Personal Antidepressant for Every Genome

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants, but they don't work for everyone. What's more, patients must often try several different SSRI medications, each with a different set of side effects, before findin one that is effective. It takes three to four weeks to see if a particular antidepressant dru works. !eanwhile, patients and their families continue to suffer.
"ow researchers at #el $viv %niversity have discovered a ene that may reveal whether people are likely to respond well to SSRI antidepressants, both enerally and in specific formulations. #he new biomarker, once it is validated in clinical trials, could be used to create a enetic test, allowin doctors to provide personali&ed treatment for depression. 'octoral students (eren )ved and $yelet !ora led the research under the uidance of 'r. 'avid *urwit& of the 'epartment of !olecular *enetics and +iochemistry at #$%'s Sackler ,aculty of !edicine and 'r. "oam Shomron of the 'epartment of -ell and 'evelopmental +iolo y at #$%'s Sackler ,aculty of !edicine and Sa ol School of "euroscience. Sackler faculty members .rof. !oshe Rehavi of the 'epartment of .hysiolo y and .harmacolo y and 'r. !etsada .asmnik/-hor of the +ioinformatics %nit were coauthors of the study, published in Translational Psychology. 0SSRIs only work for about 12 percent of people with depression,0 said 'r. *urwit&. 0$ dru from other families of antidepressants could be effective for some of the others. We are workin to move the treatment of depression from a trial/and/error approach to a best/fit, personali&ed re imen.0 Good news for the depressed !ore than 32 million $mericans each year suffer from disablin depression that re4uires clinical intervention. SSRIs such as .ro&ac, 5oloft, and -ele6a are the newest and the most popular medications for treatment. #hey are thou ht to work by blockin the reabsorption of the neurotransmitter serotonin in the brain, leavin more of it available to help brain cells send and receive chemical si nals, thereby boostin mood. It is not currently known why some people respond to SSRIs better than others. #o find enes that may be behind the brain's responsiveness to SSRIs, the #$% researchers first applied the SSRI .aro6etine // brand name .a6il // to 72 sets of cells, or 0cell lines,0 from the "ational 8aboratory for the *enetics of Israeli .opulations, a biobank of enetic information about Israeli citi&ens located at #$%'s Sackler ,aculty of !edicine and directed by 'r. *urwit&. #he #$% researchers then analy&ed and compared the R"$ profiles of the most and least responsive cell lines. $ ene calledCHL1 was produced at lower levels in the most responsive cell lines and at hi her levels in the least responsive cell lines. %sin a simple enetic test, doctors could one day use CHL1 as a biomarker to determine whether or not to prescribe SSRIs. 0We want to end up with a blood test that will allow us to tell a patient which dru is best for him,0 said )ved. 0We are at the early sta es, workin on the cellular level. "e6t comes testin on animals and people.0 Rethinking how antidepressants work #he #$% researchers also wanted to understand why CHL1levels mi ht predict responsiveness to SSRIs. #o this end, they applied .aro6etine to human cell lines for three weeks // the time it takes for a clinical response to SSRIs. #hey found that .aro6etine caused increased production of the ene ITGB3 // whose protein product is thou ht to interact with CHL1 to promote the development of new neurons and synapses. #he result is the repair of dysfunctional si nalin in brain re ions controllin mood, which may e6plain the action of SSRI antidepressants. #his e6planation differs from the conventional theory that SSRIs directly relieve depression by inhibitin the reabsorption of the neurotransmitter serotonin in the brain. 'r. Shomron adds that the new e6planation resolves the lon standin mystery as to why it takes at least three weeks for SSRIs to ease the symptoms of depression when they be in inhibitin reabsorption after a couple days // the development of neurons and synapses takes weeks, not days. #he #$% researchers are workin to confirm their findin s on the molecular level and with animal models. $dva 9adar, a master's student in 'r. *urwit&'s lab, is usin the same approach to find biomarkers for the personali&ed treatment of $l&heimer's disease.