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Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder
- Isabel Baenas, Neus Solé-Morata, Roser Granero, Fernando Fernández-Aranda, Mitona Pujadas, Bernat Mora-Maltas, Ignacio Lucas, Mónica Gómez-Peña, Laura Moragas, Amparo del Pino-Gutiérrez, Javier Tapia, Rafael de la Torre, Marc N. Potenza, Susana Jiménez-Murcia
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- Journal:
- European Psychiatry / Volume 66 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 08 November 2023, e97
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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.
AimsFasting 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.
MethodsThe 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.
ResultsPlasma 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.
ConclusionsThis 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.
Relationship between Signals Regulating Energy Homeostasis and Neuropsychological and Clinical Features in Gambling Disorder: A Case-Control Study
- F. Fernandez-Aranda, I. Baenas, M. Etxandi, B. Mora-Maltas, R. Granero, S. Tovar, C. Diéguez, M. N. Potenza, S. Jiménez-Murcia
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S328
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Introduction
The neurobiology of gambling disorder (GD) is not yet fully understood. Although dysfunctional signalling involved in energy homeostasis has been studied in substance use disorders, it should be examined in detail in GD.
ObjectivesTo compare different endocrine and neuropsychological factors between individuals with GD and healthy controls (HC), and to explore endocrine interactions with neuropsychological and clinical variables.
MethodsA case-control design was performed in 297 individuals with GD and 41 HC, assessed through a semi-structured clinical interview and a psychometric battery, adding 38 HC in the evaluation of endocrine and anthropometric variables.
ResultsIndividuals with GD presented higher fasting plasma ghrelin (p<.001) and lower LEAP2 and adiponectin concentrations (p<.001) than HC adjusting for body mass index (BMI). The GD group reported higher cognitive impairment regarding cognitive flexibility and decision-making strategies, a worse psychological state, higher impulsivity levels, and a more dysfunctional personality profile. Despite failing to find significant associations between endocrine factors and either neuropsychological or clinical aspects in GD, some impaired cognitive dimensions and lower LEAP2 concentrations significantly predicted GD presence.
ConclusionsThis study suggests distinctive neuropsychological and endocrine dysfunctions may operate in individuals with GD, predicting GD presence. Further exploration of endophenotypic vulnerability pathways in GD appear warranted, especially with respect to etiological and therapeutic potentials.
Disclosure of InterestF. Fernandez-Aranda Consultant of: Novo Nordisk , Employee of: editorial honoraria as EIC from Wiley, I. Baenas: None Declared, M. Etxandi : None Declared, B. Mora-Maltas: None Declared, R. Granero : None Declared, S. Tovar : None Declared, C. Diéguez: None Declared, M. Potenza Grant / Research support from: Mohegan Sun Casino and Connecticut Council on Problem Gambling, Consultant of: Opiant Pharmaceuticals, Idorsia Pharmaceuticals, Baria-Tek, AXA, Game Day Data and the Addiction Policy Forum; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; and has consulted for law offices and gambling entities on issues related to impulse control or addictive disorders, Employee of: patent application in Yale University and Novartis, S. Jiménez-Murcia: None Declared.
High genetic diagnostic yield in children and adolescents with psychiatric disorders
- C. Manso-Bazús, N. Spataro, L. Torrent, L. Plans, M. Casadesús, M. Tomás, N. Baena, J. P. Trujillo, N. Capdevila, A. Brunet, V. Martínez-Glez, M. Pàmias, A. Ruiz Nel·lo
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S104
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Introduction
Psychiatric disorders are more prevalent in children with mild (MID) to borderline intellectual functioning (BIF). Rare pathogenic variants in neurodevelopmental genes increase the risk for psychiatric disorders and may explain the comorbidity. Despite these patients represent up to 35% of those attended at mental health services, genetic diagnosis is usually not offered. The identification of mentioned variants could lead to improved clinical care.
ObjectivesTo identify pathogenic variants responsible of the psychiatric disorders in mild and borderline intellectual functioning.
To correlate phenotypic and genetic profiles to personalize diagnostic, clinical care and support to clinicians and families.
MethodsWhole exome sequencing (WES) was performed on 99 enrolled children/adolescent (6-18 yo) affected by a psychiatric condition diagnosed following DSM-5 criteria, and either MID (IQ 55-69) or BIF (IQ 70-85). Severity and interference of IQ and psychiatric comorbidity was evaluated using several psychometric tests (Conners, CDI, STAIC, CAARMS, CBCL and hONOSCA). Inheritance pattern was assessed through Sanger sequencing. ACMG/AMP guidelines were used for variant classification.
ResultsIn our cohort, 64% patients presented BIF and 36% MID. 45% of the patients had 2 or more psychiatric diagnoses, the most prevalent (87%) being attention deficit hyperactivity disorder and, in second place, autism spectrum disorder (51%).
WES identified pathogenic/likely pathogenic variants in 30% of analyzed patients (30/99), 80% of the variants were de novo. There is no significant difference in patient severity between those with a genetic diagnosis and those without.
ConclusionsRare deleterious and de novo variants in neurodevelopmental genes are responsible for the comorbidity that exists between psychiatric disorders and mild/borderline intellectual disability.
The high diagnostic yield obtained from our exome sequencing approach demonstrates the need to offer genetic testing in children with psychiatric disorders and comorbid mild to borderline intellectual functioning.
Finally, patients being identified with a genetic diagnosis are subsequently attended in a specialised unit for rare disorders to receive personalised clinical management.
Disclosure of InterestNone Declared
Are Neurotrophin Genes Involved in the Pathophysiology of Gambling Disorder?
- I. Baenas, N. Solé-Morata, M. Etxandi, R. Granero, M. Gené, C. Barrot, P. Gorwood, N. Ramoz, F. Fernandez-Aranda, S. Jimenez-Murcia
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, pp. S240-S241
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Introduction
Gambling Disorder (GD) is considered a multifactorial behavioral addictive disorder, leading to severe psychological, social and economic consequences. Previous studies have investigated genetic mechanisms underlying GD. Growing literature showed a possible link between addiction-related disorders and neurotrophic factors (NTF), involved in synaptic plasticity and neuronal survival. Thus, the study of NTF genes emerged as promising targets in the field of GD.
ObjectivesTo evaluate genetic implications of the NTF family in the pathophysiology GD. We hypothesized the involvement of some NTF genes polymorphisms in the onset and progression of GD as potential biological risk factors.
MethodsThe sample was composed by 166 individuals with GD and 191 healthy controls. 36 Single nucleotide polymorphisms (SNPs) from NTF (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium and haplotype constructions were assessed, related to the presence of GD. Moreover, regulatory elements overlapping the identified SNPs variants associated with GD was also analyzed.
Results6 SNPs were potentially associated to GD after the comparisons of allele frequencies between groups. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD.
ConclusionsThis study suggests the implication of NTF genes in the development of GD, being the altered cross-regulation of some NTF factors signalling pathways, a potential biological vulnerability factor in GD. Fundings and Acknowledgements: Ministerio de Ciencia, Innovación y Universidades (RTI2018-101837-B-100) Delegación del Gobierno para el Plan Nacional sobre Drogas (2017I067, 2019I47), Instituto Salud Carlos III (ISCIII) (PI17/01167, PI20/00132) and CIBERObn, an initiative of ISCIII.
DisclosureNo significant relationships.
Peripheral endocannabinoids in eating disorders and obesity and its relationship with clinical and anthropometric variables
- I. Baenas-Soto, R. Miranda-Olivos, L. Vos, R. Granero, I. Sánchez, N. Riesco, A. Del Pino-Gutiérrez, E. Codina, J. A. Fernández-Formoso, N. Vilarrasa, N. Virgili, R. Lopez-Urdiales, A. Pastor, R. De La Torrre, S. Jimenez-Murcia, C. Soriano-Mas, F. Fernandez-Aranda
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S115
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Introduction
Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) play a pivotal role in food intake and reward aspects of feeding. Aberrant functioning in the endocannabinoid system has been observed in patients with eating disorders (EDs). This dysfunction may influence the incentive processes stimulating behaviors towards food acquisition or the hedonic evaluation of ingested food.
ObjectivesThe aims of this study are to compare fasting peripheral levels of AEA and 2-AG in ED patients, obese subjects (OB) and healthy controls (HCs), and to explore their association with clinical and anthropometric variables.
MethodsThe sample included a total of 63 adult women. Peripheral blood samples were collected to investigate fasting levels of AEA and 2-AG in 31 ED patients: 22 Anorexia Nervosa (AN) and 9 Binge Eating Disorder (BED), compared to 21 OB and 11 HCs. Several clinical and anthropometric variables were also assessed.
ResultsComparing groups, significant differences in AEA levels were found (p=0.001). Specifically, individuals with AN exhibited lower AEA than OB (p<0.001) and BED (p=0.007), while OB showed higher AEA than HCs (p=0.015). 2-AG was positively correlated with hostility dimension in EDs and negatively associated with impulsive traits in OB. AEA showed a direct association with body dissatisfaction in AN, contrary to OB. Finally, in AN, AEA negatively correlated with the body mass index, while 2-AG was positively associated with the fat mass.
ConclusionsThese results suggest an interaction between biological and clinical factors defining a vulnerability pathway that could help fitting personalized therapeutic approaches in each condition.
DisclosureNo significant relationships.
Effect of the rearing system on financial returns from Murciano-Granadina breed goats
- N. Fernández, J. L. Palomares, I. Pérez-Baena, M. Rodríguez, C. Peris
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In dairy goats, the kid rearing system can have critical importance in financial returns. Commonly used criteria for the choice of rearing system are not always clear due to the high number of factors involved. The aim of this study was to quantify all those factors to facilitate decision making. So, the effect of two different kid rearing systems, mixed rearing system (MRS) and artificial rearing system (ARS), on milk yield, milk composition and somatic cell count (SCC), milk yield loss at weaning for MRS, kid growth and costs of the different traits on the financial returns in Murciano-Granadina breed goats was studied. Twenty-four goats per group were used. In the MRS, goats reared only one kid, which had free access to goat milk 24 h a day and were weaned at week 6 of lactation, whereas kids in the ARS were separated from their mothers at kidding, colostrum and artificially reared. In both systems, dams were machine-milked once a day throughout lactation and the records took place weekly. Potential milk yield was estimated according to the oxytocin method up to week 12 of lactation, and was similar for both rearing systems, although a 12.3% drop in potential milk yield at weaning was observed for MRS. During the first 6 weeks of lactation, marketable milk was lower for dams in MRS compared to those in ARS (72.1 v. 113.0 l), but similar for the rest of the experiment (101.5 v. 99.4 l, respectively). Marketable milk composition and SCC throughout the 12 weeks of lactation were unaffected by the rearing system. Artificial rearing system entailed an increment in production cost of 22.2€ per kid compared to the rearing by MRS. A similar economic return per goat and kid was obtained from ARS and MRS in this experiment, although, due to one herd’s prolificacy of 1.8, the actual results would be 16.2€ per goat in favour of MRS. The real interest of this experiment may be the possibility of extrapolation to different flocks with diverse levels of milk production, prolificacy and prices and costs for incomes and outputs, to estimate the production system that increases returns. In conclusion, the results showed an increase in the cost of €22.2 per kid bred in the ARS, compared to the MRS, and a final return of 16.2€ per goat in favour of the mixed system.