Monday, November 1, 2010

ADHD and Mom's Serotonin Deficiency

A quickie post today on this study from October's Archives of General Psychiatry, "Attention-Deficit/Hyperactivity Disorder Symptoms in Offspring of Mothers With Impaired Serotonin Production."

If you haven't noticed, I like to be somewhat hardcore about the biology of what is going on.  I use psychology all the time in my work, but psychology takes so much explaining that I don't write about it much.  Also, there's a whole vocabulary of psychology that has to be learned before it is easy to explain.  Though I do end up explaining psychology to people all the time, in appointments.  But usually I have a frame of reference (something happening in a patient's life) to hang the psychology on.  I don't have anything to hang on you.  And psychology by nature is speculative, whereas biology - speculative, but less so.  We've got DNA, after all, and neurotransmitters, and electrons and ions whizzing down a neuron.

Speaking of DNA, each of us have certain genes for our serotonin machinery.  I've dealt quite a bit with serotonin before on this blog, especially here and here.  (Check out our favorite Primal Muse Jamie Scott's complimentary post here ).  Quick review - serotonin is a neurotransmitter made from the somewhat rare protein amino acid tryptophan, and the absence of serotonin in the brain tends to make one aggressive, sad, and suicidal.   More specifically, serotonin is heavily involved in neurodevelopment, neurogenesis, and neural migration (when our little brains are forming, serotonin helps direct our neurons to the right place at the right time, so to speak). Serotonin is also involved in the formation of platelets and in gut motility, but I'm kind of a brain girl, so that's where I focus my energy understanding this wee chemical. 

To make serotonin from tryptophan, we need a couple of enzymes.  First, tryptophan hydroxylase (with iron) converts tryptophan to 5-HTP, then a second enzyme makes 5-HTP into serotonin.  Turns out we have two kinds of tryptophan hydroxylase (which everyone whose anyone calls TPH) - TPH1 and TPH2.  TPH1 is found in the periphery and the pineal gland (a teensy part of the brain that in part regulates sleep - actually serotonin can become melatonin so TPH1 is important in sleep), whereas TPH2 is found in the neurons, and does the major brain work for creating serotonin from our dietary tryptophan.  Got it?  Good.

So, in a mouse who is expecting a little mouse pup, it has been determined that maternal mouse serotonin is exceedingly important in the neural development of the mouse pup-to-be's little mouse brain.  Weirdly enough, serotonin depletion in mouse mothers leads to dopamine depletion in their inattentive and impulsive mouse offspring.  We haven't talked about dopamine all that much, so I should really get on that! Suffice it to say that a deficiency in dopamine can lead one to have symptoms of ADHD.

So what's going on in humans?  Back to one of those northern European countries with socialized medicine and no fears of losing disability insurance with genetic examination - Norway.  Random Norwegians aged 18-40 with ADHD and matched controls AND their agreeable families were sampled from the National Public Registry (which, for medical science, seems like a sparkling good idea, but if you are from Texas like me, you are suspicious of any National Public Registry of any kind.  Wut are they usin' that infermation for, anyhow?)  Controls, ADHD patients, and family members all had their DNA sequenced and special attention was paid to the genes for TPH1 and TPH2.

Results?  Well, many mutations were found for the gene for TPH1.  TPH1 is the tryptophan hydroxylase that is expressed in mom's reproductive parts and would be responsible for bathing the baby brain in serotonin.  And turns out that mom with serotonin machinery problems did have babies with more ADHD later in life.  Dads with serotonin machinery problems had more kids with ADHD, but not nearly as many as the moms did, suggesting the real issue occurs in brain development and mom's serotonin, just like in mice.  Moms with TPH1 problems were more likely to be smokers, drinkers, and drug users too.  Hmmm.  The sample size was rather small, so we can't jump to too many conclusions, but the data as it is was compelling.  TPH1 issues in mom is also a "prime candidate" for schizophrenia, autism, and Tourette's in offspring.  As if moms need to feel even more guilt.  Sorting out the effects of maternal alcohol and drug use versus TPH1 genetic status would take larger studies. 

Our brains are complex, and we need everything just so during our development.  So be nice to those moms-to-be out there.  And no smoking!

4 comments:

  1. *First, tryptophan hydroxylase (with iron) converts tryptophan to 5-HTP, then a second enzyme makes 5-HTP into serotonin*

    that caught my eye... i have trouble falling alseep and getting sleepy at night, but last night i went out with my mom for raw oysters for our bday and if memory serves me right theyre loaded with zinc and iron... and i was very sleepy last night, something i havent felt in a LONG time... would that make sense? may continue having me some raw oysters....

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  2. They are also chock-ful of magnesium! Might have been any of the above. Yummy oysters.

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  3. Very interesting. My case is just the same. I have been depressed all of my life. Lots of therapy, lots of meds on and off...my depression has been called dysthymia and "treatment-resistant". Drank alcoholically for years as well. However, by the time I became pregnant with my son, I had been sober for 8 years and was not taking any medications. It was a happy pregnancy...but very difficult once my son was born. He has been irritable and restless all of his life. Attention deficit was apparent at a very early age. Now, at 9 years old, he has been diagnosed with ADHD. He also has symptoms that suggest an autistic spectrum disorder. I had to take him out of school last year because he is too hyperactive and distracted to learn or even cope in public school. It is a daily struggle to home-school him, even though we are trying different medications.

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  4. This is quite interesting. I've always "blamed" my asthma on my mom because she also has asthma. However, I've always kind of wondered where all of my mental health issues came from. Both of my parents suffered with recurrent bouts of depression for as long as I can remember. My mom smokes, but she stopped while she was pregnant with me and her pregnancy went fine. Then out popped me. I started having mental health issues when I was 16 years-old; that's when the depression kicked-in. Then the schizophrenia started a few years later. The adhd was just always there since I was in first grade.

    Does this imply there is a relationship between schizophrenia and adhd? Is there a high amount of people who have schizophrenia that have adhd? How does OCD fit into the picture?

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