Reduced Anterior Temporal and Hippocampal Functional Connectivity During Face Processing Discriminates Individuals with Social Anxiety Disorder from Healthy Controls and Panic Disorder, and Increases Following Treatment

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 39; no. 2; pp. 425 - 434
• Main Authors: Pantazatos, Spiro P, Talati, Ardesheer, Schneier, Franklin R, Hirsch, Joy
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.01.2014
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Anxiety; Anxiety disorders. Neuroses; Biological and medical sciences; Facial Expression; Female; Hippocampus - physiopathology; Humans; Magnetic Resonance Imaging - methods; Male; Medical sciences; Middle Aged; Neural Pathways - physiopathology; Original; Panic disorder; Panic Disorder - diagnosis; Panic Disorder - physiopathology; Panic Disorder - therapy; Phobia; Phobic Disorders - diagnosis; Phobic Disorders - physiopathology; Phobic Disorders - therapy; Photic Stimulation - methods; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Temporal Lobe - physiopathology; Treatment Outcome; Young Adult; Functional connectivity; Neuroimaging; Panic; Healthy subject; Social phobia; Central nervous system; Anxiety disorder; Encephalon; Selective serotonin reuptake inhibitor; diagnostic classification; SSRI; support vector machine; Classification; Information processing; Diagnosis; Face; longitudinal; Hippocampus
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/npp.2013.211

Group functional magnetic resonance imaging (fMRI) studies suggest that anxiety disorders are associated with anomalous brain activation and functional connectivity (FC). However, brain-based features sensitive enough to discriminate individual subjects with a specific anxiety disorder and that track symptom severity longitudinally, desirable qualities for putative disorder-specific biomarkers, remain to be identified. Blood oxygen level-dependent (BOLD) fMRI during emotional face perceptual tasks and a new, large-scale and condition-dependent FC and machine learning approach were used to identify features (pair-wise correlations) that discriminated patients with social anxiety disorder (SAD, N=16) from controls (N=19). We assessed whether these features discriminated SAD from panic disorder (PD, N=16), and SAD from controls in an independent replication sample that performed a similar task at baseline (N: SAD=15, controls=17) and following 8-weeks paroxetine treatment (N: SAD=12, untreated controls=7). High SAD vs HCs discrimination (area under the ROC curve, AUC, arithmetic mean of sensitivity and specificity) was achieved with two FC features during unattended neutral face perception (AUC=0.88, P<0.05 corrected). These features also discriminated SAD vs PD (AUC=0.82, P=0.0001) and SAD vs HCs in the independent replication sample (FC during unattended angry face perception, AUC=0.71, P=0.01). The most informative FC was left hippocampus-left temporal pole, which was reduced in both SAD samples (replication sample P=0.027), and this FC increased following the treatment (post>pre, t(11)=2.9, P=0.007). In conclusion, SAD is associated with reduced FC between left temporal pole and left hippocampus during face perception, and results suggest promise for emerging FC-based biomarkers for SAD diagnosis and treatment effects.