Clinical trials for rapid changes in suicidal ideation: Lessons from ketamine

Rapid‐acting treatments for suicidal thoughts are critically needed. Consequently, there is a burgeoning literature exploring psychotherapeutic, pharmacologic, or device‐based brief interventions for suicidal thoughts characterized by a rapid onset of action. Not only do these innovative treatments have potentially important clinical benefits to patient populations, they also highlight a number of methodological considerations for suicide research. First, while most clinical trials related to suicide risk focus on suicide attempts, new clinical trials that use suicidal thoughts as the primary outcome require a number of slight modifications to their clinical trial design. Second, the rapid onset of these new interventions permits an experimental therapeutics approach to suicide research, in which psychological and neurobiological markers are embedded into clinical trials to better understand the underlying pathophysiology of suicidal thoughts. The following review discusses these methodological innovations in light of recent research using the N‐methyl‐D‐aspartate (NMDA) receptor antagonist ketamine, which has been associated with rapid effects on suicidal thoughts. We hope that “lessons learned” from the ketamine literature will provide a blueprint for all researchers evaluating rapid‐acting treatments for suicidal thoughts, whether pharmacologic or psychotherapeutic.     

Maintained nodal-distance effects in equivalence classes

Twelve subjects were trained to select one of two stimuli from a pair (the B pair) when presented with one of two stimuli from another pair (the A pair), thus establishing two AB relations, A1-B1 and A2-B2. In a similar fashion, additional stimuli were used to establish BC, CD, and DE relations. Trials used to train all relations occurred in each session. Once performances were established, probe trials were introduced that tested for the emergence of untrained relations (e.g., B1-D1 or A1-E1). These emergent relations were categorized according to nodal distance (i.e., the number of stimuli across which transitivity would have to hold in order for the relation to emerge). For example, a test for A2-C2 crosses one node (B2), whereas a test for A1-E1 crosses three nodes (B1, C1, and D1). Only 2 of the subjects formed equivalence classes. The evocation of class-appropriate responding by each emergent-relation probe was an inverse function of nodal distance for all 12 subjects. In addition, performance on the originally trained relations was disrupted by the introduction of probes. The 2 subjects who exhibited equivalence classes were then trained to make different numbers of key presses in the presence of each of the four A and E stimuli. In a response-transfer test, the B, C, and D stimuli evoked the responses trained to the A and E stimuli in the same equivalence class. Likelihood of class-appropriate responses was an inverse function of nodal distance, and this pattern persisted across testing. Reaction times in the transfer test were an inverted U-shaped function of nodal distance. Because training of the baseline relations occurred concurrently and the B, C, and D stimuli were presented an equal number of times before the transfer test, the test performances illustrate effects of nodal distance that were not confounded by order or amount of experience with the stimuli. The results imply that ordered, sequential exposure to individual stimulus relations may facilitate the development of equivalence classes and that the relatedness of stimuli within an equivalence class is a relatively permanent inverse function of nodal distance.     

Reinforcement of probe responses and acquisition of stimulus control in fading procedures

Stimulus control of pigeons' key pecking was transferred from colors to lines by the method of stimulus fading. Fading was conducted with the addition of probes consisting of the line stimuli presented alone at each fading level. Probe responding was used to measure stimulus-control acquisition by the lines. Effects of reinforcement and nonreinforcement of probe responding upon acquisition of stimulus control were assessed using a single-organism repeated-acquisition design in which three fades were conducted serially. Probe responding was not reinforced in the first and third fade but was in the second. Reinforcement of probe responding substantially reduced the number of fading levels needed to complete fading. The outcome of a control experiment ruled out the possibility of accounting for these results in terms of the specific stimuli used in each fade or in terms of the sequential exposure to the three discriminations. Although probes permitted measurement of stimulus-control acquisition in fading, a measurement/acquisition interaction was also present.     

The very same thing: Extending the object token concept to incorporate causal constraints on individual identity

The contributions of feature recognition, object categorization, and recollection of episodic memories to the re-identification of a perceived object as the very same thing encountered in a previous perceptual episode are well understood in terms of both cognitive-behavioral phenomenology and neurofunctional implementation. Human beings do not, however, rely solely on features and context to re-identify individuals; in the presence of featural change and similarly-featured distractors, people routinely employ causal constraints to establish object identities. Based on available cognitive and neurofunctional data, the standard object-token based model of individual re-identification is extended to incorporate the construction of unobserved and hence fictive causal histories (FCHs) of observed objects by the pre-motor action planning system. It is suggested that functional deficits in the construction of FCHs are associated with clinical outcomes in both autism spectrum disorders and later-stage stage Alzheimer's disease.     

On the Ollivier–Poulin–Zurek Definition of Objectivity

The Ollivier–Poulin–Zurek definition of objectivity provides a philosophical basis for the environment as witness formulation of decoherence theory and hence for quantum Darwinism. It is shown that no account of the reference of the key terms in this definition can be given that does not render the definition inapplicable within quantum theory. It is argued that this is not the fault of the language used, but of the assumption that the laws of physics are independent of Hilbert-space decomposition. All evidence suggests that this latter assumption is true. If it is, decoherence cannot explain the emergence of classicality.     

Borrowing Personal Memories

The present investigation documents memory borrowing in college‐age students, defined as the telling of others' autobiographical stories as if they are one's own. In both pilot and online surveys, most undergraduates admit to borrowing personal stories from others or using details from others' experiences to embellish their own retellings. These behaviors appear primarily motivated by a desire to permanently incorporate others' experiences into one's own autobiographical record (appropriation), but other reasons include to temporarily create a more coherent or engaging conversational exchange (social connection), simplify conveying somebody else's interesting experience (convenience), or make oneself look good (status enhancement). A substantial percentage of respondents expressed uncertainty as to whether an autobiographical experience actually belonged to them or to someone else, and most respondents have confronted somebody over ownership of a particular story. Documenting memory borrowing is important as the behavior has potential consequences for the creation of false memories. Copyright © 2015 John Wiley & Sons, Ltd.     

Visual Perceptual Thresholds of Albino Rats Obtained on the SMVDA with Striae,Single Lines,and Paired Bars

Piaget's concept of socialized speech was re-evaluated with the use of everyday preschool speech collected during free play on 174 boys and girls age 2–0 to 5–11. With one important exception, the results supported Piaget's concept of an age increment in socialized speech relative to egocentric speech. Egocentric speech (Repetition, Monologue, Collective Monologue) showed no increase with age; socialized speech (Adapted Information, Criticism and Derision, Questions and Answers) showed significant age increments. The one exception was the socialized category Commands, Requests, Threats, which like the egocentric categories, appeared early at high levels and did not increase with age. This latter finding pointed up an internal inconsistency in Piaget's formulation and suggested a possible resolution of the socialized speech controversy.     

Interactions among emergent relations during equivalence class formation

The interactions among symmetry, transitivity, and equivalence tests during the formation of 3-member equivalence classes were studied with 14 college students. After training AB and BC, a test with BA, CB, AC, and CA was conducted concurrently. Failure led to serial testing with probes for CA equivalence, BA symmetry, CA equivalence, CB symmetry, CA equivalence, AC transitivity, and CA equivalence. For five subjects, equivalence tests were passed immediately once BA and CB symmetry as well as AC transitivity had been induced. Thus, symmetry and transitivity were precursors for successful performance on equivalence tests. The conjoint function of symmetry and transitivity was assessed with the equivalence probes. As the equivalence probes were passed immediately, the presence of symmetry alone and transitivity alone were sufficient for their conjoint function without additional intervention. For different subjects, transitivity alone and symmetry were induced either directly with BA, CB, or AC probes or indirectly with equivalence probes. Equivalence probes can also induce various combinations of symmetry and transitivity. Thus, different subjects formed classes in various patterns at different rates.