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Headache responses to M-CPP in OCD and normal controls
THURSDAY, MAY 18
BIOL PSYCHIATRY 1995;37:593 683
615
activities in short segments of data, and during acute challenge studies to induce panic attacks. This method ensures that one does not lose important information during quick changes in cardiac sympathetic and parasympathetic activities. This method can also be used on long data segments, and the results are comparable to traditional spectral analysis or nonlinear techniques such as fractal dimensions. Using this technique, we found very high increases in sympathovagal ratios in patients during lactate and isoproterenol infusions, especially when they had panic attacks. Similar changes were also noted during human sexual activity at the time of orgasm, analyzed from the 24-hour Holter records of ECG. Complex demodulation also allows one to quantify time-dependent changes in the LF (0.04--0.15 Hz) power. This may be an important technique to analyze heart rate time series during heightened sympathetic activity, as there is a consistent peak in the time series of the LF amplitudes around 0.2 Hz, which is related to muscle sympathetic activity. Complex demodulation can be performed on heart rate time series using center frequencies of 0.09 and 0.31 Hz for the LF and HF powers with pass frequencies of 0.05 and 0.15 Hz. We use a 61 -term low-pass filter using a published algorithm for a zero-phase-shift least-square filter with convergence factors.
HT sensitivity. OCD patients (n ~ 42) had a blunted prolactin response to m-CPP in contrast to normal controls (n = 15) (F ~ 2.462, d = 3.62, p 0.06). Of interest, peak delta prolactin response to m-CPP significantly negatively correlated with frontal lobe set-switching impairment (r 0.37, n = 26, p - 0.03). This suggested that OCD patients with greater frontal lobe impairment (perhaps associated with increased harm avoidance) had concomitantly more substantial serotonergic dysfunction. This finding may identify a subset of OCD patients who have a favorable response to serotonin reuptake inhibitors.
82. HEADACHE RESPONSES TO M-CPP IN OCD AND NORMAL CONTROLS
The startle reslxmse has emerged as a valuable tool in the assessment of psychopathology; however, questions remain regarding the fundamental nature of the response. Functionally, the startle has been described as reflecting the operation of a behavioral interrupt system, reorienting the organism for emergency action following a sudden threatening event. A short-latency eyeblink EMG is the most typically used index of startle. Short-latency HR acceleration and some aspects of evoked EEG have also been linked to startle. The purpose of the present study was to investigate the relationships among t h e e measures while subjects were engaged in a task designed to test the behavioral interrupt hypothesis. We assessed the capacity of loud, startling sounds to interrupt performance of a time-estimation task while eyeblink EMG, HR, and EEG were recorded. Subjects were asked to observe and reproduce, by button press, the length of time a light was illuminated. During the course of observation or reproduction, subjects were occasionally and unpredictably exposed to brief, loud white noise stimuli. Measures of startle and time estimation were obtained, and relationships among these measures were analyzed. Despite the presence of significant startle, as shown by short-latency eyeblink, short-latency heart-rate acceleration, high-amplitude evoked brain response, and subjective report, no overall effect of startle on time estimation was found; however, HR acceleration was associated with underestimations of longer time intervals, consistent with previous studies suggesting that autonomic arousal can speed an internal clock mediating time estimation. These resuits are not consistent with some animal models of time estimation whereby startle would act to interrupt the accumulation of clock impulses.
C. Wong, L. Cohen, C. DeCaria, B. Aronowitz, D. Simeon, & E. Hollander M o u n t Sinai School o f M e d i c i n e , N e w York, NY 10029 The serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) has been found to induce migraine-like headaches tx~th in patients with eating disorders and normal controls, with bulimics being especially susceptible to headache induction; however, no studies of headache response in patients with obsessive-compulsive disorder (OCD), a group having 5-HT dysfunction as evidenced by blunted prolactin response to m-CPP, have been conducted. In this report, we studied headache response in 41 OCD patients and 21 normal controls who received m-CPP (0.5 mg/kg PO) and placebo. We found that both OCD patients (p < 0.03) and normal controls (p < 0.07) had more headaches following m-CPP than placebo. Of interest, induction of headaches was increased only in female subjects (p < 0.07). Female OCD patients had a 1.5-fold increase in headache response. These findings suggest that postsynaptic 5-HT mechanisms may be involved in both migraine-like headache production and OCD, especially in female patients with OCD.
83. RELATIONSHIP BETWEEN FRONTAL LOBE AND SEROTONERGIC FUNCTION IN OCD C. Wong, C. DeCaria, L. Cohen, B. Aronowitz, D. Simeon, & E. Hollander M o u n t Sinai School of Medicine, N e w York, N Y 10029 Studies of obsessive-compulsive disorder (OCD) have demonstrated both neuropsychological and serotonergic (5-HT) dysfunction; however, none have integrated these two spheres. We report concomitant abnormalities in both areas which may impact on identification and treatment in OCD patients. On neuropsychological testing, we utilized the Trailmaking B-A (cognitive set-switching) to highlight executive function abnormalities in OCD patients (n = 50) and normal controls (n - 31 ). OCD patients were found to be significantly impaired on Trails B-A. Prolactin response to double-blind, single-dose m-CPP and placebo served as a measure of 5-
84. EFFECTS OF ACOUSTIC STARTLE ON TIME ESTIMATION D.F. Fitzpatrick, S.R. Paige, & S.E. Hendricks C r e i g h t o n - N e b r a s k a D e p a r t m e n t of Psychiatry, U n i v e r s i t y o f N e b r a s k a M e d i c a l Center, O m a h a , NE 68198
85. EFFECT OF ISOPROTERENOL ON CEREBRAL BLOOD FLOW IN HEALTHY HUMANS O. Cameron & S. Minoshima T h e U n i v e r s i t y o f M i c h i g a n M e d i c a l Center, A n n Arbor, M I Central nervous system (CNS) and peripheral adrenergic mechanisms have been implicated in the pathophysiology of stress and several psychia~'ic and medical disorders. While the CNS in humans is not easily accessible, imaging techniques provide a means of determining a variety of CNS functions--cerebral blood flow (CBF), glucose metabolism, and ligand binding to many different receptor types. In order to examine the influence of systemic adrenergic activation on CNS functioning, we determined the effects of intravenous isoproterenol--a beta-adrenergic agonist which does not cross the blood-brain barrier---on whole brain and regional CBF in three male and three female healthy young adult subjects. We also determined effects on heart rate, blood pressure, arterial pC02,
BIOL PSYCHIATRY 1995;37:593 683
615
activities in short segments of data, and during acute challenge studies to induce panic attacks. This method ensures that one does not lose important information during quick changes in cardiac sympathetic and parasympathetic activities. This method can also be used on long data segments, and the results are comparable to traditional spectral analysis or nonlinear techniques such as fractal dimensions. Using this technique, we found very high increases in sympathovagal ratios in patients during lactate and isoproterenol infusions, especially when they had panic attacks. Similar changes were also noted during human sexual activity at the time of orgasm, analyzed from the 24-hour Holter records of ECG. Complex demodulation also allows one to quantify time-dependent changes in the LF (0.04--0.15 Hz) power. This may be an important technique to analyze heart rate time series during heightened sympathetic activity, as there is a consistent peak in the time series of the LF amplitudes around 0.2 Hz, which is related to muscle sympathetic activity. Complex demodulation can be performed on heart rate time series using center frequencies of 0.09 and 0.31 Hz for the LF and HF powers with pass frequencies of 0.05 and 0.15 Hz. We use a 61 -term low-pass filter using a published algorithm for a zero-phase-shift least-square filter with convergence factors.
HT sensitivity. OCD patients (n ~ 42) had a blunted prolactin response to m-CPP in contrast to normal controls (n = 15) (F ~ 2.462, d = 3.62, p 0.06). Of interest, peak delta prolactin response to m-CPP significantly negatively correlated with frontal lobe set-switching impairment (r 0.37, n = 26, p - 0.03). This suggested that OCD patients with greater frontal lobe impairment (perhaps associated with increased harm avoidance) had concomitantly more substantial serotonergic dysfunction. This finding may identify a subset of OCD patients who have a favorable response to serotonin reuptake inhibitors.
82. HEADACHE RESPONSES TO M-CPP IN OCD AND NORMAL CONTROLS
The startle reslxmse has emerged as a valuable tool in the assessment of psychopathology; however, questions remain regarding the fundamental nature of the response. Functionally, the startle has been described as reflecting the operation of a behavioral interrupt system, reorienting the organism for emergency action following a sudden threatening event. A short-latency eyeblink EMG is the most typically used index of startle. Short-latency HR acceleration and some aspects of evoked EEG have also been linked to startle. The purpose of the present study was to investigate the relationships among t h e e measures while subjects were engaged in a task designed to test the behavioral interrupt hypothesis. We assessed the capacity of loud, startling sounds to interrupt performance of a time-estimation task while eyeblink EMG, HR, and EEG were recorded. Subjects were asked to observe and reproduce, by button press, the length of time a light was illuminated. During the course of observation or reproduction, subjects were occasionally and unpredictably exposed to brief, loud white noise stimuli. Measures of startle and time estimation were obtained, and relationships among these measures were analyzed. Despite the presence of significant startle, as shown by short-latency eyeblink, short-latency heart-rate acceleration, high-amplitude evoked brain response, and subjective report, no overall effect of startle on time estimation was found; however, HR acceleration was associated with underestimations of longer time intervals, consistent with previous studies suggesting that autonomic arousal can speed an internal clock mediating time estimation. These resuits are not consistent with some animal models of time estimation whereby startle would act to interrupt the accumulation of clock impulses.
C. Wong, L. Cohen, C. DeCaria, B. Aronowitz, D. Simeon, & E. Hollander M o u n t Sinai School o f M e d i c i n e , N e w York, NY 10029 The serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) has been found to induce migraine-like headaches tx~th in patients with eating disorders and normal controls, with bulimics being especially susceptible to headache induction; however, no studies of headache response in patients with obsessive-compulsive disorder (OCD), a group having 5-HT dysfunction as evidenced by blunted prolactin response to m-CPP, have been conducted. In this report, we studied headache response in 41 OCD patients and 21 normal controls who received m-CPP (0.5 mg/kg PO) and placebo. We found that both OCD patients (p < 0.03) and normal controls (p < 0.07) had more headaches following m-CPP than placebo. Of interest, induction of headaches was increased only in female subjects (p < 0.07). Female OCD patients had a 1.5-fold increase in headache response. These findings suggest that postsynaptic 5-HT mechanisms may be involved in both migraine-like headache production and OCD, especially in female patients with OCD.
83. RELATIONSHIP BETWEEN FRONTAL LOBE AND SEROTONERGIC FUNCTION IN OCD C. Wong, C. DeCaria, L. Cohen, B. Aronowitz, D. Simeon, & E. Hollander M o u n t Sinai School of Medicine, N e w York, N Y 10029 Studies of obsessive-compulsive disorder (OCD) have demonstrated both neuropsychological and serotonergic (5-HT) dysfunction; however, none have integrated these two spheres. We report concomitant abnormalities in both areas which may impact on identification and treatment in OCD patients. On neuropsychological testing, we utilized the Trailmaking B-A (cognitive set-switching) to highlight executive function abnormalities in OCD patients (n = 50) and normal controls (n - 31 ). OCD patients were found to be significantly impaired on Trails B-A. Prolactin response to double-blind, single-dose m-CPP and placebo served as a measure of 5-
84. EFFECTS OF ACOUSTIC STARTLE ON TIME ESTIMATION D.F. Fitzpatrick, S.R. Paige, & S.E. Hendricks C r e i g h t o n - N e b r a s k a D e p a r t m e n t of Psychiatry, U n i v e r s i t y o f N e b r a s k a M e d i c a l Center, O m a h a , NE 68198
85. EFFECT OF ISOPROTERENOL ON CEREBRAL BLOOD FLOW IN HEALTHY HUMANS O. Cameron & S. Minoshima T h e U n i v e r s i t y o f M i c h i g a n M e d i c a l Center, A n n Arbor, M I Central nervous system (CNS) and peripheral adrenergic mechanisms have been implicated in the pathophysiology of stress and several psychia~'ic and medical disorders. While the CNS in humans is not easily accessible, imaging techniques provide a means of determining a variety of CNS functions--cerebral blood flow (CBF), glucose metabolism, and ligand binding to many different receptor types. In order to examine the influence of systemic adrenergic activation on CNS functioning, we determined the effects of intravenous isoproterenol--a beta-adrenergic agonist which does not cross the blood-brain barrier---on whole brain and regional CBF in three male and three female healthy young adult subjects. We also determined effects on heart rate, blood pressure, arterial pC02,