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Comment & Response
February 2016

Use of 5-Hydroxytryptophan Labeled With Carbon 11 in Social Anxiety Disorder—Reply

Author Affiliations
  • 1Department of Psychology, Uppsala University, Uppsala, Sweden
  • 2Department of Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden
JAMA Psychiatry. 2016;73(2):177-178. doi:10.1001/jamapsychiatry.2015.2751

In Reply Dr Jacobsen raises some concerns regarding our interpretation1 of increased influx rate of the positron emission tomography (PET) radiotracer 5-hydroxytryptophan labeled with carbon 11 ([11C]5-HTP) in patients with social anxiety disorder (SAD). First, to clarify, we did not propose that “elevated extracellular serotonin causes SAD.” The serotonergic alterations could reflect a causal effect, a risk factor, or a “scar” from the disorder, but it is not possible to discriminate between these using our correlational design. Dr Jacobsen argues that, because selective serotonin reuptake inhibitors (SSRIs) increase extracellular serotonin and reduce anxiety, our results paradoxically imply that cause and cure are the same. However, SSRIs acutely increase serotonergic tone and anxiety. The anxiolytic mechanisms of chronic SSRI administration and the reasons for the 2- to 3-week therapeutic delay are largely unknown, with theories ranging from perturbations of the serotonergic system to neurogenesis. Chronic SSRI administration may actually attenuate serotonin synthesis.2 Etiological theories involving excessive serotonin have been discussed both in anxiety3 and depression.4

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