Variation in Key Genes of Serotonin and Norepinephrine Function Predicts Gamma-Band Activity during Goal-Directed Attention

Recent evidence shows that genetic variations in key regulators of serotonergic (5-HT) signaling explain variance in executive tasks, which suggests modulatory actions of 5-HT on goal-directed selective attention as one possible underlying mechanism. To investigate this link, 130 volunteers were genotyped for the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) and for a variation (TPH2-703 G/T) of the TPH2 gene coding for the rate-limiting enzyme of 5-HT synthesis in the brain. Additionally, a functional polymorphism of the norepinephrine transporter gene (NET -3081 A/T) was considered, which was recently found to predict attention and working memory processes in interaction with serotonergic genes. The flanker-based Attention Network Test was used to assess goal-directed attention and the efficiency of attentional networks. Event-related gamma-band activity served to indicate selective attention at the intermediate phenotype level. The main findings were that 5-HTTLPR s allele and TPH2 G-allele homozygotes showed increased induced gamma-band activity during target processing when combined with the NET A/A genotype compared with other genotype combinations, and that gamma activity mediates the genotype-specific effects on task performance. The results further support a modulatory role of 5-HT and NE function in the top-down attentional selection of motivationally relevant over competing or irrelevant sensory input

Cumulative Dopamine Genetic Score predicts behavioral and electrophysiological correlates of response inhibition via interactions with task demand

Functional genetic polymorphisms in the brain dopamine (DA) system have been suggested to underlie individual differences in response inhibition, namely the suppression of a prepotent or inappropriate action. However, findings on associations between single DA polymorphisms and inhibitory control often are mixed, partly due to their small effect sizes. In the present study, a cumulative genetic score (CGS) was used: alleles previously associated with both impulsive behavior and lower baseline DA level, precisely the DRD4 Exon III 7-repeat, DAT1 VNTR 10-repeat and the COMT 158val allele, each added a point to the DA-CGS. Participants (N = 128) completed a Go/No-Go task varying in difficulty and EEG recordings were made with focus on the NoGo-P3, an ERP that reflects inhibitory response processes. We found a higher DA-CGS (lower basal/tonic DA level) to be associated with better performance (lower %FA and more adaptive responding) in the very demanding/rapid than in the less demanding/rapid condition, whereas the reverse pattern was true for individuals with a lower DA-CGS. A similar interaction pattern of DA-CGS and task condition was found for NoGo-P3 amplitude. In line with assumptions of distinct optimum DA levels for different cognitive demands, a DA-CGS-dependent variation of tonic DA levels could have modulated the balance between cognitive stability and flexibility, thereby affecting the optimal DA level required for the specific task condition. Moreover, a task demand-dependent phasic DA release might have added to the DA-CGS-related basal/tonic DA levels, thereby additionally affecting the balance between flexibility and stability, in turn influencing performance and NoGo-P3

Patients' Perceptions of Opioid Replacement Therapy: a Comparison of Diamorphine and Methadone/Levomethadone

Diamorphine was first legalized as a novel treatment option for heroin dependence in Germany in 2009. Today, specialized clinics in ten German cities provide diamorphine to heavily addicted patients. As the medical and societal context of diamorphine-assisted therapy is evolving, continued research into patients’ perceptions of opioid replacement therapy remains important. From February 2018 to June 2018, we conducted a survey study of outpatients on maintenance treatment with either diamorphine (n = 85) or methadone/levomethadone (n = 126). Patients were asked to complete a self-report questionnaire querying, besides socio-demographic information, the study participant’s satisfaction with the substitute drug, relapse with illicit drugs, patterns of craving, and alcohol consumption. Duration of opioid dependence did not differ significantly between groups. Patients on diamorphine were approximately 3 years younger than patients on methadone/levomethadone. They also had a higher frequency of daily intake of their substitute drug and had had their dosage adjusted more often during the preceding 6 months. Still, diamorphine patients reported greater satisfaction with their substitute drug in tandem with significant reductions in relapse-related behaviors and cravings. While the most common relapse reported by patients on methadone replacement was heroin relapse (68%), most instances of illicit drug use in the diamorphine group involved cocaine (48%). Although self-reported alcohol consumption did not differ significantly between groups, a higher percentage of diamorphine patients than methadone patients endorsed decreased alcohol consumption since entering therapy. Taken together, these findings point to meaningful differences between diamorphine and methadone/levomethadone in opioid replacement therapy