The Influence of Dopamine Receptor D4 Polymorphism on Resting EEG in Healthy Young Females

Tien-Wen Lee 1, Younger W.-Y Yu 2, Chen-Jee Hong3, 4, Shih-Jen Tsai 3, 4, Hung-Chi Wu 5, Tai-Jui Chen*, 6
1 Laureate Institute for Brain Research, Tulsa, OK 74136, USA
2 Yu’s Psychiatric Clinic, Kaohsiung, Taiwan
3 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
4 School of Medicine, National Yang-Ming University, Taipei, Taiwan
5 Kai-Suan Psychiatric Hospital, Kaohsiung, Taiwan
6 Department of Psychiatry, E-DA Hospital, Kaohsiung County, Taiwan

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* Address correspondence to this author at the Department of Psychiatry, E-DA Hospital, Kaohsing County, Taiwan; Tel: +886-(0)7-6150011; Fax: +886-(0)7-6155352; E-mails:;


The polymorphism of variable number of tandem repeat (VNTR) in dopamine receptor D4 (DRD4) gene exon III has been linked to various neuro-psychiatric conditions with disinhibition/impulsivity as one of the core features. This study examined the modulatory effects of long-allele variant of DRD4 VNTR on the regional neural activity as well as inter-regional neural interactions in a young female population. Blood sample and resting state eyes-closed EEG signals were collected in 233 healthy females, stratified into two groups by polymerase chain reaction: long-allele carriers (>4- repeat) and non-carriers (<=4-repeat/<=4-repeat). The values of mean power of 18 electrodes and mutual information of 38 channel pairs across theta, alpha, and beta frequencies were analyzed. Our connectivity analysis was based on information theory, which combined Morlet wavelet transform and mutual information calculation. Between-group differences of regional power and connectivity strength were quantified by independent t-test, while between-group differences in global trends were examined by non-parametric analyses. We noticed that DRD4 VNTR long-allele was associated with decreased global connectivity strength (from non-parametric analysis), especially over bi-frontal, biparietal and right fronto-parietal and right fronto-temporal connections (from independent t-tests). The between-group differences in regional power were not robust. Our findings fit with the networks of response inhibition, providing evidence bridging DRD4 long-allele and disinhibition/impulsivity in neuropsychiatric disorders. We suggest future DRD4 studies of imaging genetics incorporate connectivity analysis to unveil its impact on cerebral network.

Keywords: Electroencephalography (EEG), mutual information, connectivity, power spectrum, DRD4, polymorphism.