In vivo brain levels of acetylcholine and 5-hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement.

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep-wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake-promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5-hydroxytryptamine (5-HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5-HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5-HT were collected from the basal forebrain, a wake-related brain area. These pharmacological treatments significantly increased the contents of ACh and 5-HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK-886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5-HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake-related neurotransmitters.

Measuring Knowledge, Attitudes, and Barriers to Medication Adherence in Potential Bariatric Surgery Patients.

BACKGROUND: Bariatric surgery is an effective treatment for the obesity epidemic, but the poor attendance and adherence rates of post-surgery recommendations threaten treatment effectiveness and health outcomes. Preoperatively, we investigated the unique contributions of clinical (e.g., medical and psychiatric comorbidities), sociodemographic (e.g., sex, age, and educational level), and psychopathological variables (e.g., binge eating severity, the general level of psychopathological distress, and alexithymia traits) on differing dimensions of adherence in a group of patients seeking bariatric surgery. METHODS: The final sample consisted of 501 patients (346 women). All participants underwent a full psychiatric interview. Self-report questionnaires were used to assess psychopathology, binge eating severity, alexithymia, and three aspects of adherence: knowledge, attitude, and barriers to medical recommendations. RESULTS: Attitude to adherence was associated with alexithymia (ß = -2.228; p < 0.001) and binge eating disorder (ß = 0.103; p = 0.047). The knowledge subscale was related to medical comorbidity (ß = 0.113; p = 0.012) and alexithymia (ß = -2.256; p < 0.001); with age (ß = 0.161; p = 0.002) and psychiatric comorbidity (ß =0.107; p = 0.021) manifesting in the barrier subscale. CONCLUSION: We demonstrated that alexithymia and psychiatric and eating disorders impaired adherence reducing attitude and knowledge of treatment and increasing the barriers. Both patient and doctor can benefit from measuring adherence prior to surgery, with a qualitative approach shedding light on the status of adherence prior to the postsurgical phase when the damage regarding adherence is, already, done. Graphical Abstract.

The Role of Peroxisome Proliferator-Activated Receptor in Addiction: A Novel Drug Target.

The peroxisome proliferator activated receptors (PPARs) are a superfamily of well-recognized ligand-binding nuclear receptors comprising three isoforms: PPARα, PPARγ, and PPARß/δ. In response to endogenous lipid messengers, PPARs trigger the transcription of genes related to a wider spectrum of physiological phenomena, including fatty acid oxidation, inflammation, adipogenesis, among many others. Thus, the importance of PPARs as putative protective therapy in health issues has increased the interest of studying these nuclear receptors, including the management of neurodegenerative disorders, multiple sclerosis, and likely addiction. In recent years, several pieces of evidence from animal models have demonstrated the promising role of PPARs as a critical element for interventions in addictive behaviors by reducing the reinforcing properties of addictive substances such as alcohol. However, there is a lack of data in the scope and has so far been unexplored the function of PPARs in additional drugs such as cannabis, opioids, methamphetamine, or cocaine. A similar scenario has been found for the management of binge-type eating disorders. Thus, here we review recent advances in understanding the relevance of the PPAR controlling addiction.

Neurocognitive and Psychopathological Predictors of Weight Loss After Bariatric Surgery: A 4-Year Follow-Up Study.

Twenty to thirty percent of patients experience weight regain at mid and long-term follow-up. Impaired cognitive functions are prevalent in people suffering from obesity and in those with binge eating disorder, thereby, affecting the weight-loss outcomes. The aim of our study was to investigate neurocognitive and psychopathological predictors of surgical efficacy in terms of percentage of excess weight loss (%EWL) at follow-up intervals of one year and 4-year. Psychosocial evaluation was completed in a sample of 78 bariatric surgery candidates and included psychometric instruments and a cognitive battery of neuropsychological tests. A schedule of 1-year and 4-year follow-ups was implemented. Wisconsin Sorting Card Test total correct responses, scores on the Raven's Progressive Matrices Test, and age predicted %EWL at, both, early and long-term periods after surgery while the severity of pre-operative binge eating (BED) symptoms were associated with lower %EWL only four years after the operation. Due to the role of pre-operative BED in weight loss maintenance, the affected patients are at risk of suboptimal response requiring ongoing clinical monitoring, and psychological and pharmacological interventions when needed. As a result of our findings and in keeping with the latest guidelines we encourage neuropsychological assessment of bariatric surgery candidates. This data substantiated the rationale of providing rehabilitative interventions tailored to cognitive domains and time specific to the goal of supporting patients in their post-surgical course.

Assessing psychopathology in bariatric surgery candidates: discriminant validity of the SCL-90-R and SCL-K-9 in a large sample of patients.

PURPOSE: Pre-surgical psychosocial evaluation of bariatric surgery (BS) patients should identify psychiatric issues that could worsen after surgery and those requiring additional ongoing intervention. In this view, the use of reliable, appropriate and concise evaluating instruments is of critical importance. The aim of the present study was to investigate the clinical utility of both the Symptom Checklist 90-Revised (SCL-90-R) and its brief unidimensional version, the so-called Symptom-Checklist-K-9 (SCL-K-9) in detecting the presence of psychiatric disorders among bariatric surgery (BS) candidates. METHODS: Seven-hundred-and-ninety-eight BS candidates (563 women and 235 men; mean age: 44.15 ± 11.45) were enrolled in the present study. All participants underwent a full psychiatric interview and were administered the SCL-90-R. RESULTS: Three-hundred-and-sixty-two patients (45.4%) met the criteria for a diagnosis of at least one psychiatric disorder and ninety-nine patients (12.4%) had psychiatric comorbidities. In the current sample, 219 patients (27.4%) met the criteria for binge eating disorders (BED), 158 (19.8%) met the criteria for major depressive disorder (MDD), and 67 (8.4%) met both criteria. A receiver operating characteristic (ROC) curves procedure showed that both the SCL-90-R and the SCL-K-9 satisfactorily categorize patients with any psychiatric disorder, both BED and MDD (area under the ROC curve ≥ 0.70, p < 0.001). CONCLUSION: Our results suggest that the SCL-90-R and the SCL-K-9 may represent first-level screening tests identifying at-risk patients, eligible for a more expensive or time-consuming clinical assessment. LEVEL OF EVIDENCE: Level V, cross-sectional, descriptive study.

Bariatric Surgery Closure During COVID-19 Lockdown in Italy: The Perspective of Waiting List Candidates.

Background: From the beginning of March 2020, lockdown regimens prevented patients with obesity from receiving bariatric surgery. Surgical emergencies and oncological procedures were the only operations allowed in public hospitals. Consequently, patients with morbid obesity were put in a standby situation. With the aim at exploring the viewpoint of our future bariatric surgery patients, we built a questionnaire concerning obesity and COVID-19. Method: A total of 116 bariatric surgery candidates were approached using a telephonic interview during the Italian lockdown. Results: Of the total sample, 73.8% were favorable to regular bariatric surgery execution. Forty percent were concerned about their own health status due to the COVID-19 emergency, and 61.1% were troubled by the temporary closure of the bariatric unit. The majority of the sample were eating more. Forty-five percent and the 27.5% of patients reported a worsening of the emotional state and physical health, respectively. Most of the patients (52.2%) considered themselves more vulnerable to COVID-19, especially individuals with class III obesity. Patients who reported an increased consumption of food were younger (43.44 ± 12.16 vs. 49.18 ± 12.66; F = 4.28, p = 0.042). No gender difference emerged. Conclusion: The lockdown had a negative result on Italian patients' psychological well-being and eating habits. The majority of patients would have proceeded with the surgery even during the COVID-19 emergency. Effective management and bariatric surgery should be restarted as soon as possible.

COVID-19 Related Distress Is Associated With Alcohol Problems, Social Media and Food Addiction Symptoms: Insights From the Italian Experience During the Lockdown.

Background: Several scholars hypothesize that one of the most negative impacts of the coronavirus disease 2019 (COVID-19) crisis would concern the increase of prevalence and severity of both substances and behavioral addiction. Despite the general concerns about the increase of prevalence and severity of addictions related to the COVID-19 emergency, few data are still available. Thus, the main aim of this study was to investigate the association between COVID-19 related distress and: (i) alcohol problems, (ii) social media addiction (SMA) symptoms, (iii) food addiction (FA) symptoms. Methods: A national online-survey was carried out during the Italian lockdown (i.e., 9 March 2020-4 May 2020). In the current study, 1,519 participants (365 men and 1,154 women, mean age: 28.49 ± 10.89 years) were included. The survey included socio-demographic related items (e.g., age, sex, residential regions, education level, civil status, tobacco use, etc.), as well as ad-hoc developed questions aimed to investigate COVID-19 related variables (e.g., isolation/quarantine, personal diagnosis to COVID-19, friends or relatives with COVID-19 diagnosis, etc.). Participants also completed the following self-report measures in order to investigate: the psychological impact of COVID-19, alcohol problems, SMA symptoms, FA symptoms, and impulsivity. Results: The psychological impact of COVID-19 was independently associated with alcohol problems (ß = 0.058, p = 0.043), SMA symptoms (ß = 0.259, p < 0.001), and FA symptoms (ß = 0.150, p < 0.001). Conclusion: Taken together, our results seem to confirm the general concerns about the negative impacts of the COVID-19 emergency on addictive behaviors, suggesting that this issue should be carefully monitored.

Mentalization Impairment Is Associated with Problematic Alcohol Use in a Sample of Young Adults: A Cross-Sectional Study.

Background: Alcohol is one of the most widely used drugs among adolescents and young people, and problematic alcohol use (PAU) is related to significant long-term biological, clinical, and psychosocial sequelae. Although preliminary reports have linked deficits in mentalization to increased vulnerability to addiction, no studies have specifically explored this phenomenon in relation to PAU. Methods: The association between mentalization impairment and PAU severity was investigated in a sample of 271 young adults (183 females, 65.9%; mean age: 23.20 ± 3.55 years; range: 18-34). Self-report measures investigating PAU and mentalization were administered to all participants. Results: Individuals with PAU reported a more frequent use of tobacco and illicit drugs in the last 12 months. PAU severity was negatively associated with mentalization capacity (rho = -0.21; p < 0.001), and also, when possible, confounding variables (i.e., gender, age, occupation, education, tobacco and illegal drugs use) were controlled for (rho = -0.17; p = 0.004). Conclusion: The present data showed that mentalization impairment is significantly associated with PAU among young adults, suggesting that it may have a role in the development and/or maintenance of alcohol use.

The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats.

RATIONALE: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. OBJECTIVES: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. METHODS: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. RESULTS: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. CONCLUSIONS: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation.

Increased Resting State Triple Network Functional Connectivity in Undergraduate Problematic Cannabis Users: A Preliminary EEG Coherence Study.

An increasing body of experimental data have suggested that aberrant functional interactions between large-scale networks may be the most plausible explanation of psychopathology across multiple mental disorders, including substance-related and addictive disorders. In the current research, we have investigated the association between problematic cannabis use (PCU) and triple-network electroencephalographic (EEG) functional connectivity. Twelve participants with PCU and 24 non-PCU participants were included in the study. EEG recordings were performed during resting state (RS). The exact Low-Resolution Electromagnetic Tomography software (eLORETA) was used for all EEG analyses. Compared to non-PCU, PCU participants showed an increased delta connectivity between the salience network (SN) and central executive network (CEN), specifically, between the dorsal anterior cingulate cortex and right posterior parietal cortex. The strength of delta connectivity between the SN and CEN was positively and significantly correlated with higher problematic patterns of cannabis use after controlling for age, sex, educational level, tobacco use, problematic alcohol use, and general psychopathology (rp = 0.40, p = 0.030). Taken together, our results show that individuals with PCU could be characterized by a specific dysfunctional interaction between the SN and CEN during RS, which might reflect the neurophysiological underpinnings of attentional and emotional processes of cannabis-related thoughts, memories, and craving.

The Symptom-Checklist-K-9 (SCL-K-9) Discriminates between Overweight/Obese Patients with and without Significant Binge Eating Pathology: Psychometric Properties of an Italian Version.

A general personality and psychopathology evaluation is considered to be crucial part of the multidisciplinary assessment for weight-related problems. The Symptom Checklist-90-Revised (SCL-90-R) is commonly used to assess general psychopathology in both overweight and obese patients seeking weight-loss treatment. The main purpose of the present research was to investigate the psychometric properties of the brief form of the SCL-90-R (i.e., the SCL-K-9) in a clinical sample (N = 397) of patients seeking weight-loss treatment (i.e., bariatric surgery and a nutritional weight-loss program). The results of the confirmatory factor analysis supported a one-factor solution of the SCL-K-9, with all nine items loading significantly on the common latent factor (lambdas ≥ 0.587). The ordinal α (= 0.91), the inter-item mean indices of correlation (rii = 0.53), and the convergent validity were also satisfactory. A receiver operating characteristic curves procedure showed that both SCL-90-R and SCL-K-9 were able to classify patients with and without significant binge eating pathology according to the Binge Eating Scale (BES) total score. Overall, our results suggest that the SCL-K-9 has adequate psychometric properties and can be applied as a short screening tool to assess general psychopathology in overweight/obese individuals seeking weight-loss treatment and at follow-up interviews when time restraints preclude the use of the full-length form.

Prevalence of Food Addiction and Binge Eating in an Italian sample of bariatric surgery candidates and overweight/obese patients seeking low-energy-diet therapy.

AIM: The main aim of the present study was to investigate the prevalence of Food Addiction (FA) and clinical level of Binge Eating in an Italian sample of overweight/obese patients attending low energy-diet therapy, and in an Italian sample of obese bariatric surgery candidates. METHODS: Participants were: i) 122 overweight/obese patients (86 women) referred to a medical center in Rome (Italy), specialized in nutritional treatment of obesity (i.e., non-surgery patients group), and ii) 281 surgery candidates (207 women) referred to the center for Bariatric Surgery at the University of Rome Tor Vergata (i.e., surgery candidates group). All patients were administered self-report measures investigating FA, binge eating, and psychopathology. RESULTS: Non-surgery patients and surgery candidates did not differ in the prevalence of FA (31.1% vs 26.3%), moderate level of binge eating (32.0% vs 31.8%), and severe level of binge eating (11.05% vs 13.6%). Compared to non-surgery patients, surgery candidates reported higher prevalence in two FA symptoms: i) food consumed more than planned (13.9% vs 25.3%; p=0.011) and ii) persistent desire or repeated unsuccessful attempts (89.3% vs 96.8; p=0.002). DISCUSSION AND CONCLUSION: Our results confirm that both FA and clinical level of binge eating are common problems in both overweight/obese patients seeking low-energy-diet therapy and in obese bariatric surgery candidates, justifying the clinical utility of assessing these dysfunctional eating patterns.