Foundations of Mental Illness

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he claims that there is “no reason to suppose” that this trend “could not gen- erate the same kind of revolutionary discoveries in the future”. One wonders. Simple apparatus was perfectly suited for picking what (fairly or not) now looks like the low-hanging fruit of science — and there was a vast garden of fundamental discoveries, from microorganisms to the laws of motion, to be picked. I have had the impression over the years that some historians of science dislike using the word ‘progress’ for fear of implying that all history was building towards the modern age. But although human history is under no obligation to make or demonstrate progress (by whatever measure), science is explicitly designed for it. My fruit-picking refer- ence might make me sound like a pillager of the environment, out of tune with modern sensibilities, but that’s a problem with our metaphors, not with our reality. Science really does build on its history, those shoulders of giants and bricks of knowledge. That’s its point. And as a working scientist myself, I can’t help but believe that our knowledge becomes more complex, refined and complete as time goes on. We “Reality seems revise, we reassess, increasingly we revisit — but always in the inter- complicated est of comparing as we make our ideas against better physical reality. measurements And although that of it.” reality also seems increasingly complicated as we make better measurements of it, that forces our theories and experiments to keep pace. All too often, it forces our equipment and funding to keep pace, as well. I grew up in a small farming town, and know exactly what it’s like to be passion- ately interested in science, making do without many of the resources needed to explore it. If I saw some unusual creature under my microscope, no one could tell me what it was. I would have loved to have seen Comet West when it passed through the inner Solar System No. 348. Candid Portrait of a Woman on a Street Corner by Trent Parke (2013). in 1976, but the local newspapers never mentioned it. I am very sympathetic to EVOLUTIONARY PSYCHIATRY ‘makers’ and basement experimenters. But no matter how appealing the pros- pect might be, I think that the chances of revolutionary experiments happening Foundations of with simple materials are dwindling by the year. ■ Derek Lowe has worked in early-stage mental illness drug discovery for decades. He writes In the Pipeline, one of the world’s longest- running science blogs. Adrian Woolfson weighs up a study on the role of e-mail: [email protected] evolution in conditions such as depression and anxiety.

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lobally, the burden of depression not like machine components, each with neural behaviour. And common genetic and other mental-health conditions a set function; instead, they are embed- variations with large effects on mental dis- is on the rise. In North America and ded in complex overlapping biochemical orders are elusive. The various incarnations GEurope alone, mental illness accounts for pathways. of the American Psychiatric Association’s up to 40% of all years lost to disability. And In 1994, Nesse teamed up with Williams Diagnostic and Statistical Manual of Mental molecular medicine, which has seen huge for Why We Get Sick, a manifesto for Disorders (DSM) have enabled diagnos- success in treating diseases such as cancer, “Darwinian medicine”. Their insights tic consistency and the objectification of has failed to stem the tide. Into that alarming opened up new perspectives on the ori- mental illnesses. But the DSM has resulted context enters the thought-provoking Good gins of diseases, arguing for ‘proximate’ in overlapping diagnoses, and contrived Reasons for Bad Feelings, in which evolu- causes (driven by anatomy, biochemistry symptom-cluster checklists. At times, it tionary psychiatrist Randolph Nesse offers and physiology) and higher-level ‘ulti- impinges on the territory of healthy men- insights that radically reframe psychiatric mate’ (evolutionary) causes. They noted tal function. Allen Frances, chair of the conditions. that evolution selects for reproductive task force that wrote the manual’s fourth In his view, the roots of mental illnesses, success rather than for health and happi- edition in 1994, revolted against out-of- such as anxiety and depression, lie in essen- ness; hence, the existence of human dis- control mental diagnosis in his 2013 book tial functions that evolved as building blocks eases and disorders. They also detailed DSM: Saving Normal. of adaptive behavioural and cognitive func- the contingent and sometimes ‘irrational’ tion. Furthermore, like the legs of thorough- nature of biological legacies, such as the FROM ADAPTIVE TO MALADAPTIVE bred racehorses — selected for length, but nerves and blood vessels that run across Nesse argues that evolutionary theory could tending towards weakness — some dys- the human eye’s retinal surface. Cephalo- foster therapeutic breakthroughs by provid- functional aspects of mental function might pod eyes don’t have this ‘flaw’. ing a robust theoretical foundation for psy- have originated with selection for unrelated Good Reasons for Bad Feelings builds chiatry. He posits that it might also help to traits, such as cognitive capacity. Intrinsic on these insights. Adopting an “engineers’ prevent people from equating psychiatric vulnerabilities in the human mind could point of view” on mental illnesses, Nesse symptoms with diseases and viewing be a trade-off for optimizing unrelated suggests that anxiety, although apparently extremes of emotion such as anxiety as features. undesirable, is a disorders. Nesse also suggests that mental Similar ideas have surfaced before, in design compo- “Evolution illnesses might result from the disruption different contexts. Evolutionary biologists nent with utility in selects for of regulators that maintain equilibrium in Stephen Jay Gould and Richard Lewontin, certain situations reproductive the body, such as the endocrine system. The for example, critically examined the blind — for instance, as normally adaptive function of thoughts and faith of ‘adaptationist’ evolutionary theoriz- a “smoke detec- success rather emotions could, in such instances, become ing. Their classic 1979 paper ‘The spandrels tor” for potentially than for health maladaptive. of San Marco and the Panglossian para- life-threatening and happiness; The future success of clinical psychiatry digm’ challenged the idea that every aspect events. Depression hence, the might depend on an evolutionary frame- of an organism has been perfected by natu- might also perform existence work being integrated with whole-genome ral selection (S. J. Gould et al. Proc. R. Soc. adaptive functions. of human sequence-data analysis; this could help to Lond. B 205, 581–598; 1979). Instead, like The psychiatrist diseases.” identify mutations predisposing people to the curved triangles of masonry between Aubrey Lewis mental illness. Given the small contributions arches supporting domes in medieval argued that by signalling distress, depres- of individual genes and the diverse mecha- and Renaissance architecture, some parts sion could prompt others into providing nisms involved, this will demand analysis are contingent structural by-products. assistance through foraging and other of the genomes of hundreds of thousands These might have no discernible adaptive activities. It has even been suggested that of people. As a result of the extensive and advantage, or might even be maladaptive. depressive behaviour in vervet monkeys often paradoxical entanglement of genetic Gould and Lewontin’s intuition has, to (Chlorocebus pygerythrus) evolved to sig- networks, future treatments might, by neces- some extent, been vindicated by molecular nal loss of status, deflecting attacks from sity, require mental circuits to be engineered genetics. Certain versions of the primitive dominant males. to release them from hard-wired evolution- immune-system protein complement 4A, Yet, however functional its components ary constraints. for instance, evolved for reasons unrelated when appropriately regulated, mental ill- In Theodicy (1710), German philoso- to mental function, and yet are associated nesses cause suffering, and evidence-based pher Gottfried Leibniz argued that God, with an increased risk of schizophrenia. treatments are sparse. Indeed, the field being omniscient, must have created the has seen no signifi- best of all possible worlds. (Fifty years GENETIC TRADE-OFFS cant pharmaceutical later, in his novel Candide, Voltaire lam- Decades earlier, the evolutionary theorist breakthroughs for pooned Leibniz as Doctor Pangloss, George C. Williams explored perhaps the many years. Biologi- who opined that faults in the world are most perplexing aspect of human biol- cal causes remain elu- necessary, like contrasting shadows in a ogy: our inconvenient tendency to age sive, and biomarkers painting.) and die. He suggested in 1957 that some non-existent. Ironic readings aside, the philosopher’s of the genes that cause ageing evolved Psychiatry as a optimism might now be shown to have

TRENT PARKE/MAGNUM because they enhanced fitness early in life field, meanwhile, rational echoes in contemporary science. As (G. C. Williams Evolution 11, 398–411; quivers with theo- Good Reasons for Bad Feelings boldly posits, 1957). Such ‘antagonistic pleiotropy’ — in Good Reasons retical uncertainty. many of the core dysfunctional components which a single gene controls at least one for Bad Feelings: It has not become of mental illness ultimately help to make us Insights From ■ beneficial and one detrimental trait — the Frontier of a sub-speciality of human. suggests that the design of biological struc- Evolutionary neurology, as one tures is a complex optimization problem Psychiatry might have expected Adrian Woolfson is the author of Life involving multiple trade-offs. Emotions RANDOLPH M. NESSE if mental illness Without Genes. and other aspects of mental function are Dutton (2019) mapped directly to e-mail: [email protected]