A genotype-endophenotype-phenotype path model of depressed mood: Integrating cognitive and emotional markers.

Gatt JM Clark CR, Kemp AH, Liddell BJ, Dobson-Stone C, Kuan SA, Schofield P & Williams LM (2007). A genotype-endophenotype-phenotype path model of depressed mood: Integrating cognitive and emotional markers, Journal of Integrative Neuroscience, 6, 75-104.

genotype phenotype endophenotype path model

Aims: Following an integrative neuroscience perspective, we propose that cognitive and emotional functions are integrally linked, and that genetic polymorphisms which impact upon neural processes may have complementary effects on these functions. The brain-derived neurotrophic factor (BDNF) 66Met allele may contribute to both cognitive and emotional aspects of the depression phenotype.

Methods: In 374 nonclinical subjects, BDNF genotype differences in task-related ERPs, emotion, memory, and EEG cortical arousal were examined.

Results: Using path modeling, higher negative affect in Met homozygotes was predicted by slow-wave EEG via the mediating effects of neuroticism. Both negative affect and working memory deficits were predicted by disturbances in emotion- and cognitive-related ERPs. This model held across groups with varying levels of depressed mood.

Discussion: Since impairments in emotion and working memory are core features of major depression, the BDNF Met allele may contribute to vulnerability for this disorder. An integrative approach in which genotypes are considered in combination with brain function and behavioral measures may be important in identifying profile markers of depression.

Integrative significance: This study directly demonstrates that cognitive and emotional neural networks are not parallel independent systems, but rather highly integrated with effects on both cognitive performance and emotional behavior.