Proton Magnetic Resonance Spectroscopy in Social Anxiety Disorder

A total of 24 consecutive nonmedicated patients (12 women and 12 men) with generalized subtype of SAD, who were seen in the Anxiety Disorders Outpatient Clinic of the Psychiatry Department of Istanbul Faculty of Medicine between September 2011 and December 2012, and fulfilled the DSM-IV¹ diagnostic criteria, were included in this study. Twenty-four healthy control subjects were individually matched with the patients for their age ±2 years, gender, and years of education. They were also screened for the absence of psychiatric disorders, as well as any family history of psychiatric disorder, and they were recruited on a voluntary basis. All the patients and control subjects were right-handed.

Inclusion criteria were 1) diagnosis of SAD with use of the Structured Clinical Interview for DSM-IV/Clinical Version (SCID-I/CV),¹⁰ 2) age between 18 and 50 years, and 3) medication-free status for at least the previous 6 weeks. Exclusion criteria were 1) any current psychiatric disorder other than SAD diagnosed with the SCID-I/CV, 2) a history of alcohol or drug abuse/dependence, 3) any serious concomitant general medical condition or neurologic disease, 4) a history of medical disorders that may have a causal relationship with SAD, and 5) pregnancy or lactation. Exclusion criteria for the patients and control subjects also included any contraindication for MRI and any history of neurodegenerative disease, seizure, central nervous system infection, cerebrovascular disease, diabetes mellitus, and head trauma that caused loss of consciousness lasting more than 30 minutes or that required hospitalization. Although mild traumatic brain injury was not excluded, none of our patients have such a history.

Among our patients, 16 (66.6%) were treatment naïve and 8 (33.3%) had taken different types of antidepressants, with different dosages, before the 6-week drug-free period.

The ethics committee of Istanbul University Istanbul Faculty of Medicine approved the study. Written informed consent was obtained from all participants after the procedures had been fully explained. This study adheres to the Declaration of Helsinki.

Diagnosis was made during the initial interview by trained psychiatrists. The Liebowitz Social Anxiety Scale (LSAS),¹¹ the Hamilton Anxiety Rating Scale (HAM-A),¹² the Hamilton Depression Rating Scale (HAM-D),¹³ and the Sheehan Disability Scale (SDS)¹⁴ were conducted in the patients during the second interview. A semistructured interview form prepared by the authors was used to evaluate the demographic features of the participants.

Cranial MRI and ¹H-MRS examinations were performed on a 1.5-T superconducting whole-body MRI scanner and spectroscopic system (Philips Medical Systems; The Netherlands) with a 16-channel head coil. Cranial MR images were acquired to position the MRS volume of interest (voxels) and to identify any cerebral pathology defined in the exclusion criteria (Figure 1). MR images included the following: 1) axial fast spin-echo (SE) T2-weighted images (TR=5800 ms, TE=105 ms, number of excitations=2, matrix=368×512, section thickness=5 mm, intersection distance=1.0 mm); 2) coronal SE T1-weighted images (TR=530 ms, TE=30 ms, number of excitations=2, matrix=196×256, section thickness=3 mm, intersection distance=1 mm); and 3) sagittal fast SE T2-weighted images (TR=5800 ms, TE=105 ms, number of excitations=4, matrix=196×256, section thickness=3 mm, intersection distance=1 mm).

Single-voxel ¹H-MRS examinations of the patients and control subjects were conducted in the same session with conventional cranial MRI. An experienced neuroradiologist (K.A.) placed the voxels on the left anterior cingulate, insula, putamen, and caudate nuclei using the conventional MR images. The voxels for the insula and cingulate were placed in a manner to maximize the gray matter and minimize white matter and CSF. A 18×12×10-mm–sized voxel on the anterior cingulate gyrus was placed for the anterior cingulate gyrus using the sagittal T2-weighted and coronal T1-weighted images as described by Yücel et al.¹⁵ A 10×10×10-mm–sized voxel was positioned for the head of the caudate region. The voxel sizes for the putamen and insula were 14×10×10 and 16×12×10 mm, respectively. The localization of the proton spectra was acquired using the stimulated echo acquisition mode (STEAM; TR=2500 ms, TE=30 ms, 164 acquisitions) sequence. The signals over the voxels were shimmed to within a linewidth of 6–7 Hz. Water suppression was performed with three chemical shift selective saturation pulses at the water resonance. Spectral postprocessing included zero filling to 2048 points, an exponential filter corresponding to 1 Hz of line broadening, Fourier transformation, zero-order phase, and automatic baseline corrections by polynomial interpolation. Spectra with a full width at half maximum smaller than 0.1 ppm and a signal-to-noise ratio above 3 were included in the statistical analysis. The MR system manufacturer’s software package was used for curve fitting and measurement of peak integrals. Major metabolite peaks were assigned to NAA at 2.02 ppm, Cr at 3.02 ppm, Cho at 3.22 ppm, and mI at 3.56 ppm. Cr was used as an internal reference metabolite, and NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated.

The SPSS 11.5 for Windows program was used for statistical analyses. For comparisons between the two groups, Student’s t test was used for continuous variables, and the chi-square test was used for categorical variables. Fisher’s exact test was used when indicated. Pearson’s correlation coefficients were computed between the clinical variables and levels of neural metabolites.