Effect of Antidepressant Medication Use on Emotional Information Processing in Major Depression

We recruited 49 patients with major depression and 47 never-depressed participants through Internet, television, and radio advertisements. Two participants in the depression group were excluded from the analyses because of inadequate eye-tracking data, resulting in a group size of 47 patients with major depression, of whom 21 were currently taking antidepressant medication and 26 were not. The 47 never-depressed comparison subjects were not taking any antidepressant medications. Comparison subjects were matched as closely as possible with participants in the major depression group for age and years of education.

Inclusion criteria for depressed participants were a DSM-IV diagnosis of major depressive disorder and a score >20 on the Beck Depression Inventory-II (BDI-II) (14). Inclusion criteria for the nondepressed comparison subjects were no history of major depression and a score <13 on the BDI-II. Inclusion criteria for all participants were age between 22 and 55 years, normal or corrected-to-normal vision, and ability to speak, read, and understand English. Exclusion criteria for all participants were a current or past DSM-IV diagnosis of substance abuse in the past 6 months; a current or past DSM-IV diagnosis of substance dependence, bipolar disorder, psychotic disorder, obsessive-compulsive disorder, social phobia, panic disorder, posttraumatic stress disorder, or generalized anxiety disorder; and a history of epilepsy or head trauma. Participants provided written informed consent after receiving a complete description of the study. All procedures were approved by the institutional review board of the University of Texas at Austin.

The electronic version of the Mini International Neuropsychiatric Interview (15), a short structured screening interview that provides DSM-IV and ICD-10 diagnoses, was used to screen for study eligibility. The patient version of the Structured Clinical Interview for DSM-IV (SCID) (16) was administered on the day of study participation to provide psychiatric diagnoses for the inclusion and exclusion criteria. Two assessors were doctoral students with master’s degrees in clinical psychology and at least 2 years of clinical training and assessment experience, and a third assessor was a full-time research assistant with a bachelor’s degree in psychology who had completed more than 40 hours of training in the administration of the SCID. Twenty percent of all interviews were rated by an independent assessor who was a doctoral student with a master’s degree in clinical psychology and 4 years of assessment experience. Agreement for diagnoses of major depressive disorder between study interviewers and the independent assessor was excellent (k=1.00, p<0.0001).

The BDI-II, a 21-item self-report questionnaire with demonstrated validity in psychiatric outpatient and inpatient samples (17), was used to assess depression severity. The Beck Anxiety Inventory (BAI) (18), a 21-item self-report questionnaire with good internal and test-retest reliability and convergent validity with other measures of anxiety (18, 19), was used to assess symptoms of anxiety.

On each trial in this task, four images selected from the International Affective Picture System (IAPS) (20) were presented simultaneously, with one image appearing in each quadrant of a 20-inch LCD computer monitor. On every trial, one image was selected from each of four stimulus categories: dysphoric, threat, positive, or neutral (see Figure S1 in the data supplement that accompanies the online edition of this article). The method for selecting and categorizing these images has been described previously (11). The location of each image was randomly assigned for each participant by the stimulus presentation software (E-Prime 2.0; Psychology Software Tools, Sharpsburg, Pa.) with the constraint that each stimulus category must appear in each of the four positions three times across 12 trials. In addition to the 12 study trials, four filler trials comprising all neutral images were presented to obscure the nature of the task, resulting in a total of 16 trials. Presentation order of stimuli was randomized for each participant. Each trial lasted 30 seconds. Trials were preceded by a central fixation cross that remained on-screen until the participant fixated within approximately 1° of visual angle of the cross for 1 second.

Participants sat approximately 60 cm from the screen. Each image measured 14.2×10.7 cm (13.5°×10.2° of visual angle). The horizontal distance between the centers of the images was 20.7 cm (19.6° of visual angle) and the vertical distance between the centers of images was 15.5 cm (14.8° of visual angle).

Line of visual gaze was assessed using a Model R6 remote optics eye-tracking system from Applied Science Laboratories (Bedford, Mass.). Head location was fixed using a chin rest and forehead bar. The location of gaze was sampled every 16.7 ms (60 Hz). Eye movements that were stable for more than 100 ms within a 1° visual angle were classified as a fixation. The total area of each stimulus on a trial was identified as an area of interest. For each area of interest, three selective attention indices were calculated with the GazeTracker software program (Applied Science Laboratories): total gaze time per trial, number of fixations per trial, and mean fixation duration. Greater gaze time represents greater sustained attention. Greater number of fixations represents repeated attentional engagement, whereas greater fixation duration represents greater attentional capture or difficulty disengaging attention.

Participants were interviewed with the SCID to determine study eligibility. Eligible participants completed a demographic form, the BDI-II, and the BAI and provided the following information regarding antidepressant use: current use (yes/no), name of medication, medication dosage, and length of time on medication. For eye tracking, participants were seated in a height-adjustable chair, which was adjusted to minimize discomfort with the participant’s head location fixed with the chinrest and forehead bar. Camera adjustments were made to best capture pupil and corneal reflection of the participant’s right eye. A 9-point calibration was conducted to confirm recording line of visual gaze within 1° of visual angle for each calibration point. Calibration was repeated until this criterion was met.

Participants were instructed verbally and via computer screen to view the images naturally, as if watching television or viewing a photo album. The only constraint was that they view the images at all times during each trial. To minimize demand effects, instructions emphasized that the study measured processing of emotional information without specifically mentioning the measurement of eye movements. Participants were instructed to look at the fixation cross preceding each trial to standardize the starting location of their gaze. An experimenter located in an adjacent room monitored the stimulus presentation and eye-tracking quality throughout the task.

Descriptive statistics for the sample are presented in Table 1. There were no significant differences between groups in age or years of education. The medicated and unmedicated depression groups did not differ in severity of depression, severity of anxiety, number of depressive episodes, or length of current depressive episode. The medicated and unmedicated depression groups both reported greater severity of depression and anxiety than the comparison group. The majority of participants were women, and there were no significant differences between the comparison group, the medicated depression group, and the unmedicated depression group in proportion of women (81%, 81%, and 85%, respectively). There was substantial variability in length of time medicated depression participants had been on their primary antidepressant medication (range, 1.5–520 weeks). (Medication information provided by participants in the medicated depression group is presented in Table S1 in the online data supplement.) A majority of participants in the medicated depression group (N=16) reported taking a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) as their primary medication. Three participants reported that bupropion was their primary medication, and two participants endorsed currently taking an antidepressant medication but did not provide any information about their medication. Analyses of data only from participants reporting an SSRI or SNRI as their primary medication were nearly identical to those of the full sample, so results from the full sample are reported below.