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Being Human:The Science of Memory, Consciousness and
Personality.
Research Centre for Cognitive Neuroscience and Centre for Brain Research, University of Auckland.
Ian Kirk
3
Single nucleotide polymorphisms (SNPs)
mapping between tri-nucleotide sequences, called codons, and amino acids.
AUG codes methionineGUG codes for valineval/val; val/met; met/met
1. Val158met COMT (catechol-O-methyltranferase)
Val/val = fast breakdown of dopamineMet/met = slow breakdown of dopamine
Ascending dopamine systems
Val = faster breakdown of DA = more efficient transmissiongreater frontal BOLD =and fewer perseverative errors.
Val158met COMT“Warriors” (val,val)- high COMT enzymatic activity- efficient transmission- Attentional allocation advantage- Advantage in processing in stressful or aversive situations.- Association with schizophrenia
“Worriers” (met, met)- Low COMT, high levels of dopamine- Novelty seeking- Exploratory- Memory advantage- Association with drug use and anxiety
(A;A) met met(A;G) val met(G;G) val val
• Dunedin Multidisciplinary Health and Development Research Unit (DMHDRU)• Gene x environment (COMT x cannabis use). Caspi et al., Biol Psychiatry 57 1117-
1127 (2005). • A polymorphism in catechol-O-methyltranferase (COMT – involved in
metabolism of DA in synapse; COMT Val158Met; val=faster breakdown of DA)
2. val66met Brain-derived neurotrophicfactor (BDNF)
Polymorphism in SNP for brain derived neurotrophic factor (BDNF), val66met BDNF.
Val–more efficient pro-BDNF to BDNF (val/val, val/met, met/met)
• WMS-IV
• Immediate and Delayed memory measured
• Working memory also measured
• Faces and Family Pictures subtests used for delayed memory
Egan et al.,Cell, 112: 257–269 (2003)
Hipp activation val/val > val/metEgan et al Cell 112: 257–269 (2003)
50.00
75.00
100.00
125.00
150.00
-0.50 0.00 0.50 1.00 1.50
Mem
ory
Scor
e
Voltage increase (µV)
BDNF and Human LTP
r = .613, p < .005r = .613, p < .005
=val/val=met
BDNF and personality:
Met carriers more likely to test as introverted and neurotic!
So, best to be BDNF val/val??
Maybe – better hippocampal activation, better LTP and better recall memory (as measured by Weschler Mem Scale).
Mets more susceptible to Alzheimer’s?
Geriatric Major Depressive Disorder – more likely with met allele
Mets introverted and neurotic and bad drivers!!!
However, Childhood sexual abuse correlated with adult suicide attempts only in val/val individuals.
val associated with susceptibility to bipolar disorder and depressive disorders generally
(A;A) met met(A;G) val met(G;G) val val
Thanks to…• Chris Thompson
• Ushtana Antia
• Nick McNair
• Yvette Lamb
• Steve Wannenberg
• Karen Waldie
• Andrew Shelling
• Bruce Russell
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