Psychoanalysis and Genomics: Strange Bedfellows with Chance for a Future

For years, biologically based psychiatrists have forecasted a “genetic revolution” in which we learn the details of how most, if not all, disorders of the mind are predicted more by the genetic code than by some effect of early life or family. Psychiatric epidemiologists demonstrated decades ago, mainly by studying pairs of identical and fraternal twins, that psychiatric disorders are inherited to a significant degree. Yet, without exception, no simple gene or genetic mechanism has emerged to explain the etiology or pathophysiology of a major psychiatric illness, despite billions of dollars spent in this pursuit.

Caspi and colleagues demonstrated in 2002 and 2003 that the interaction of environment and gene (in one case, childhood maltreatment and the monoamine oxidase A [MAOA] gene, in another, stressful life events and the serotonin transporter gene [5-HTT]) is a far more powerful predictor of psychiatric outcome than either alone. Since then, most psychiatric research has focused on looking for more such interactions, rather than studying the relationships between single disorders and genes. Still, the clinically relevant results have been few and far between.

All this may now be about to change. In 2003, the Human Genome Project was completed, which means that the entire 3 billion base pair sequence of a single individual was recorded. Then, in 2007, two further advances brought the goal of identifying the genetic basis of psychiatric illness a great deal closer. Last October the International HapMap Project published its entire dataset. This project identified the segments within the 3 billion base pair sequence that show variation between human beings (reflecting the fact that the DNA sequence of any two people is 99.9 percent identical). The HapMap project tells us that one only needs to capture 500,000 pieces of information (rather than 3 billion) about an individual's genetic code in order to fully identify his or her unique genetic fingerprint. Second, and just as astonishing, “gene chip” technology was developed to efficiently capture these 500,000 pieces of information (in the form of single nucleotide polymorphisms, or SNPs, pronounced “snips”) from a specimen of human DNA quickly (on the order of hours) and inexpensively (on the order of $1,000 per sample).

Leading figures in genomic research, such as Eric Lander, a professor at MIT and director of the Broad Institute, are saying that these advances have brought about an inflection point in our ability to identify the role of the genetic code in human traits, including those relevant to psychiatry. Prior to 2007, scientists needed to be lucky to find a direct link between a gene and a visible trait because these associations were usually not where they expected them to be. However, with the HapMap project finished and gene chips cheaply available, it has become possible to thoroughly scan the entire genome for associations to human traits with little or no a priori hypotheses about where to look. Lander advised psychiatrists to start collecting genetic samples of 1,000 or more subjects with whatever trait interests them and subjecting them to gene chip analysis. He believes that this shotgun approach will lead to a revolution in how we understand the genetic basis of human variation and psychopathology.

Enter psychoanalysis. Contemporary psychiatry is notoriously bad at identifying the myriad of continuous traits that capture temperamental variation among individuals, having long ago opted for discrete categories that fit more neatly with drug trials and insurance reimbursement. Personality psychologists study these issues, but with little attention to psychopathology or to their relevance to treatment and change. Psychoanalytically oriented theorists and clinicians, on the other hand, have devoted enormous energy to describing how individuals vary from one another and how this is manifested in their development, character structure, unconscious processes, defenses, response to treatment, and long-term outcome. Of course, psychoanalysis has traditionally focused on the environmental and personal-historical roots of such variation. However, from Freud on down, this has always come with the implicit or explicit acknowledgement that a significant part of psychic variability is inborn. The chance has come then, for the psychoanalyst to use his or her ability to describe such variation by partnering with those doing genetic studies.

This work has already begun. Marian Bakerman-Kranenburg and Marinus van IJzendoorn, pioneers of attachment research at Leiden University, published a review in 2007 of genetic links to attachment. From the dozen or so existing studies, they conclude that a variant of a specific dopamine transporter gene (DRD4) is associated with both an increased risk for disorganized attachment and a bad outcome when the environment is bad and an increased risk for positive outcome when the environment is favorable.

Somehow, then, we need to understand how a difference in a neurotransmitter signaling system in the brain leads to an interaction of early experience and the formation of internal working models (i.e., attachment style).

Meanwhile, the same DRD4 gene has been linked in a new meta-analysis (Munafò, Yalcin, Willis-Owen, and Flint, Biological Psychiatry, 2008) to certain “approach behaviors” such as “novelty-seeking” and “impulsivity” but not to “extraversion” as defined in the personality research literature. Personality theorists are at a loss on how to understand this. Psychoanalysis remains the only comprehensive meta-psychology with the theoretical complexity to help tease apart these questions, and certainly the only one linked to a method for gathering the data about such structures.

It makes sense that individual psychological variation be this complicated and requires an appreciation of not only superficial traits but meaning as well. Science needs the input of psychoanalytically trained clinicians and researchers to help sort out how better to understand and study the ways this variation interacts with environment to shape personality and psychopathology.