The roots of mental illness

Image by Jennifer Mathis
Image by Jennifer Mathis

There’s been a lot of buzz in the media this week about a new study on the genetic component of some mental illnesses. This is the largest genome wide association study of the genetic component of mental illness to date (33,332 affected individuals and 27,888 control individuals had their genomes examined for single base pair genetic differences.  The affected individuals were diagnosed with one of five disorders: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, or schizophrenia. This particular study focused on finding genetic changes that were common to all five disorders as opposed to any genetic changes that cause the individual disorders. The genetic associations uncovered by this study were shocking to many in the field.

It turns out that 4 single base pair genetic changes are associated with ALL of these diseases, suggesting a common disruption that can manifest itself in different ways in each person depending on their environment and other changes in their genome. Two of the genetic changes are located between genes in what is likely regulatory sequence. It is hard to know how these two changes relate to the psychiatric disorders. The other two genetic changes are within genes CACNA1C and CACNB2 which are two subunits of L-type voltage gated calcium channels. These channels are critical for the function of neurons and other cells.

These two genes are also known as Cav1.2 alpha and Cav1.2 beta. The alpha subunit is necessary for the channel’s function because it actually makes the channel through which calcium will pass in response to a change in voltage. The beta subunit is also necessary for this channel to function. Voltage-gated calcium channels are responsible for the release of neurotransmitters (signaling molecules) from a neuron in response to a change in voltage or electrical signal (action potential). These two genes underly the basic function of many neurons. However, that is not their only role. These channels are also present in heart muscle cells, and are responsible for maintaining the rhythmic beat. When these channels are defective, serious heart problems ensue like Timothy Syndrome and Brugada Syndrome.

This new study points to a defect in very basic function and/or development of neurons contributing to a range of psychiatric disorders. This knowledge of genetic changes will help define psychiatric diagnoses that often have overlapping symptoms and can occur simultaneously and this was the intention of the study. It isn’t clear from this study that these particular changes are the root of these illnesses (and a target for treatment) or just a contributing factor. However, many media outlets have jumped on the fact that there are several drugs known to target these calcium channels. These drugs are not going to be the be-all, end-all for these psychiatric disorders.

Like I mentioned before, these channels are acting in the heart as well as the brain so if you’d like to try to cure your disorder with a side effect of stopping your heart then please start yourself on some verapamil. I do think this surprising new information argues for a continued focus on basic neuroscience research. These disorders are influenced by a disruption at the most fundamental functional level of a neuron. Until we understand how these genetic changes affect the way these nerve cells operate, we cannot develop drugs and techniques that specifically repair calcium channel function in the correct nerve cells. The drugs on the market now will effectively be a boulder to kill a flea. At least now, basic neuroscience researchers know they are headed in the right direction.


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