Real-Time fMRI Neurofeedback in Patients With Tobacco Use Disorder During Smoking Cessation: Functional Differences and Implications of the First Training Session in Regard to Future Abstinence or Relapse

One of the most prominent symptoms in addiction disorders is the strong desire to consume a particular substance or to show a certain behavior (craving). The strong association between craving and the probability of relapse emphasizes the importance of craving in the therapeutic process. Former studies have demonstrated that neuromodulation using real-time fMRI (rtfMRI) neurofeedback (NF) can be used as a treatment modality in patients with tobacco use disorder. The aim of the present project was to determine whether it is possible to predict the outcome of NF training plus group psychotherapy at the beginning of the treatment. For that purpose, neuronal responses during the first rtfMRI NF session of patients who remained abstinent for at least 3 months were compared to those of patients with relapse. All patients were included in a certified smoke-free course and took part in three NF sessions. During the rtfMRI NF sessions tobacco-associated and neutral pictures were presented. Subjects were instructed to reduce their neuronal responses during the presentation of smoking cues in an individualized region of interest for craving [anterior cingulate cortex (ACC), insula or dorsolateral prefrontal cortex]. Patients were stratified to different groups [abstinence (N = 10) vs. relapse (N = 12)] according to their individual smoking status 3 months after the rtfMRI NF training. A direct comparison of BOLD responses during the first NF-session of patients who had remained abstinent over 3 months after the NF training and patients who had relapsed after 3 months showed that patients of the relapse group demonstrated enhanced BOLD responses, especially in the ACC, the supplementary motor area as well as dorsolateral prefrontal areas, compared to abstinent patients. These results suggest that there is a probability of estimating a successful withdrawal in patients with tobacco use disorder by analyzing the first rtfMRI NF session: a pronounced reduction of frontal responses during NF training in patients might be the functional correlate of better therapeutic success. The results of the first NF sessions could be useful as predictor whether a patient will be able to achieve success after the behavioral group therapy and NF training in quitting smoking or not

A fresh look to the phenotype in mono-allelic likely pathogenic variants of the leptin and the leptin receptor gene

Leptin (LEP) and leptin receptor (LEPR) play a major role in energy homeostasis, metabolism, and reproductive function. While effects of biallelic likely pathogenic variants (-/-) on the phenotype are well characterized, effects of mono-allelic likely pathogenic variants (wt/-) in the LEP and LEPR gene on the phenotype compared to wild-type homozygosity (wt/wt) have not been systematically investigated. We identified in our systematic review 44 animal studies (15 on Lep, 29 on Lepr) and 39 studies in humans reporting on 130 mono-allelic likely pathogenic variant carriers with 20 distinct LEP variants and 108 heterozygous mono-allelic likely pathogenic variant carriers with 35 distinct LEPR variants. We found indications for a higher weight status in carriers of mono-allelic likely pathogenic variant in the leptin and in the leptin receptor gene compared to wt/wt, in both animal and human studies. In addition, animal studies showed higher body fat percentage in Lep and Lepr wt/- vs wt/wt. Animal studies provided indications for lower leptin levels in Lep wt/- vs. wt/wt and indications for higher leptin levels in Lepr wt/- vs wt/wt. Data on leptin levels in human studies was limited. Evidence for an impaired metabolism in mono-allelic likely pathogenic variants of the leptin and in leptin receptor gene was not conclusive (animal and human studies). Mono-allelic likely pathogenic variants in the leptin and in leptin receptor gene have phenotypic effects disposing to increased body weight and fat accumulation