Calcium dynamics & psychiatric illness.

calcium transientsThe alpha subunit of the L-type calcium channel (CaV1.2) is encoded by the gene CACNA1C. An apparently obscure protein, CaV1.2 has risen to prominence in the last five years.

Several large scale genome-wide association (GWAS) studies are in agreement that variation in CACNA1C is associated with bipolar disorder and schizophrenia. Additionally, mutations in CACNA1C are a direct cause of autism. As a consequence, Ca2+ signalling has begun to receive attention amongst psychiatrists.

A recent review by Michael Berridge is the ideal introduction to Ca2+ dynamics. Calcium does not only enter cells via channels. There are intracellular stores, which can be stimulated to release Ca2+ into the cytosol. Neurotransmitters such as serotonin, noradrenaline and glutamate can invoke the release of Ca2+  from intracellular stores by way of an intermediate 2nd messenger pathway, the phosphatidylinositol 4,5 biphosphate (PIP2) system. Berridge is best known for having deciphered the foundations of the PIP2 system in the 1980’s and as such he is an authoratative guide for the relevance of calcium signalling to psychiatric disorders.

The full paper is available here.

History repeats. Revelation ends up as show-business


The dorsolateral prefrontal cortex (DLPFC) and frontal eye fields (FEF) are larger in people who spend more time playing video games.

An elegant new study has revealed that video game enthusiasts have an enlarged (left) dorsolateral prefrontal cortex [DLPFC]. This is the region of the brain which is believed to organise and plan mental activity, the central executive. It appears that we can choose to expand our central executive by practice, much in the same way that a muscle responds to repetitive exercise.

But is there really anything new? The brain is plastic at multiple levels. Synapses and circuits are moulded by the environmental information which they process. For instance the part of the brain which processes music is known to enlarge in people who develop musical expertise. Cortical thickness is not predestined. Instead, the cortex is a dynamic structure upon which an impoverished (or enriched) environment will impact. The brain/mind assembles it’s world and is assembled by the world – essentially a Hegelian insight.

The findings from this new study should caution those repeated efforts to reveal something about psychiatric patients on the basis of the size/thickness of their prefrontal cortices. There are many variables, aside from psychiatric diagnostic status [itself an art rather than a science], which determine the size/thickness of the cortex. The irony of course is that such a trivial, mindless pastime as playing video games can enlarge the physical correlate of what is usually regarded as a higher mental faculty.

The full paper can be read here.