Thursday November 29 2012
Genes and environment are known to contribute to depression
Teenage depression has hit the headlines, with the The Guardian claiming that a "Computer test could spot children at risk of developing depression", while the Daily Mail warns that "Arguing parents can give a child teenage depression".
Both headlines are based on a complex piece of research into how our genes and our environment interact to influence how we process emotions.
The researchers classified a group of teenagers according to variations in a specific gene involved in the recycling of serotonin (a 'neurotransmitter' which is often simplistically referred to as a 'mood-boosting' chemical).
The teenagers' mothers were asked about their children's exposure to family arguments, stress or other adversities before the age of six.
Both genetic and family environment factors have previously been shown to be associated with differences in a person's response to emotional situations, referred to as 'cognitive and emotional processing'.
The researchers were interested in how these factors interact to influence processing. They assessed processing using several computer tests and then determined if the test score was associated with whether the teenager met the criteria for depression or anxiety.
The researchers suggest that this study shows that the ability to detect and respond to emotions, as measured by the tests, may serve as a useful marker for identifying young people at high risk of developing depression.
Where did the story come from?
The study was carried out by researchers from the University of Cambridge and was funded by the Wellcome Trust, the Medical Research Council, the National Institute for Health Research and the Department of Health.
The study was published in the peer-reviewed open-access journal PLoS ONE.
The media coverage of this research was mixed, The Guardian reported on the screening ability of the computer test, and appropriately reported that this research was preliminary.
The Daily Mail instead focused on the role of parental arguing in the development of depression with the implication that children exposed to parental argument had an increased risk of developing depression. This does not appropriately reflect the results of the research. The research actually suggested that individuals who are exposed to such environments may be at increased risk of depression, but the extent of this risk depends on their genetic make-up.
What kind of research was this?
This was a cohort study that assessed how genes and the environment interact to influence our ability to process emotions.
The researchers were interested in two factors that have been shown in previous research to be associated with difficulties in mental and emotional processes: variations in a gene that plays a role in the recycling of serotonin and childhood history.
Effects of genetic variations
Serotonin is known to have an effect on mood, and low levels of serotonin may make people more vulnerable to feelings of depression and anxiety. This research looked at the gene that carries instructions for making the protein responsible for the recycling of serotonin. This gene has two alternate forms – a short (S) form and a long (L) form. Each person carries two copies of the gene – we inherit one copy from each of our parents.
For this particular gene we can have:
- two short copies of the gene (SS),
- two long copies of the gene (LL), or
- one long and one short copy of the gene (LS)
People with two short copies (SS) have been found to be more sensitive to the environment around them, and to process emotional information differently from individuals with different genetic variations.
Effects of childhood history of adversity
Exposure to early childhood (before the age of 6) adversities, including ‘discord’ between parents or neglect, has also been shown to be associated with high emotional sensitivity and difficulties processing emotional information.
How these factors interact
The study authors say that while each of these factors has been independently associated with differences or difficulties in cognitive and emotional processing, they were interested in how the two factors interact to influence such reactions.
They were also interested in whether difficulties in cognitive and emotional processing were associated with self-reported symptoms of depression or diagnoses of depression or anxiety.
The researchers thought that teenagers with an SS genetic variation and exposure to early childhood adversity would report more emotional symptoms and perform worse on tests of attention, response to negative feedback and memory than teenagers with an LL variation and similar childhood adversity.
What did the research involve?
The researchers recruited 238 teenagers between the ages of 15 and 18 years old and collected information on the two factors of interest:
- Variations in a gene that plays a role in the recycling of serotonin (5-HTTLPR), a neurotransmitter implicated in mood.
- Exposure to early childhood (before the age of 6 years) adversities, which were reported mainly by the teenagers’ mothers. This included information on family discord, ranging from mild (constant bickering) to moderate (shouting, throwing things) to severe (domestic violence) as well as experiences of physical, sexual or emotional abuse.
The teenagers were then classified into six groups according to their results on these two measures.
Teenagers with a genetic variation leading to two short copies of the gene (SS) and who had been exposed to early childhood adversity were considered at risk of difficulties in cognitive and emotional processing.
The teenagers then completed a series of tests that assessed their response to negative feedback, their ability to put the emotional tone of words into ‘happy’, ‘sad’ or ‘neutral’ categories, and their visuo-spatial memory (such as understanding routes on a map).
Additional information on the experience of symptoms of anxiety or depression (reported by the teenagers themselves) and diagnosis of anxiety or depression was collected both before and after the study.
The researchers carried out a series of analyses to determine how genetic variation and exposure to early childhood adversity interact and are associated with cognitive and emotional processes, as well as current depression symptoms. The three analyses tested for:
- An association between genetic variation in combination with childhood adversity and experiencing symptoms of anxiety or depression.
- An association between genetic variation in combination with childhood adversity and a tendency to concentrate on negative words and respond poorly to negative feedback. The researchers also looked to see if there was any impact on memory.
- An association between test performance and likelihood of depression or anxiety diagnosis.
The researchers appropriately corrected for multiple statistical tests and lowered the threshold at which they considered a result significant.
What were the basic results?
The researchers found that there was a significant interaction between genetic variation and exposure to early childhood adversity.
Having one or two short copies of the gene (LS or SS) and early childhood experiences of family discord was associated with higher depressive and anxiety symptoms compared with individuals with the same genetic variation but no exposure to early childhood adversity. However, having two long copies of the gene (LL) and early family discord had no significant association with current depressive symptoms.
Combined, these results suggest that living in a family that has a lot of fights may be associated with self-reported symptoms of depression or anxiety in teenagers, if the child has a specific genetic variation.
On their own, neither genetic variations nor early childhood exposure to family discord were associated with performance on any of the computer tests. But when considered together, the researchers found that individuals who carried the SS variation and experienced adversities during childhood performed significantly worse on tests measuring response to negative feedback and judging the emotional tone of words than individuals with the SS variation and no childhood exposure.
In other words, they were worse at classifying negative and neutral stimuli and made more errors in response to ambiguous negative feedback. There were no significant interactions for the LS or LL groups.
Finally, when they assessed the association between test performance and the diagnosis of anxiety or depression, the researchers found that poor performance on the tasks measuring response to negative feedback and understanding of the emotional tone of words was associated with increased odds of a diagnosis at the age of 17.
How did the researchers interpret the results?
The researchers concluded that difficulties in a person’s ability to classify and respond to emotional information are seen in teenagers with a specific genetic variation (SS) and who were exposed to adversities during early childhood.
This study found that a genetic variation in combination with exposure to adverse family events before the age of six was associated with self-reported depression and anxiety symptoms and specific deficits in cognitive and emotional processing.
This interaction was only significant among individuals with two copies of the SS variation in the gene encoding the serotonin transporter who experienced childhood adversities.
Interestingly, graphs of the research results indicated that individuals with the SS variation and no exposure to early family discord had the lowest self-reported depression and anxiety, and had better performance on aspects of the computer tests compared with other teenagers with no childhood exposure.
Because the paper did not specifically seek to assess individual relationships, and provided no information on the significance of these patterns, it is not possible to say whether or not these are true differences.
However, the researchers suggest that their analyses may “reflect only the negative pole of individuals who carry the SS variant and the trend in these results may reveal that SS carriers are more susceptible to their social environments both good as well as bad”.
It is important to remember, especially when assessing factors as complicated as these, that how you measure the variables can have an impact on the results. For instance, while in-depth interviews mainly with mothers were used to assess childhood exposure to family disputes, this may not accurately classify the teenagers’ childhood experiences. Bias could be introduced due to difficulties accurately recalling events from that time, or if the mother did not accurately report such experiences.
The study included a relatively small number of participants with both the SS variation and early childhood adversity. The study authors report that given these numbers, their analyses had low statistical power.
As such, the results should be interpreted cautiously, and further studies with a larger number of participants are needed to replicate the results before we can be sure that the interactions reported in this research represent true associations.
An additional limitation to the current study is that it did not assess whether the computer test could accurately predict future depression or anxiety.
Having said that, this study serves as a useful and necessary preliminary step to such further research. But the research is not sufficient on its own to determine that the “computer test could spot children at risk of developing depression” as suggested by the Guardian.
Overall, this was interesting preliminary research into the complex interactions between genetics and the environment that may make us susceptible to emotional disorders. But further research, in the form of a much larger cohort study, would be required to understand the impact that genetics and family history could have on an individual’s depression risk.
In its current state, however, the research does not support today’s media claims that arguing parents cause depression or that a simple computer test could be used to screen children for depression.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.