Gender Differences in the Psychopathology of Obesity: How Relevant Is the Role of Binge Eating Behaviors?

Background: Obesity is a condition that affects humans both physically and mentally. Moreover, many psychopathological conditions can be observed in obese patients that may threaten the positive outcomes of bariatric surgery. Purpose: The aim of this study was to identify the main psychopathological correlates of obese candidates for bariatric surgery, with particular attention on the relationship between psychopathology and gender. Methods: In total, 273 candidates for bariatric surgery for obesity underwent a psychiatric evaluation using a compilation of psychometric scales: the Revised Symptom Checklist 90-R (SCL-90-R), the Eating Disorder Examination Questionnaire (EDE-Q), the Binge Eating Scale (BES), the Body Uneasiness Test (BUT) and the Obesity-Related Well-Being (ORWELL 97). The sample was divided on the basis of gender and binge eating disorder (BED) severity. Comparisons between the groups were performed using an analysis of variance model (ANOVA) or a Pearson's chi-squared test. Further, we also divided our sample into a severe binge eating group (score > 27), a mild to moderate group (18 < score < 26) and a low/no symptoms group (score < 17). Results: Male and female subjects showed different results for the BES, with higher scores reported among women (17.50 ± 9.59) compared to men (14.08 ± 8.64). Women also showed higher scores across most of the SCL-90-R domains and worse outcomes in terms of quality of life. Both women and men in the severe binge eating group reported higher scores for the SCL-90-R. Conclusion: The symptoms of BED, along with body image dissatisfaction (BID), are among the most important to investigate for candidates for bariatric surgery in order to improve the surgery outcomes. Level of evidence: Level III as the evidence came from a cohort analytic study.

Analysis of female enrollment in clinical trials for alcohol and substance use disorders: Is it time for sex-informed pharmacotherapy?

BACKGROUND: Women represent an increasing number of individuals with alcohol and substance use disorders (ASUDs), and sex-differences might affect results of interventional clinical trials (CTs). We aim at assessing the proportion of women and the reporting of sex-stratified and female-specific data in CTs for ASUDs. METHODS: We extracted data from ClinicalTrials.gov on Phase 1-3 CTs of investigational drugs for ASUDs conducted from 2000 to 2021 and identified articles related to these trials. We determined the average proportions of women enrolled per trial overall, over time, and by disease area and trial phase. Next, we calculated the proportion of articles reporting sex-stratified and female-specific data. RESULTS: In the 234 CTs identified, the overall proportion of women was 33.4% [95% CI: 32.7%-33.9%]), with an increasing temporal trend. Women's participation was higher in CTs of investigational drugs for tobacco (43.5% [95% CI: 42.4% -44.5%]) and alcohol use disorder (35.9% [95% CI: 34.54%-37.21%]), and closely mirrored their representation in the disease populations (46% and 37%). Conversely, women were underrepresented in clinical trials of drugs for cocaine and stimulant use disorders (25.8% [95% CI: 24.6%-27.1%]) and opioid use disorders (25.9% [95% CI:24.2%-27.7%]). Nine publications reported sex-stratified data in the method and/or result section, whereas none documented female-specific data. CONCLUSIONS: Enrollment of women in ASUDs CTs has increased over time but remains low in several disease areas. This, together with the low rates of reporting of sex-stratified data, calls for an adequate inclusion of sex in the design and analysis of CTs for ASUDs.

Repetitive transcranial magnetic stimulation in treatment-seeking subjects with cocaine use disorder: A randomized, double-blind, sham-controlled trial.

BACKGROUND: Cocaine use disorder (CUD) is a chronic and relapsing brain disorder with no approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in open label and single-blind studies, reducing cocaine craving and consumption. Although, large randomized, double-blind, controlled trials are still missing. OBJECTIVE: This multi-center, randomized, double-blind, sham-controlled study was designed to evaluate the safety and efficacy of multiple sessions of active rTMS compared to sham stimulation in patients with CUD. METHODS: rTMS (15 Hz, 2 daily sessions for 5 days/week,for a total of 20 stimulation sessions) was delivered over the left DLPFC for two weeks of continuous treatment followed by 12 weeks of maintenance (1 day/week, twice a day), in a double-blind, randomized sham-controlled design. Our primary outcomes included self-reported cue-induced craving and cocaine consumption, as measured by percentage of negative urine tests. Our secondary outcomes included: 1) changes in depressive symptoms; 2) changes in cocaine withdrawal symptoms; and 3) changes in self-reported days of cocaine use. RESULTS: Forty-two outpatients with CUD were enrolled in the active rTMS group and 38 patients in the sham group. We observed a significant decrease in self-reported cue-induced cocaine craving and consumption in both the active rTMS and sham, whereas no main effect of treatment was found. However, the active rTMS group showed greater changes in depressive symptoms. The improvement on depressive symptomatology was particularly marked among patients receiving a total number of rTMS sessions greater than 40 and those reporting more severe depressive symptoms at baseline. CONCLUSIONS: A significant improvement of CUD symptoms during active rTMS treatment was observed. However, we did not observe significant differences in cocaine craving and consumption between treatment groups, highlighting the complexity of factors contributing to CUD maintenance. A significant improvement in depressive symptoms was observed in favour of the active group. Clinical trial registration details:clinicaltrials.govidentifierNCT03333460.

Mechanistic insights into the efficacy of memantine in treating certain drug addictions.

The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. In this review, we summarize preclinical evidences and clinical trials that investigated the efficacy of memantine in treating patients with alcohol, opiate, cocaine, and nicotine use disorders and discuss the results from a mechanistic point of view. Memantine has shown efficacy in reducing alcohol and opiate craving, consumption, and withdrawal severity. However, in cocaine and nicotine use disorders, memantine did not have significant effect on cravings or consumption. Additionally, memantine was associated with increased subjective effects of alcohol, cocaine, and nicotine. We discuss possible mechanisms behind this variability. Since memantine transiently blocks NMDA receptors and protects neurons from overstimulation by excessive synaptic glutamate, its efficacy should be observed in drug phases that cause hyperglutamatergic states, while hypoglutamatergic drug use states would not resolve with blocking NMDA receptors. Second, memantine pharmacokinetic studies have been done in rodents and healthy volunteers, but not in patients with substance use disorder. Memantine, opiates, cocaine, and nicotine share the same transporter family at the blood brain barrier. This shared transport mechanism could impact brain concentrations of memantine and its effects. In conclusion, memantine remains an intriguing compound in our pharmacopeia with controversial results in treating certain aspects of drug addiction. Further studies are needed to understand the clinical and biological correlates of its efficacy.

Clinical presentation of strokes confined to the insula: a systematic review of literature.

BACKGROUND AND PURPOSE: The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). METHODS: We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords "insular stroke" and "insular infarction", to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. RESULTS: We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. CONCLUSIONS: The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.

Non-invasive brain stimulation targets and approaches to modulate gambling-related decisions: A systematic review.

INTRODUCTION: Despite intense neuroscience research on the neurobiological underpinnings of Gambling Disorder (GD) and gambling-related decision-making, effective treatments targeting these dysfunctions are still lacking. Non Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), selectively modulate activity of brain circuits and have the potential to reverse alterations sustaining GD symptoms. Therefore, the aim of this systematic review was to determine the impact of different NIBS interventions on gambling-related decision processes. METHODS: We conducted a comprehensive and translational search in three online databases (MEDLINE via PubMed, Scopus, Web of Science), in accordance with the PRISMA guidelines. We included studies applying neuromodulation (TMS, tDCS) techniques in GD patients or assessing gambling-related decision-making in healthy subjects. In addition, we explored the potential impact of NIBS in drug-induced GD (e.g., Parkinson's Disease). RESULTS: Twenty-seven studies have been included. We summarized results to detect the impact of different targets and stimulation/inhibition protocols in terms of gambling-related decision-making. The majority of both tDCS and TMS studies targeted the dorsolateral prefrontal cortex. Although heterogeneous in protocols and parameters, results from tDCS and TMS studies converge in indicating that the stimulation (instead of inhibition) of prefrontal regions could be beneficial to contrast dysfunctional gambling-related decision processes. CONCLUSION: NIBS interventions show promise to be further tested in controlled clinical settings for the treatment of behavioral addictions. Further studies are also necessary to investigate connectivity changes and laterality issues (unilateral versus bilateral; left versus right) of NIBS application in GD.

Outcome after single-site robotic cholecystectomy: An initial single center's experience.

BACKGROUND: Although laparoscopic cholecystectomy (LC) is the gold standard for symptomatic gallbladder disease, a single-incision approach may be a new challenge in order to achieve minimization of surgical trauma. Single-site robotic cholecystectomy (SSRC) is able to offset the ergonomic limitation of laparoscopic single-site cholecystectomy and improves cosmesis. METHODS: We present a single-institution initial experience of SSRC for cholecystolithiasis. Intra-operative and post-operative data of patients were reviewed to assess the technical feasibility and cosmetic outcome. RESULTS: We evaluated a series of 27 consecutive patients retrospectively analyzed and prospectively collected who underwent SSRC. One patient was excluded from the final analysis because they converted to open procedure. The female/male ratio was 17/9, with mean age of 48 ± 12 years. The body mass index mean value was 26.0 ± 4.2. The mean operative time was 99.6 ± 21.5 minutes. No intra- or post-operative complications and readmissions were recorded. At 12 months follow up, every patient received the Body Image Questionnaire (BIQ) and a Photo Series Questionnaire. We recorded three patients (11.5%) with post-operative incisional hernia. Scores of the BIQ subscale for body image perception were 6 ± 1.2, while the scores of scar cosmesis were 21.1 ± 3.0. A statistically significant improvement in scar self-rating from T0 to T1 (P < .01) was found. CONCLUSION: In our initial experience SSRC may be preferred to treat patients with higher needs in terms of cosmesis and body image perception. Lower costs for rent, maintenance and consumables may allow the spread of robotic surgery also for singe site cholecystectomy.

Club Drugs: Psychotropic Effects and Psychopathological Characteristics of a Sample of Inpatients.

BACKGROUND: Growing evidence supports the possibility of significant psychiatric consequences related to novel and traditional psychoactive substance consumption. The problem of differential diagnosis has hampered research on specific psychopathologies with unclear outcomes. The aim of our study was to report psychiatric and clinical features of subjects admitted to a psychiatric ward in Ibiza, Spain, with a clinical diagnosis of substance abuse or intoxication. METHODS: A survey was administered to a sample of inpatients hospitalized due to psychiatric symptoms related to recent use of psychoactive substances. The questionnaire investigated sociodemographic factors, familiar and personal anamnesis, substance use habits, general and psychopathological features. Urine samples were collected and analyzed in a toxicology laboratory using gas chromatography and mass spectrometry. RESULTS: A total of 110 patients were included in the study. Most patients (70%) declared multiple substance use, and 33% of patients reported more than two substances; nevertheless, it was possible to identify 17 (15%) depressor users, 44 (40%) stimulant users and 49 (45%) psychodysleptics users. A positive association with a lifetime diagnosis of bipolar disorder was found (two-tailed Fisher's exact test: p = 0.013). Psychomotor agitation, reference, and paranoid delusions, affective symptoms, consciousness disorders, and aggressiveness represented some of the most frequent symptoms at entry evaluation. CONCLUSIONS: In this study, we described the acute psychiatric presentations related to recreational drug use in subjects on holiday in Ibiza. The use of psychoactive substances was characterized by poly-use of both traditional and novel substances, with several psychopathological consequences. Future research should focus on a better understanding of the psychopathological effects of specific substances, defining signs and symptoms to help make a differential diagnosis and prospectively examine long-term effects.

Multiple Sessions of High-Frequency Repetitive Transcranial Magnetic Stimulation as a Potential Treatment for Gambling Addiction: A 3-Month, Feasibility Study.

Gambling disorder (GD) is a behavioral addiction, in which dysfunctions in prefrontal activity have been proposed as relevant pathophysiological correlates. The aim of the present study was to preliminarily investigate the feasibility of a noninvasive neuromodulation intervention targeting the prefrontal cortex to treat GD in an open-label setting. We included 8 treatment-seeking patients with GD (7 males; 1 female; mean age: 40.6 ± 11.2). The study consisted of 3 phases: (1) outpatient screening phase, (2) 2-week intensive repetitive transcranial magnetic stimulation (rTMS) treatment phase (twice daily, 5 days/week for 2 weeks); and (3) 3-month maintenance follow-up phase (twice daily, once a week). Each high-frequency (15 Hz) rTMS session was delivered targeting the left dorsolateral prefrontal cortex. GD severity and treatment response were assessed at the baseline and during the follow-up. No relevant side effect was reported. We found a 71.2% Gambling Symptom Assessment Scale mean score reduction after 2 weeks of rTMS treatment; the days spent gambling decreased from 19.63 ± 7.96 to 0.13 ± 0.35 days. Clinical improvements were maintained throughout the study period. The lack of a control group limits the interpretation of these results. In conclusion, these results consolidate the rationale that rTMS interventions deserve further investigation as a potential treatment for GD. These protocols should be tested in larger randomized controlled studies, to determine the real benefits of neuromodulation in the clinical course of patients with GD. Registration Number: ClinicalTrials.gov Identifier NCT03336879.

rTMS Reduces Psychopathological Burden and Cocaine Consumption in Treatment-Seeking Subjects With Cocaine Use Disorder: An Open Label, Feasibility Study.

Introduction: Cocaine use disorder (CUD) currently represents a notable public health concern, linked with significant disability, high chances of chronicity, and lack of effective pharmacological or psychological treatments. Repetitive transcranial magnetic stimulation (rTMS) is supposed to be a potential therapeutic option for addictive disorders. Aim of this study was to evaluate the feasibility of rTMS on (1) cocaine craving and consumption and (2) other comorbid psychiatric symptoms. Methods: Twenty treatment seeking CUD subjects underwent 2 weeks of intensive rTMS treatment (15Hz; 5 days/week, twice a day for a total of 20 stimulation sessions) of the left dorsolateral prefrontal cortex, followed by 2 weeks of maintenance treatment (15Hz, 1 day/week, twice a day). Sixteen patients completed the study. Patients were evaluated at baseline (T0), after 2 weeks of treatment (T1), and at the end of the study (T2; 4 weeks), with the following scales: Cocaine Selective Severity Assessment (CSSA), Zung Self-Rating Anxiety Scale, Beck Depression Inventory (BDI), Symptom Checklist-90 (SCL-90), and the Insomnia Severity Index. Results: After four weeks of rTMS treatment, 9 out of 16 subjects (56.25%) had a negative urinalysis test, with a significant conversion rate with respect to baseline (Z = -3.00; p = 0.003). Craving scores significantly improved only at T2 (p = 0.020). The overall psychopathological burden, as measured by the SCL-90 Global Severity Index (GSI), significantly decreased during the study period (Z = -2.689; p = 0.007), with a relevant improvement with regards to depressive symptoms, anhedonia, and anxiety. Subjects exhibiting lower baseline scores on the SCL-90 were more likely to be in the positive outcome group at the end of the study (Z = -3.334; p = 0.001). Discussion: Findings from this study are consistent with previous contributions on rTMS use in subjects with cocaine use disorder. We evidenced a specific action on some psychopathological areas and a consequent indirect effect in terms of relapse prevention and craving reduction. A double-blind, sham-controlled, neuro-navigated rTMS study design is needed, in order to confirm the potential benefits of this technique, opening new scenarios in substance use disorders treatment.

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Transcranial Direct Current Stimulation Reduces Craving in Substance Use Disorders: A Double-blind, Placebo-Controlled Study.

OBJECTIVES: The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms. METHODS: In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1). RESULTS: Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found. CONCLUSIONS: Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.

Novel Pathways in the Treatment of Major Depression: Focus on the Glutamatergic System.

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further "neurobiological targeted" approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.

Dopaminergic and clinical correlates of high-frequency repetitive transcranial magnetic stimulation in gambling addiction: a SPECT case study.

Repetitive Transcranial Magnetic Stimulation (rTMS) shows the potential to modulate local brain activity, thus resulting in a modulatory action on neurocircuitries implicated in the pathophysiology of Gambling Disorder (GD). We report the case of a GD patient treated with two weeks of high frequency (15 Hz) rTMS over the dorsolateral prefrontal cortex (DLPFC). At baseline and after rTMS treatment the patient underwent a SPECT examination with (123)I-FP-CIT tracer, to test changes in dopamine transporter (DAT) availability. The patient was followed up for six months, to explore safety and clinical correlates of a weekly high frequency rTMS maintenance treatment. Over the six-month follow-up the patient reported no episodes of gambling relapse. Also, the patient did not report craving for gambling or gambling-related symptoms. After two weeks of left DLPFC-rTMS treatment, we found a decrease in DAT availability in striatal regions, that represents a putative neurobiological substrate of dopaminergic pathways modulation. This study suggests that high frequency DLPFC-rTMS deserves further investigations in larger samples, using controlled study designs, to assess its real potential as a treatment for GD.

Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives.

Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD.