Nicholas J. Voudouris

Conditioned response models of placebo phenomena: Further support.

&NA; Following our earlier research [37], we further investigated a model that conceptualizes placebo phenomena as the result of conditioning [40] and attempted to extend and replicate the finding that placebo responses can be conditioned in human subjects. Two groups of 10 subjects were told that they were receiving an analgesic which was in fact a placebo. During the conditioning, placebo administration was surreptitiously paired with an increase in the painful stimulus for half of the subjects and with a decrease for the other half. Subjects were tested pre and post conditioning for a placebo response. A second type of experimental pain was also used to determine stimulus generalization. The results confirmed a previous finding that placebo responses can be conditioned in human subjects. The implications for clinical practice of a learning model of placebo behavior are discussed.

Conditioned placebo responses.

Following earlier animal research, we attempt to condition placebo effects in human subjects. Four groups of 8 voluntary subjects were told that the experimenters would test a powerful new analgesic cream over three sessions by assessing its ability to reduce experimentally induced pain. The analgesic cream was, in fact, a placebo. In the first session all subjects were tested with and without the cream to assess their placebo response. In the second session, to condition two groups (with differing stimulation levels) to experience pain relief in response to the placebo, we repeatedly paired a reduction in nocioceptive stimulation with placebo administration. (Subjects were unaware that stimulation levels were manipulated). To condition the other two groups (with different stimulation levels) to experience an exacerbation of the pain, we paired an increase in nocioceptive stimulation with placebo administration. In the third session, all subjects were again tested for placebo response. Results suggested that placebo responses are conditionable in the laboratory in both a positive and negative direction. The clinical implications of a learning theory of placebo behavior are discussed.

Intelligence and Duchenne muscular dystrophy: Full-Scale, Verbal, and Performance intelligence quotients

Duchenne muscular dystrophy (DMD) is a disease which has as its hallmarks progressive muscle weakness and degeneration of skeletal muscle. Also observed among those with DMD is a higher rate of mental retardation* than in the normally developing population. While estimates for the prevalence of mental retardation in the normally developing population are approximately 9%,1 estimates of mental retardation based on the administration of the Wechsler Intelligence Scales (WIS)2,3 or the Stanford-Binet4 to children with DMD have ranged from 20%5 to as high as 50% in some studies.6–8 There have been intermittent review articles9 focusing on this issue, with authors noting aspects of the prevalence discrepancy, but no large-scale collation of the considerable published DMD intelligence data has yet been undertaken. The purpose of this paper is to provide an up-to-date review of this literature, and to report, as well as to summarize, the preliminary results of a metaanalysis of the available data, focusing on on global intelligence measures and DMD.

Test-retest reliability and internal consistency of a variety of measures of dietary restraint and body concerns in a sample of adolescent girls

OBJECTIVE Internal consistency and test-retest reliability were examined in a variety of measures relating to body concerns and dieting and eating behaviors. METHOD Grade 9 females (n = 363) from nine schools completed questionnaires with the aid of a definitions glossary at Time 1, including the five subscales of the Eating Attitudes Test, the Dutch Eating Behavior Questionnaire-Restraint scale, a variety of measures of current size and ideal size (self, parents) based on the Body Figure Rating Questionnaire, the Appearance Evaluation and Appearance Orientation subscales of the Multidimensional Body Self-Rating Questionnaire, and the Weight Loss Behaviors Scale. Four to 5 weeks later, 164 girls completed the questionnaires again. RESULTS AND DISCUSSION Findings indicated adequate internal consistency and high test-retest correlations for all measures. Some measures, particularly those related to body size and dietary restraint, showed a slight increase in group means over time.

Association between intellectual functioning and age in children and young adults with Duchenne muscular dystrophy: Further results from a meta-analysis

This study used meta‐analytical techniques to explore the association between intelligence and age in children with Duchenne muscular dystrophy (DMD). The sample comprised 1224 children and young adults with DMD (mean age 12y 3mo, SD 4y; range 2y to 27y). Standardized measures including the Wechsler Intelligence Scales (WIS) and the Stanford‐Binet Intelligence Scales were used to estimate intelligence. No age‐related difference was noted for Full‐scale and Performance intelligence quotients (IQ). However, Verbal IQ increased significantly with age. Age‐related increases were noted for the WIS Information, Similarities, Arithmetic, Comprehension, Digit Span, Picture Arrangement, Block Design, and Coding subscales. These results support the notion that younger children with DMD have deficits in verbal reasoning and verbal processing. Older children with DMD, particularly those of 14 years and older, were less likely to present with these problems. Implications of these findings and possible future research directions are discussed.

Does melatonin modulate beta-endorphin, corticosterone, and pain threshold?

Converging lines of evidence suggest that the pineal hormone, melatonin, may regulate changes in pain threshold by modulating fluctuations in opioid receptor expression and levels of beta-endorphin (beta-END). This study investigated whether the circadian oscillation in plasma melatonin is involved in the modulation of plasma beta-END immunoreactivity (beta-END-ir), and whether fluctuations in pain threshold measured using the hotplate test are contingent upon the fluctuation of these two hormones in Rattus Norvegicus. The role of melatonin was explored using light-induced functional pinealectomy (LFPX) to suppress nocturnal melatonin release. Pinealectomized rats were found to have significantly elevated levels of beta-END-ir compared to control animals at both photophase (398 +/- 89 pg/ml versus 180 +/- 23 pg/ml) and scotophase (373 +/- 45 pg/ml versus 203 +/- 20 pg/ml) test-periods, thus supporting the putative melatonin-opioid axis. Similarly, latency to pain threshold of LFPX rats was significantly longer when compared to control animals at photophase (7.3 +/- 1.4 sec versus 4.8 +/- 0.7 sec) and scotophase (6.3 +/- 0.7 sec versus 5.1 +/- 0.7 sec). Previous studies have produced conflicting data regarding the role of the pineal system in modulating levels of corticosterone (CORT). We observed a moderate, but non-significant, increase in the CORT concentration of LFPX rats during the photophase test period.

The role of CCK2 receptors in energy homeostasis: insights from the CCK2 receptor-deficient mouse

The present study explored the contribution of type 2 cholecystokinin (CCK) receptors in energy regulation. A total of 78 CCK2 receptor-deficient mice and 80 wild-type controls were acclimated to a 12:12 light-dark cycle at 30 +/- 1 degrees C. Using a computer-monitored biotelemetry system, circadian patterns of body temperature, food intake, and activity were monitored for 4 days. Body weight and water consumption were manually recorded during this period. Results indicate that CCK2 receptor invalidation produces elevated body temperature during both the photophase and scotophase (by 0.38 and 0.12 degrees C, respectively), increased body weight (29.3 +/- 0.2 vs. 26.8 +/- 0.2 g) and water consumption (4.1 +/- 0.1 vs. 3.2 +/- 0.1 ml), and decreased scotophase locomotor activity (WT: 7.0 +/- 0.2 vs. KO: 6.1 +/- 0.2 counts/min). These findings suggest an important role for CCK2 receptors in processes underlying energy regulation during basal and possibly pathological states.

The effect of lipopolysaccharide on cholecystokinin in murine plasma and tissue

Several mechanisms have been proposed for neuroimmune communication supporting sickness behavior (fever, anorexia, inactivity, and cachexia) following infection. We examined the role of cholecystokinin as a neurochemical intermediary of sickness behavior by determining plasma, duodenum, hypothalamus, and brainstem cholecystokinin concentrations 30 and 60 min and 12 h following intraperitoneal lipopolysaccharide (LPS) (0.25 and 2.5 mg/kg). Hypothalamic cholecystokinin was significantly lower in LPS- versus saline-treated mice 30 min (0.25 and 2.5 mg/kg) and 12 h (2.5 mg/kg) post-injection. Plasma cholecystokinin of LPS-treated mice was significantly lower than that of controls 1 and 12 h post-injection, a finding consistent with a non-endocrine action of peripheral cholecystokinin.

Metabotropic glutamate receptors mediate lipopolysaccharide-induced fever and sickness behavior

Several mechanisms have been proposed for neuroimmune communication supporting the sickness syndrome (fever, anorexia, inactivity, and cachexia) following infection. We examined the role of glutamate as a neurochemical intermediary of sickness behavior induced by intraperitoneal lipopolysaccharide (LPS). Mice implanted with biotelemetry devices capable of detecting body temperature (Tb) were administered LPS (50 or 500 microg/kg i.p., serotype 0111:B4) with or without i.p. pretreatment with vehicle or broad-spectrum antagonists selective for N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA)/kainite, or metabotropic glutamate (mGlu) receptors. While NMDA and AMPA/kainate receptor antagonism failed to attenuate LPS-induced sickness behavior, antagonism of metabotropic receptors with l(+)-AP3 reduced the febrile (0-11h: control: 37.32+/-0.16 degrees C, l(+)-AP3: 36.66+/-0.27), anorexic (control: -87+/-5%, l(+)-AP3: 48+/-12% scotophase food intake), and cachexic (control: -8.9+/-0.4%, l(+)-AP3: -6.1+/-1.3% body weight) effects of 500 microg/kg LPS, and produced a biphasic Tb effect in response to 50 microg/kg LPS (1h: -0.90+/-0.26; 6h: 1.78+/-0.35 degrees C relative to baseline). At this dose the Tb of l(+)-AP3-treated mice was 1.18 degrees C lower than controls 2h post-injection, and 0.68 degrees C greater that controls 8h post-injection. These results suggest a role for mGlu receptors in mediating fever, anorexia, and cachexia possibly via activation of extra-vagal pathways, since the attenuating effect of l(+)-AP3 increased with increasing dosages of LPS. Given the critical role ascribed to mGlu receptors in neurotransmitter release and astrocytic processes, it is possible that these observations reflect an l(+)-AP3-induced attenuation of these systems.

The effect of single oral doses of zopiclone on nocturnal melatonin secretion in healthy male volunteers

The effects of single oral doses of zopiclone and temazepam were investigated in eight healthy male volunteers using a single blind, placebo controlled cross over study. Doses of zopiclone were 7.5 and 15 mg while the dose of temazepam was 20 mg. Each dose was separated by at least a one-week washout period. For each subject the dim light melatonin onset (DLMO) was determined on a screening night and the drugs were administered at the time of the DLMO. Melatonin concentrations were determined by radioimmunoassay from plasma samples collected throughout the night. Both temazepam and zopiclone tended to reduce the amount of melatonin secreted, as determined by the area under the plasma concentration time curve. The differences from placebo were not statistically significant (F 3.31 = 1.07, P > 0.1). Similarly a repeated measures analysis of variance on the plasma concentration-time curves did not show any statistically significant differences between drugs and placebo (F 3.28 = 1.15, P > 0.1). There was no evidence from this study of a phase shifting effect of the drugs used. The reasons for the lack of effect on melatonin may be due to the differences in potency of the interaction of these drugs with the GABA-benzodiazepine-chloride ion channel.