Father knows best: How a $650M grant will help bring psychiatry into the 21st century

Whoa! One of biggest ever medical research donations. $650m to Broad Institute to study genetics of psychiatry. http://t.co/3Klsz1II2j

— Matthew Freeman (@mjafreeman) July 22, 2014

Everyone and their mother has been atwitter about this, including myself and my father, who was peripherally involved in the Broad’s broad study. I’ve been working out of Boston this week, commuting in and out of suburbia with my dad, a schizophrenia researcher at Harvard. While stuck in this city’s infernal traffic, Pops and I – and a couple of his cronies – talked about the implications of such a gift and such a study. This led to the question: Why has psychiatry lagged behind the rest of medicine?

Psychiatry is the ginger-haired stepkid in medicine. Compared to the rest of the medical field, it’s enormously underfunded, it’s stigmatized, and it’s definitely not well-understood. I’m told psychiatry is today where the rest of medicine was a century ago. Here’s why:

Psychiatric disorders don’t have any kind of diagnostic laboratory test. You can’t find some sort of “schizococcus” pathogen under the microscope; no daily blood test exists to monitor the deficiency levels of your attention. The diagnostic criteria for mental illness remains symptom-based, and it remains subjective.

“So we’ve got imprecise disease definitions, and imprecise classifications,” the elder Keshavan said.

Treatments work, but not particularly well. There are 62 antipsychotic drugs, for instance, but they all work the same way: They block one neurotransmitter, dopamine, even though there may be multiple different systems in the brain that go awry to produce the symptoms of what we call schizophrenia. There are probably a similar number of diabetes drugs, but each one works with a fairly different mechanism, and most have unique properties.

“Psychiatry uses the same sledgehammer to solve all the same problems,” the smarter Keshavan said. “Other branches of medicine use more of a Swiss Army Knife approach.”

This isn’t helped by the fact that pharmaceutical companies have, of late, been backing out of developing new psychiatric drugs. Companies like Merck and Eli Lilly pulled the plug on their psych compounds; this is largely because drugmakers, thanks to the general lack of knowledge about the biological processes behind mental illness, often feel like they have to guess about what their targets are. Animal models aren’t really predictive of a drug’s efficacy in clinical trials, and clinical trials themselves can be flawed: Blurry lines in diagnostic criteria mean rather mixed groups of participants wind up in clinical trials.

“And then the results come out seeming inconclusive, which is why drugs turn out to not be useful,” according to Poppa Kesh.

Not to belabor the point, but a 2012 article from Schizophrenia Bulletin puts it nicely:

Psychopharmacology is in crisis. The data are in, and it is clear that a massive experiment has failed: despite decades of research and billions of dollars invested, not a single mechanistically novel drug has reached the psychiatric market in more than 30 years.

I spoke – again during said commute – with Steve McCarroll, director of genetics for the Stanley Center for Psychiatric Research at the Broad Institute. He addressed what the $650 million could do for the field of psychiatry and people living with mental illness – and the best outcome could be increased awareness.

“Although it’s a large gift, it’s a much larger problem,” McCarroll said. “Ultimately, it costs billions of dollars to develop just one drug. To really accomplish something here, we’ll need the concerted action of governments and other philanthropists.”

Part of the reason psychiatry has been underfunded, McCarroll suggested, is this awareness problem – there’s been confusion over whether diseases of the mind are even biological. But researchers are now finding that diseases like schizophrenia and bipolar disorder have distinct molecular signatures. The hope among psychiatrists now is to design therapies based on a deep understanding of the biological mechanisms behind mental illness, McCarroll said.

“Hopefully, finding large numbers of genetic influences can dispel that confusion, and advance the conversation beyond that point,” McCarroll said.

He added that Ted Stanley‘s financial commitment will allow Broad to do long-term planning. This could build a scientific foundation that could actually lead to successful psychiatric drug discovery – and draw drug companies back into the field.

What psychiatry really needs is to enter the era of personalized medicine, said Dr. Rajiv Tandon, a University of Florida schizophrenia researcher whose opinion I solicited while in my parents’ driveway.

“I think the challenge is that we don’t do with the $650 million what we’ve done with the several billion dollars we’ve devoted to psychiatric research over the past several decades,” Tandon said. “Instead of coming up with global, broad hypotheses about psychiatric diseases and treatments, we won’t find any kinds of solutions without putting in step-by-step work to really understand these diseases.

Tandon thinks we’re looking at a 10- to 20-year framework to bring personalized medicine to psychiatry – a large donation and a go-round in the media circus won’t make a huge dent in the long slog to bringing better mental health therapies to fruition.

“If something happens in the next year, beta [Hindi for ‘my dear’], I’d be very dubious about its veracity,” Tandon said.

Bringing personalized medicine to psychiatry will have to be a slow, cautious, step-by-step process – “but I think this is the only way we’re going to develop specific and efficacious treatments,” he said. The fine chisel approach, as opposed to the sledgehammer is the way researchers – and the private sector – should find their way back into psychiatric drug development.

My progenitor, Tandon and McCarroll agree on this point: Cancer care has been heralded as the low-hanging fruit of personalized medicine; it’s also a model that’s working and worth aspiring toward.

“We’re surrounded by people who are cured of cancer,” McCarroll said. “That’s the kind of future we need to work to create for mental illness.”