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ORIGINAL ARTICLES |
From the Department of Psychiatry (U.B., S.W., T.D., S.L.R., R.K.P.), Massachusetts General Hospital and Harvard Medical School, Boston, MA; Research Service (S.P.O.), Veterans Affairs Medical Center, Manchester, NH.
Address correspondence and reprint requests to Ulrike Buhlmann, OCD Clinic, Massachusetts General Hospital, Simches Research Building, Office 2.280, 185 Cambridge Street, Boston, MA 02114. E-mail: buhlmann{at}psych.mgh.harvard.edu
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ABSTRACT |
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Methods: Twenty participants with OCD and 21 mentally healthy control participants were presented with 15 consecutive 95-db, 500-msec, 1000-Hz tones with 0-msec rise and fall times at the same time orbicularis oculi electromyogram (EMG), heart rate (HR), and skin conductance (SC) responses were measured.
Results: Participants with OCD produced larger average HR responses and a slower decline in SC responses across the 15-tone presentations. A trend for larger than average eyeblink EMG responses in participants with OCD was also observed.
Conclusion: These results provide laboratory support for enhanced HR reactivity and a slower decline in SC responses to startling stimuli in individuals with OCD.
Key Words: obsessive-compulsive disorder • startle reaction • heart rate • galvanic skin response • skin conductance • electromyogram
Abbreviations: OCD = obsessive-compulsive disorder; PTSD = posttraumatic stress disorder; EMG = orbicularis oculi electromyogram; HR = heart rate; SC = skin conductance; SCID = Structured Clinical Interview for DSM-IV; YBOCS = Yale-Brown Obsessive-Compulsive Scale; STAI = State-Trait Anxiety Inventory; BDI-II = Beck Depression Inventory-II.
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INTRODUCTION |
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There has been little research investigating the psychophysiologic characteristics of OCD, including the startle response. Whereas some studies have provided support for enhanced startle reactivity (6,7), other studies have failed to find such differences (8,9). Nearly all of this work has used eyeblink electromyogram (EMG) as the primary measure of startle reactivity. For example, Kumari et al. (6) presented 10 participants with OCD and 10 mentally healthy participants with startle-eliciting noise stimuli superimposed on a series of film clips that varied in emotional valence (negative, positive, and neutral), and the participants’ eyeblink EMG responses to the tones were measured. Participants with OCD exhibited larger eyeblink responses during all film clips, irrespective of emotional valence.
In a preliminary assessment of sensorimotor gating in 11 individuals with OCD and 13 healthy controls, Swerdlow et al. (9) did not find any group differences in eyeblink startle response habituation. Hoenig’s study (8) also failed to find any group differences in eyeblink startle habituation among 30 individuals with OCD and 30 healthy controls. This observation is similar to findings in the literature on PTSD demonstrating that individuals with PTSD consistently show eyeblink response habituation comparable to that of individuals without the disorder (5). Only one study of individuals with OCD investigated autonomic responses to startling stimuli. Lelliott et al. (7) observed slower habituation of SC responses to startling tones in participants with OCD, a finding also documented in individuals with PTSD (5). However, conclusions from the study by Lelliott’s group (7) are weakened by its failure to include a control group. Results for the group with OCD were compared with those individuals from a mentally healthy comparison group tested in an earlier study (10). Curiously, OCD research examining autonomic responses to stressful tasks has reported smaller skin conductance (SC), heart rate (HR), and EMG responses (11). Thus, research on the psychophysiology of OCD has yielded mixed or inconclusive results, although the limited findings from studies of reactivity to startling sounds have produced results similar to those observed in patients with PTSD.
To our knowledge, there is no published research comparing autonomic responses to startling stimuli between persons with OCD and mentally healthy individuals within the same study. Furthermore, no study of individuals with OCD has examined HR reactivity to startling stimuli. One of the most consistent psychophysiologic findings in the literature on PTSD has been that of larger average HR responses to sudden loud tones in individuals with PTSD, compared with persons without PTSD (5). The present study tested if participants with OCD are characterized by larger eyeblink startle and/or autonomic responses to sudden, loud tones.
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METHODS |
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Control participants included 21 individuals (11 females). They were recruited through flyers posted at locations throughout the greater Boston area. The SCID confirmed the absence of any current or past axis I mental disorder. The groups did not differ with respect to mean age (t(39) = 0.96, p = .35) or gender (
2(1) = 1.26, p = .35). Two participants were Hispanics and the remaining participants were Caucasians.
The study protocol was approved by the Partners Human Research Committee, which has oversight responsibility for research at MGH. The study was conducted between 2003 and 2005. Written informed consent of the participants was obtained after the procedures had been explained.
Self-Reported Anxiety and Depression
The participants with OCD completed the clinician-administered Yale-Brown Obsessive-Compulsive Scale (YBOCS) (13). Before the experiment, the participants also completed the State-Trait Anxiety Inventory (STAI) (14) and the Beck Depression Inventory-II (BDI-II; 15).
Stimuli and Dependent Psychophysiologic Measures
The stimuli and laboratory assessment procedures were the same ones used in previous studies on patients with PTSD (16,17). The stimuli consisted of 15, 95-dB (sound pressure level), 1000-Hz pure tones presented for 500 msec, with 0-msec rise and fall times. Stimuli were presented binaurally over headphones, and intertrial intervals were chosen randomly by the computer to range between 27 and 52 sec.
The dependent psychophysiologic measures were the same measures used in previous studies on PTSD (16). Left orbicularis oculi EMG, SC, and HR were recorded using a modular instrument system (LabLinc V, Coulbourn, Allentown, PA). EMG signals were amplified (Hi Gain Bioamplifier, Coulbourn, Allentown, PA) and filtered to include a range from 90 to 1000 Hz. The signals were integrated (Contour Following Integrator, Coulbourn, Allentown, PA) using a 10-msec time constant. SC was measured directly (Isolated Skin Conductance Coupler, Coulbourn, Allentown, PA) with a constant value of 0.5 V. HR was recorded from standard limb electrocardiogram leads connecting to the bioamplifier. Interbeat interval was measured from the electrocardiogram and then converted to HR. All psychophysiologic analog signals were digitized at 1000 Hz (LabLinc Analog to Digital Converter, Coulbourn, Allentown, PA).
Procedure
Participants were asked not to use nicotine and caffeine for at least 2 hours before the testing. After providing written informed consent, participants completed a SCID and a hearing test to verify that they could readily discern a 25-dB, 1000-Hz pure tone. Participants were then asked to provide urine samples to test for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, methaqualone, opiates, phencyclidine, and propoxyphene. They were seated in a sound-attenuated room, connected by cables to an adjoining laboratory containing the experimental apparatus. Also, participants were initially exposed to a series of mild electric shocks to the fingers, which ranged in intensity from imperceptible to highly annoying but not painful. This exposure to varying intensities of shock was intended to determine the level of shock that would be used in a conditioning procedure to be performed after the startle experiment. The selected levels (t(39) = 1.07, p = .29, Cohen’s d = 0.34) of shock intensity did not differ between the groups. Data from the conditioning procedure will be reported at a later date. Once the shock level was determined, the electrodes were removed. Next, the physiologic recording electrodes were attached. Approximately 20 minutes elapsed between the last shock and the first tone of the startle procedure. Participants were instructed that the procedure would begin with 5 minutes of relaxation, followed by a series of tones presented through the headphones. The tones were then administered without warning. Sampling of the physiologic signals began 4 sec before each tone presentation and continued until 8.5 sec after tone onset. Physiologic responses were scored as previously described (16). EMG response scores were calculated for each trial by subtracting the mean level during the 1-sec interval immediately preceding the tone onset from the highest level after the tone onset within 40 to 200 msec. SC response scores were calculated for each tone trial by subtracting the mean level during 1 sec immediately preceding tone onset from the highest level after the tone onset within 1 to 4 sec. Accelerative HR response scores were calculated for each tone trial by subtracting the mean HR, as determined from the two heartbeats immediately preceding the tone onset, from the highest HR level within 1 to 4 sec after the tone onset. Square-root transformations were performed for all response scores to reduce skewness and heteroscedasticity.
To investigate possible group differences in absolute habituation of SC and EMG responses, we assessed the number of trials before reaching a criterion of two successive nonresponse trials (SC 
0.05 µS; EMG 0.30 µV). We calculated relative habituation for all measures from the slope of the regression equation, Y = bx + a, for trials 2 to 15, whereby Y is the square root of the response score and x is the log trial number.
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RESULTS |
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Resting and Pretone Physiologic Levels
No group differences were observed for any of the resting or pretone physiologic levels (Table 2).
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Responses to Tone Presentations
Group mean physiologic responses averaged across the 15 trials, slopes, and trials to habituation are presented in Table 2.
Heart Rate Responses
Group comparisons showed that the participants with OCD exhibited significantly larger average HR responses to the tone presentations (Table 2 and Figure 1). No group difference was observed for the HR response slope.
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Skin Conductance Responses
Group comparisons showed no significant differences with respect to average SC response or number of SC trials to habituation. A significant group difference was found for the SC response slope, indicating that participants with OCD exhibited a slower decline in SC response magnitude, compared with that in controls (Table 2 and Figure 1).
Orbicularis Oculi EMG Responses
Group comparisons of average EMG responses to the 15 tone trials demonstrated a nearly significant difference (Table 2 and Figure 1). No group differences were found for either measure of EMG habituation.
Correlations With Self-Report Measures
To assess if subjective anxiety and depression influenced our results, we examined correlations between self-report measures and the psychophysiologic responses. No significant correlation responses (r < 0.19, p > .30) were found between STAI-state- or STAI-trait and average HR response, and SC response. Furthermore, no significant correlations (r < 0.26, p > .12) were found between depressive symptoms, as measured by the BDI-II (15) and average HR response, and the average EMG response; however, the correlation between the SC response slope and depressive symptoms was nearly significant (r = 0.31, p = .08).
Subgroup Analyses
Due to our small sample size and limited power, we did not test for statistical significance for the subgroup comparisons described below. Instead, for the physiologic measures that produced significant or nearly significant differences in the primary analyses, we calculated Cohen’s d effect sizes between the control group and the subgroups of participants with OCD who were free from the following potentially confounding factors. The mean and standard deviation values of the subgroups are presented below and for the control group in Table 2.
Comorbid Anxiety Disorders
Comparisons between the participants with OCD and free from any comorbid anxiety disorders (n = 13) and the controls yielded a moderate effect size for average HR response, d = 0.44 (OCD subgroup: 0.9 ± 1.0), a large effect size for SC response slope, d = 1.34 (OCD subgroup: –0.2 ± 0.1), and for average EMG response, d = 0.77 (OCD subgroup: 2.9 ± 1.9). Participants with OCD and without a comorbid anxiety disorder had less severe OCD symptoms, d = 1.23 (YBOCS total score = 18.2 ± 4.6) than did participants with OCD and a comorbid anxiety disorder (YBOCS total score = 24.7 ± 5.9).
Comorbid Depressive Disorders
Comparisons between the participants with OCD and free from comorbid depression (n = 16) and the controls produced a moderate to large effect size for average HR response, d = 0.66 (OCD subgroup: 1.1 ± 1.0), and for SC response slope, d = 0.78 (OCD subgroup: –0.3 ± 0.2), and a moderate effect size for average EMG response, d = 0.63 (OCD subgroup: 2.5 ± 1.4).
Psychotropic Medication
Comparisons between the unmedicated participants with OCD (n = 9) and the controls yielded a large effect size for average HR response, d = 0.79 (OCD subgroup: 1.6 ± 1.8), and a moderate to large effect size for SC response slope, d = 0.67 (OCD subgroup: –0.3 ± 0.3). No difference was observed for average EMG response, d = 0.00 (OCD subgroup: 1.8 ± 0.8).
Drug Screens
Three participants with OCD had a positive drug screen (opiates: n = 2; amphetamines: n = 1). Comparisons between the participants with OCD and negative drug screens (n = 17) and the controls yielded a large effect size for average HR response, d = 0.83 (OCD subgroup: 1.4 ± 1.3), a moderate to large effect size for SC response slope, d = 0.67 (OCD subgroup: –0.3 ± 0.3), and a moderate effect size for average EMG response, d = 0.54 (OCD subgroup: 2.5 ± 1.7).
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DISCUSSION |
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Increased HR reactivity in the absence of a larger SC response could be mediated by a particular region of the amygdala. Studies of rats have demonstrated that activity of the central nucleus of the amygdala (CeA) plays a key role in modulating cardiovascular responses (19). In particular, Wiersma et al. (20) observed that infusions of corticotrophin-releasing hormone directly into the CeA selectively reduced the parasympathetic outflow, although leaving the sympathetic outflow unchanged. For some individuals, exposure to high-intensity, long-duration tone stimuli may serve to activate the CeA, thereby reducing the parasympathetic outflow and causing increased HR responses without a corresponding increase in SC, i.e., sympathetic reactivity.
Results from neuroimaging studies provided support for heightened amygdala sensitivity in patients with PTSD (21). However, neuroimaging studies of patients with OCD have provided mixed results. Some functional neuroimaging studies of patients with OCD, employing symptom provocation by exposure to disorder-related stimuli, have shown exaggerated amygdala responses (22,23) as documented in studies of patients with PTSD (24), although other studies of patients with OCD have failed to find such amygdala activation (25). To the extent that ventromedial prefrontal/orbitofrontal cortical activation has been associated with diminished amygdala responses (26,27) and diminished autonomic reactivity (28), the consistent finding of orbitofrontal hyperactivity in patients with OCD (29–31) would lead one to expect attenuated autonomic responses in patients with OCD. However, it remains unclear how increased orbitofrontal activity in patients with OCD might influence the autonomic responses to acoustic startle stimuli. Of interest, Roberts et al. (32) showed that orbitofrontal damage was associated with deficient autonomic responses to anticipated acoustic startle stimuli, but intact autonomic responses to unanticipated startle stimuli. Thus, responses to unpredictable startle stimuli observed in the current experiment may not have been principally influenced by orbitofrontal function. Future imaging studies should consider the use of startle paradigms to directly investigate amygdala responses in patients with OCD.
In sum, conclusions about OCD that are derived from neuroimaging findings are partly inconsistent with the present findings of heightened autonomic reactivity. This raises an interesting conceptual dilemma. Findings of increased HR reactivity, slower SC habituation, and a tendency toward larger eyeblink responses to loud tones suggest that OCD has psychophysiologic commonality with other anxiety disorders including PTSD. However, mixed results of neuroimaging research, as well as recent research comparing OCD and related disorders such as body dysmorphic disorder or hypochondriasis (33), contribute to the discussion that OCD may be substantively different from other anxiety disorders. This latter view has also led to a proposed reclassification of OCD as a nonanxiety disorder (34) or as an OCD-spectrum disorder (33).
The trend toward larger average eyeblink responses in patients with OCD, compared with controls, suggests that the group with OCD may have experienced more anxiety during the startle assessment. Eyeblink reactivity has been shown to be influenced by the experimental context. For example, Grillon et al. (35) previously noted that the presence of a threatening context can influence whether individuals with PTSD exhibit larger eyeblink responses to startling sounds. Specifically, male Vietnam Veterans diagnosed with PTSD only produced increased eyeblink startle responses in the context of threat (i.e., anticipation of a shock) and not during a nonthreatening baseline startle session. Before our startle experiment, participants received several mild electrical stimuli as part of a second experiment that was conducted after the completion of the startle experiment. Although the shock electrodes were removed before the startle procedure and the participants were explicitly told that they would not receive any electrical stimulation during the startle experiment, it is possible that this circumstance may have produced a threatening context. However, the two groups did not differ in their chosen level of shock intensity (p = .29) and did not differ in their resting HR, SC, and EMG levels, which were measured after the administration of shocks and before the onset of tones (p > .56). This finding suggests that the shock procedure seems unlikely to have influenced our startle results. Although the present group with OCD did not produce a larger average SC response to the tones, it did demonstrate slower relative habituation of SC responses as shown by the SC slope measure. This pattern has also been observed in some studies on PTSD (16), whereby the slower relative habituation appeared in the absence of larger SC responses. Other studies on PTSD observed both slower relative SC habituation and larger average SC responses (17), as did a study on panic disorder (36). It is likely that these two measures of electrodermal activity reflect relatively independent processes (16), thereby allowing for patterns of SC response magnitude and SC habituation results that can differ across studies.
It is unlikely that the presence of comorbid disorders, medication use, or substance abuse substantively influenced our findings. The effect sizes remained moderate to large when individuals without these potentially confounding factors were separately removed from the analyses. However, when controlling for psychotropic medication, the comparison for average EMG response yielded an effect size of d = 0.00. To investigate the influence of comorbidities on the psychophysiologic measures, future research is needed to evaluate patients with OCD and also that same group with and without comorbid diagnoses.
It should be noted that participants with OCD and with a comorbid anxiety disorder also had substantially more severe OCD symptoms, compared with participants with OCD and free from a comorbid anxiety disorder. Thus, the presence of a comorbid anxiety disorder was confounded with OCD severity, thereby making it difficult to attribute the reduction in effect size for average HR response to the absence of a comorbid anxiety disorder, as opposed to less severe OCD. No group differences were observed for the resting period or pretone physiologic levels, suggesting that individuals with OCD were not characterized by higher tonic physiologic arousal. Neither state- nor trait-anxiety was significantly correlated with the psychophysiologic measures. Furthermore, depressive symptoms were not significantly correlated with the psychophysiologic measures. Thus, it seems unlikely that the results were determined by subjective anxiety or depressive symptoms.
The reason why the group difference for EMG fell short of significance may have resulted from the use of pure tones. Kumari and associates (6) used noise stimuli and observed significantly larger EMG responses in their group with OCD. However, loud tone stimuli can clearly produce larger eyeblink startle responses in clinical samples, as noted in some studies on PTSD (16,37). The larger HR responses to loud tones observed in individuals with OCD and PTSD may reflect "defensive" responses. The generation of such responses appears to require longer duration (e.g., 500 msec) stimuli (38). The durations of noise stimuli used in startle research typically are very short (e.g., 40 msec); although they can generate eyeblink startle responses, they would not be expected to generate larger HR responses.
In conclusion, our findings of heightened psychophysiologic reactivity to startling tones suggest that OCD may share psychophysiologic commonalities with other anxiety disorders. This finding poses a challenge for views that would reclassify OCD as a nonanxiety disorder. Directions for future work will necessarily include an examination of the reliability of the observed psychophysiologic findings in OCD and clarification regarding the conditions that mediate or moderate this heightened reactivity, such as when the stimuli are presented in a threatening versus a nonthreatening context.
It is unknown if enhanced autonomic reactivity in OCD is "constitutional" or acquired through fear-related experiences. Orr et al. (39) investigated startle responses in monozygotic twins who were Vietnam combat veterans (diagnosed with either PTSD or never had PTSD) and their noncombat-exposed brothers without PTSD. Results suggested that larger HR responses to startling tones were not a pretrauma vulnerability factor but rather an acquired PTSD sign. In addition, Shalev et al. (40) prospectively investigated trauma survivors at 1 week and up to 4 months after a traumatic event. After 4 months, participants were assessed for PTSD. This study found that at 1 week posttrauma, the group with PTSD and the non-PTSD group did not differ in the magnitude of their HR responses to startling tones. However, when tested 1 and 4 months later, the group with PTSD exhibited significantly larger HR responses compared with the non-PTSD group (40), indicating that the larger HR response developed over time. The origin of the increased autonomic startle responses in OCD found in this study has yet to be investigated. If larger HR responses in OCD are associated with the development of the disorder, as appears to be the case for PTSD, one might expect such responses to diminish with effective treatments such as cognitive behavioral therapy. It would be interesting to determine if successful treatment reduces or normalizes the larger HR response observed in patients with OCD, thereby testing its potential usefulness as a biological marker of psychosocial treatment outcome.
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NOTES |
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DOI:10.1097/PSY.0b013e31802f2799
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