!

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Strange, I was going to write about suicide and all day I have been seeing references to it, either written, or on TV, or on a billboard. Must be very attuned to it, I suppose, like when you are pregnant, you see pregnant women everywhere. Sorry guys, let me find an example that you with the Y chromosome can also relate to: like when you are thinking about the next football game, and you see cheer leaders everywhere, is that good?

Anyway, this is an appeal to anyone out there who is thinking of suicide. Please don’t. You are embroiled in emotions, or have taken this decision based on emotions. Emotions change. You don’t have to do this. Your frame of mind will change and you will not think about this anymore. Reach out to someone, anyone, a hotline, a friend, a stranger. Anyone at all. Please don’t do it. When people who attempted suicide, but either were unsuccessful, or were saved, they ALL said that they were happy they were still here. Not one of them said any different. So please, write to me, call someone, check yourself into a hospital (stigma be damned), but don’t do it. Don’t even attempt it.

You have this thing called life to live. Right now, it may see, may even be intolerably sad, horrible, whatever, but things change. Moods change, especially in people who have mood disorders. What is unbearable now may become something from which you springboard into being ok or happy, or normal and strong, or who knows, jubilant. Feelings change, emotions change. Dead doesn’t change. So don’t do it. Sit tight, call for help and begin another day.

If you think of your loved ones, if you still have that capacity, you know they will never get over losing you. It will be an unbearably sad event for them, for your children. For goodness’ sake, don’t take that step. Respect life, I know that’s not what people mean when they say that, but I mean it. Respect your own life and live it. It will get better.

Love and hugs and may you have peace of mind and peace in your soul.

A little boy on a plane.


I saw a family on the plane from Nantucket to JFK, yesterday. It was a young mom and dad, in their thirties, with a baby girl and a 5 or so year old son. Our plane was late, and the couple was very upset they were going to miss their connection to Cincinnati. They tried to speak to the flight attendant to get them to hold the plane for them, but no dice. The mom was holding the baby girl, who was all smiles and coos. The little boy however was very upset because he “wanted his mama!” The dad kept deriding the boy for crying and being a ninny. He told the boy, who was sobbing, to stop making things hard for all of them. And the boy literally implored him, saying “Please don’t say that.” The mother was just ignoring this little boy and the father was being extremely negative and angry with him. And the little boy just kept saying “But I want my mama!” It was plain for me to see that he was in emotional distress, for whatever reason. His parents were doing nothing to help him, in fact their actions were hurting him more. They were annoyed at the possibility of missing their flight and had no time to address this little boy’s emotional needs. I just wanted to say “Mom, hand the baby to your husband, and comfort your son.” That’s all it would have taken. Instead, they did nothing, and the little boy cried heart rendingly. It was hard for me to listen to him. Is this the way mood disorders begin, by needs that are unmet and perhaps, repeatedly remain unmet? Was this little boy simply more sensitive, his genetic makeup, and simply felt things at a much greater depth than the rest of his family? I know that sensitivity is a key feature of mood disorders. Also, his parents inability to soothe his upset mood, does this then lead to the inability to self soothe for the little boy, leading to anxiety and possibly even depression in the future? Just something I saw that upset me a lot. It just wasn’t right for the parents to ignore this beautiful, little boy’s pleas. It also made me think of how much parents affect our life, how empathy and love would make any situation you find yourself in better. Especially empathy and love from your parents when you are little and need them to have a healthy, happy life. 

Also, it made me think of how these kinds of traumatic events affect the grown up men into which these little boys grow up. 

And what is the relationship of these types of things to people developing mood disorders.