PMID- 17472225
OWN - NLM
STAT- MEDLINE
DCOM- 20070724
LR  - 20191110
IS  - 0219-6352 (Print)
IS  - 0219-6352 (Linking)
VI  - 6
IP  - 1
DP  - 2007 Mar
TI  - A genotype-endophenotype-phenotype path model of depressed mood: integrating 
      cognitive and emotional markers.
PG  - 75-104
AB  - 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.
FAU - Gatt, Justine M
AU  - Gatt JM
AD  - 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
FAU - Clark, C Richard
AU  - Clark CR
FAU - Kemp, Andrew H
AU  - Kemp AH
FAU - Liddell, Belinda J
AU  - Liddell BJ
FAU - Dobson-Stone, Carol
AU  - Dobson-Stone C
FAU - Kuan, Stacey A
AU  - Kuan SA
FAU - Schofield, Peter R
AU  - Schofield PR
FAU - Williams, Leanne M
AU  - Williams LM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Singapore
TA  - J Integr Neurosci
JT  - Journal of integrative neuroscience
JID - 101156357
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adult
MH  - Analysis of Variance
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cognition/*physiology
MH  - Depression/classification/*genetics/*physiopathology/psychology
MH  - Electroencephalography/methods
MH  - Emotions/*physiology
MH  - Evoked Potentials, Visual/physiology
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Memory, Short-Term/physiology
MH  - Methionine/genetics
MH  - Middle Aged
MH  - Models, Biological
MH  - Neuropsychological Tests
MH  - Neurotic Disorders/diagnosis/genetics/physiopathology
MH  - *Phenotype
MH  - Polymorphism, Genetic
MH  - Valine/genetics
EDAT- 2007/05/03 09:00
MHDA- 2007/07/25 09:00
CRDT- 2007/05/03 09:00
PHST- 2006/11/06 00:00 [received]
PHST- 2007/02/14 00:00 [revised]
PHST- 2007/05/03 09:00 [pubmed]
PHST- 2007/07/25 09:00 [medline]
PHST- 2007/05/03 09:00 [entrez]
AID - S0219635207001398 [pii]
AID - 10.1142/s0219635207001398 [doi]
PST - ppublish
SO  - J Integr Neurosci. 2007 Mar;6(1):75-104. doi: 10.1142/s0219635207001398.