Biomarker for Depression

How much is really known about depression?  It seems like a common disorder with all of the media advertisement for anti-depressants, but what actually occurs in this disorder?  Dr. Silton introduced the idea that depression and anxiety frequently occur together.  Both disorders consist of attention control deficits marked by changes in the frontocingulate network.  Depression and Anxiety affect this network in different ways, but the activity is correlated in Dr. Silton's research.  Depression is associated with low activity of the dorsal lateral prefrontal cortex (DLPFC), and anxiety is associated with dorsal anterior cingulate cortex (dACC).  Participants with depression took the Stroop test, a pardigm where the name of the color is written in a color that does not match its name and participant is instructed to pay attention to one or the other.  In participants with low levels of depression (reduced DLPFC activity) the  dACC was activated which resulted in more interference in the Stroop test.  However, at higher levels of depression the correlation did not follow.  The increase of dACC activity with low levels of depression suggests that their is an increase in apprehension/anxiety which then interferes with the attention network as seen by lower performances on the Stroop task.  The higher the activation in that area of the brain then the worse the participants performed.  The comorbidity of depression and anxiety pose an interesting question of how to best treat suffering patients.  If the common factor between the two is a problem with attention control, then perhaps various cognitive-behavioral therapies would be the most beneficial.  Furthermore, Dr. Silton brought a surprising point to attention: the DSM-IV-TR does not have any biological makers for classifying depression, but this might change in the near future.

A study done at the University of Cambridge may have discovered a biomarker for depression and anxiety.  The short form of the 5-HTTLPR gene, which encodes for a serotonin transporter, in conjunction with exposure to early childhood adversities (CA) is being thought of as a predictor of depression susceptibility.  238 adolescences between the ages of 15-18 were sampled.  They composed of people that were homozygous for the long gene, homozygous for the short gene, and heterozygotes.  This sample was also seperated by whether they did or did not experience CA before the age of 6.  All of the participants were interviewed, filled out self-report surveys, and were assesed according to the DSM-IV for anxiety, depression and dysthemia.   The particpants then took the Probability Reversal Task (PRT), where they were shown two stimuli and they had to choose the correct one based on feedback.  They were instructed that sometimes the correct stimuli would be wrong but they should always respond with the stimuli that is correct most often.  The participants also had an Affective Go/No-Go Task (AGN) were they were instructed to respond to the emotionally positive words and the neutral and negative words served as distractors.  Finally there was a Paired Associates Learning Task that served to asses to their visou-spatial memory.

Participants that had high scores on the self reported depression and anxiety scale correlated with the homozygous allele for the short version of the 5-HTTLPR and CA before the age of 6. Other combinations of the gene alleles with or without CA show a lower score on the depression and anxiety scale which suggest that the homozygous short allele with  CA has a differential effect.  This group showed an attentional bias to the neutral stimuli in the AGN task, as well as increased attention to negative stimuli in the PRT.   The increased sensitivity to negative feedback caused these participants to change their responses more often than the other groups, even when the task to keep the same answer.  The answer switching resulted in more errors than the other groups as well.  These results also displayed that their is an attentional bias towards the neutral and negative emotional stimuli which could explain why these participants are more susceptible to depression.  The study found the the participants with the homozygous short allele and CA did have an emotional disorder within a year after testing.

Previous research has associated people with the short version of the gene and CA to have a maladjusted cognitive processing of emotion.  The lack of ability to correctly interpret others' emotions is seen as a biomarker for low resilience to mental disorders. Therefore, if a person is homozygous for the 5-HTTLPR short alleles they will be more susceptible to develop a mental disorder if they are in a negative environment like childhood adversities.  The team of researchers at the University of Cambridge is working on a  less expensive method to screen for the short version of 5-HTTLPR, so that children in negative environments can be tested.  A biomarker for mental disorders along with the knowledge of  which networks in the brain are activated for people with depression and anxiety might lead to a whole new look on such disorders. If this gene can accurately screen for susceptibility then a prevention program can be implemented to decrease the development of mental disorders. Perhaps depression will even have biological criteria in a future DSM.  This study just scratched the surface by suggesting the 5-HTTLPR gene as biomarker for depression and anxiety.  More research needs to be conducted in order to better correlate the gene with environment.  There is a whole realm of possibilities that is still out there for a disorder that we think we know so much about. 

source
news article:
http://www.sciencedaily.com/releases/2012/11/121128182949.htm

study:
Owens M, Goodyer IM, Wilkinson P, Bhardwaj A, Abbott R, et al. (2012) 5-HTTLPR and Early        Childhood Adversities Moderate Cognitive and Emotional Processing in Adolescence. PLoS ONE 7(11): e48482. doi:10.1371/journal.pone.0048482