Convergent Functional Genomics and the Web

The Convergent Functional Genomics approach leads to a powerful Bayesian-based prioritization of ours and existing data in the field, and identifies known as well as novel genes, and thus provides novel leads and validation way beyond the perusal of animal and postmortem literature published already. One way to conceptualize it is by similarity to the way the Google PageRank algorithm organizes the masses of amorphous data on the web- the more the links to a page, the more it comes up to the top of your list. Similarly, the more the number of independent lines of evidence converging on a gene, the higher it is on our priority lists. The pyramids of prioritization described in some of our publications should make this point visually clear. (Some of the postdoctoral fellows in the lab do remark on similarities with ancient Egypt also in terms of the painstaking labor involved). A significant amount of new experimental data as well as laborious critical manual curation of existing literature, organized in constantly updated internal databases in our laboratory, goes into our approach-similar to what Tim Berners-Lee calls the “Semantic Web”.

Metabolic syndrome: defense mechanism to side-effect

Metabolic syndrome is a general problem in the population at large, a particular problem in mental health patients such as schizophrenics, and an acute problem in patients on the pine class of second-generation antipsychotics (clozapine, olanzapine, quetiapine). One way to interpret the facts is that the individuals who end up having metabolic syndrome are suffering the consequences of an unhealthy lifestyle on top of a genetic predisposition, and that metabolic syndrome is also a side-effect of pines.

Another way to look at the facts, however, is that the metabolic syndrome is an adaptive atavistic defense reaction of the organism to buffer a perceived stressful and hostile environment, mobilizing and storing resources for anticipated unfavorable circumstances ahead. The pines may be acting on neurobiological pathways involved in this defense reaction, and their metabolic syndrome-inducing side-effect may actually be part of why these medications are effective. One way to test this hypothesis is to see if patients who experience an increase in metabolic syndrome after starting a pine do better from a psychiatric standpoint than patients who do not experience an increase in metabolic syndrome after the start of the pine, particularly in regard to suicidality.

If the above hypothesis turns out to be true, then the solution would be to find ways of activating the central neurobiology involved in this response while blocking the peripheral consequences. This may not be feasible, however, if the peripheral feedback loops triggered by food ingestion, hyperglycemia, hyperlipidemia and sodium retention are necessary for the central effects. If so, a proactive behavioral lifestyle strategy, focused on a concerted daily exercise regimen, coupled with a diet rich in vegetables and fruits, may be the way to mitigate the peripheral effects of metabolic syndrome while maintaining a sense of well-being and promoting health in patients. Mitigating the perception of a hostile environment by an anxiolytic such as an SSRI may also help reduce metabolic syndrome. This is why the combination of a pine and an SSRI may be particularly effective long-term, and with less health liability.