Acoustic respiration rate and pulse oximetry-derived respiration rate: a clinical comparison study.

Respiration rate (RR) is a critical vital sign that provides early detection of respiratory compromise. The acoustic technique of measuring continuous respiration rate (RRa) interprets the large airway sound envelope to calculate respiratory rate while pulse oximetry-derived respiratory rate (RRoxi) interprets modulations of the photoplethsymograph in response to hemodynamic changes during the respiratory cycle. The aim of this study was to compare the performance of these technologies to each other and to a capnography-based reference device. Subjects were asked to decrease their RR from 14 to 4 breaths per minute (BPM) and then increase RR from 14 to 24 BPM. The effects of physiological noise, ambient noise, and head movement and shallow breathing on device performance were also evaluated. The test devices were: (1) RRa, Radical-7 (Masimo Corporation), (2) RRoxi, Nellcor™ Bedside Respiratory Patient Monitoring System (Medtronic), and (3) reference device, Capnostream20p™ (Medtronic). All devices were configured with their default settings. Twenty-nine healthy adult subjects were included in the study. During abrupt changes in breathing, overall RRoxi was accurate for longer periods of time than RRa; specifically, RRoxi was more accurate during low and normal RR, but not during high RR. RRoxi also displayed a value for significantly longer time periods than RRa when the subjects produced physiological sounds and moved their heads, but not during shallow breathing or ambient noise. RRoxi may be more accurate than RRa during development of bradypnea. Also, RRoxi may display a more reliable RR value during routine patient activities.

A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression.

Antagonism of N-methyl-D-aspartate glutamatergic receptors (NMDAR) may represent an effective antidepressant mechanism. D-cycloserine (DCS) is a partial agonist at the NMDAR-associated glycine modulatory site that at high doses acts as a functional NMDAR antagonist. Twenty-six treatment-resistant major depressive disorder patients participated in a double blind, placebo-controlled, 6-wk parallel group trial with a gradually titrated high dose (1000 mg/d) of DCS added to their antidepressant medication. DCS treatment was well tolerated, had no psychotomimetic effects and led to improvement in depression symptoms as measured by Hamilton Depression Rating Scale (HAMD; p = 0.005) and Beck Depression Inventory (p = 0.046). Of the 13 subjects treated with DCS, 54% had a ≥ 50% HAMD score reduction vs. 15% of the 13 patients randomized to placebo (p = 0.039). A significant (p = 0.043) treatment× pre-treatment glycine serum levels interaction was registered. These findings indicate that NMDAR glycine site antagonism may be a cost-effective target for development of mechanistically novel antidepressants. Larger-sized DCS trials are warranted.

High glycine levels are associated with prepulse inhibition deficits in chronic schizophrenia patients.

Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is decreased in schizophrenia. The validity of a glutamatergic, N-methyl-d-aspartate receptor (NMDAR)-mediated model of PPI disruption is presently equivocal. The NMDAR antagonist ketamine disrupts PPI in rodents, but may increase PPI in healthy volunteers. Glycine (GLY), which acts as an obligatory co-agonist at the NMDAR-GLY site, induces PPI deficits in rats although, consistent with the hypo-NMDAR hypothesis, improves negative and cognitive symptoms in schizophrenia patients. We assessed the hypothesis that GLY serum levels may affect PPI parameters in schizophrenia. Forty-five chronically ill medicated schizophrenia patients and 37 matched healthy comparison subjects were tested for PPI of the eyeblink component of the startle reflex measured by electromyogram recording. Patients' demographic variables, symptom severity scores and GLY, serine and glutamate serum levels were obtained. Patients showed deficient PPI in blocks two and three of the PPI session and differed from controls in terms of change of degree of PPI as a function of the prepulse to eliciting stimulus interval. GLY levels correlated negatively with PPI parameters, such that patients with the highest GLY levels showed decreased PPI (rs=-0.4, p=0.03). These preliminary findings indirectly support previous observations on ketamine effects upon PPI in humans and suggest a dissociation of symptomatology and PPI changes as function of NMDAR modulation in schizophrenia.

Think Yourself Thin: Concern for Appropriateness Mediates the Link Between Hypnotizability and Disordered Eating.

There has been no research examining why people with disordered eating tend to be highly hypnotizable. The authors examine the hypothesis that concern for appropriateness mediates the association between hypnotizability and disordered eating. Fifty participants aged 15 to 30 completed the Eating Attitudes Test-26 (EAT-26) and the Concern for Appropriateness Scale (CAS) and were administered the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C). EAT-26 scores predicted CAS scores (ß = 0.24, p < .001), CAS scores predicted SHSS:C scores (ß = 0.38, p < .001), and the mediation model was significant (Sobel Test; R(2) = .24, z = 2.54, p < .01). Individuals with problematic eating attitudes may tend to be more hypnotizable than those with normal eating attitudes at least in part because they are highly influenced by interpersonal messages.

Medical Clowning and Psychosis: A Case Report and Theoretical Review.

The medical clown has become an accepted therapeutic figure in non-psychiatric hospital departments in recent years. However, the potential role of the clown in psychiatry, especially for the treatment of psychosis, has not been investigated. We report here on the functioning of a medical clown in an inpatient psychiatric department. A program using psychodramatic group therapy techniques with the clown serving as moderator was developed. We describe the case of one individual diagnosed with schizophrenia who in the course of four and a half months of group therapy led by the medical clown was able to adopt a succession of surprising roles. This process may have contributed to the patient's remission. We discuss the special capacity of medical clowns to encourage communication and indulge in fantasy while returning to consensual reality. We suggest that this may have particular relevance in work with psychotic individuals.

Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: initial findings.

The efficacy of compounds having agonistic activity at the glycine site associated with the N-methyl-D-aspartate receptor (NMDAR) is presently assessed in psychiatric disorders. In contrast to NMDAR antagonists, the neuropsychiatric effects of NMDAR agonists in the healthy human organism are not known. We studied neuropsychiatric and neurochemical effects of the NMDAR-glycine site obligatory co-agonist d-serine (DSR) in healthy subjects using a randomized, controlled crossover challenge design including a baseline assessment day and two DSR/placebo administration days. Thirty-five subjects aged 23-29 years participated in the study and received a 2.1 g orally administered DSR dose. The main outcome measures were the changes in scores of mood-related Visual Analogue Scale (VAS), Continuous Performance Test-Identical Pairs (CPT-IP), and Rey Auditory Verbal Learning Test (RAVLT). DSR acute administration: (1) was well tolerated and resulted at 2 h in ≥ 200 times increase in DSR serum levels; (2) elicited reduced VAS-measured depression and anxiety feelings; (3) improved attention and vigilance as measured by CPT-IP D-prime score; (4) preferentially improved performance in RAVLT list 7 reflecting ability to retain information over interference; (5) had significant but nonspecific effects on Category Fluency and Benton Visual Retention tests; and (6) did not affect glycine and glutamate serum levels. These data indicate that in healthy subjects, DSR reduces subjective feelings of sadness and anxiety and has procognitive effects that are overall opposed to the known effects of NMDAR antagonists. The findings are relevant to translational research of NMDAR function and the development of NMDAR-glycine site treatments for specific psychiatric entities. ClinicalTrials.gov: Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans; http://www.clinicaltrials.gov/ct2/show/NCT02051426?term=NCT02051426&rank=1; NCT02051426.

Hypnotizability is associated with a protective but not acquisitive self-presentation style.

Self-presentation refers to the behavioral strategies a person adopts to convey desired social images of oneself to other people. The Concern for Appropriateness Scale (CAS) measures a defensive and fearful social approach aimed at avoiding social threats whereas the Revised Self-Monitoring Scale (RSMS) measures an active and flexible social approach aimed at gaining power and status. In this study, a significant correlation was found between hypnotizability, as measured by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) scores and CAS (r = .43, p = .002) but not between hypnotizability and RSMS (r = .070, p = .631). These results suggest that a protective self-presentation style may incline certain individuals to cooperate with hypnotic suggestions.

Preventive pharmacological treatment --an evolving new concept in schizophrenia.

Treatment for schizophrenia remains one of the major challenges of modern medicine. The development of innovative pharmacological approaches for this disorder can potentially alleviate tremendous human suffering and revolutionize mental health delivery systems. While current treatment guidelines for schizophrenia refer to the post-psychosis onset phase of illness, presently there is a strong resurgent interest in secondary prevention intervention applied during schizophrenia prodrome. This development stems largely from the recognition that neurobiological deficit processes associated with schizophrenia severity and chronicity are already active by the time clinical onset is recognized. Proposed preventive treatments include presently used medications and experimental compounds that hypothetically may influence ongoing pathophysiological processes earlier in their development. The future establishment of the early recognition and intervention concept in schizophrenia is critically dependent on the outcome of ongoing research assessing the feasibility of prodrome diagnosis, the efficacy of specific medications and the alleviation of the risks associated with early pharmacological treatment.

Defensive self-presentation style is associated with reduced prepulse inhibition.

Prepulse inhibition (PPI) of the startle response is a cross-species measure of sensorimotor gating that provides a valuable tool for assessing the capacity to effectively screen out irrelevant sensory input. Accumulating evidence suggests that PPI deficits may correlate with impairments in social cognition, i.e. the ability to construct representation about others, oneself and the relations between others and oneself. Social cognition deficits are commonly encountered within the framework of psychiatric disorders. In this study 113 healthy volunteers completed psychopyhsiological measures of sensorimotor gating (PPI) and social self-presentation style (the Concern for Appropriate (CAS) and the Revised Self-Monitoring (RSMS) scales). CAS measures a defensive and fearful social approach aiming at avoiding social threats; RSMS measures an active and flexible social approach aiming at gaining power and status. Analyses revealed an inverse correlation between PPI at the 120 ms prepulse-to-pulse interval and total CAS scores (r=-0.19, p=0.04), as well as with the Attention to Social Comparison Information (ASCI) subscale of the CAS (r=-0.23, p=0.01). These findings suggest that reduced PPI may contribute to the tendency to adopt a defensive and fearful "getting along" social approach. This study is, to our knowledge, the first to assess the relationship between sensorimotor gating and self-presentational style in humans. Its findings suggest that very basic perceptual deficits that can be assessed using the PPI paradigm, may reflect information processing abnormalities that impact negatively upon the perception of complex social interactions.

Hypnotizability and sensorimotor gating: a dopaminergic mechanism of hypnosis.

Dopaminergic mechanisms have been theorized to influence hypnotizability and sensorimotor gating. In this study, the authors investigated an association between sensorimotor gating, as measured by prepulse inhibition (PPI), and hypnotizability, as assessed by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). They found an inverse correlation between the SSHS:C and PPI. This finding, which replicates an earlier study, provides further evidence for a dopaminergic basis for hypnotizability and suggests additional avenues for research, including a method for possibly enhancing hypnotizability through pharmacological interventions.

Association between arginine vasopressin 1a receptor (AVPR1a) promoter region polymorphisms and prepulse inhibition.

Arginine vasopressin and the arginine vasopressin 1a (AVPR1a) gene contribute to a range of social behaviors both in lower vertebrates and in humans. Human promoter-region microsatellite repeat regions (RS1 and RS3) in the AVPR1a gene region have been associated with autism spectrum disorders, prosocial behavior and social cognition. Prepulse inhibition (PPI) of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. Reduced PPI has been observed in disorders including schizophrenia that are distinguished by deficits in social skills. In the current investigation association was examined between PPI and the AVPR1a RS1 and RS repeat regions and PPI in a group of 113 nonclinical subjects. Using a robust family-based strategy, association was observed between AVPR1a promoter-region repeat length, especially RS3) and PPI (30 ms: global p=0.04; 60 ms p=0.006; 120 ms p=0.008). Notably, longer RS3 alleles were associated with greater levels of prepulse inhibition. Using a short/long classification scheme for the repeat regions, significant association was also observed between all three PPI intervals (30, 60 and 120 ms) and both RS1 and RS3 polymorphisms (PBAT: FBAT-PC(2) statistic p=0.047). Tests of within-subject effects (SPSS GLM) showed significant sexxRS3 interactions at 30 ms (p=0.045) and 60 ms (p=0.01). Longer alleles, especially in male subjects, are associated with significantly higher PPI response, consistent with a role for the promoter repeat region in partially molding social behavior in both animals and humans. This is the first report in humans demonstrating a role of the AVPR1a gene in contributing to the PPI response to auditory stimuli.

Hypnotizability and blink rate: a test of the dopamine hypothesis.

Evidence suggests a role for central dopaminergic activity in determining an individual's level of hypnotizability. The authors measured the correlation between blink rate, which has been shown to correlate with central dopaminergic activity, and hypnotizability. Forty-eight healthy participants were evaluated for hypnotizability by the Harvard Group Scales of Hypnotic Susceptibility and the Stanford Hypnotic Susceptibility Scale: Form C. Blink rate was assessed under conditions of conversation, staring at a cross, listening to music, and resting. Contrary to their hypothesis, the authors found a negative correlation between hypnotizability and blink rate, accounted for primarily by the higher blink rates at rest in medium as compared to high hypnotizables. The results do not provide evidence for a role of dopamine in determining hypnotizability.

Reduced prepulse inhibition is associated with increased hypnotizability.

Hypnosis involves the manipulation of conscious attentional discrimination. The prepulse inhibition (PPI) paradigm assesses primary unconscious information processing. We investigated the correlation between hypnotizability and PPI of the startle reflex. Forty-eight healthy subjects were evaluated with the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) and acoustic PPI. Subjects were divided into low, medium, and high hypnotizable groups. The low-hypnotizable group showed a significantly higher inhibition of the startle response, at lead intervals 60 ms and 120 ms, than did the medium- and high-hypnotizable groups. We conclude that hypnotizability and PPI may be negatively correlated. These findings lend further support for the role of dopaminergic neurotransmission mechanisms in the determination of hypnotizability levels.