A Place to Heal: Environmental Sources of Satisfaction Among Hospital Patients1

Telephone interviews with 380 discharged inpatients were conducted to identify environmental sources of satisfaction with the hospital, to determine the relative contribution of environmental satisfaction to overall satisfaction with the hospital experience, and to explore differences in satisfaction across 4 departments (medical, obstetrics, orthopedics, and surgical) and 6 hospitals. Analyses indicate that interior design, architecture, housekeeping, privacy, and the ambient environment were all perceived as sources of satisfaction. Environmental satisfaction was a significant predictor of overall satisfaction, ranking below perceived quality of nursing and clinical care. There were no significant differences between hospitals or departments in the level or sources of environmental satisfaction. Results suggest potential directions for architects, designers, and health care providers.     

Genetic inactivation of D-amino acid oxidase enhances extinction and reversal learning in mice

Activation of the N-methyl-d-aspartate receptor (NMDAR) glycine site has been shown to accelerate adaptive forms of learning that may benefit psychopathologies involving cognitive and perseverative disturbances. In this study, the effects of increasing the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO), were examined in behavioral tests of learning and memory. In the Morris water maze task (MWM), mice carrying the hypofunctional Dao1^G181R mutation demonstrated normal acquisition of a single platform location but had substantially improved memory for a new target location in the subsequent reversal phase. Furthermore, Dao1^G181R mutant animals exhibited an increased rate of extinction in the MWM that was similarly observed following pharmacological administration of D-serine (600 mg/kg) in wild-type C57BL/6J mice. In contextual and cued fear conditioning, no alterations were found in initial associative memory recall; however, extinction of the contextual fear memory was facilitated in mutant animals. Thus, an augmented level of D-serine resulting from reduced DAO activity promotes adaptive learning in response to changing conditions. The NMDAR glycine site and DAO may be promising therapeutic targets to improve cognitive flexibility and inhibitory learning in psychiatric disorders such as schizophrenia and anxiety syndromes.The N-methyl-d-aspartate receptor (NMDAR) has an important role in excitatory neurotransmission and contributes to numerous brain processes, including synaptic plasticity, learning, and memory formation (Nicoll 2003). Activation of NMDARs requires membrane depolarization in addition to concurrent binding of glutamate to NMDAR2 (NR2) and glycine to the NMDAR1 (NR1) subunit (Johnson and Ascher 1987; Clements and Westbrook 1991). D-serine has also been shown to be an endogenous co-agonist for the NR1 glycine site, acting with high selectivity and a potency similar to or greater than that of glycine (Matsui et al. 1995). In the brain, the localization of D-serine closely resembles that of NMDARs (Schell et al. 1997), and D-serine has been reported to be the predominant physiologic co-agonist for the maintenance of NMDAR-mediated currents in the hippocampus, retina, and hypothalamus (Mothet et al. 2000; Yang et al. 2003). Moreover, in vivo studies have demonstrated that the NMDAR glycine site is not saturated at the synapses of several brain regions (Fuchs et al. 2005). Consequently, increasing D-serine levels may modulate neurotransmission and behavioral responses reliant on NMDAR activity.The NMDAR glycine site has been implicated in the pathophysiology and treatment of a number of psychiatric conditions (Coyle and Tsai 2004; Millan 2005). Blockade of the NMDAR with noncompetitive antagonists like phencyclidine results in the production and exacerbation of schizophrenic-like symptoms in humans and animals (Javitt and Zukin 1991; Krystal et al. 1994). Genetic studies have associated genes that mediate D-serine synthesis and degradation with a vulnerability to schizophrenia, and levels of D-serine are decreased in the CSF and serum of schizophrenic patients (Chumakov et al. 2002; Hashimoto et al. 2003, 2005; Schumacher et al. 2004; Morita et al. 2007). These observations prompted clinical trials with direct and indirect activators of the NMDAR glycine site, including D-serine, and improvements were revealed when these compounds were added to conventional antipsychotic regimes, particularly with the negative and cognitive symptoms of schizophrenia (Tsai et al. 1998; Coyle and Tsai 2004; Heresco-Levy et al. 2005). Furthermore, altered NMDAR activation has also been shown to affect extinction, a learning process that may be of benefit in anxiety illnesses, such as post-traumatic stress syndrome and obsessive-compulsive disorder (Davis et al. 2006). In rodents, extinction was shown to be impaired following inhibition of NMDARs in contextual fear conditioning, inhibitory avoidance, and eyeblink conditioning tasks (Kehoe et al. 1996; Lee and Kim 1998; Szapiro et al. 2003). In contrast, the partial NMDAR agonist D-cycloserine facilitated the extinction of fear memories in rodents and individuals with phobias and other anxiety disorders (Ressler et al. 2004; Ledgerwood et al. 2005; Norberg et al. 2008). Thus, the NMDAR glycine site and its related modulatory proteins may be important targets for the amelioration of psychopathologies involving cognitive dysfunction and maladaptive behaviors.Endogenous levels of D-serine in the brain are regulated by its catabolic enzyme, D-amino acid oxidase (DAO); by the D-serine synthesis enzyme, serine racemase (Srr); and by neuronal and glial transporters (Foltyn et al. 2005; Martineau et al. 2006). Agents targeting such proteins may prove to be an effective method of increasing cerebral D-serine and occupancy of the NMDAR glycine site, which could overcome the difficulties D-serine and similar compounds have with penetrating the blood-brain barrier (Coyle and Tsai 2004; Bauer et al. 2005). Inhibiting DAO function in the brain is of particular interest as it would circumvent any nephrotoxicity associated with high levels of systemic D-serine (Maekawa et al. 2005a). DAO is a peroxisomal flavoprotein that at physiological pH is highly selective for D-serine, and in the brain, DAO is located predominantly in astrocytes (Mothet et al. 2000). An inverse correlation between the brain distribution of DAO and D-serine evinces the efficacy of this enzyme, with the most abundant DAO expression located in the D-serine-sparse hindbrain and cerebellum (Schell et al. 1995; Moreno et al. 1999). To study the effects of limiting DAO function, we tested a line of mice carrying a single point mutation (G181R) that results in a complete lack of DAO activity and consequently augmented D-serine in serum and brain (Sasaki et al. 1992; Hashimoto et al. 1993). These mice have previously been shown to exhibit an in vitro increase in NMDAR-mediated excitatory postsynaptic currents in dorsal horn neurons of the spinal cord and an in vivo elevation of cGMP that is indicative of augmented NMDAR activity (Wake et al. 2001; Almond et al. 2006). This demonstrates that reduced DAO function is capable of augmenting NMDAR activation, and it may follow that cognitive and extinction processes influenced by NMDARs are enhanced in Dao1^G181R mutant mice. To investigate this possibility, we assessed the effects of the Dao1^G181R mutation on learning, memory, and extinction in Morris water maze (MWM) and in contextual and cued fear conditioning paradigms.     

Repetition proportion affects masked priming in nonspeeded tasks

Masked repetition priming is often greater when a larger proportion of trials involve repetition primes, suggesting that a context-sensitive unconscious process may be operating. Two recent studies have failed to obtain an effect of prime proportion in the perceptual identification (PI) task, suggesting that the effect may not occur in nonspeeded tasks. Contrary to this possibility, we report proportion effects with masked repetition primes in two nonspeeded tasks: PI and fragment completion (FC). A proportion effect occurred in the accuracy measure only in the FC task, but it occurred in the reaction time measure in both tasks. Prior failures to find proportion effects in the PI task thus may have been due, in part, to the dependent measure used. We interpret our findings in light of several recent accounts of prime proportion effects with brief primes.     

The origins and function of the reference point in risky group decision making the case of the Cuban missile crisis

This case study explores reference level effects on group decision making during the Cuban missile crisis of 1962. The group is composed of American President John F. Kennedy and his advisers. The results are consistent with much experimental evidence showing that reference levels play an important role in determining preferences. The results also extend the notion of reference-dependent risky choice to the group level, where the group consists of seasoned experts who each have a different role to play within the group and who are dealing with an issue of great importance.     

Discussion of “The Ketamine Model of the Near-Death Experience: A Central Role for the N-Methyl-D-Aspartate Receptor,” by Earl L. R. Jansen

We review strengths and weaknesses of Karl Jansen's approach to the near-death experience (NDE). Strengths include his limited goals and avoidance of the trap of explaining all features of the NDE with his theory, although he surprisingly misunderstood our previously published position. Additionally, we applaud the possible intersection of psychological and biological theories, demonstrated in Jansen's biochemical explanations for the individualized variations in manifestation and adaptive role of the NDE. However, he failed to take into account the pitfalls in the use of analogy, modeling oversimplification, and in taking association as causality and causes as meaningful, in the arguments for his theory.     

Expressing Intrinsic Motivation Through Acts of Exploration and Facial Displays of Interest

Intrinsically-motivated behavior has been defined through participants' task persistence, during a free-choice interval. While fruitful, this operational definition assesses only the person's postperformance reaction to an activity. Presumably, people experience and express intrinsic motivation during task engagement as well. The need therefore exists for a supplemental in-performance behavioral measure of intrinsic motivation. To test the viability of constructing such a measure, we recorded the extent to which five acts of exploration and four facial displays of interest corresponded to self-reports of interest, self-determination, and competence for 60 undergraduates as they solved SOMA puzzles. Correlational and LISREL analyses confirmed the validity of three acts of exploration and two facial displays of interest We concluded that just as task persistence is a valid postperformance indicator of intrinsic motivation, acts of exploration and facial displays of interest are valid in-performance indicators.     

Testing latent longitudinal models of social ties and depression among the elderly: a comparison of distribution-free and maximum likelihood estimates with nonnormal data.

Using a latent-variable modeling approach, relationships between social ties and depression were studied in a sample of 201 older adults. Both positive and negative ties were related to concurrent depression, whereas only negative ties predicted future depression. Nonnormally distributed scores were observed for several variables, and results based on maximum likelihood (ML), which assumes multivariate normality, were compared with those obtained using Browne's (1982, 1984) arbitrary distribution function (ADF) estimator for nonnormal variables. Inappropriate use of ML with nonnormal data yielded model chi-square values that were too large and standard errors that were too small. ML also failed to detect the over-time effect of negative ties on depression. The results suggest that the negative functions of social networks may causally influence depression and illustrate the need to test distributional assumptions when estimating latent-variable models.