Wednesday, March 5, 2014

Can genes alter the impact of prevention programs?

Prevention scientists have often speculated that children’s genes play a part in determining how receptive they will be to early intervention. A long-term study of a program for reducing impulsive and aggressive behavior among American schoolchildren provides hard evidence that this may, indeed, be the case.
Recent advances in neuroscience and statistical analysis have enabled researchers at Johns Hopkins University to test the theory that genetic factors can help to explain why prevention programs are more effective with some children than others. In particular, they drew on developments in modeling genetic structures that make it possible to identify clusters of single-nucleotide polymorphisms (SNPs) within a single gene.
While there are many genes that may influence aggression, or impulsive behavior, previous research has linked the brain-derived neurotrophic factor (BDNF) gene to both. Variations in the structure of the BDNF gene have been associated with differences in impulsive behaviors of people diagnosed with attention-deficit / hyperactivity disorder (ADHD), as well as differences in the level of aggression of patients with schizophrenia.
Behavioral interventions
To investigate the possibility of interaction between preventive intervention and the BDNF gene, the researchers used longitudinal data from a randomized control trial comparing the impact of two different school-based programs: the Good Behavior Game, and the Family School Partnership program.
Both interventions had been developed to reduce disruptive behaviors among children starting elementary school. However, the Good Behavior Game was the main component in a classroom-centered intervention, whereas the Family School Partnership sought to improve collaboration between parents, teachers and mental health professional.

Nine urban schools in Baltimore, Maryland took part in the trial, where three first grade classrooms per school were randomized to receive either the Good Behavior Game, the Family School Partnership program, or serve as a control group. The vast majority of participants were African American and altogether 678 children and their caregivers agreed to take part.
The intervention started in 1993 when the children were in in grade 1, aged between 5 and 7. But while the programs were only delivered during in the first year, data collection – based on teacher, parent and child interviews –continued annually until grade 12. Genetic material subsequently gathered through cheek swabs or blood samples after the young people completed high school, was genotyped, extracting the SNPs from the BDNF gene.
Genetic influences on behavior change
Analysis showed that participation, 14 years earlier, in either intervention was significantly linked to less impulsive and aggressive behavior in late adolescence compared with the control group. As expected, young people’s behavior was predicted by factors, such as gender, and how impulsive they had been as a child. But did the BDNF gene also play a role?
Examination of the genetic data identified three different clusters of SNPs among the trial participants, including one found among almost half the sample (46 per cent). Statistical analysis showed that young people in this group who had taken part in the classroom-centered program scored significantly lower on measurements of impulsiveness and aggression than participants in the other two clusters.
The relationship between the BDNF gene cluster and participation in the Family School Partnership program did not quite achieve statistical significance, but the data revealed a trend in the same, expected direction.
The research team describe their findings as an important and novel addition to existing reports detailing the durable, long-term results achieved by the two interventions. They provide preliminary evidence for a “gene by interaction” involving an SNP cluster within the BDNF gene – and may, in turn, explain some of the previously reported variability in the impact of the classroom-centered program.
From the perspective of practitioners and those designing preventive interventions, the researchers also usefully note that their findings support the hypothesis advanced almost 20 years ago by Sir Michael Rutter that programs aiming to reinforce protective factors are likely to have the greatest impact on individual children at greatest risk.
They also, rightly, caution that further research will be needed to properly understand the relationship between genetic make up and behavior. Although the study was able to identify patterns of SNPs within the BDNF gene, it could not specify how a particular SNP cluster was driving behavior change. Other child, family and community influences not allowed for in the analysis may have also affected the impact of the interventions.