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!