Increased Serotonin and Dopamine Transporter Binding in Psychotropic Medication–Naïve Patients with Generalized Social Anxiety Disorder Shown by¹²³I-β-(4-Iodophenyl)-Tropane SPECT

Abstract

There is circumstantial evidence for the involvement of serotonergic and dopaminergic systems in the pathophysiology of social anxiety disorder. In the present study, using SPECT imaging we examined the 123 I-b-(4-iodophenyl)-tropane binding potential for the serotonin and dopamine transporters in patients with a generalized social anxiety disorder and in age-and sex-matched healthy controls. Methods: Twelve psychotropic medicationnaïve patients with social anxiety disorder, generalized type (5 women and 7 men) and 12 sex-and age-matched healthy controls were studied. Volumes of interest were constructed on MRI-coregistered SPECT scans. Binding ratios were compared using the Mann-Whitney U test. Possible correlations between binding patterns and symptomatology were assessed using the Spearman rank correlation coefficient. Results: Significantly higher binding potentials were found for the serotonin in the left and right thalamus of patients. Patients had also a significantly higher binding potential for the dopamine transporter in the striatum. Conclusion: The present study provided direct evidence for abnormalities in both the dopaminergic and the serotonergic systems in patients with generalized social anxiety disorder.

Hyper-Connectivity of Subcortical Resting-State Networks in Social Anxiety Disorder

“…Taken together, the hyper-connectivity of cingulate gyrus with the caudate and putamen seeds, as demonstrated in this work, could be indicative of disturbances in striatal function specific to SAD. This is consistent with previous reports from nuclear imaging (van der Wee et al, 2008). Enhanced connectivity in pre-motor regions suggests that SAD patients are in a state of "motor readiness", either due to abnormal input to the striatum (from amygdala or mid-brain dopaminergic neurons) as proposed as a testable model for anxiety disorders by (Marchand, 2010).…”

Extrastriatal dopamine D2-receptor availability in social anxiety disorder

“…Coordinates are reported in the Montreal Neurological Institute standard space. investigating the DA system in SAD have provided only partial support for this hypothesis (van der Wee et al, 2008;Tiihonen et al, 1997;Warwick et al, 2012). Previous studies of striatal D2-R have reported no differences (Schneier et al, 2009), or lower levels in patients (Schneier et al, 2000), as compared to the present results of elevated extrastriatal D2-R availability.…”

“…Investigations comparing SAD patients to control subjects have reported both decreased (Tiihonen et al, 1997), increased (van der Wee et al, 2008) and unchanged (Schneier et al, 2009) dopamine transporter (DAT) availability, as well as reduced (Schneier et al, 2000) or unchanged D2-R availability (Schneier et al, 2009). It is noteworthy that all of these studies have focused on the striatum, whereas blood flow and activation studies have mainly shown extrastriatal regions to be involved in the pathophysiology.…”

Diagnosing social anxiety in Parkinson's disease: characteristics and frequencies according to two diagnostic criteria

“…SAD may be a psychosocial reaction to the stigmatizing PD symptoms such as tremor and bradykinesia, but abnormal function of the striatum has been pointed as one of the key pathophysiological mechanism implicated in SAD [20][21][22][23] and it is also plausible that the profound disruption of the main catecholaminergic and serotonergic pathways that occurs in PD 24 predispose patients to SAD. In our sample, SAD was associated with the intensity of motor symptoms, younger age and with earlier age at disease onset, all of which imply both in higher psychosocial stress and in more severe nigrostriatal dopaminergic denervation 25,26 .…”