Genes and Environment and the World of Psychiatry

I have recently returned from the 15th World Congress of Psychiatry, held in Buenos Aires. It was a remarkable and enormously successful event. Mario Maj, outgoing president of the World Psychiatric Association (WPA), deserves hearty congratulations for organizing a first-rate program, one that attracted an estimated 14,000 attendees and showcased presentations by leading researchers and clinicians from around the world.

For the last three years, Mario has worked closely with the WPA president-elect, our own Pedro Ruiz, who was installed as president at the end of the meeting. In plenary sessions and at the Assembly, Mario summarized an impressive set of WPA accomplishments during his tenure. In turn, Pedro outlined nine major goals that he will prioritize during the next three years, emphasizing worldwide education and collaboration about the mental health needs of citizens from all cultures and populations.

The prominence of American psychiatry in the work of the WPA is notable. Pedro is president for a three-year term. In addition, Michelle Riba was elected to the post of secretary of sections, and Jack McIntyre was elected as the new zonal representative for Zone 2 (United States). Also, Donna Stewart was elected to serve as zonal representative for Zone 1 (Canada)—and, yes, I know she is Canadian, but she is an active leader in APA, so she counts! American psychiatry was also in high profile among the keynote speakers and symposia chairs. Among a total of 40 individuals in these two categories, 50 percent were from the United States, and 55 percent are APA members. In addition, many more presenters from APA (including me) were participants in program components.

At the WPA Congress, as I listened to the many presentations from all over the world, I was impressed (as I often am) by the exponential advances in our scientific technology and by the many ways in which our world is becoming interconnected. There is clearly a worldwide spirit of collaboration and determination to eradicate stigma and to develop better understanding, prevention, and treatment of brain disorders. The contrast is interesting, by the way, between this international teamwork and the dissensions, wars, and political/cultural/religious animosities that scream from our headlines daily. That may be a little unfair to say, since there are plenty of positive media reports about advances in medicine, but news about terrorism, disasters, and tragedies (all too real, I acknowledge) seems to trump the good news about the growing international partnerships that are making our world better.

So why do I choose a title for this column referring to genetics and environment and the world of psychiatry? While there are many rapidly developing frontiers of progress, one that has enormous promise yet remains dauntingly challenging is the work to unravel the complex genetics of psychiatric disorders. At the Opening Session of the WPA Congress, the Jean Delay Prize Lecture was presented by Ken Kendler. The lecture, titled "Genes, Environment, and Psychopathology," was a masterpiece, translating the complicated science of genetics into a language that was easy to understand. After illustrating many advances in our understanding of the structure and environmental risk factors for Axis I and Axis II disorders, he warned that we "suffer from repeated episodes of naïve exuberance" and that the "causes of psychiatric illness are ‘dappled’—spread through many levels of nature and therefore the focus of a number of different kinds of science."

Another outstanding lecture at the Congress was presented by Peter McGuffin, from the Institute of Psychiatry at King's College, London, titled "Past, Present, Future of the Genetics of Mental Disorders." He reviewed the major benefits of the Human Genome Project, such as the development of a map of markers or "signposts" for genome searching. One study on which he focused was the important 2003 New Zealand study by Caspi and colleagues of serotonin transporter gene polymorphisms, life events, and depression. McGuffin argued that 17 out of 34 subsequent studies replicated this finding and that eight partially did so, and he added that all of the nonreplication studies tended to be in adolescent or older subjects and were based on brief self-report questionnaire measures of life events. He elaborated on what he viewed as the "hot topics" of the present: genome-wide association studies, copy number variants, epigenetics, and pharmacogenomics.

Coincidentally, this theme of gene/environment interaction is featured in the October American Journal of Psychiatry. In "A Critical Review of the First 10 Years of Candidate Gene-by-Environment Interaction Research in Psychiatry," Duncan and Keller present a careful analysis of all 103 studies published from the first decade of gene-by-environment research in psychiatry. Like McGuffin, they selected the important 2003 study by Caspi and colleagues to examine the controversy about replication attempts, some of which supported the Caspi results and some of which did not.

Their results "suggest the existence of a strong publication bias toward positive findings that makes [gene-by-environment] findings appear more robust than they actually are." Nevertheless, they believe that these interactions "are likely to be common and that they may well prove to be important or even central for understanding the etiology of psychiatric disorders."

In an editorial, Brzustowicz and Freedman thoughtfully discuss the Duncan and Keller findings, plus the results of three other papers on the genetics of psychiatric illness in the October issue. Among their considerations, Brzustowicz and Freedman pointed out that studies that do not replicate major findings may "involve other genes or alternative definitions of what is stressful," which "differ across populations."

Populations differ in many ways, and these are but some of the hurdles to clear as we continue our international work to refine psychiatric diagnoses and their genetic and environmental causes. Events such as the World Congress bring us together to improve our common language of science and clinical care. Yet as we clarify how we are alike and how we are different, we must remain culturally sensitive and recognize the variety and diversity of our world, which we must celebrate and preserve.