I was in the modern agora of Walmart this winter when I started to lose it. I began to feel the onset of insanity, a sudden sense of depersonalization and an anticipation of impending doom. The more I tried to control it, alarmed at the spike in cortisol, the more acute the sensation was that I was losing consciousness and in serious danger. People continued shopping in the isles. One was throwing toothpaste in her cart. I was rapidly losing memory of basic procedural things, even who I am, of anything that happened even seconds ago.
This experience, commonly called a panic attack (if it makes you feel better to call it something), resolved in less than 15 minutes, against my belief that I was losing my mind, if not my life. I first noticed these acute events when I was about 20 years old. It did not help that at that time I was drinking heavily and often kept a Ziploc bag of psilocybin mushrooms in my jeans pocket. I was starting to become withdrawn. For a brief time I was put on a number of drugs, including the heavy-duty antipsychotic Zyprexa. Only after taking a thyroid replacement drug for a couple of years did my sense of well-being restore. I have not seen a psychiatrist or taken prescription or illegal drugs in two decades.
It is easy to see how such acute events can turn into secondary symptoms. For instance, if you do not know when you might slip into a state of panic, or acute insanity, you may avoid social situations, and that can lead to excessive guilt, even mild depression. Last year I skipped out on an invitation to Tom Ashbrook’s radio talk show On Point, live on WBUR. For a moment I felt terrible, as if I had let down my publisher, Cambridge University Press. But it turns out my publisher and Ashbrook’s team did not make it into a big deal—and that enabled me to let it go. The positive social feedback loop made a difference, and that relates to the concept of low-expressed emotion, the value in other people’s perception of such an event as transitory, or of little alarm.
A year ago I wrote an essay for the Boston Globe titled “Fixing Genes Won’t Fix Us,” which was deeply critical about the state of psychiatric genetics. Since I have a master’s degree in genetics and have published some technical papers on schizophrenia and bipolar disorder, I figured I had at least some qualification to write such an essay, and it generated a lot of feedback. Since many people think I am antiscience or against biotech, I wanted to spend some ink to clarify my positions.
The first is that most genetic variants that influence psychiatric conditions only contribute to a weak effect, often less than a single percentage point on the risk of having such experience or condition. Many of these genetic variants are pleiotropic, meaning they have different enhancing or canceling effects on other genetic variants, or different effects in different cell types. Deleterious mutations can even stick around in the population if they contribute to balancing selection, meaning they add to genetic diversity. In a broad sense of heritability, genetics influence endophenotypes—underlying psychology tendencies or traits—but nothing comes without trade-offs.
People with panic disorder are often more interoceptive, meaning they have an awareness of their heart beating (think Edgar Allan Poe) or their fluids moving, or their thoughts creaking; in effect, they often have a heightened degree of self-consciousness. In The Noonday Demon, Andrew Solomon wrote about one theory suggesting that depressive types are often more realistic than average.
Eminent poets and fiction writers, who have an acute sense of the transitory, are more apt to be bipolar or depressive, according to research by Arnold Ludwig in the 1990s. In The Trip to Echo Spring, Olivia Laing wrote of five writers, including Tennessee Williams, who as a young person on the streets of Paris became afraid of what he called “the process of thought” and came within “a hairsbreadth of going quite mad,” describing his experiences as “the most dreadful, the most nearly psychotic, crisis that occurred in my early life.” The point is not to venerate disorders through their connection to the arts—I would never do that—but to suggest the primal experience of human existence is a loss of control rather than a default of stability.
Various studies suggest genetic mutations introduce a degree of risk, make us more sensitive or alter concentration, with effects that depend on the genetic background. One gene variant can lead to a fourfold reduction in the product of the gene COMT, which builds an enzyme that breaks down dopamine in the prefrontal cortex. The variant can lead to more dopamine, which can enhance concentration but also make you more neurotic or jittery. Such risk-benefit trade-offs are the reason I believe that autism and psychiatric disorders will be with us for the next thousand years. And yet we often hear fundraisers speak of hope for a cure for autism, for example. The progressive, neoliberal view that we can improve upon human nature is now widely accepted in the public consciousness. But it is possible that such disorders are nothing more than another way of coping with the realities of existence.
The concept of normal has a complicated history in medicine. In the 19th century the French physiologist Claude Bernard wrote of identifying statistical deviations from population norms to identify the causes of diseases. Around the same time, Jonathan Sholl writes in a recent essay in Aeon, Adolphe Quetelet applied “statistics to the human body to find a series of ‘types’ across a range of individual variations. Because every variation could be subject to this statistical tool, it seemed that averages could explain anything: hence, height, weight, blood pressure, heart rate, birth and death rates etc. could all be presented in nice, even bell curves.”
For instance, he invented the controversial body mass index (BMI). The average became the ideal, writes Sholl. “[T]he individual was synonymous with error, while the average person represented the true human being.” The standards set by population averages are controversial. I have elevated levels of bilirubin, for example, a compound that breaks down heme, a product of red blood cells. My bilirubin is statistically high enough to be potentially harmful to my health, but other people in my family also have high bilirubin and suffer no undue effects.
In Le Normal et le Pathologique (1943), writes Sholl, French philosopher Georges Canguilhem “challenged the status quo of normality, suggesting it failed to capture what evolutionary biology says about variation. He sought to use the term norm to refer to the different processes, from the internal regulation of hormones to shifting dietary regimes, to remind us that, no matter how rare or deviant an individual seems, he could still be viewed as normal if the behavior ensured survival in a given environment.” In 1978 Czech philosopher Jiří Vácha distinguished the meanings of normality; it could mean frequent (as a mode) or average (as a mean) in the population as represented in a typical bell curve. It could also mean adequate as in free from deficiency or defect or optimal in the sense of being physically fit or mentally sharp. The meaning of normal, Sholl writes, often “slip-slides among these different meanings and tropes, from the orthodox and standard to what is expected and good” and “has important consequences, especially if it is given a privileged position in the world.”
Venture capital has a huge influence on scientists who want to develop drugs to sell to market. For instance, the Stanley Center for Psychiatric Research at Broad Institute, which was started with a $650 million donation from Ted Stanley and family, appears to be mainly geared to advance scientific insight and monetize psychiatric disorders.
But scientific research continues to provide very few actionable biological targets, or to identify gene variants that contribute more than subtle effects on risk, while socioeconomic effects such as chronic arousal and physiological stress are major known factors. For instance, there is the fascinating insight into the allostatic, as compared to homeostatic, nature of human biology. As an example, blood pressure may shift its baseline based on social demands, so people who live in a state of poverty or have to cope with constant economic or social pressures may live in a chronic state of arousal; their baseline blood pressure may be higher.
The other important concept is the inverted U, which suggests that elevation in stress is connected to creativity and peak performance, but that when stress becomes chronic, it can lead to a rapid collapse in productivity. This suggests how important socioeconomic influences are on health, psychology and even mortality. The recognition of genetic trade-offs and allosteric effects show that human biology exists along a dynamic continuum and defies categories inherent to the normalization of medicine. Nothing in evolution comes for free.
Genetics science may contribute to subtle insights in the genetics of psychiatric disorders, but it will certainly not lead to the elimination of psychiatric disorders, and it is not even likely to lead to a new generation of more effective drugs. If scientists make any advances in psychiatry, there is so far no reason to believe they will be anything but small steps, not big breakthroughs. The best thing that has emerged in recent years is ketamine, otherwise known as the street drug Special K, which stabilizes structural synaptic connections rather than correcting chemical imbalances.
If there are no strong singular genetic causes or biological targets, it is likely that the money spent on new drugs could be just as well spent for psychotherapy or other forms of social and economic support—but there is no business model for that.
So, it is not so much that I am against the venture vision of engineering our way out of psychological turmoil and despair, as I am for empathy that derives its effects from a decentralized position in nature, and for the concept of neurodiversity.
Canguilhem’s interpretation of normalcy is compelling insofar as it provides a basis for the belief that psychiatric disorders are not deviations from the norm but expressions of attributes that can be normal in their contribution to human variation and persistence in the population. Autism, schizophrenia, depression and panic have been around since ancient times and will be around for thousands of years, if the subtle genetic variants that influence those conditions have some evolutionary use. People who live at the psychological margins of society challenge the privileged position of social norms and expose the reality of accidental qualities of human nature. Insofar as this is true, psychiatric disorders are not deviations from humanity as much as definitions of it.