Increased brain activity to unpleasant stimuli in individuals with the 7R allele of the DRD4 gene.

The aim of the study was to examine functional brain activity in response to unpleasant images in individuals with the 7-repeat (7R) allele compared to individuals with the 4-repeat (4R) allele of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3). Based on the response ready hypothesis, individuals with the DRD4-4R/7R genotype were expected to show greater functional brain activity in response to unpleasant compared to neutral stimuli in specific regions of the frontal, temporal, parietal and limbic lobes, which form the networks involved in attentional, emotional, and preparatory responses. Functional Magnetic Resonance Imaging activity was studied in 26 young adults (13 with the DRD4-4R/7R genotype and 13 with the DRD4-4R/4R genotype). Participants were asked to look at and subjectively rate unpleasant and neutral images. Results showed increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the DRD4-4R/7R genotype versus participants with the DRD4-4R/4R genotype. The increase in right temporal lobe activity in individuals with DRD4-4R/7R suggests greater involvement in processing negative emotional stimuli. Intriguingly, no differences were found between the two genotypes in the subjective ratings of the images. The findings corroborate the response ready hypothesis, which suggests that individuals with the 7R allele are more responsive to negative emotional stimuli compared to individuals with the 4R allele of the DRD4 gene.

Prefrontal hemodynamic changes during cigarette smoking in young adult smokers with and without ADHD.

Individuals with attention-deficit/hyperactivity disorder (ADHD) have elevated smoking prevalence and reduced cessation rates compared to the general population. However, the effects of cigarette smoking on underlying brain activity in smokers with ADHD are not well characterized. Non-invasive near-infrared spectroscopy (NIRS) was used to characterize how cigarette smoking affects prefrontal brain hemodynamics in smokers with and without ADHD. Prefrontal changes of oxy- and deoxyhemoglobin (HbO2 and HHb) were measured in six male adult smokers with ADHD and six age- and gender-matched control smokers. NIRS measurements were separated into four sequential time intervals, i.e., before smoking, during smoking, after smoking, and during a breath hold. Prefrontal HbO2 was lower during smoking in smokers with ADHD compared to control smokers. More specifically, smokers with ADHD showed decreased prefrontal HbO2 during smoking compared to breath hold, before and after smoking periods. In contrast, control smokers showed increased prefrontal HbO2 from before smoking to breath hold. Decreased prefrontal HbO2 in smokers with ADHD may reflect a smoking-induced change in prefrontal brain activity and microvasculature, which is not found in smokers without ADHD. The lower prefrontal HbO2 may be a biomarker for increased susceptibility to tobacco smoke in smokers with ADHD. Smoking in individuals with ADHD may increase vasoconstriction of cerebral arteries in the prefrontal cortex, which may contribute to a reduction in HbO2. The findings highlight the importance of smoking cessation, in particular in those smokers who use nicotine to self-medicate ADHD symptoms.