The World in 2009 and beyond:

1. Singapore will make big strides towards becoming for biomedicine what Switzerland is for financial services.

2. Smart pharma companies will start to realize that sleek packages, integrating diagnostics, combinations of medications, and lifestyle advice, are where the field will be 10 years from now, and will start to take steps in that direction. The end user would personalize and customize such packages just as they do an iPhone now.

3. Healthcare organizations will then become like cell phone carrier companies, selling service plans for the packages mentioned above. Your doctor will become a consultant to help you optimize your iHealth package.

Alexander B. Niculescu, III, MD, PhD

Mindscape- mental landscape

The latest genomic, neurobiological and clinical evidence suggest that normal mental functioning and psychiatric disorders can be classified in three broad and overlapping domains: the anxiety domain, the mood domain and the cognitive domain. This is superficially reminiscent of the Freudian classification of id, ego and superego. The mind works to optimize organism-environment interactions through anxiety, mood and cognition. Psychiatry can provide a magnifying glass for identifying the normal functions of the mind by studying their disruptions.

At a particular moment in time, a person’s mind state can be represented as a point in this 3D space, determined by x, y, z coordinates of quantitative scores on anxiety, mood and cognition measures, respectively. Rating scales as well as blood biomarkers levels and other objective correlates for mood (such as neuromotor activity measures), anxiety (such as galvanic skin response) and cognition (such as EEG gamma band measures), can be used to generate the scores.

Over time, the fourth dimension, each person is represented by a distribution of points (cloud) in the three-dimensional Mindscape. The topology (shape) of the Mindscape cloud is unique for each person, similar to how each person has a fairly unique physical appearance. In fact, it may differentiate between identical twins.

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.