Fifteen adult patients with DSM-IV generalized anxiety disorder (seven men and eight women; mean age=39.3 years, SD=13.3) and 15 healthy volunteers (mean age=39.1, SD=13.5) recruited through advertisements and clinic/physician referrals were prospectively pair-matched with respect to age and sex. As determined with the Structured Clinical Interview for DSM-IV Axis I Disorders (5), comorbid disorders in the generalized anxiety disorder group were dysthymia (N=5), social anxiety disorder (N=2), and concurrent social anxiety disorder and dysthymia (N=1). Inclusion criteria required that generalized anxiety disorder precede onset of comorbid axis I disorders. Exclusion criteria were a major depressive episode or substance abuse within 6 months of study entry; a lifetime history of psychotic, bipolar, obsessive-compulsive, posttraumatic stress, or eating disorder; substance dependence (other than nicotine); mental retardation or learning disability; autism; or significant medical or neurological conditions. Of the generalized anxiety disorder patients, six were medication-naive, and no subject had psychotropic exposure at least 4 weeks before scanning. Healthy participants had no history of axis I disorder, either personally or in first-degree relatives. All participants had unremarkable urine toxicology, urinalysis, CBC, blood chemistry, and ECG results. Timing of scans in female participants was matched relative to their menstrual phase. Groups did not differ in ethnic composition, educational level, IQ, height, weight, or use of hormonal contraception. Patients had screening and day-of-scan scores of at least 18 on the Hamilton Anxiety Rating Scale (mean=22.6, SD=3.5) and at least 45 on the Penn State Worry Questionnaire (mean=63.3, SD=8.1). Scores of healthy participants were substantially lower, and did not overlap those of patients (Hamilton anxiety scale mean=0.2 [SD=0.4]; Penn State Worry Questionnaire mean=29.1 [SD=8.6]). Participants were classified as having experienced early trauma (six generalized anxiety disorder patients, no comparison subjects) if they reported recurrent and severe prepubertal physical or sexual abuse, as determined with a modified Early Trauma Inventory (6, 7). The current study was approved by the Columbia University Institutional Review Board; all subjects provided written informed consent before participation.
Scans were carried out on a 1.5-T GE Signa scanner, using the multislice 1H-MRS imaging sequence of Duyn et al. (8). Following sagittal scout images, a four-section T1-weighted axial/oblique localizer image, angulated parallel to the Sylvian fissure, was acquired with a slice thickness of 15 mm and an interslice gap of 3.5 mm matching the subsequent 1H-MRS scan. Spectroscopy was conducted with TE/TR 280/2300 msec, field of view 24 mm, 32×32 phase-encoding steps with circular k-space sampling, and 256 points along the signal acquisition domain, using nominal voxel sizes of 1.5×0.75×0.75 cm. Metabolite resonance area ratios (N-acetylaspartate/creatine, choline-containing compounds/creatine) were computed for the bilateral hippocampus and dorsolateral prefrontal cortex, with two investigators, masked to diagnosis, conducting the curve-fitting.