David Rackham and Dr. Michael Larson, Psychology
Anxiety and depression disorders have a high rate of prevalence in the adult U.S. population (anxiety 18.1%; depression 9.5%; “Mental Disorders,” 2010). Indeed, it is estimated that by the year 2020 depression will be the second most prevalent health concern worldwide for all ages and both sexes (“Depression,” n.d., para. 2). Many disciplines are seeking effective treatment options, as well as exploring potential preventative solutions for these disorders. One such preventative possibility is the elucidation of endophenotypes, which are unobservable characteristics that are linked with a behavior known to be a phenotype of the disorder. Research on the etiology of various psychological disorders suggests a strong genetic link. Various studies have demonstrated a greater probability of developing a psychological disorder if one parent has a disorder (Beidel & Turner, 1997; Downey & Coyne, 1990). Thus far, efforts to identify genetic causal factors of psychopathology have failed to produce clear findings, however the possibility of identifying endophentoypes remains strong.
Recently, the error-related negativity (ERN) has been proposed as such an indicator (Olvet & Hajcak, 2008). The ERN is a reflection of dendrictic electrical activity that is occurring in the brain as measured by sensors that are placed on the scalp. To record the ERN an individual is asked to perform a computerized task while the electrical activity is recorded using electroencephalogram (EEG) methodologies.
Despite the assertion that the ERN may be an endophenotype of anxiety and depression disorders, the literature reports mixed findings, and as such the potential of the ERN as a biological marker is clouded. The differences in findings of individual studies make it difficult to assess the viability of the ERN as an endophenotype.
In order to further evaluate the proposed idea, we utilized meta-analytic techniques by determining the average effect size of ERN amplitude for participants with an anxiety or depression disorder versus controls. It is hypothesized that for depression disorders a moderate effect of ERN amplitude attenuation will be observed (i.e., smaller ERN amplitude relative to controls), and for anxiety disorders it is hypothesized that a moderate effect of larger ERN amplitude will be observed.
Methods
Studies were included in the analysis if they meet the following criteria: measured ERN amplitude, included participants with a formal DSM-IV diagnosis of an anxiety or depression disorder, performed analyses that compared the pathology group (i.e. anxiety or depression) with a healthy control group, and reported sufficient data that an effect size was able to be calculated or estimated. We searched for studies that met the inclusion criteria by searching PsychInfo, Medline and Dissertation Abstract International databases. The initial search yielded 666 articles. We selected 46 studies to be coded. Of those studies selected to be coded 7 met all of the inclusion criteria. Six of these studies evaluated ERN amplitude relative to healthy controls for participants with a depression disorder. One of the studies evaluated ERN amplitude relative to healthy controls for GAD (generalized anxiety disorder).
A study level effect size of Cohen’s d was calculated for each included study. To assess the overall relationship between ERN amplitude and anxiety and depression pathologies, a random effects model of ERN amplitude was computed using R statistical software (R64 version 2.10.1).
Results
Depression Studies
The random-effects model (k = 8) computed a non-significant moderate overall effect size (d = -.31; 95% CI = .15, -.76) reflecting larger ERN amplitude for the pathology group relative to healthy control.
Anxiety Studies
Only one study evaluating anxiety and the ERN met all of the inclusion criteria. The calculated Cohen’s d for this study was -.66 indicating a larger ERN amplitude for the pathology group.
Discussion
Careful analysis of results suggests that the potential of using the ERN as an endophenotype of psychopathology is still clouded. Despite the moderate effect sizes reported, the lack of significance does not allow for direct support of the endophenotype hypothesis. It is likely that in the future after a larger number of studies have been conducted, that significant effect sizes can be determined. If with the inclusion of additional studies the determined effect sizes reflect the reported findings, the ERN would have strong evidence of its potential endophenotype.
Interestingly, individuals with Major Depressive Disorder appear to have a greatly reduced capacity that is reflective in the ERN monitoring system relative to other depression disorders. One possible explanation for these findings is that less severe forms of depression exhibit an over-recruitment of cognitive resources that contributes to the observed symptomology. As the severity of depression increases it appears that a greatly attenuated ERN pathway suggests a diminished recruitment of cognitive resources.
In conclusion the evidence provided by the conducted meta-analysis remains inconclusive. A larger number of studies that evaluate the relationship between ERN amplitude and pathology groups need to be conducted. With the inclusion of additional studies future metaanalytic work can be conducted to provide more conclusive evidence of using the ERN as an endophenotype.
References
- Beidel, D. C., & Turner, S. M. (1997). At risk for anxiety: I. Psychopathology in the offspring of anxious parents. Journal of the American Academy of Child and Adolescent Psychiatry, 36(7), 918-924.
- Depression. (n.d.). In World Health Organization. Retrieved from http://www.who.int/mental_health/management/depression/definition/
- Downey, G., & Coyne, J. C. (1990). Children of depressed parents: An integrative review. Psychological Bulletin, 108(1), 50-76.
- Mental Disorders. (2010). In NIMH The numbers count: Mental disorders in America. Retrieved from http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disordersin- america/index.shtml
- Olvet, D. M., & Hajcak, G. (2008). The error-related negativity (ern) and psychopathology: Toward an endophenotype. Clinical Psychology Review, 28(8), 1343-1354. doi: 10.1016/j.cpr.2008.07.003
- Shadish, W. R., Robinson, L., & Lu, C. (1999). ES: A computer program for effect size calculation. The University of Memphis, Memphis, Tennessee.