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Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [11C]DASB and [11C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo. Funding: Swedish Research Council; Swedish Brain Foundation; Riksbankens Jubileumsfond - the Swedish Foundation for Humanities and Social Sciences

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 BPND were 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.

Objectives The aim was to examine health-related quality of life (HRQoL), patient characteristics and reasons for visits to general practitioners (GPs) by frequent attenders (FAs) and a comparison group (CG) in primary care. Methods Patients aged 18–64 years were eligible for the study. Medical records were scrutinised concerning reasons for visits. Questionnaires including short-form health survey (SF-36) were mailed to 331 FAs (≥5 visits at GPs during 2000) and 371 patients in a CG randomly selected from two healthcare centres and returned by 49% and 57%, respectively. FAs’ SF-36 health profiles were compared both to CG and general Swedish population norms. Results FAs report lower HRQoL than CG and below the general Swedish population norms in all eight SF-36 domains including both mental and physical component summary scores (MCS and PCS). Effect sizes (ESs) for differences between FAs and norms ranged from 0.79 to 1.08 for specific domains and was 0.94 for PCS and 0.71 for MCS. ESs of FAs versus CG ranged between 0.60 and 0.95 for the domains and was 0.76 for PCS and 0.49 for MCS. There were no significant differences between the FAs and CG with regard to sex, being married or cohabiting, number of children in household or educational level. FAs were more often unemployed, obese, slightly older and used complementary medicine more frequently. Except for injuries, all health complaints as classified in 10 categories were more common among FAs than CG, particularly musculoskeletal pain and psychosocial distress related to compromised HRQoL. Conclusion The HRQoL is compromised in FAs, both when compared with patients who do not often seek care and to general Swedish population norms. Commonly reported reasons for visiting GPs among FAs were musculoskeletal pain and psychosocial distress. Thus, perceived ill health, particularly pain and distress, seems important for high utilisation of healthcare resources. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Aim The aim of the study is to investigate if cognitive behavioral therapy given in a group setting affects anxiety and depression, stress, pain, coping strategies during daily life, and health‐related quality of life (HRQoL), among frequent attenders (FAs) in primary care. Methods Cognitive behavioral therapy was offered to 331 FAs between 18 and 65 years of age, of whom 89 accepted and 54 completed all steps in the protocol; patients were assigned to 1 of 3 groups: 0, 6, and 12‐month waiting time. The therapy consisted of 12 sessions administered in group format. Outcome measures were Beck's Anxiety Inventory (BAI), Beck's Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Everyday Life Stress (ELS), Coping Strategy Questionnaire, Multidimensional Pain Inventory‐Swedish version, and Short Form‐36. Results Mean age among patients who completed cognitive behavioral therapy was 49.9 years, with a female majority (79.6%). Anxiety and depression scores were reduced after treatment (BAI 16.7 vs 13.6; BDI 16.3 vs 15.7; HADS‐Anxiety 8.41 vs 6.05; HADS‐Depression 7.09 vs 5.69). Because waiting time itself did not affect symptoms, differences reflect treatment effects. Stress ratings were not affected by treatment. Use of nonadaptive coping strategies like praying and hoping and catastrophizing decreased. Frequent attenders experienced a higher sense of life control. Frequent attenders reported significantly lower HRQoL than general Swedish population norms in all 8 Short Form‐36 domains including mental and physical component summary scores (MCS and PCS), and all domains were unaffected by treatment. Conclusion Cognitive behavioral therapy exerts some beneficial effects in FAs. Content of treatment addressed musculoskeletal pain, stress, anxiety, and depression. This broad approach resulted in reduced anxiety, depression, and impact of pain because of enhanced life control., Aim: The aim of the study is to investigate if cognitive behavioral therapy given in a group setting affects anxiety and depression, stress, pain, coping strategies during daily life, and health‐related quality of life (HRQoL), among frequent attenders (FAs) in primary care. Methods: Cognitive behavioral therapy was offered to 331 FAs between 18 and 65 years of age, of whom 89 accepted and 54 completed all steps in the protocol; patients were assigned to 1 of 3 groups: 0, 6, and 12‐month waiting time. The therapy consisted of 12 sessions administered in group format. Outcome measures were Beck's Anxiety Inventory (BAI), Beck's Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Everyday Life Stress (ELS), Coping Strategy Questionnaire, Multidimensional Pain Inventory‐Swedish version, and Short Form‐36. Results: Mean age among patients who completed cognitive behavioral therapy was 49.9 years, with a female majority (79.6%). Anxiety and depression scores were reduced after treatment (BAI 16.7 vs 13.6; BDI 16.3 vs 15.7; HADS‐Anxiety 8.41 vs 6.05; HADS‐Depression 7.09 vs 5.69). Because waiting time itself did not affect symptoms, differences reflect treatment effects. Stress ratings were not affected by treatment. Use of nonadaptive coping strategies like praying and hoping and catastrophizing decreased. Frequent attenders experienced a higher sense of life control. Frequent attenders reported significantly lower HRQoL than general Swedish population norms in all 8 Short Form‐36 domains including mental and physical component summary scores (MCS and PCS), and all domains were unaffected by treatment. Conclusion: Cognitive behavioral therapy exerts some beneficial effects in FAs. Content of treatment addressed musculoskeletal pain, stress, anxiety, and depression. This broad approach resulted in reduced anxiety, depression, and impact of pain because of enhanced life control.

SummaryWe aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive–behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential biomarker for SAD treatment selection.Declaration of interestNone.

The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n=17) and healthy controls (n=17) using positron emission tomography and the radiotracer [11C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.