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


CONCLUSIONS
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.


CONCLUSIONS
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.
Gatt
Justine M
JM
The Brain Dynamics Center, Westmead Millennium Institute, Westmead Hospital and Western Clinical School, University of Sydney, NSW 2145, Australia. justine_gatt@wmi.usyd.edu.au
Clark
C Richard
CR
Kemp
Andrew H
AH
Liddell
Belinda J
BJ
Dobson-Stone
Carol
C
Kuan
Stacey A
SA
Schofield
Peter R
PR
Williams
Leanne M
LM
D000328:Adult; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003863:Depression / Q000145:classification / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D004569:Electroencephalography / Q000379:methods; D004644:Emotions / Q000502:physiology*; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D009483:Neuropsychological Tests; D009497:Neurotic Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D011110:Polymorphism, Genetic; D014633:Valine / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine