Being Human:The Science of Memory, Consciousness and

Personality.

Research Centre for Cognitive Neuroscience and Centre for Brain Research, University of Auckland.

Ian Kirk

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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