Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis

Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22-7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39-16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis us

Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis

Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects’ sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22–7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39–16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosisinducing effect of cannabis use

“Ectomosphere”: Insects and Microorganism Interactions

This study focuses on interacting with insects and their ectosymbiont (lato sensu) microorganisms for environmentally safe plant production and protection. Some cases help compare insect-bearing, -driving, or -spreading relevant ectosymbiont microorganisms to endosymbionts’ behaviour. Ectosymbiotic bacteria can interact with insects by allowing them to improve the value of their pabula. In addition, some bacteria are essential for creating ecological niches that can host the development of pests. Insect-borne plant pathogens include bacteria, viruses, and fungi. These pathogens interact with their vectors to enhance reciprocal fitness. Knowing vector-phoront interaction could considerably increase chances for outbreak management, notably when sustained by quarantine vector ectosymbiont pathogens, such as the actual Xylella fastidiosa Mediterranean invasion episode. Insect pathogenic viruses have a close evolutionary relationship with their hosts, also being highly specific and obligate parasites. Sixteen virus families have been reported to infect insects and may be involved in the biological control of specific pests, including some economic weevils. Insects and fungi are among the most widespread organisms in nature and interact with each other, establishing symbiotic relationships ranging from mutualism to antagonism. The associations can influence the extent to which interacting organisms can exert their effects on plants and the proper management practices. Sustainable pest management also relies on entomopathogenic fungi; research on these species starts from their isolation from insect carcasses, followed by identification using conventional light or electron microscopy techniques. Thanks to the development of omics sciences, it is possible to identify entomopathogenic fungi with evolutionary histories that are less-shared with the target insect and can be proposed as pest antagonists. Many interesting omics can help detect the presence of entomopathogens in different natural matrices, such as soil or plants. The same techniques will help localize ectosymbionts, localization of recesses, or specialized morphological adaptation, greatly supporting the robust interpretation of the symbiont role. The manipulation and modulation of ectosymbionts could be a more promising way to counteract pests and borne pathogens, mitigating the impact of formulates and reducing food insecurity due to the lesser impact of direct damage and diseases. The promise has a preventive intent for more manageable and broader implications for pests, comparing what we can obtain using simpler, less-specific techniques and a less comprehensive approach to Integrated Pest Management (IPM).The present work acknowledges the support from: European Union’s Horizon 2020 research and innovation programme under Grant Agreements No. 635646-POnTE “Pest Organisms Threatening Europe”, No. 727987-XF-ACTORS “Xylella Fastidiosa Active Containment Through a multidisciplinary-Oriented Research Strategy”, Grant number 952337-MycoTWIN “Enhancing Research and Innovation Capacity of Tubitak MAM Food Institute on Management of Mycotoxigenic Fungi and Mycotoxins”, and CURE-Xf, H2020-Marie Sklodowska-Curie Actions—Research and Innovation Staff Exchange. Reference number: 634353, coordinated by CIHEAM Bari. The EU Funding Agency is not responsible for any use that may be made of the information it contains. European Union’s StopMedWaste “Innovative Sustainable technologies TO extend the shelf-life of Perishable MEDiterranean fresh fruit, vegetables and aromatic plants and to reduce WASTE” a PRIMA project ID: 1556. European Union’s Euphresco BasicS “Basic substances as an environmentally friendly alternative to synthetic pesticides for plant protection” project ID: 2020-C-353. The work was partially carried out in the framework of the National Projects: RIGENERA, granted by MASAF n. 207631, 9 May 2022, and GENFORAGRIS, granted by MASAF n. 207631, 9 May 2022; and regional projects “Laboratory network for the selection, characterisation and conservation of germplasm and for preventing the spread of economically-relevant and quarantine pests (SELGE) No. 14”, founded by the Apulia Region, PO FESR 2007–2013—Axis I, Line of intervention 1.2., Action 1.2.1; Research for Innovation (REFIN) POR Puglia 2014–2020 Project: 8C6E699D, and PON AIM, COD. AIM 1809249-Attività 1 Linea 1

Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2

Peer reviewe

DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine

Rationale: Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. Objective: We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). Methods: Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p < 0.05, family-wise error corrected) was used. Results: On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. Conclusions: These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load

Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non -responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI &lt;10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person