title: A genotype-endophenotype-phenotype path model of depressed mood: integrating cognitive and emotional markers.
abstract: 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.
authors.affiliation: 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
authors.forename: Justine M
authors.initials: JM
authors.lastname: Gatt
authors.forename: C Richard
authors.initials: CR
authors.lastname: Clark
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kemp
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Liddell
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Kuan
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
mesh_terms: 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
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine