Is the variant of the dopamine-processing gene DRD4 the cause of ADHD (Attention Deficit Hyperactivity Disorder), the key to accelerating human enlightenment – or both?
At CDD, we are honored to support researchers’ collective quests to discover new drug candidates. In fields as broad as chemistry interacting with biology, better mining and collaborative tools facilitate better insight when used right. What may seem like a liability or adverse effect in one context, can be the cat’s meow in an alternative context.
Reading David Dobb’s fascinating article “The Science of Success” (published in the Atlantic and selected to the prestigious 2010 Best American Scientific Writing Collection) recently reminded us of that subtle dichotomy. It is also a great example of how new insights arise from scientific ingenuity, combined with statistical mining and collaborative platforms – such as the scientific literature and, even better, real-time web-based collaborative platforms like CDD.
At the heart of the DRD4 story, is a new insight into the nature-nurture dichotomy dubbed by David Dobbs as the orchid gene hypothesis. As the name suggests, one can think of our and other organisms’ genetic dispositions in terms of plasticity, rather than merely as risk factors. Plasticity is determined by key factors such as parents and countless strongly impressionable interactions.
Under one set of conditions (nurturing settings and also perhaps pharmacologically or genetically guided), studies suggest what was once considered a predisposition towards dysfunction in unfavorable contexts, can actually enhance function in more favorable contexts. What Marian Bekermans-Kranenburg and co-workers found, is that an intervention they had developed to help mothers with children with ADHD master obedience and cooperation, not only worked with ADHD children….but to their surprise, these children scored the very best. It is useful to be aware of the behavioral and biological mechanisms that can lead to healthier children, and by extension, a more enlightened society. From her website:
“Our growing interest in the interplay between nature and nurture has led to several studies on gene-environment interaction, with a special focus on the ‘differential susceptibility’ of children to rearing influences. Our series of molecular genetic studies on the role of Dopamine D4 Receptor gene polymorphisms did not show genetic main effects, but suggested vulnerability of children with the DRD4-7R allele to adverse environmental influences. We demonstrated increased levels of externalising behaviour problems and disorganised attachment for children with the DRD4-7R allele and environmental risk (Bakermans-Kranenburg & Van IJzendoorn, 2006; Van IJzendoorn & Bakermans-Kranenburg, 2006). However, these children were not only vulnerable to environmental risk, they also showed remarkably positive outcomes when they received supportive care. Our results suggest that the supposed vulnerability of carriers of the DRD4-7R allele is only part of the story: DRD4 may also be considered as a potential genetic marker of differential susceptibility or biological plasticity in response to environmental influences (Bakermans-Kranenburg & Van IJzendoorn, 2007).”
In the case of genes that effect our emotions and personalities, such as dopamine and serotonin receptors, transporters, uptake inhibitors and the like – certain mutations seem to encode for heightened sensitivity. By sensitivity, I mean sensitivity in both senses of the word – personal awareness and emotional susceptibility.
Molly Zametkin, the so-called Poster Child for ADHD, recently wrote a highly personal editorial railing against the inappropriate stigma and prejudice associated with what researchers now understand can be an asset as much as a liability.
We all know the concept of the classic troubled artist driven to brilliance, paraphrased in the famous quote by George Bernard Shaw, “The reasonable man adapts himself to the world; the unreasonable one persists in trying to adapt the world to himself. Therefore all progress depends on the unreasonable man.”
Within a heterogeneous society, for both monkeys and humans, having some individuals with mutations causing heightened sensitivity, is a key to progress.
Taking genetic variation as a metaphor for unique, new insight, at CDD, we’re doing what we humbly think is our little part to support innovation with new technologies that support more selective, secure private collaboration and data analysis. And public resources for free, such as chemically searchable GPCR gene-family wide SAR (courtesy of Bryan Roth’s PDSP) and other data sets to better guide research efforts. The hypothesis is while working together, to the maximum extent possible while preserving IP (intellectual property), we can all learn and evolve faster.
While researchers are focused on the painstakingly detailed work of basic scientific and applied drug discovery research, it can be inspiring to broaden one’s perspective to marvel at the collective progress we can and will make over the years, decades, and centuries.
Over time, collaboration is the key to accelerating the rate of progress.
This blog is authored by members of the CDD Vault community. CDD Vault is a hosted drug discovery informatics platform that securely manages both private and external biological and chemical data. It provides core functionality including chemical registration, structure activity relationship, chemical inventory, and electronic lab notebook capabilities!
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