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      Genetic polymorphisms in monoamine systems and outcome of cognitive behavior therapy for social anxiety disorder.

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          Abstract

          The role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703T polymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.

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          Serotonin transporter genetic variation and the response of the human amygdala.

          Ahmad R Hariri, Venkata S. Mattay, Alessandro Tessitore … (2002)
          A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5- hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
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            Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.

            S Sabol, K-P Lesch, Russell D Hamer … (1996)
            Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
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              The liebowitz social anxiety scale as a self-report instrument: a preliminary psychometric analysis.

              Nina Heinrichs, Kate Baker, Bianca T. Hofmann … (2002)
              The Liebowitz social anxiety scale (LSAS) is a commonly used clinician-administered instrument. The present study reports on the properties of a self-report version of the LSAS (LSAS-SR). About 175 participants diagnosed with social phobia participated in the study. The LSAS-SR showed overall good psychometric properties as indicated by the results of test-retest reliability, internal consistency, and convergent and discriminant validity. Furthermore, the scale was sensitive to treatment change. The construct validity of the LSAS-SR, however, remains to be further explored. These findings support the utility of the LSAS-SR, which has the advantage of saving valuable clinician time compared to the clinician-administered version.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): PLoS ONE
                Title: PloS one
                Publisher: Public Library of Science (PLoS)
                ISSN (Electronic): 1932-6203
                ISSN (Print): 1932-6203
                Publication date (Electronic): 2013
                Volume: 8
                Issue: 11
                Affiliations
                [1 ] Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
                Article
                Publisher Item ID: PONE-D-13-03648
                DOI: 10.1371/journal.pone.0079015
                PMC ID: 3829855
                PubMed ID: 24260145
                SO-VID: 82de88f8-9693-458b-9ad8-c8f25e522c7e
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