Effects of dopaminergic and serotonergic genes on attention Marie Braasch Brain Development Lab 8/22/08 SPUR Symposium Marie Braasch Brain Development Lab 8/22/08 SPUR Symposium

Definitions G Attention: selective focus G Executive function: ability to self- regulate; e.g. attention, self-control, etc. G Attention: selective focus G Executive function: ability to self- regulate; e.g. attention, self-control, etc.

Genes and attention G Neurotransmitters of interest  Dopamine (DA)  Serotonin (5-HT) G Neurotransmitters of interest  Dopamine (DA)  Serotonin (5-HT) Sparknotes.com

Genes and attention G Dopamine (DA)  Executive attention (EA) brain regions (prefrontal cortex (PFC) and anterior cingulate cortex (ACC)) are part of DA pathways  Stimulants change the amount of DA available in brain G Dopamine (DA)  Executive attention (EA) brain regions (prefrontal cortex (PFC) and anterior cingulate cortex (ACC)) are part of DA pathways  Stimulants change the amount of DA available in brain

Genes and attention G Serotonin (5-HT)  Also acts upon prefrontal areas  Associated with impulsivity and aggression  Reduce DA release  Stimulants change 5-HT levels G Serotonin (5-HT)  Also acts upon prefrontal areas  Associated with impulsivity and aggression  Reduce DA release  Stimulants change 5-HT levels

Question: How does variation in dopaminergic and serotonergic genes affect attention and executive function?

Materials and Methods G Subjects: 3-5 year old children G Genotyping: DNA collected from buccal swabs G Behavioral measures: IQ, language, and cognitive tests G Electrophysiology: EEG and ERPs G Subjects: 3-5 year old children G Genotyping: DNA collected from buccal swabs G Behavioral measures: IQ, language, and cognitive tests G Electrophysiology: EEG and ERPs

EEG and ERPs G Electroencephalography (EEG): electrical brain activity at the scalp G Event-related potential (ERP): small brain wave in response to the processing of a specific stimulus G Electroencephalography (EEG): electrical brain activity at the scalp G Event-related potential (ERP): small brain wave in response to the processing of a specific stimulus EEGERP

Auditory Attention ERP Paradigm

Materials and Methods G Subjects: 3-5 year old children G Genotyping: DNA collected from buccal swabs G Behavioral measures: IQ, language, and cognitive tests G Electrophysiology: EEG and ERPs G Subjects: 3-5 year old children G Genotyping: DNA collected from buccal swabs G Behavioral measures: IQ, language, and cognitive tests G Electrophysiology: EEG and ERPs

Genes of interest G COMT G DAT1 G DBH G DRD2 G DRD4 G COMT G DAT1 G DBH G DRD2 G DRD4 G 5-HTT G TPH2 G MAOA G BDNF G CHRNA4

Genes of interest G COMT G DAT1 G DBH G DRD2 G DRD4 G COMT G DAT1 G DBH G DRD2 G DRD4 G 5-HTT G TPH2 G MAOA G BDNF G CHRNA4 DA 5-HT DA & 5-HT

DAT1 G Dopamine transporter  Takes DA from the synaptic cleft back into the presynaptic neuron  Polymorphism: Short and long alleles  Long allele (10-r) is associated with ADHD, poorer sustained attention, and worse executive attention scores G Dopamine transporter  Takes DA from the synaptic cleft back into the presynaptic neuron  Polymorphism: Short and long alleles  Long allele (10-r) is associated with ADHD, poorer sustained attention, and worse executive attention scores

DAT1 G Results: significant difference between short/long vs long groups Short (n=6), short/long (n=30), long (n=47)

DAT1 G Results: significant differences on two behavioral measures Short (n=8), short/long (n=45), long (n=60)

5-HTT G Serotonin reuptake transporter G Repeat length polymorphism - short and long forms G Short form is not transcribed as efficiently and associated with better cognitive performance G Serotonin reuptake transporter G Repeat length polymorphism - short and long forms G Short form is not transcribed as efficiently and associated with better cognitive performance

5-HTT G Results: significant difference between short/long vs long Short (n=7), short/long (n=43), long (n=34)

5-HTT G Results: significant difference on one behavioral measure Short (n=8), short/long (n=64), long (n=42)

Conclusions  DAT1 & 5-HTT: sig. differences in behavior and ERPs  DRD2, MAOA, TPH2 & CHRNA4: sig. behavior, non-sig. ERPs  DRD4 & BDNF: sig. behavior  COMT & DBH: sig. ERPs  DAT1 & 5-HTT: sig. differences in behavior and ERPs  DRD2, MAOA, TPH2 & CHRNA4: sig. behavior, non-sig. ERPs  DRD4 & BDNF: sig. behavior  COMT & DBH: sig. ERPs

Future Directions G More subjects G Different polymorphisms G Gene X gene interactions G More subjects G Different polymorphisms G Gene X gene interactions

G Dr. Helen Neville G Dr. Ted Bell G The rest of the BDL G Dr. Peter O’Day and SPUR G Dr. Helen Neville G Dr. Ted Bell G The rest of the BDL G Dr. Peter O’Day and SPUR Acknowledgments

Questions?