Local patterns of genetic sharing challenge the boundaries between neuropsychiatric and insulin resistance-related conditions.

The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a complex public health challenge. Evidence of the genetic links between these phenotypes is emerging, but little is currently known about the genomic regions and biological functions that are involved. To address this, we performed Local Analysis of [co]Variant Association (LAVA) using large-scale (N=9,725-933,970) genome-wide association studies (GWASs) results for three IR-related conditions (type 2 diabetes mellitus, obesity, and metabolic syndrome) and nine neuropsychiatric disorders. Subsequently, positional and expression quantitative trait locus (eQTL)-based gene mapping and downstream functional genomic analyses were performed on the significant loci. Patterns of negative and positive local genetic correlations (|rg|=0.21-1, pFDR<0.05) were identified at 109 unique genomic regions across all phenotype pairs. Local correlations emerged even in the absence of global genetic correlations between IR-related conditions and Alzheimer's disease, bipolar disorder, and Tourette's syndrome. Genes mapped to the correlated regions showed enrichment in biological pathways integral to immune-inflammatory function, vesicle trafficking, insulin signalling, oxygen transport, and lipid metabolism. Colocalisation analyses further prioritised 10 genetically correlated regions for likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants were found within or in close proximity to genes, such as SLC39A8 and HLA-DRB1, that can be targeted by supplements and already known drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, and cholesterol-lowering drugs. Overall, our findings underscore the complex genetic landscape of IR-neuropsychiatric multimorbidity, advocating for an integrated disease model and offering novel insights for research and treatment strategies in this domain.

Association between endocrine and neuropsychological endophenotypes and gambling disorder severity.

BACKGROUND: Neurobiological characteristics have been identified regarding the severity of gambling disorder (GD). The aims of this study were: (1) to examine, through a path analysis, whether there was a relationship between neuroendocrine features, potentially mediational GD variables, and GD severity, and (2) to associate neuroendocrine variables, with GD severity-related variables according to gambling preferences. METHODS: The sample included 297 outpatients with GD. We analyzed endocrine concentrations of different appetite-related hormones (ghrelin, liver antimicrobial peptide 2 [LEAP-2], leptin, adiponectin), and neuropsychological performance (working memory, cognitive flexibility, inhibition, decision making, premorbid intelligence). Path analysis assessed mechanisms between neuroendocrine features and GD severity, including mediational GD variables (impulsivity traits and gambling-related cognitive distortions). Partial correlations evaluated the associations between neuroendocrine variables, including impulsivity traits, and variables related to GD severity (DSM-5, South Oaks Gambling Screen, illness duration, and gambling-related cognitive distortions). RESULTS: Lower adiponectin concentrations predicted greater GD severity, while higher LEAP-2 concentrations predicted more gambling-related cognitive distortions. Likewise, better neuropsychological performance directly predicted GD severity, but worse neuropsychological performance was associated with GD severity through the mediational variables of impulsivity traits and gambling-related cognitive distortions. Also, in non-strategic individuals with GD, poor working memory was associated with gambling expectancies and predictive control. In strategic individuals with GD, poor cognitive flexibility was associated with illusion of control, predictive control, and inability to stop gambling. CONCLUSIONS: These results provide updated information about the comprehension of the interaction between neuroendocrine features, clinical variables, and severity of GD. Thus, neurobiological functions seem to be strongly related to GD severity.

Eating disorders and obesity: bridging clinical, neurobiological, and therapeutic perspectives.

Eating disorders (EDs) and obesity are complex health conditions sharing various risk and maintenance factors, intensified in cases of comorbidity. This review explores the similarities and connections between these conditions, examining different facets from a multidisciplinary perspective, among them comorbidities, metabolic and psychological factors, neurobiological aspects, and management and therapy implications. We aim to investigate the common characteristics and complexities of weight and EDs and explore their interrelationships in individuals who experience both. The rising prevalence of EDs in people with obesity necessitates integrated approaches to study this comorbidity and to identify and analyze both common and distinct features of these conditions. This review may offer new opportunities for simultaneous prevention and management approaches, as well as future lines of research.

Probiotic and prebiotic interventions in eating disorders: A narrative review.

AIMS: The review aimed to summarise and discuss findings focused on therapeutic probiotic and prebiotic interventions in eating disorders (ED). METHODS: Using PubMed/MEDLINE, Cochrane Library, and Web of Science all published studies were retrieved until February 2023, following PRISMA guidelines. From the 111 initial studies, 5 met the inclusion criteria for this review. RESULTS: All studies included in this narrative review were focused on anorexia nervosa (AN). Three longitudinal, randomised, controlled trials aimed to evaluate interventions with probiotics (Lactobacillus reuteri, yoghurt with Lactobacillus, and Streptococcus) in children and adolescents. These studies primarily emphasised medical outcomes and anthropometric measures following the administration of probiotics. However, the findings yielded mixed results in terms of short-term weight gain or alterations in specific immunological parameters. With a lower level of evidence, supplementation with synbiotics (probiotic + prebiotic) has been associated with improvements in microbiota diversity and attenuation of inflammatory responses. CONCLUSIONS: Research on probiotics and prebiotics in ED is limited, primarily focussing on anorexia nervosa (AN). Their use in AN regarding medical and anthropometric outcomes needs further confirmation and future research should be warranted to assess their impact on psychological and ED symptomatology, where there is a notable gap in the existing literature.

Spanish Validation of the Long and Short Versions of the Problematic Pornography Consumption Scale (PPCS and PPCS-6) in Adolescents.

Although 1-14% of adolescents may experience problematic pornography use (PPU), psychometrically sound instruments for assessing PPU in Spanish-speaking adolescents are scarce. Given the advantages of the different forms of the Problematic Pornography Consumption Scale (PPCS), the aim of the present study was to assess the psychometric properties of the PPCS and PPCS-6, and to examine associations between PPU and age among boys and girls. Two school-based adolescent samples were recruited in Spain (n = 650; Mage = 16.0 [SD = 1.1]; 50% girls and 50% boys) and Mexico (n1, 160; Mage = 15.8 [SD = 1.1]; 68% girls) to assess the psychometric properties of the PPCS and PPCS-6. Confirmatory factor analysis was applied and convergent and discriminant validity with other measures related to PPU was also tested. The results provided empirical support for the six-factor structure of the PPCS and the one-factor structure of the PPCS-6. Boys with older age showed higher levels of tolerance than girls on the PPCS in both countries. Both the PPCS and the PPCS-6 may be considered valid psychometric instruments for the assessment of PPU in Spanish-speaking adolescents from Spain and Mexico.

How to assess eating disorder severity in males?The DSM-5 severity index versus severity based on drive for thinness.

Using a male eating disorder (ED) sample, this study assessed the clinical utility of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) severity indices for males with anorexia nervosa (AN) and bulimia nervosa (BN) and compared it to an alternative transdiagnostic severity categorisation based on drive for thinness (DT). The participants included 143 males with an ED (60 [42.0%] AN and 83 [58.0%] BN) diagnosis, who were classified using these two severity classifications. The different severity categories were then compared based on ED symptoms, general psychopathology, and personality traits. Our results revealed that the DSM-5 "mild" and DT "low" severity categories were most prevalent in the AN and BN male patients. Clinically significant findings were strongest for the DT categorisation for both AN and BN. The current findings provide initial support for an alternative transdiagnostic DT severity classification for males that may be more clinically meaningful than the DSM-5 severity indices.

Differences in gambling disorder recovery capital toolkits in mothers versus childless women.

This study focused on mothers and childless women in recovery from a gambling disorder (GD) in the context of risk society. Mothers with GD suffer from dual social stigma as gamblers and as women who put their children at risk. Mothers in "risk society" tend to recognize that their choices can affect their children's future. The recovery capital (RC) toolkit comprises internal and external resources and barriers enacted in recovery. This longitudinal study: (a) compared the RC toolkits of mothers versus childless women and their effects on these women's dropout and relapse rates; (b) explored the resources and barriers that predict dropout and relapse in each group. Analysis of the clinical data of 211 women with GD (N = 146 mothers) who received cognitive behavioral therapy for 16 weeks in Spain indicated that mothers reported lower levels of education and were from more disadvantaged socioeconomic groups, were older, and developed gambling-related problems in older age. Mothers had significantly lower relapse rates but not lower dropout rates. There were more personal predictors of dropout among childless women, whereas low levels of family support and the absence of gambling debts predicted dropout in the mothers' group. These findings were interpreted by combining the concepts of risk society and recovery capital in action, highlight the differences between resources and barriers in the RC toolkits used by mothers versus childless women and their interplay with the sociocultural contexts of risk society and childfree lifestyles. Therapists and policymakers should consider these differences during recovery. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cluster analysis in gambling disorder based on sociodemographic, neuropsychological, and neuroendocrine features regulating energy homeostasis.

BACKGROUND: The heterogeneity of gambling disorder (GD) has led to the identification of different subtypes, mostly including phenotypic features, with distinctive implications on the GD severity and treatment outcome. However, clustering analyses based on potential endophenotypic features, such as neuropsychological and neuroendocrine factors, are scarce so far. AIMS: This study firstly aimed to identify empirical clusters in individuals with GD based on sociodemographic (i.e., age and sex), neuropsychological (i.e., cognitive flexibility, inhibitory control, decision making, working memory, attention, and set-shifting), and neuroendocrine factors regulating energy homeostasis (i.e., leptin, ghrelin, adiponectin, and liver-expressed antimicrobial peptide 2, LEAP-2). The second objective was to compare the profiles between clusters, considering the variables used for the clustering procedure and other different sociodemographic, clinical, and psychological features. METHODS: 297 seeking-treatment adult outpatients with GD (93.6% males, mean age of 39.58 years old) were evaluated through a semi-structured clinical interview, self-reported psychometric assessments, and a protocolized neuropsychological battery. Plasma concentrations of neuroendocrine factors were assessed in peripheral blood after an overnight fast. Agglomerative hierarchical clustering was applied using sociodemographic, neuropsychological, and neuroendocrine variables as indicators for the grouping procedure. Comparisons between the empirical groups were performed using Chi-square tests (χ2) for categorical variables, and analysis of variance (ANOVA) for quantitative measures. RESULTS: Three-mutually-exclusive groups were obtained, being neuropsychological features those with the greatest weight in differentiating groups. The largest cluster (Cluster 1, 65.3%) was composed by younger males with strategic and online gambling preferences, scoring higher on self-reported impulsivity traits, but with a lower cognitive impairment. Cluster 2 (18.2%) and 3 (16.5%) were characterized by a significantly higher proportion of females and older patients with non-strategic gambling preferences and a worse neuropsychological performance. Particularly, Cluster 3 had the poorest neuropsychological performance, especially in cognitive flexibility, while Cluster 2 reported the poorest inhibitory control. This latter cluster was also distinguished by a poorer self-reported emotion regulation, the highest prevalence of food addiction, as well as a metabolic profile characterized by the highest mean concentrations of leptin, adiponectin, and LEAP-2. CONCLUSIONS: To the best of our knowledge, this is the first study to identify well-differentiated GD clusters using neuropsychological and neuroendocrine features. Our findings reinforce the heterogeneous nature of the disorder and emphasize a role of potential endophenotypic features in GD subtyping. This more comprehensive characterization of GD profiles could contribute to optimize therapeutic interventions based on a medicine of precision.

Do attention-deficit/hyperactivity symptoms influence treatment outcome in gambling disorder?

BACKGROUND AND AIMS: Numerous studies point to the comorbidity between gambling disorder (GD) and attention deficit hyperactivity disorder (ADHD). However, there is a lack of research exploring how ADHD symptoms might influence psychological treatment outcomes for GD. Therefore, we aimed to explore differences between patients with GD with and without self-reported ADHD symptoms regarding psychopathology, personality, sociodemographic and treatment outcome measures. METHOD: This longitudinal study included 170 patients with GD receiving cognitive behavioral therapy. Multiple self-reported instruments were used to assess clinical variables and sociodemographic measures prior to treatment. RESULTS: A clinical profile characterized by greater GD severity, higher psychopathology and impulsivity, and less adaptive personality features was observed in patients with self-reported ADHD symptoms compared to those without. No significant differences in treatment response (measured by dropout and relapse rates) were observed between the two groups. However, patients with self-reported ADHD symptoms experienced more severe relapses (i.e., gambled more money) and GD patients who relapsed scored higher on measures of ADHD, particularly inattention. CONCLUSION: Individuals with GD and self-reported symptoms of ADHD may experience more severe relapses following treatment, suggesting a need for more vigilant follow-up and interventions for patients with this comorbidity.

Plasma concentration of leptin is related to food addiction in gambling disorder: Clinical and neuropsychological implications.

Background: Data implicate overlaps in neurobiological pathways involved in appetite regulation and addictive disorders. Despite different neuroendocrine measures having been associated with both gambling disorder (GD) and food addiction (FA), how appetite-regulating hormones may relate to the co-occurrence of both entities remain incompletely understood. Aims: To compare plasma concentrations of ghrelin, leptin, adiponectin, and liver-expressed antimicrobial peptide 2 (LEAP-2) between patients with GD, with and without FA, and to explore the association between circulating hormonal concentrations and neuropsychological and clinical features in individuals with GD and FA. Methods: The sample included 297 patients diagnosed with GD (93.6% males). None of the patients with GD had lifetime diagnosis of an eating disorder. FA was evaluated with the Yale Food Addiction Scale 2.0. All patients were assessed through a semi-structured clinical interview and a psychometric battery including neuropsychological tasks. Blood samples to measure hormonal variables and anthropometric variables were also collected. Results: From the total sample, FA was observed in 23 participants (FA+) (7.7% of the sample, 87% males). When compared participants with and without FA, those with FA+ presented both higher body mass index (BMI) (p < 0.001) and leptin concentrations, after adjusting for BMI (p = 0.013). In patients with FA, leptin concentrations positively correlated with impulsivity, poorer cognitive flexibility, and poorer inhibitory control. Other endocrine measures did not differ between groups. Discussion and conclusions: The present study implicates leptin in co-occurring GD and FA. Among these patients, leptin concentration has been associated with clinical and neuropsychological features, such as impulsivity and cognitive performance in certain domains.

Understanding the Co-occurrence of Gambling Disorder and Problematic Pornography Use: Exploring Sociodemographic and Clinical Factors.

The co-occurrence between gambling disorder (GD) and problematic pornography use (PPU) has not yet been explored. Therefore, the present study compared (a) sociodemographic variables, (b) GD-related factors, (c) substance use, (d) psychopathology, (e) personality features, (f) impulsivity, and (g) emotion regulation between individuals with GD (GD group) and those with co-occurring GD and PPU (GD+PPU group). The sample consisted of 359 treatment-seeking individuals with GD: n = 332 individuals had GD only (GD group) and n = 37 individuals had GD and co-occurring PPU (GD+PPU group). GD severity, impulsivity, psychopathology, personality, emotion regulation, and other sociodemographic and clinical variables were assessed. No between-group differences in sociodemographic measures were observed. The GD+PPU group demonstrated greater GD severity and a higher likelihood of substance use compared to those without PPU. Furthermore, the presence of PPU was associated with worse psychopathology, higher impulsivity (except for lack of premeditation and positive urgency), more difficulties in emotion regulation (except for non-acceptance of emotions and limited access to emotions), and a personality profile characterized by lower levels of self-directedness and cooperativeness. The co-occurrence of GD and PPU seems associated with a more dysfunctional clinical profile.

Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder.

INTRODUCTION: Different components of the endocannabinoid (eCB) system such as their most well-known endogenous ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been implicated in brain reward pathways. While shared neurobiological substrates have been described among addiction-related disorders, information regarding the role of this system in behavioral addictions such as gambling disorder (GD) is scarce. AIMS: Fasting plasma concentrations of AEA and 2-AG were analyzed in individuals with GD at baseline, compared with healthy control subjects (HC). Through structural equation modeling, we evaluated associations between endocannabinoids and GD severity, exploring the potentially mediating role of clinical and neuropsychological variables. METHODS: The sample included 166 adult outpatients with GD (95.8% male, mean age 39 years old) and 41 HC. Peripheral blood samples were collected after overnight fasting to assess AEA and 2-AG concentrations (ng/ml). Clinical (i.e., general psychopathology, emotion regulation, impulsivity, personality) and neuropsychological variables were evaluated through a semi-structured clinical interview and psychometric assessments. RESULTS: Plasma AEA concentrations were higher in patients with GD compared with HC (p = .002), without differences in 2-AG. AEA and 2-AG concentrations were related to GD severity, with novelty-seeking mediating relationships. CONCLUSIONS: This study points to differences in fasting plasma concentrations of endocannabinoids between individuals with GD and HC. In the clinical group, the pathway defined by the association between the concentrations of endocannabinoids and novelty-seeking predicted GD severity. Although exploratory, these results could contribute to the identification of potential endophenotypic features that help optimize personalized approaches to prevent and treat GD.

Impulsivity and compulsivity in gambling disorder and bulimic spectrum eating disorders: Analysis of neuropsychological profiles and sex differences.

BACKGROUND: Gambling disorder (GD) and bulimic spectrum eating disorders (BSDs) not only share numerous psychopathological, neurobiological, and comorbidity features but also are distinguished by the presence of inappropriate behaviours related to impulsivity and compulsivity. This study aimed to emphasise the differences and similarities in the main impulsivity and compulsivity features between GD and BSD patients, and to analyse the potential influence of sex in these domains. METHODS: Using self-reported and neurocognitive measures, we assessed different impulsive-compulsive components in a sample of 218 female and male patients (59 with BSD and 159 with GD) and 150 healthy controls. RESULTS: We observed that GD and BSDs exhibited elevated levels of impulsivity and compulsivity in all the dimensions compared to healthy controls. Moreover, these disorders showed differences in several personality traits, such as high novelty seeking in GD, and low persistence and high harm avoidance in BSDs. In addition, patients with BSDs also displayed a trend towards greater impulsive choice than GD patients. Regarding sex effects, GD women presented higher overall impulsivity and compulsivity than GD men. Nevertheless, no sex differences were found in BSDs. CONCLUSIONS: Clinical interventions should consider these deficits to enhance their effectiveness, including adjunctive treatment to target these difficulties. Our findings also provide support to the relevance of sex in GD, which should also be considered in clinical interventions.

Eating Disorders and Addictive Behaviors: Implications for Human Health.

Eating disorders (EDs) are mental health diseases characterized by dysfunctional eating patterns, including restrictive eating, avoidance of foods, binge eating, and compensative behaviors to avoid weight increases and promote thinness (purging, vomiting, laxative/diuretics misuse, and compulsive exercise) [...].

Exploring the influence of circulating endocannabinoids and nucleus accumbens functional connectivity on anorexia nervosa severity.

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.

Cognitive flexibility and DSM-5 severity criteria for eating disorders: assessing drive for thinness and duration of illness as alternative severity variables.

BACKGROUND: The severity criteria for eating disorders (EDs) proposed in the DSM-5 have been established without sufficient empirical support. Drive for thinness (DT) and duration of illness have been proposed as two alternative severity measures, however their empirical evidence is also limited. To date, no research has assessed the validity of current eating disorder (ED) severity criteria regarding cognitive flexibility factors. Cognitive flexibility is often impaired in EDs, becoming a possible severity symptom. The current study assessed for the first time (1) whether the severity indexes for EDs proposed in the DSM-5 were associated with deficits in cognitive flexibility and, (2) whether drive for thinness and illness duration, acted as an alternative, more meaningful severity indices for deficiencies in cognitive flexibility. METHODS: Participants were 161 patients diagnosed with an ED, who were categorized according to DSM-5 severity categories, DT and duration of illness. Discriminative capacity of each classification was assessed for cognitive flexibility measured by Wisconsin card sorting test (WCST). RESULTS: The findings for the DSM-5 classification comprised: (a) In the anorexia nervosa (AN) group, patients with moderate severity showed better scores in WCST than patients with mild and severe/extreme severity. Also, patients with moderate severity showed lower percentage of cognitive flexibility deficits than the other two severity categories; (b) For the binge spectrum disorders (BSD) group, the patients with mild severity showed a higher percentage of cognitive flexibility deficits than did the moderate and severe/extreme categories. When assessing the alternative severity index of DT, no differences were found in cognitive flexibility in any of the groups. Regarding illness duration, in the AN group the task performance of the patients with longer illness duration was worse than the performance of the short duration group and, in the BSD group, patients with longer duration also showed more deficits in cognitive flexibility than the patients with shorter duration of illness. CONCLUSIONS: Our findings point out the limitations of the DSM-5 severity criteria to categorize cognitive flexibility in EDs and support illness duration as an alternative severity approach for EDs.

Dynamic fronto-amygdalar interactions underlying emotion-regulation deficits in women at higher weight.

OBJECTIVE: The regulation of negative emotions entails the modulation of subcortical regions, such as the amygdala, by prefrontal regions. There is preliminary evidence suggesting that individuals at higher weight may present with hypoactivity in prefrontal regulatory systems during emotional regulation, although the directionality of these pathways has not been tested. In this study, we compared fronto-amygdalar effective connectivity during cognitive reappraisal as a function of BMI in 48 adult women with obesity and 54 control participants. METHODS: Dynamic causal modeling and parametric empirical Bayes were used to map effective connectivity between the dorsomedial prefrontal cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and the amygdala. RESULTS: Difficulty in Emotion Regulation Scale scores were higher in the obesity group compared with control participants (p < 0.001). A top-down cortical model best explained our functional magnetic resonance imaging data (posterior probability = 86%). Participants at higher BMI were less effective at inhibiting activity in the amygdala via the orbitofrontal cortex and dorsomedial prefrontal cortex during reappraisal compared with those at lower BMI. In contrast, increased excitatory modulation of dorsolateral prefrontal cortex-to-amygdalar connectivity was found in participants at lower BMI. CONCLUSIONS: These findings support a framework involving alterations in fronto-amygdalar connectivity contributing to difficulties in regulating negative affect in individuals at higher weight.