Subject to further validation, says Professor Tomlinson, the insight has "important implications for scientists designing and evaluating interventions to benefit as many people as possible in South Africa and worldwide. Without taking genetics into account, it is possible that other studies have under-estimated the impact of their interventions, as we originally did."
Researchers caution that this study involved a relatively small sample and only measured one gene and one outcome — attachment.
Says Dr. Peter A. Singer, Chief Executive Officer of Grand Challenges Canada: "This is a startling finding that changes the way I think about child development. Why is it important? Because child development is the ladder of social mobility used to climb out of the hole of inequity by millions of children around the world."
Clear recognition of the damaging effects of poverty on early childhood development has fueled an interest in interventions aimed at mitigating these harmful consequences. Psychosocial interventions aimed at alleviating the negative impacts of poverty on children are frequently shown to be of benefit, but effect sizes are typically small to moderate. However, averaging outcomes over an entire sample, as is typically done, could underestimate efficacy because weaker effects on less susceptible individuals would dilute estimation of effects on those more disposed to respond. This study investigates whether a genetic polymorphism of the serotonin transporter gene moderates susceptibility to a psychosocial intervention.
Methods and findings
We reanalyzed data from a randomized controlled trial of a home-visiting program delivered by community health workers in a black, isiXhosa-speaking population in Khayelitsha, South Africa. The intervention, designed to enhance maternal-infant attachment, began in the third trimester and continued until 6 mo postpartum. Implemented between April 1999 and February 2003, the intervention comprised 16 home visits delivered to 220 mother–infant dyads by specially trained community health workers. A control group of 229 mother–infant dyads did not receive the intervention. Security of maternal-infant attachment was the main outcome measured at infant age 18 mo. Compared to controls, infants in the intervention group were significantly more likely to be securely attached to their primary caregiver (odds ratio [OR] = 1.7, p = 0.029, 95% CI [1.06, 2.76], d = 0.29). After the trial, 162 intervention and 172 control group children were reenrolled in a follow-up study at 13 y of age (December 2012–June 2014). At this time, DNA collected from 279 children (134 intervention and 145 control) was genotyped for a common serotonin transporter polymorphism. There were both genetic data and attachment security data for 220 children (110 intervention and 110 control), of whom 40% (44 intervention and 45 control) carried at least one short allele of the serotonin transporter gene. For these 220 individuals, carrying at least one short allele of the serotonin transporter gene was associated with a 26% higher rate of attachment security relative to controls (OR = 3.86, p = 0.008, 95% CI [1.42, 10.51], d = 0.75), whereas there was a negligible (1%) difference in security between intervention and control group individuals carrying only the long allele (OR = 0.95, p = 0.89, 95% CI [0.45, 2.01], d = 0.03). Expressed in terms of absolute risk, for those with the short allele, the probability of secure attachment being observed in the intervention group was 84% (95% CI [73%, 95%]), compared to 58% (95% CI [43%, 72%]) in the control group. For those with two copies of the long allele, 70% (95% CI [59%, 81%]) were secure in the intervention group, compared to 71% (95% CI [60%, 82%]) of infants in the control group. Controlling for sex, maternal genotype, and indices of socioeconomic adversity (housing, employment, education, electricity, water) did not change these results. A limitation of this study is that we were only able to reenroll 49% of the original sample randomized to the intervention and control conditions. Attribution of the primary outcome to causal effects of intervention in the present subsample should therefore be treated with caution.
When infant genotype for serotonin transporter polymorphism was taken into account, the effect size of a maternal-infant attachment intervention targeting impoverished pregnant women increased more than 2.5-fold when only short allele carriers were considered (from d = 0.29 for all individuals irrespective of genotype to d = 0.75) and decreased 10-fold when only those carrying two copies of the long allele were considered (from d = 0.29 for all individuals to d = 0.03). Genetic differential susceptibility means that averaging across all participants is a misleading index of efficacy. The study raises questions about how policy-makers deal with the challenge of balancing equity (equal treatment for all) and efficacy (treating only those whose genes render them likely to benefit) when implementing psychosocial interventions.
About Grand Challenges Canada
Grand Challenges Canada is dedicated to supporting Bold Ideas with Big Impact® in global health. We are funded by the Government of Canada and we support innovators in low- and middle-income countries and Canada. The bold ideas we support integrate science and technology, social and business innovation - we call this Integrated Innovation®. Grand Challenges Canada focuses on innovator-defined challenges through its Stars in Global Health program and on targeted challenges in its Saving Lives at Birth, Saving Brains and Global Mental Health programs. Grand Challenges Canada works closely with Canada's International Development Research Centre (IDRC), the Canadian Institutes of Health Research (CIHR) and Global Affairs Canada to catalyze scale, sustainability and impact. We have a determined focus on results, and on saving and improving lives. http://www.grandchallenges.ca
About Saving Brains
Saving Brains is a partnership of Grand Challenges Canada, Aga Khan Foundation Canada, the Bernard van Leer Foundation, the Bill & Melinda Gates Foundation, The ELMA Foundation, Grand Challenges Ethiopia, the Maria Cecilia Souto Vidigal Foundation, the Palix Foundation, UBS Optimus Foundation and World Vision Canada. It seeks and supports bold ideas for products, services and implementation models that protect and nurture early brain development relevant to poor, marginalized populations in low- or middle-income countries. http://www.savingbrainsinnovation.net