Brain Plasticity and Cellular Aging After Internet-delivered CBT for Social Anxiety Disorder (UMEII)

The Brain´s Plasticity and Change in Cellular Aging After Internet-delivered Cognitive Behavior Therapy for Social Anxiety Disorder

This study evaluates underlying psychological and biological mediators in Internet-delivered cognitive behavior therapy for adults with social anxiety disorder.

Internet-delivered cognitive behavior therapy for social anxiety disorder has previously demonstrated to target and affect the brain´s fear network, typically neural response in the amygdala ameliorate after effective psychological treatment. Commonly, neuroimaging studies have performed brain imaging at pre- and post-intervention, yet, longitudinal study designs including several repeated measures of neural response over the course of treatment are currently missing in anxiety disorder. In the current study the participants will undergo magnetic resonance imaging (MRI) at four occasion. a) Twice before treatment initiation (9 weeks apart), b) at week 4 (during treatment), c) and directly after treatment termination. Biological aging can be quantified at the individual cell level by measuring telomere length in peripheral immune cells (leukocytes). Telomeres are located at the end of each chromosome and protect the genetic material during cell division. Telomerase is an enzyme that can lengthen telomeres, and have in this way a protective function against accelerated cellular aging. Variations in these bodily processes have been associated with psychiatric manifestations such as anxiety and depression. In the current study the participant´s telomere length and telomerase activity will be assessed at three occasion. a) Twice before treatment initiation (9 weeks apart), and b) directly after treatment termination.

Internet-delivered cognitive behavior therapy for social anxiety disorder. Similar to previous studies in our research group, the treatment will be delivered during 9 weeks. Each week the participant will be introduced to a module containing text material and homework assignments. The participants will receive feedback via text by a clinical psychologist once a week.

Clinician administrated telephone-interview to determine the participant´s treatment response rates (very much worse to very much improved)

Self reported social anxiety symptoms on fear (scoring 0-3) and avoidance (scoring 0-3) in 24 social situations.

Screening, Baseline 1 (week 0), Baseline 2 (week 9), weekly during treatment (week 10-19), week 20 (post-treatment), and at 6, 12, and 60 months

Screening, Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment), and at 6, 12, and 60 months

Before experimental tasks while undergoing MRI, at Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)

Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment), and at 6, 12, and 60 months

Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment), and at 6, 12, and 60 months

Inclusion Criteria: Social Anxiety Disorder as primary diagnosis (DSM-5) Otherwise somatically healthy Willingness to participate in a symptom provocation brain imaging trial Exclusion Criteria: Concurrent psychological treatment Treatment of social anxiety within the three months preceding the study Chronic use of prescribed medication that could influence the results (anxiolytic or antidepressant drugs, certain hypnotics or herbs like St Johns Wort) Contraindications for MRI investigation (implants or other metal objects in the body, brain and heart operations) Pregnancy or planned pregnancy during the first 6 months of the study period Postmenopausal women Any neurological disorders Depressive symptoms, as determined by scoring more than 20 on the MADRS questionnaire (self-report version) Suicidal ideation (scoring more than 2) on the self-report version of MADRS, item 9 Suicide at moderate risk (MINI v7) Bipolar disorder (MINI v7) Psychotic syndromes (MINI v7) Substance abuse disorders (MINI v7) Alcohol abuse (MINI v7) Any eating disorder (MINI v7) Antisocial personality disorder (MINI v7)

Mansson KN, Carlbring P, Frick A, Engman J, Olsson CJ, Bodlund O, Furmark T, Andersson G. Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder. Psychiatry Res. 2013 Dec 30;214(3):229-37. doi: 10.1016/j.pscychresns.2013.08.012. Epub 2013 Sep 21.

Mansson KN, Frick A, Boraxbekk CJ, Marquand AF, Williams SC, Carlbring P, Andersson G, Furmark T. Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning. Transl Psychiatry. 2015 Mar 17;5(3):e530. doi: 10.1038/tp.2015.22.

Lindqvist D, Epel ES, Mellon SH, Penninx BW, Revesz D, Verhoeven JE, Reus VI, Lin J, Mahan L, Hough CM, Rosser R, Bersani FS, Blackburn EH, Wolkowitz OM. Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging. Neurosci Biobehav Rev. 2015 Aug;55:333-64. doi: 10.1016/j.neubiorev.2015.05.007. Epub 2015 May 18.

Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Langstrom B, Fredrikson M. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry. 2002 May;59(5):425-33. doi: 10.1001/archpsyc.59.5.425.