Anhedonia, apathy, pleasure, and effort-based decision-making in adult and adolescent cannabis users and controls

BACKGROUND: Cannabis use may be linked with anhedonia and apathy. However, previous studies have shown mixed results and few have examined the association between cannabis use and specific reward sub-processes. Adolescents may be more vulnerable to harmful effects of cannabis than adults. This study investigated (1) the association between non-acute cannabis use and apathy, anhedonia, pleasure, and effort-based decision-making for reward, and (2) whether these relationships were moderated by age-group. METHODS: We used data from the 'CannTeen' study. Participants were 274 adult (26-29 years) and adolescent (16-17 years) cannabis users (1-7 days/week use in the past three months), and gender- and age-matched controls. Anhedonia was measured with the Snaith-Hamilton Pleasure Scale (n=274), and apathy was measured with the Apathy Evaluation Scale (n=215). Effort-based decision-making for reward was measured with the Physical Effort task (n=139), and subjective wanting and liking of rewards was measured with the novel Real Reward Pleasure task (n=137). RESULTS: Controls had higher levels of anhedonia than cannabis users (F1,258=5.35, p=.02, ηp2=.02). There were no other significant effects of User-Group and no significant User-Group*Age-Group interactions. Null findings were supported by post hoc Bayesian analyses. CONCLUSION: Our results suggest that cannabis use at a frequency of three to four days per week is not associated with apathy, effort-based decision-making for reward, reward wanting, or reward liking in adults or adolescents. Cannabis users had lower anhedonia than controls, albeit at a small effect size. These findings are not consistent with the hypothesis that non-acute cannabis use is associated with amotivation

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Multidimensional Functional Profiling of Human Neuropathogenic <i>FOXG1</i> Alleles in Primary Cultures of Murine Pallial Precursors

FOXG1 is an ancient transcription factor gene mastering telencephalic development. A number of distinct structural FOXG1 mutations lead to the “FOXG1 syndrome”, a complex and heterogeneous neuropathological entity, for which no cure is presently available. Reconstruction of primary neurodevelopmental/physiological anomalies evoked by these mutations is an obvious pre-requisite for future, precision therapy of such syndrome. Here, as a proof-of-principle, we functionally scored three FOXG1 neuropathogenic alleles, FOXG1G224S, FOXG1W308X, and FOXG1N232S, against their healthy counterpart. Specifically, we delivered transgenes encoding for them to dedicated preparations of murine pallial precursors and quantified their impact on selected neurodevelopmental and physiological processes mastered by Foxg1: pallial stem cell fate choice, proliferation of neural committed progenitors, neuronal architecture, neuronal activity, and their molecular correlates. Briefly, we found that FOXG1G224S and FOXG1W308X generally performed as a gain- and a loss-of-function-allele, respectively, while FOXG1N232S acted as a mild loss-of-function-allele or phenocopied FOXG1WT. These results provide valuable hints about processes misregulated in patients heterozygous for these mutations, to be re-addressed more stringently in patient iPSC-derivative neuro-organoids. Moreover, they suggest that murine pallial cultures may be employed for fast multidimensional profiling of novel, human neuropathogenic FOXG1 alleles, namely a step propedeutic to timely delivery of therapeutic precision treatments

Nuovo complesso parrocchiale dello Spirito Santo, Benevento (IT) - FINALISTA SECONDA FASE

Progetto per il nuovo complesso parrocchiale dello Spirito Santo a Benevento (chiesa, locali di ministero pastorale, canonica, aree esterne). Il progetto è stato elaborato nell'ambito del Concorso di idee in due fasi indetto dall'Arcidiocesi di Benevento e dall'Ufficio Nazionale per i beni culturali ecclesiastici e l'edilizia di culto della CEI. Progetto finalista nella seconda fase della procedura concorsuale. Gruppo di progettazione: Manuela Antoniciello (Architetto Capogruppo); Felice De Silva, Renato Capozzi, Federica Visconti ; (Consulenti Scientifici Esperti Di Progettazione Architettonica); Carmine Andreotti (Consulente Esperto In Strutture); Claudio Guarnaccia (Consulente Scientifico Esperto Di Acustica Ambientale E Architettonica); Don Marco Valentini (Liturgista); Oliviero Rainaldi (Artista); Salvatore Giugliano, Giuseppe Sabatino, Giammarco Gioia (Collaboratori)

Copy Number Variants Account for a Tiny Fraction of Undiagnosed Myopathic Patients

Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5–9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5–9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.Peer reviewe

VISTA enhancer loci deleted in our patients.

*<p>deleted regions as detected by sequencing.</p

VISTA enhancer loci localized in polymorphic CNV regions.

<p>VISTA enhancer loci localized in polymorphic CNV regions.</p

New CNVs overlapping VISTA enhancers.

<p>aCGH results for sample 1 (<b>a</b>), 25 (<b>b</b>) and 27 (<b>c</b>) showing deletions overlapping enhancers hs775, hs676 and hs607, respectively. (<b>d</b>) Genotyping assay for deletions in enhancers hs775 (upper panel), hs676 (middle panel) and hs607 (lower panel): triplex PCR with a forward primer (bpF) located 5' to the breakpoint, a reverse primer within the deleted region (in red) and a second one 3′ the distal breakpoint (box represents the enhancer elements). Bands of 264 bp, 380 bp and 360 bp, respectively, correspond to bpF-IntR amplicons, the lower bands represent bpF-bpR amplicons. Only sample 1 (* in upper panel), 25 (• in middle panel) and 27 (♦ in lower panel) show, respectively, the double bands, all the other analyzed samples show a normal pattern.</p