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Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4′-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPNDwere also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.

Well-being (WB) is defined as a healthy state of mind and body. It is a state in which an individual is able to contribute to its society, able to work productively and overcome the normal stress of life. WB is a multi-dimensional concept and covers different aspects, including life satisfaction and quality of life. Little is known as to whether there are differences in connectivity patterns between healthy individuals with different WB states. We evaluated the WB state of healthy individuals with no prior diagnosis of any psychological disorder using the “General habitual WB questionnaire”, covering mental, physical and social domains. Subjects with mean age 25±4 years were divided into two groups, high WB state (n = 18) and low WB state (n = 14). We investigated and compared the groups for their resting state (rs-fMRI) functional connectivity (FC) patterns using DPARSF compiled with SPM12 toolbox. WB specific seeds were chosen for FC analysis. In the high WB group we found significantly increased connectivity between bilateral angular gyrus and frontal regions comprising the orbitofrontal cortex (OFC), right frontal superior gyrus and left precuneus. The low-WB group showed increased connectivity between the bilateral amygdala and the occipital lobe and the right anterior OFC. To conclude connectivity results with a quantitative approach, suggest differences in cognitive and decision-making processing between people with varying WB states. The high-WB group when compared to low-WB group had higher cognitive processing and decision making based on their internal mental processes and self-referential processing, whereas connectivity between amygdala and OFC relates to decreased attentional processing and promotes effective emotional regulation that may be a lead to rumination.