Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates

Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here, we assessed psychological traits in 50 healthy controls as to their capacity to predict placebo analgesic effects, placebo-induced activation of μ-opioid neurotransmission and changes in cortisol plasma levels during a sustained experimental pain challenge (hypertonic saline infused in the masseter muscle) with and without placebo administration. Statistical analyses showed that an aggregate of scores from Ego-Resiliency, NEO Altruism, NEO Straightforwardness (positive predictors) and NEO Angry Hostility (negative predictor) scales accounted for 25% of the variance in placebo analgesic responses. Molecular imaging showed that subjects scoring above the median in a composite of those trait measures also presented greater placebo-induced activation of μ-opioid neurotransmission in the subgenual and dorsal anterior cingulate cortex (ACC), orbitofrontal cortex, insula, nucleus accumbens, amygdala and periaqueductal gray (PAG). Endogenous opioid release in the dorsal ACC and PAG was positively correlated with placebo-induced reductions in pain ratings. Significant reductions in cortisol levels were observed during placebo administration and were positively correlated with decreases in pain ratings, μ-opioid system activation in the dorsal ACC and PAG, and as a trend, negatively with NEO Angry Hostility scores. Our results show that personality traits explain a substantial proportion of the variance in placebo analgesic responses and are further associated with activations in endogenous opioid neurotransmission, and as a trend cortisol plasma levels. This initial data, if replicated in larger sample, suggest that simple trait measures easily deployable in the field could be utilized to reduce variability in clinical trials, but may also point to measures of individual resiliency in the face of aversive stimuli such as persistent pain and potentially other stressors

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Psychiatric comorbidities in autism spectrum disorder:A comparative study between DSM-IV-TR and DSM-5 diagnosis

AbstractBackground/Objective: The heterogeneous clinical presentations of individuals with Autism Spectrum Disorders (ASD) pose a significant challenge for sample characterization. Therefore the main goal of DSM-5 must be to identify subgroups of ASD, including comorbidity disorders and severity. The main goal of this study is to explore the psychiatric comorbidities and the severity of symptoms that could be relevant for the phenotype characterization in ASD and also to compare these results according to the different classification criteria between the DSM-IV-TR and the DSM-5. Method: A comparative study of severity and psychiatric comorbidities was carried out between a sample of participants that only met criteria for Pervasive Developmental Disorder (PDD) according to the DSM-IV-TR and a sample of participants that also met ASD criteria according to DSM-5 classification. The recruitment of children was via educational (N=123). The psychiatric symptoms, comorbid disorders and severity of symptoms were assessed through The Nisonger Child Behavior Rating Form, clinical interview and The Inventory of Autism Spectrum Disorder, respectively. The psychiatric comorbidities considered were: anxiety, eating behavioural problems, self-aggressiveness, hetero–aggressiveness, self-harm, obsessive compulsive disorder and attention deficit and hyperactivity disorder. Results: Statistically significant differences between both groups were found regarding obsessive compulsive disorder, eating behavioural problems and severity. Conclusions: The results support the hypothesis that patients who meet the DSM-5 criteria have more severe symptoms, not only regarding the core autistic symptoms but also in relation with psychiatric comorbidities

μ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement

Background: Like placebo analgesia, the antidepressant placebo effect appears to involve cortical and subcortical endogenous opioid signaling, yet the mechanism through which opioid release affects mood remains unclear. The orbitofrontal cortex (OFC)—which integrates various attributes of a stimulus to predict associated outcomes—has been implicated in placebo effects and is rich in μ opioid receptors. We hypothesized that naltrexone blockade of μ opioid receptors would blunt OFC-dependent antidepressant placebo effects. Methods: Twenty psychotropic-free patients with major depressive disorder completed a randomized, double-blind, placebo-controlled crossover study of 1 oral dose of 50 mg of naltrexone or matching placebo immediately before completing 2 sessions of the antidepressant placebo functional magnetic resonance imaging task. This task manipulates placebo-associated expectancies and their reinforcement while assessing expected and actual mood improvement. Results: Behaviorally, manipulations of antidepressant placebo expectancies and their reinforcement had positive, interactive effects on participants’ expectancy and mood ratings. The high-expectancy condition recruited the dorsolateral and ventrolateral prefrontal cortex, as well as dorsal attention stream regions. Interestingly, increased dorsolateral and ventrolateral prefrontal cortex brain responses appeared to attenuate the antidepressant placebo effect. The administration of 1 oral dose of naltrexone, compared with placebo, partially abolished the interaction of the expectancy and reinforcement manipulation on mood and blocked reinforcement-induced responses in the right central OFC. Conclusions: Our results show preliminary evidence for the role of μ opioid central OFC modulation in antidepressant placebo effects by positively biasing the value of placebo based on reinforcement and enhancing subsequent hedonic experiences.12 month embargo; available online 06 March 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Examining psychosocial correlates of loneliness and perceived isolation among marginalized youth

Adolescents and emerging adults from marginalized groups (e.g., racial/ethnic, sexual, and gender minorities; rural-living) have disproportionately higher risk of mental health problems (e.g., depression, anxiety, suicidal thoughts and behaviors) and substance use than their peers from non-marginalized groups. Loneliness and perceived isolation are well-known predictors of mental health problems, and their prevalence among youth and emerging adults has significantly increased in the last decade. However, there is limited research to identify modifiable psychosocial, familial, interpersonal (in person and on social media), and structural factors that could reduce loneliness and perceived isolation in this population. We will partner with community-based organizations that serve marginalized youth and emerging adults with lived experience, to contextualize the experiences of feeling lonely and isolated. Then, we will leverage mixed methods (longitudinal survey study, focus groups/individual interviews) and social media data to uncover psychosocial, familial, interpersonal, and structural correlates of loneliness and perceived isolation, which can be used as targets for behavioral interventions for reducing loneliness, isolation, and associated mental health problems. We will use our findings to apply for extramural funding at the National Institutes of Health, which has calls directly related to loneliness and isolation (funding opportunities PAR-21-131, PAR-21-350, and PAR-21-134)

Comorbilidades psiquiátricas en los trastornos del espectro autista: estudio comparativo entre los criterios DSM-IV-TR y DSM-5

Antecedentes/Objetivo: Los Trastornos del Espectro Autista (TEA) incluyen un grupo heterogéneo en cuanto a su presentación clínica, lo que supone un desafío a nivel de caracterización diagnóstica. Por consiguiente, el objetivo principal de la clasificación DSM-5 debería de ser identificar subgrupos de ASD que incluyan severidad y comorbilidades psiquiátricas. El objetivo principal de este estudio es explorar las comorbilidades diagnósticas que pueden ser relevantes como descriptores de fenotipos autistas así como la severidad de los síntomas de autismo y comparar los resultados de las diferentes criterios de clasificación entre el DSM-IV-TR y el DSM-5. Método: Se realiza un estudio comparati - vo de severidad y comorbilidades psiquiátricas entre una muestra con diagnóstico de Trastorno Generalizado del Desarrollo, según criterios DSM-IV-TR, y una muestra que cumplía también criterios para TEA según la clasificación DSM-5. La muestra fue obtenida en centros educativos ( n =123). Las comorbilidades psiquiátricas y la severidad de los síntomas se evaluaron a través del The Nisonger Child Behavior Rating Form , entrevista clínica y el Inventario de Trastorno del Espectro Autista, respectivamente. Las comorbi - lidades estudiadas fueron ansiedad, alteraciones de la conducta alimentaria, auto-agre - sividad, hetero-agresividad, autolesiones, trastorno obsesivo-compulsivo y déficit de atención e hiperactividad. Resultados: Se encontraron diferencias estadísticamente sig - nificativas entre ambos grupos para trastorno obsesivo-compulsivo , alteraciones de la conducta alimentaria y severidad . Conclusiones: Se apoya la hipótesis de que los indivi - duos que cumplen criterios diagnósticos según DSM-5 tienen mayor severidad sintomáti - ca, no sólo con respecto a los síntomas autistas centrales, sino también en relación con comorbilidades psiquiátricas

Selection of sucrose concentration depends on the effort required to obtain it: studies using tetrabenazine, D₁, D₂, and D₃ receptor antagonists

RationaleLow doses of dopamine (DA) antagonists and accumbens DA depletions reduce food-reinforced instrumental behavior but do not impair primary food motivation, causing animals to reallocate behavior away from food-reinforced tasks with high response requirements and select less effortful alternatives. However, it is uncertain if this same pattern of effects would occur if sucrose was used as the reinforcer. Objectives These experiments studied the impact of DA depletion and antagonism on performance of an effort-related choice task using sucrose as the reinforcer, as well as sucrose consumption, preference, and taste reactivity tests. Methods The effects of DA manipulations were assessed using a task in which rats chose between lever pressing on a fixed ratio 7 schedule for 5.0 % sucrose versus freely consuming a less concentrated solution (0.3 %). Results The DA depleting agent tetrabenazine shifted effort-related choice, decreasing lever pressing for 5.0 % sucrose but increasing intake of the concurrently available 0.3 % sucrose. Tetrabenazine did not affect sucrose appetitive taste reactivity, or sucrose consumption or preference, in free consumption tests. The D1 antagonist ecopipam and the D2 antagonist haloperidol also shifted choice behavior at doses that did not alter sucrose consumption or preference. In contrast, sucrose pre-exposure reduced consumption across all conditions. D3 antagonism had no effects. Conclusions D1 and D2 receptor blockade and DA depletion reduce the tendency to work for sucrose under conditions that leave fundamental aspects of sucrose motivation (intake, preference, hedonic reactivity) intact. These findings have implications for studies employing sucrose intake or preference in animal models of depression