Letheby’s "Philosophy of Psychedelics" relies on Predictive Processing to try and find unifying explanations relevant to understanding how serotonergic psychedelics work in psychiatric therapy, what subjective experiences are associated with their use and whether such experiences are epistemically defective. But if Predictive Processing lacks genuinely explanatory unifying power, Letheby’s account of psychedelic therapy risks being unwarranted. In this commentary, I motivate this worry and sketch an alternative interpretation of psychedelic therapy within the Reinforcement Learning framework.

The possible role of the neurotransmitter serotonin in human affiliative behavior is under-examined in the review by Depue & Morrone-Strupinsky (D&M-S). This commentary reviews evidence indicating that serotonin not only inhibits aggressive behavior that may be detrimental to affiliative bonds with others in a social group but serotonin also enhances prosocial behaviors that may facilitate ties to the social group.

Whether or not trait affiliation correlates with human behaviour needs investigating. One should be careful generalizing neuropsychological mechanisms for affiliation, and generalizing an analysis based on one or two neuropsychological mechanisms and mostly studies on rodents, to complex human social interactions. Serotonin is an example of a neurotransmitter playing an important role in cooperation and interacting with the dopaminergic system.

Jonathan A. Oler,1,4 Andrew S. Fox,2,5 Steven E. Shelton,1,4 Bradley T. Christian, 1,3,5 Dhanabalan Murali,3,5 Terrence R. Oakes,5 Richard J. Davidson,1,2,4,5 and Ned H. Kalin1,2,4,5..

Stigmata, wounds resembling those of Christ, have been reported since the 13th century. The wounds typically appear in association with visions following prolonged fasting. This paper argues that self-starvation holds the key to understanding this unique event. Stigmata may result from self-mutilation occurring during dissociation, phenomena precipitated in part by dietary constriction. Psychophysiological mechanisms produced by natural selection adjust the salience of risk in light of current resource abundance. As a result, artificial dietary constriction results in indifference to harm. A (...) variety of data links dramatic dietary constriction, reduced serotonergic functioning, altered states of consciousness, and self-injurious behavior. Catholic representations of Christ's crucifixion provide a cultural context that both motivates and lends meaning to the experiences of individuals whose predispositions and life histories increase the likelihood of dietary constriction, dissociation, and self-mutilation. Examining this case raises interesting questions about both the evolutionary and the cultural grounds for defining individual psychopathology. (shrink)

Interpreting VTA dopamine activity as a facilitator of affective engagement fits Depue & Collins's agency dimension of extraverted personality and also Watson's and Tellegen's (1985) engagement dimension of state mood. Serotonin, by turning down the gain on dopaminergic affective engagement, would permit already prepotent responses or habits to prevail against the behavior-switching incentive-simulation-driven temptations of the moment facilitated by fickle VTA DA. Intelligent switching between openly responsive affective engagement and constraint by long-term plans, goals, or values presumably involves environment-sensitive (...) balancing of these neuromodulators, such as socially dominant primates may show. (shrink)

Animal research suggests that central serotonergic neurons are involved in behavioral suppression, particularly anxiety-related inhibition. The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts, and increased anxiety. The target article attempts to (...) reconcile such human and animal findings by investigating whether anxiety reduction or increased impulsivity is more Likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin in experimental anxiety paradigms in animals (punishment, extinction, novelty) are reviewed and compared with the effects of antianxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior toward facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are involved not only in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors that are usually suppressed, though not necessarily because of the alleviation of anxiety, which might contribute to the suppression. (shrink)

We describe a neural monitor of environmental and physiological resources that informs effort expenditure. Depending on resources and environmental stability, serotonergic and dopaminergic neuromodulations favor different behavioral controls that are organized in corticostriatal loops. This broader perspective produces some suggestions and questions that may not be covered by the foraging approach to vigor of Shadmehr and Ahmed (2020).

The serotonin transporter plays an important role in regulating serotonergic transmission via removal of serotonin from synaptic clefts. Alterations in 5-HTT expression and subsequent 5-HT transmission have been found to be associated with changes in behaviour, such as fearfulness or activity, in humans and other vertebrates. In humans, alterations in 5-HTT expression have been suggested to be able to lead to better learning performance, with more fearful persons being better at learning. Similar effects of the variation in the (...) 5-HTT on fearfulness have been found in chickens, and in this study, we investigated effects on learning. Therefore, we tested 52 adult laying hens, differing in their functional 5-HTT genotype in an operant learning paradigm in three different phases and in a tonic immobility test for fearfulness. We found that the 5-HTT polymorphism affects the initial learning performance of laying hens, with homogeneous wild-type hens being the slowest learners, and the most fearful birds. W/W hens, showed significantly more choices to solve the initial learning task and had the highest latencies in a tonic immobility test, indicating the highest fearfulness. Our results provide interesting first insights into the role of 5-HTT in chickens and its sensitive interaction with the environment. We further suggest that the 5-HTT gene can be an interesting target gene for future breeding strategies as well as for further experimental studies. (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR (...) gene. RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

The goal of the paper is to offer a model of self-awareness that fits the testimony of both good and bad responders to selective serotonin reuptake inhibitors (SSRIs), of which fluoxetine (Prozac; Lilly, Indianapolis, IN) is probably the most well known. After a review of troubling current uncertainties concerning how and for whom SSRIs are therapeutic, it is argued that SSRIs, as a rule, lessen the emotionality of SSRI subjects in favor of an increased cognitive and volitional orientation. Traditional (...) empiricist and rationalist accounts self-awareness fail to provide models that adequately explain how such a shift from an active emotional response to an increased cognitive/volitional orientation is possible. Instead, notions of self-awareness, as understood by founding phenomenologist, Edmund Husserl, fit the testimony of SSRI subjects. (shrink)

The sudden infant death syndrome (SIDS) is the sudden, unexpected death of an infant that is not explained by autopsy, death scene examination, and history. The etiology is unknown. Recent postmortem studies have discovered abnormalities in brainstem serotonergic neurons, but how these translate into dysfunction and cause SIDS is uncertain. Recently, lethal effects in transgenic mice with overexpression of the serotonin 1A autoreceptor have been described. Many die spontaneously between postnatal day 40 (P40) and P80, and some spontaneously exhibit (...) bradycardias and drops in body temperature. The severity of the autonomic dysfunction and its age dependence suggest relevance to SIDS. However, SIDS cases have decreased serotonin 1A autoreceptor binding, which is opposite to its overexpression in the mice, and the peak incidence of SIDS is between 2 and 6 months of age, which is arguably younger (in relative terms) than the ages at which the mice die. Nevertheless, the description of an animal model with serotonin defects that has autonomic dysfunction and spontaneous mortality at a young age is an exciting finding of possible importance for understanding SIDS. (shrink)

Correcting the relationship between tonic and burst firing modes in dopamine neurons may help normalise stimulus-reinforcement gradients and contingent behaviour in attention-deficit/hyperactivity disorder (ADHD) children. But appropriate evaluations of stimuli for developing adaptive plans and controlling impulsivity will not occur without moderating the gain-like functions of serotonin. The “dynamic theory” correctly highlights the need to account for variability in ADHD. The dysmaturation of pre-executive information processing is proposed as an explanation. At the core of the article by Sagvolden and (...) colleagues there is a set of data that throws light on an aspect of the ADHD phenomenon. But one asks if the authors are a measure too brave to generalise so broadly from the unusually steep reinforcement gradients reported for the human condition and an animal model to the syndrome as a whole. (shrink)

OBJECTIVES: Early-emerging, temperamental differences in fear-related traits may be a heritable vulnerability factor for anxiety disorders. Previous research indicates that the serotonin transporter promoter region polymorphism is a candidate gene for such traits. METHODS: Associations between 5-HTTLPR genotype and indices of fearful child temperament, derived from maternal report and standardized laboratory observations, were examined in a community sample of 95 preschool-aged children. RESULTS: Children with one or more long alleles of the 5-HTTLPR gene were rated as significantly more nervous (...) during standardized laboratory tasks than children who were homozygous for the short alleles. Children homozygous for the short alleles were also rated as significantly shyer, by maternal report, than those with at least one copy of the long allele of the 5-HTTLPR gene. CONCLUSIONS: This study extends the literature linking the short alleles of the serotonin transporter promoter region polymorphism to fear and anxiety-related traits in early childhood and adulthood, and is one of very few studies to examine the molecular genetics of preschoolers' temperament using multiple measures of traits in a normative sample. (shrink)

Revisiting the history of postwar LSD research illuminates how the work of a chemist at the Rockefeller Institute contributed to the development of a biochemical paradigm for mental functioning. Dilworth Wayne Woolley proposed one of the first theories of the biochemistry of mental illness based on empirical evidence. His research with LSD and serotonin had wide-ranging repercussions for pharmacology and fit neatly into the emerging medicalization of mental illness. Reevaluating Woolley’s ideas and the fruits of psychopharmacology leads to possible (...) new approaches toward mental health and illness when considered alongside lessons learned from past research with psychedelic substances, and exemplifies a broader paradigm shift in cultural studies toward a biopsychosocial model that acknowledges the intersections between biology and culture. (shrink)

Aversive experiences have been thought to provoke or exacerbate clinical depression. The present review provides a brief survey of the stress-depression literature and suggests that the effects of stressful experiences on affective state may be related to depletion of several neurotransmitters, including norepinephrine, dopamine, and serotonin. A major element in determining the neurochemical changes is the organism's ability to cope with the aversive stimuli through behavioral means. Aversive experiences give rise to behavioral attempts to cope with the stressor, coupled (...) with increased utilization and synthesis of brain amines to contend with environmental demands. When behavioral coping is possible, neurochemical systems are not overly taxed, and behavioral pathology will not ensue. However, when there can be no behavioral control over the stressful stimuli, or when the aversive experience is perceived as uncontrollable, increased emphasis is placed on coping through endogenous neurochemical mechanisms. Amine utilization increases appreciably and may exceed synthesis, resulting in a net reduction of amine stores, which in turn promotes or exacerbates affective disorder. The processes governing the depletions may be subject to sensitization or conditioning, such that exposure to traumatic experiences may have long-term repercussions when the organism subsequently encounters related stressful stimuli. With continued uncontrollable stimulation, adaptation occurs in the form of increased activity of synthetic enzymes, and levels of amines approach basal values. It is suggested that either the initial amine depletion provoked by aversive experiences or a dysfunction of the adaptive processes, resulting in persistent amine depletion, contributes to behavioral depression. Aside from the contribution of behavioral coping, several organismic, experiential, and environmental variables will influence the effects of aversive experiences on neurochemical activity, and may thus influence vulnerability to depression. (shrink)

This article addresses the serotonin hypothesis of depression, as it was formulated in clinical and laboratory experiments during the 1950s. In the first instance I argue that the `challenge' posed by patients' subjectivities in clinical investigations into the potentially anti-depressant drug iproniazid was not solely due to the tensions generated by the subject/object dichotomy, but to an excess that exceeds the properties of the objects of the experiment, as well as its requirements and conditions. I then suggest that the (...) serotonin hypothesis too is possessed of an excess, and that this can be understood in terms of a real (actual and virtual) existence in duration. By exploiting the notions of the event and of duration, I offer an under-standing of the hypothesis that pertains not to reduction, reproducibility and sameness, but to differentiation, innovation and creation. (shrink)

Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly (...) higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin‐targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top‐down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression. (shrink)

This chapter sets the scene for the subsequent philosophical discussions by surveying a number of biological interventions that have been used, or might in the future be used, for the purposes of crime prevention. These interventions are pharmaceutical interventions intended to suppress libido, treat substance abuse or attention deficit-hyperactivity disorder (ADHD), or modulate serotonin activity; nutritional interventions; and electrical and magnetic brain stimulation. Where applicable, we briefly comment on the historical use of these interventions, and in each case we (...) discuss the evidence that they are effective, or might become so with further refinement. The chapter concludes with a comment on some potentially significant differences between the varieties of intervention that we canvass. (shrink)

Since the introduction of Prozac (fluoxetine), a number of so‐called selective serotonin reuptake inhibitors (SSRIs) have been developed and introduced. These mood enhancers are being presently prescribed for people whose problems are not recognized mental illnesses. It is probable that in the near future the combination of data from advanced biochips and brain imaging will accelerate the development of neurotechnology. So‐called neuroceuticals, used for therapy and enhancement, and to improve different aspects of mental health, will be efficient neuromodulators. The (...) scientific, ethical, and social issues raised by mood enhancement and alteration of personal resilience require further exploration. The chapter talks about the notion of personal autonomy, cosmetic psychopharmacology, power for autonomous, and moral accountability in this context. It suggests that empirical research should also cover psychological and sociological research into perceptions and experiences of individuals who have used these drugs. (shrink)