Wednesday, November 2, 2011

The color blue for promoting mental health initiatives

The breast cancer community has done a terrific job of decreasing stigma, raising funds for research and treatment, and increasing awareness using the color pink in marketing and promotional campaigns. We should learn from them.

Mental health is as important an issue for women -and men, but less well publicized. I would propose we use blue as a color for mental health in marketing and promotional campaigns, for exactly the same reasons as in breast cancer- to decrease stigma, raise funds and increase awareness.

In popular culture, blue has already been associated with depression (“having the blues”), or it’s opposite (“blue sky thinking”). It is a soothing color that may decrease anxiety and increase cognition. So the full triad of major mental health domains (anxiety, mood and cognition) can be linked to blue and be well represented by it. There is some research supporting its use as well:

Who wants to help promote this? Email us and spread the word.

Alexander B. Niculescu, MD, PhD

Monday, July 25, 2011

Psychiatric genetics: contextual cumulative combinatorics of gene variants and environment

Classic genetics research in psychiatric disorders has provided an abundance of data but a paucity of insight. Things will only get worse in terms of this ratio, as massive sequencing of genomes becomes routine.

The reasons are four-fold. First, psychiatric disorders are genetically complex, with many (hundreds, if not thousands) genes involved. We first proposed that over a decade ago, based on our pioneering gene expression work cross-matched with human genetic data (Convergent Functional Genomics). Second, psychiatric disorders are genetically heterogeneous, with different mutations in the same gene present in different individuals. Many of these mutations are in fact common variants present in non-psychiatrically ill individuals as well. Third, psychiatric disorders as currently defined by DSM are overlapping and interdependent, with genes and biological pathways shared among disorders. Fourth, the environment plays a major role in modulating gene expression and the development or not of illness.

The key to progress is to acknowledge reality in the four areas mentioned above. Illness or lack of illness are the result of cumulative combinatorics of common gene variants and environmental stressors (or favorable factors). Genetic context and environmental context are important to whether a mutation contributes or not to the illness.  Gene expression studies are more informative than classic genetics, as they reflect the actual results of the interaction between genes and environment, and underlie the subsequent patho-physiological outcomes. Biological pathways and mechanistic-level analyses will show more commonality and reproducibility across individuals, and from study to study. A dimensional approach to psychiatric profiling of individuals will eliminate the confusion and overlap of DSM, as well as permit a better mapping and tracking of biological reality. Our group has provided comprehensive proof and solutions over the years in all these areas, and we will continue to do our bit.

Alexander B. Niculescu, III, MD, PhD

Saturday, July 2, 2011

Clock Genes and Mood

"There can be no transforming of darkness into light and of apathy into movement without emotion"
      - Carl Jung     

      After more than a decade of work on understanding mood, using the magnifying glass of severe mood dysregulation disorders such as bipolar disorder, our group has proposed and provided evidence for mood being related to levels of activity, energy and growth, in response to internal and external environment cues. When the environment is favorable, levels of activity and growth are (or should be) high. When the environment is unfavorable, levels of activity are (or should be) low. When there is a discongruence between levels of activity of the organism and the environment, we are dealing with a mood disorder, manifested as depression or (hypo)mania.
      Following early hypotheses from W. Bunney and R. Lennox, our group has provided over the last decade cumulative empirical evidence that supports a model where circadian clock genes are the core mechanism of mood regulation and dysregulation. They serve as a thermostat, increasing or decreasing the level of activity of cells, brain and of the whole organism. Some key circadian clock genes we have identified and provided evidence for involvement in mood are ARNTL, RORB, and DBP. DBP, first identified by us as a candidate gene for bipolar disorder over a decade ago, has provided a basis for us developing the first broad-spectrum genetic mouse model of bipolar disorder, which mimics both phases of the illness, depression and mania, as well as mimics the sensitivity to stress and the propensity to substance abuse.
      Due to the genetic overlap and biological interdependence between mood, anxiety and cognition, circadian clock genes have also appeared in screens conducted by us and others for genes involved in other disorders, such as anxiety disorders and schizophrenia. It is understandable how levels of energy (mood) can influence signal transduction reactivity (anxiety) or brain connectivity (cognition).

      Clock genes are present in every cell in the body, regulating the expression of thousands of other genes. They are likely going to become key targets for therapeutic intervention and new drug development, and provide a biological rationale for circadian medicine, circadian psychiatry, and other subspecialties of the future.

Alexander B. Niculescu, III, MD, PhD

Saturday, March 5, 2011

The Biomarkers Solution: How to Improve Pharma Drug Discovery

The drug discovery process is currently flawed at both pre-clinical and clinical levels. Biomarkers are an emerging “bridge over troubled waters” between these two areas, and a solution for their respective ills.

Preclinically, gene expression networks, not single gene products, need to be targeted for comprehensive and successful treatment of diseases. Combinations of drugs need to be developed and used from the beginning for broad impact. Profiling baseline gene expression and response to drugs in animal models using biomarkers can ensure the right combinations of drugs are selected and advanced towards clinical testing.

Clinically, one size does not fit all. The blockbusters of the future will not be blockbusters in terms of patient population sizes treated, but rather due to precision and efficacy, commanding a deserved premium price that way. Some of the same biomarkers derived from discovery work and pre-clinical studies can be used in clinical studies, providing solutions for their current limitations: better diagnosis and patient stratification, objective monitoring of response to treatment, and a handle on the placebo effect. Early biomarker information from clinical trials will provide in an iterative fashion intelligence for improved selection criteria and outcomes in later clinical trials, leading to an enhanced rate of successfully approved medications, albeit for more narrow indications.

Alexander B. Niculescu, III, MD, PhD

Friday, January 7, 2011

Trend of the Year in 2011: Social connections, lower stress

Isolation is a powerful stressor-in people, animals, and probably all the way to single cells. It is associated with higher anxiety, lower mood and lower cognition, and myriad health problems. Isolation leads to uncertainty about safety, ability to thrive and ability to influence events. It is becoming more prevalent in modern societies, where social, familial and intergenerational bonds are frayed by geographic relocations/dislocations. On the dark side, social isolation has also been used as a way of punishing and/or coercing individuals.

Real or perceived social connections, from online connections such as Facebook to the local pub, exert a powerful soothing effect, and people are willing to pay for that with their attention, time and money, despite less than nourishing offerings (flimsy online friends, grubby pub fare).

As in the popular old TV series “Friends”, “Seinfeld” and “Cheers”, people go to these places (coffeehouses, corner deli, bars) as much for the actual fare served as for the fact that there (hopefully) “everybody knows your name, and they’re always glad you came”.

More positively, the health promoting effects of church attendance have been well documented. Proactive ways of social integration- from reconnecting with families, friends to joining social groups with a cause in a contributory fashion, will improve individual health and the health of society as a whole. Fads and companies come and go, but the importance of social connections is a perennial lesson that bears learning and relearning.

Alexander B. Niculescu, III, MD, PhD