Blue genes


On an av­er­age NHS ward, one in three peo­ple is de­pressed (pro­vid­ing you don’t count the doc­tors and nurses). The great ma­jor­ity of these pa­tients are not there for de­pres­sion. It’s most likely that they’re el­derly with a long ‘prob­lem list’, and psy­chi­atric con­di­tions will be

near the bot­tom. Hope­fully there’s been an at­tempt to treat their low mood, start­ing with an SSRI (se­lec­tive sero­tonin re­up­take in­hibitor) an­tide­pres­sant. It is prob­a­bly work­ing a bit. To hear a pa­tient wheeze with ev­ery breath, see­ing their con­torted joints or smelling their sup­pu­rat­ing wounds, it’s easy to think, in their con­di­tion, who wouldn’t feel de­pressed?

Through the cen­turies, de­pres­sion has been un­der­stood as black bile in the blood, moral fail­ure, psy­chic strife, and a chem­i­cal im­bal­ance of neu­ro­trans­mit­ters. But no clear mech­a­nism for how and why de­pres­sion oc­curs has ever been proved. Phar­ma­ceu­ti­cal com­pa­nies are with­draw­ing from re­search into new psy­chi­atric med­i­ca­tions, due to spi­ralling costs and low re­turn. Prozac was the last break­through. That was over thirty years ago. With de­pres­sion, a stub­bornly stig­ma­tised dis­ease, set to be­come the largest cause of dis­abil­ity world­wide by 2030, a new par­a­digm is over­due.

Ed­ward Bull­more, head of psy­chi­a­try at the Uni­ver­sity of Cam­bridge, is fed up with mod­ern medicine’s in­debt­ed­ness to Descartes: mind on one side, body on the other. He ar­gues that phys­i­cal health con­di­tions are not only in­di­rectly linked to de­pres­sion by pain, fear and iso­la­tion. There is a more in­ti­mate, phys­i­o­log­i­cal con­nec­tion. An in­flam­ma­tory dis­ease – whether in­fec­tive, au­toim­mune, can­cer­ous or de­gen­er­a­tive – can lead to in­flam­ma­tion in the brain. Even a pass­ing re­ac­tion to flu can make you blue for the same rea­son. More­over, pa­tients with de­pres­sion of­ten have raised in­flam­ma­tory mark­ers in their blood.

Bull­more is not say­ing that de­pres­sion is phys­i­cal rather than men­tal. He chal­lenges the di­vi­sion al­to­gether. Your im­mune sys­tem’s bil­lion or so white blood cells pro­duce cy­tokines and an­ti­bod­ies in re­sponse to in­va­sion or dam­age. Some­what hereti­cally, Bull­more ar­gues that these chem­i­cal mes­sen­gers can cross the ‘blood brain bar­rier’, which was tra­di­tion­ally thought to pro­tect your grey mat­ter. His the­ory con­tra­dicts what he – and I, a grad­u­ate of 2018 – were taught in med­i­cal school. We are still Carte­sians now.

Not ev­ery­one with de­pres­sion is in­flamed; and not ev­ery­one who is in­flamed will be de­pressed. But Bull­more, him­self a part-time em­ployee of Glax­osmithk­line, reck­ons about a third of pa­tients with ma­jor de­pres­sive dis­or­der will one day be iden­ti­fi­able via a blood test at their GP surgery, and will ben­e­fit from anti-in­flam­ma­tory drugs. These fu­ture med­i­ca­tions could be twice as ef­fec­tive as SSRIS, he pre­dicts. How­ever, ‘the mech­a­nis­tic nar­ra­tive is not yet crys­tal clear’ in terms of cau­sa­tion and placebo ef­fect.

If Bull­more is right, why does it mat­ter? In­flam­ma­tion is as vogu­ish as the mi­cro­biome, and has been im­pli­cated in al­most all dis­eases. But that’s the power of his book. De­pres­sion could – at least in part – be much more like other dis­eases than pre­vi­ously thought. As with rheuma­toid arthri­tis or mul­ti­ple scle­ro­sis, say, per­sonal cul­pa­bil­ity is ir­rel­e­vant. Like can­cer, de­pres­sion can hap­pen to any­one, and may take many forms with var­i­ous causes, some ge­netic (44 genes have been im­pli­cated so far), some en­vi­ron­men­tal; of­ten both.

The In­flamed Mind is rad­i­cal in its op­ti­mism and also its in­clu­siv­ity. Bull­more makes space for the fact that many pa­tients do ben­e­fit from SSRIS, and that de­pres­sion has so­cial as well as bio­chem­i­cal de­ter­mi­nants. Pa­tients with poor men­tal health are more likely to be ex­pe­ri­enc­ing stress, dis­crim­i­na­tion and a lower stan­dard of liv­ing, all of which have been shown to in­crease bod­ily in­flam­ma­tion. In turn, psy­chother­apy, mind­ful­ness, lifestyle changes and sun­shine may play a role in its treat­ment.

I don’t sup­pose it will be the pub­lic who are most resistant to this book. Bull­more en­cour­ages scep­ti­cism but is dis­ap­pointed by some col­leagues’ re­flex sneer­ing at the men­tion of im­munopsy­chi­a­try. It will take ‘a new breed of doc­tors’ to fol­low this re­search through, he says: rheuma­tol­o­gists who rou­tinely ask about mood, and psy­chi­a­trists who are will­ing to dust off their stetho­scopes. It may be the pro­fes­sion­als, not their pa­tients, who need to pull them­selves to­gether.

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