“Decades of negative results”: the failure of psychiatric genetics

My post the other day discussed how admissions from prominent proponents of biopsychiatry that should be devastating to the enterprise are framed such that they not only avoid directly challenging the brain-disease model but continue to prop it up. This is accomplished through hedging about the invalidity of the model by making or repeating unsupported claims that it’s merely a partial or simplified but still real and important aspect of a more complex reality and by diverting people’s attention with (also unfounded) suggestions that, whatever its scientific shortcomings, the model has been individually or culturally beneficial.

The final element in this spinning of biopsychiatric failure is the repeated presentation of fantastical futuristic scenarios in which new lines of research will provide scientific grounding to the model and vindicate it. This is almost always combined with the implication that recent discoveries have demonstrated this potential to rebuild biopsychiatry on a new, but vaguely related, biological foundation.

What strikes me most about these projections is, for one, their childlike enthusiasm and overconfidence. Here’s a portion of one such dream I quoted yesterday:

“I hope I'll be able to give a patient with possible bipolar a proper clinical assessment,” Craddock says. “I'll do a blood test and look for genetic risks and send them into a brain scanner and ask them to think of something mildly unhappy to exercise their emotional system.” The results could be used to trace the underlying cause — such as a problematic chemical signal in the brain. “I'll then be able to provide lifestyle advice and treatment.” He pauses. “Actually it won't be me, because I will have retired by then.”

The possibilities, and even probabilities, claimed for genetic psychiatry seem to know no bounds. And the sense of tangible promise is heightened by its presentation as cutting-edge area of research where exciting discoveries are now being made, awaiting only the technological and intellectual capacity to convert them into powerful to clinical therapies.

But peel back the rhetorical façade and we find that psychiatric genetic research isn’t new at all. It’s been ongoing for decades, and its record is as dismal and disappointing as that of biopsychiatry itself. (This shouldn’t be surprising when we understand the fundamental flaws in the brain-disorder model itself: people are looking for genetic causes of constructs for which there’s no evidence of a real biological basis in the first place.)

So the very lines of research proclaimed as biopsychiatry’s best new hope are really just part of the same sorry history of disappointed expectations. And this isn’t news, either. A recent book chapter by Jay Joseph and Carl Ratner* (full text available here) tells this story of failure. They describe a 2012 meta-analysis by Neil Risch et al.:

Risch and colleagues concluded that ‘few if any of the genes identified in candidate gene association studies of psychiatric disorders have withstood the test of replication’. They further concluded:

Despite progress in risk gene identification for several complex diseases, few disorders have proven as resistant to robust gene finding as psychiatric illnesses. The slow rate of progress in psychiatry and behavioral sciences partly reflects a still-evolving classification system, absence of valid pathognomonic diagnostic markers, and lack of well-defined etiologic pathways. Although these disorders have long been assumed to result from some combination of genetic vulnerability and environmental exposure, direct evidence from a specific example has not been forthcoming.

Thus the fields of behavioral genetics and psychiatric genetics are rapidly approaching a period of crisis and reexamination. In the words of a leading group of psychiatric genetics investigators, writing in 2012 about the decades-long failure to uncover any genes that cause schizophrenia (the most studied psychiatric disorder), these negative results ‘suggest…that many traditional ideas about the genetic basis of SCZ [schizophrenia] may be incorrect’.

Joseph and Ratner note that “[T]hree genetically oriented Nobel Prize-winning researchers and their colleagues, in a 2010 Science ‘Policy Forum’ article, recognized the ‘frustrating lack of progress in understanding the genetics of mental disorders'.”

It’s fascinating: the fields that are supposed to rescue biopsychiatry are themselves in full crisis. But, as in biopsychiatry more generally, people have failed to recognize or appreciate the scientific significance of the “decades of negative results” in psychiatric genetics. This failure to discover genetic factors is interpreted, based on assumptions drawn from earlier kinship studies, as the problem of “missing hereditability.” Joseph and Ratner’s goal in their chapter is “to suggest that the misreading of previous kinship studies of families, twins, and adoptees has led the scientific community to the premature conclusion that genes for psychiatric disorders and psychological trait variation must exist.” They argue for dropping the assumptions about missing hereditability based on these kinship studies, arguing that the reasonable interpretation of the failure of decades of research in psychiatric genetics is nonexistent hereditability.

It’s not the purpose of their chapter, but it’s worth noting that Joseph and Ratner – like Erich Fromm, but unlike biopsychiatry’s enthusiasts like the one quoted above** – think about the social and political significance of our approaches to human problems, “not only scientific and social issues that form the assumptions that guide this work but also the scientific and social consequences of this work.” They appreciate that, as I argued in my earlier post, the continuing emphasis on genetic psychiatry serves socially to buttress the notion “that these disorders have biochemical causes, and that psychology has biochemical causes,” and vice versa. They’re also attuned to the fact that “[g]enetic-determinist ideas divert society’s attention from these environmental conditions and shift blame onto people’s brains and bodies.” Their hope is that “research into these issues will support the rejection of the genetic paradigm of psychiatric disorders and will give grounds for an alternative paradigm that emphasizes the role of familial, social, cultural, and political influences.”

* Joseph, J., and Ratner, C. 2013. “The Fruitless Search for Genes in Psychiatry and Psychology: Time to Reexamine a Paradigm.” In S. Krimsky and J. Gruber (Eds.), Genetic Explanations: Sense and Nonsense (pp. 94-106). Cambridge, MA: Harvard University Press.

** It’s interesting how profoundly politically naïve and unthinking these futuristic biopsychiatrists appear. It’s almost as though they’ve never given a moment’s thought to the human implications of their model, either as current practice or as a future clinical possibility. It’s adjustment psychiatry carried to its antihumanistic extreme.