Enhanced Startle Reactions to Acoustic Stimuli in Patients With Obsessive-Compulsive Disorder

Anxiety states, e.g., during anticipation of noxious events or imagery of fearful situations, potentiate the human startle response to strong sensory stimuli (1). This response, elicited by auditory, visual, or tactile stimuli, is also influenced by concomitant presentation of affect-toned material. If the tone of the material has a positive affect, the reflex is attenuated, and if the tone is negative the reflex is potentiated (1).

Startle modulation offers a tool to study the pathophysiology of anxiety disorders. Patients with agoraphobia or panic disorder show larger startles than patients with other anxiety disorders, both during fear imagery and during neutral-imagery and no-imagery conditions (1). Increased startle has been observed in military veterans with posttraumatic stress disorder tested under stressful conditions (2). The present study investigates startle modulation by affective stimuli in obsessive-compulsive disorder (OCD). We examined whether patients with OCD might display generally larger startle reflexes or exaggerated startle potentiation by stimuli with a negative affective tone.

Method

Participants were 10 inpatients (three men, seven women; mean age=31.80 years, SD=12.34) and 10 healthy volunteers, matched in age (plus or minus 2 years) and sex and screened for psychiatric disorder. The comparison subjects were recruited by advertisement and paid £5 each. All participants were screened for neurological disorder, drug abuse, and hearing deficits. Written consent was obtained from all participants after experimental procedures had been fully explained.

The diagnosis of OCD (main symptoms: cleaning, washing, and checking) was determined by using DSM-IV criteria. Patients were also given the Hospital Anxiety and Depression Scale (3); their mean depression score was 6.60 (SD=2.01), and their mean anxiety score was 16.00 (SD=3.16). Six of 10 patients were taking medication.

Participants were shown nine brief film clips (mean length=2 minutes) on a video recorder (VC–A30 HM) (Sharp Electronics, Manchester, U.K.) connected to a Sharp 20-inch color television monitor (DV–5101 A). The first three clips had no affective valence and were used only to familiarize subjects with the procedure. The last six were arranged in two three-clip blocks and shown in the following order: 1) neutral (house objects), 2) positive (comedy turn), 3) negative (toe surgery), 4) neutral (street scene), 5) negative (gangsters dragging a terrified victim into the forest), 6) positive (a dance sequence). Clips were separated by a blank blue screen of 4–10 seconds. Three acoustic stimuli (50-msec presentation of a 92.5-dB [A] white noise) were superimposed on the sound tracks (40–60 dB) at moments of relatively low sound level and presented binaurally during each clip (20–90 seconds after clip onset with varying interstartle intervals) through headphones (TDH-39P, Telephonics, Farmingdale, N.Y.).

Participants were told that the aim of the experiment was to assess their responses to the film clips; they were asked to watch each sequence and ignore occasional bursts of noise they would hear throughout the experiment. Affective ratings were obtained for each clip during the blank intervals by using a single 11-point scale on which a score of –5 indicated that the clip was extremely unpleasant, a score of 0 indicated that it had no affective impact, and a score of 5 indicated that it was extremely pleasant. An experimenter was present throughout the session.

A commercial human startle response monitoring system (Mark I, SR-Lab, San Diego Instruments, San Diego, Calif.) was used to present acoustic stimuli and to record and score the eyeblink component of the response (i.e., electromyographic [EMG] activity of the right orbicularis oculi muscle) (4). Baseline EMG activity (arbitrary analog-to-digital units), latency of response onset (milliseconds), response amplitude (analog-to-digital units; main measure for hypothesis testing), and response probability were the dependent measures.

The data on all measures were subjected (separately) to two-by-three multivariate repeated measures analyses of variance with Wilks’s lambda (group [patients or comparison subjects] by valence [positive, neutral, or negative]). The assumption of homogeneity of variance was not upheld for the data on amplitude measure (standard deviations increased linearly with means). These data were subjected to natural logarithmic transformation. Alpha was set at p<0.05 for all analyses.

Results

Patients showed larger startle responses than comparison subjects during all film clips (Table 1) (F=7.69; for transformed scores, F=7.58, df=1, 9, p=0.02). As expected, startle response amplitude increased linearly from positive to negative clips (F=22.89; for transformed scores, F=10.58, df=2, 8, p<0.01). The group-by-valence interaction was not significant (F=3.39; for transformed scores, F=1.53, df=2, 8, p<1.00).

Patients had shorter response latencies than comparison subjects (Table 1) (F=9.70, df=1, 9, p=0.01). All subjects had shorter response latencies during negative clips than they did during positive clips (Table 1) (F=6.28, df=2, 8, p=0.02). Response probability was greater during neutral and negative clips than during positive clips for all subjects (Table 1) (F=18.35, df=2, 8, p=0.001). No significant effects were observed for baseline EMG. The ratings confirmed the categorization of film clips as positive and negative (F=13.93, df=2, 8, p=0.002); there was no difference between patients and comparison subjects in affective ratings.

Discussion

We found greater startle response amplitudes and shorter response latencies in patients with OCD than in normal comparison subjects. Patients showed larger baseline responses, as opposed to short-term potentiation of startle responses by frightening or negative stimuli. Although the amygdala is known to be critical for fear-potentiated startle (5), corticotropin-releasing hormone (CRH) in the nucleus reticularis pontis caudalis plays a major role in basic startle modulation (6), raising the possibility of CRH abnormalities in OCD. However, abnormalities of other neurotransmitters (e.g., dopamine and glutamate) may also account for excessive startle reactivity and thus be implicated in OCD (7).

It has been proposed (8) that pathological anxiety seen in clinical populations reflects hyperexcitability of fear circuits, including the amygdala and extended amygdala. The larger baseline startle amplitude seen in OCD and other anxiety disorders may indicate constant hyperexcitability of fear circuits in these populations. Drugs that effectively treat OCD symptoms have been shown in animals to affect receptors located, inter alia, in the amygdaloid nuclei (9). However, we did not control for medication effects in this preliminary study.

We conclude that patients with OCD are more reactive to startle probes and showed stronger reflexes than comparison subjects. This effect may be associated with the development and/or maintenance of OCD and may involve CRH abnormalities. Future studies using stimuli specific to the patients’ concerns, e.g., while they listen to OCD-specific scripts, may shed further light on startle abnormalities in patients with OCD.

TABLE 1

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