02 July 2009

Why neurotransmitter genes probably aren’t involved in mental disorders

I was listening to this week’s Nature podcast, in particular the first story on the genetics of schizophrenia. The interviewer, Kerri Smith, made a comment about “neurotransmitter genes.”

I had one of those rare moments where I thought, “Wait! I have enough knowledge to know that’s really unlikely!”

Let’s start with what genes do. Very briefly, genes (segments of DNA) interact with a set of molecules to generate shorter pieces of RNA, which in turn interact with other molecules to make proteins.

So, you could expect to find neurotransmitter genes if neurotransmitters were protein molecules. But most neurotransmitters are not proteins, but other kinds of chemicals. Turns out that neurotransmitters are a total ragbag collection of molecules, and it’s difficult to generalize, but to pick a few examples...

Acetycholine, the first chemical discovered to act as a neurotransmitter, is a small molecule with no relationship to proteins at all.

Glutamate, the major neurotransmitter in vertebrate brains, is an animo acid, for example. Amino acids are building blocks for proteins, but you don’t have genes for amino acids, just like an architect doesn’t have a blueprint for a brick. Amino acids are made by other pathways in your body or ingested.

Serotonin and dopamine, to name a couple of other well known neurotransmitters, are monoamines.

That said, there very definitely are small proteins that act as neuroactive chemicals. One I happen to know is proctolin. So it isn’t completely wrong to say that there are genes for neuroactive chemicals – but they are not major players. “Neurotransmitter genes” wouldn’t be the first place I’d look for causes of mental disorders.

Of course, it is entirely possible that what was meant was not “neurotransmitter genes” in the strict sense, but “genes involved in neurotransmitter synthesis” or “genes involved in neurotransmitter release” or some other pathway where proteins have major roles to play.

With that, I will stop showing off and stop nitpicking on interviewer Smith, who generally does a fine job.

1 comment:

AK said...

When I hear "neurotransmitter genes" without explanation, I think first of genes that code for receptors, or perhaps reuptake transporters. Of course, the real problem could be in the control of alternative splicing, etc.